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The discovery of the glymphatic system, crucial for cerebrospinal and interstitial fluid exchange, has enhanced our grasp of brain protein balance and its potential role in neurodegenerative disease prevention and therapy. Detecting early neurodegenerative shifts via noninvasive biomarkers could be key in identifying at-risk individuals for Alzheimer's disease (AD). Our research explores a diffusion tensor imaging (DTI) method that measures cortical mean diffusivity (cMD), potentially a more sensitive indicator of neurodegeneration than traditional macrostructural methods. We analyzed 67 post-traumatic stress disorder (PTSD)-diagnosed veterans from the Alzheimer's Disease Neuroimaging Initiative database. Participants underwent structural MRI, DTI, Aβ PET imaging, and cognitive testing. We focused on the DTI-ALPS technique to assess glymphatic function and its relation to cMD, cortical Aβ accumulation, and thickness, accounting for age and APOE ε4 allele variations. The cohort, all male with an average age of 68.1 (SD 3.4), showed a strong inverse correlation between DTI-ALPS and cMD in AD-affected regions, especially in the entorhinal, parahippocampal, and fusiform areas. Higher DTI-ALPS readings were consistently linked with greater cortical thickness, independent of Aβ deposits and genetic risk factors. Age and cMD emerged as inversely proportional predictors of DTI-ALPS, indicating a complex interaction with age. The study confirms a meaningful association between glymphatic efficiency and cMD in AD-sensitive zones, accentuating cortical microstructural alterations in PTSD. It positions DTI-ALPS as a viable biomarker for assessing glymphatic function in PTSD, implicating changes in DTI-ALPS as indicative of glymphatic impairment. • We explored the association between human glymphatic function, cMD, cortical Aβ deposition, and cortical thickness. • Significant associations were identified between glymphatic function and cMD in AD-susceptible brain regions. • Associations among DTI-ALPS, aging, and cortical thickness were noted. • We suggested the potential of DTI-ALPS as a biomarker of glymphatic function in PTSD. • Moreover, changes in DTI-ALPS occur in PTSD, possibly due to glymphatic system impairment. [ABSTRACT FROM AUTHOR]

The serotonin 2A (5-HT2A) receptor is an important target for drug development and the main receptor through which classical psychedelics elucidate their hallucinogenic effects. The 5-HT2A receptor antagonist ketanserin has frequently been used as a tool to block the receptor. Here, we establish the dose-occupancy relation of ketanserin and the cerebral 5-HT2A receptor in healthy participants by conducting a positron emission tomography (PET) study. 120-min PET scans using the 5-HT2A receptor agonist radiotracer [11C]Cimbi-36 were conducted at baseline and after oral doses of either 10, 20, or 40 mg of ketanserin; each participant underwent one or two scans after ketanserin administration. Occupancy was defined as the percent change in neocortex binding potential (BP ND), estimated using the simplified reference tissue model (SRTM) with the cerebellum as reference region. Peroral ketanserin intake resulted in a plasma concentration-related increase in cerebral 5-HT2A receptor occupancy with the highest plasma ketanserin concentrations measured after ∼2 h. The relation between mean plasma ketanserin concentrations and 5-HT2A receptor occupancy conformed to a single-site binding model with an estimated EC 50 (95 % CI) of 2.52 (0.75; 8.1) ng/mL, which corresponds to a peroral dose of ketanserin of approximately 10 mg. These data elucidate for the first time in humans the cerebral pharmacodynamics of ketanserin, both benefitting its use as a pharmacological tool for probing brain function and adding to its potential for therapeutic use in rescuing a bad psychedelic experience. [ABSTRACT FROM AUTHOR]

Radionuclide therapy, in particular peptide receptor radionuclide therapy (PRRT), has emerged as a valuable means to combat malignant tumors. The specific affinity of ACUPA peptide toward prostate-specific membrane antigen (PSMA) renders the successful development of PRRT for prostate cancer. The clinical outcome of PRRT is, however, generally challenged by moderate tumor uptake and off-target toxicity. Here, we report on a novel design of Sigma-1 receptor and PSMA dual-receptor targeted peptide (S1R/PSMA-P) for superior radionuclide imaging and therapy of prostate cancer. S1R/PSMA-P was acquired with good purity and could efficiently be labeled with 177Lu to yield 177Lu-S1R/PSMA-P with high specific activity and radiostability. Interestingly, 177Lu-S1R/PSMA-P revealed greatly enhanced affinity to LNCaP cells over single-targeted control 177Lu-PSMA-617. The single photon emission computed tomography (SPECT) imaging demonstrated exceptional uptake and retention of 177Lu-S1R/PSMA-P in LNCaP tumor, affording about 2-fold better tumor accumulation while largely reduced uptake by most normal tissues compared to 177Lu-PSMA-617. The selective uptake in LNCaP tumor was also visualized by positron emission tomography (PET) with 68Ga-S1R/PSMA-P. In accordance, a single and low dosage of 177Lu-S1R/PSMA-P at 11.1 MBq effectively suppressed tumor growth without causing apparent side effects. This dual-targeting strategy presents an appealing radionuclide therapy for malignant tumors. Sigma-1 receptor and PSMA dual-receptor targeted peptide (S1R/PSMA-P) labeled with 177Lu or 68Ga can efficiently target and bind to LNCaP prostate cancer cells, inducing superior radionuclide therapy and imaging of prostate tumor in mice. [Display omitted] [ABSTRACT FROM AUTHOR]

Understanding the neurobiological effects of stress is critical for addressing the etiology of major depressive disorder (MDD). Using a dimensional approach involving individuals with differing degree of MDD risk, we investigated 1) the effects of acute stress on cortico-cortical and subcortical-cortical functional connectivity (FC) and 2) how such effects are related to gene expression and receptor maps. Across 115 participants (37 control, 39 remitted MDD, 39 current MDD), we evaluated the effects of stress on FC during the Montreal Imaging Stress Task. Using partial least squares regression, we investigated genes whose expression in the Allen Human Brain Atlas was associated with anatomical patterns of stress-related FC change. Finally, we correlated stress-related FC change maps with opioid and GABA A (gamma-aminobutyric acid A) receptor distribution maps derived from positron emission tomography. Results revealed robust effects of stress on global cortical connectivity, with increased global FC in frontoparietal and attentional networks and decreased global FC in the medial default mode network. Moreover, robust increases emerged in FC of the caudate, putamen, and amygdala with regions from the ventral attention/salience network, frontoparietal network, and motor networks. Such regions showed preferential expression of genes involved in cell-to-cell signaling (OPRM1 , OPRK1 , SST , GABRA3 , GABRA5), similar to previous genetic MDD studies. Acute stress altered global cortical connectivity and increased striatal connectivity with cortical regions that express genes that have previously been associated with imaging abnormalities in MDD and are rich in μ and κ opioid receptors. These findings point to overlapping circuitry underlying stress response, reward, and MDD. [ABSTRACT FROM AUTHOR]

Recurrent head and neck cancer presents a therapeutic challenge because of cumulative toxicity from initial radiation therapy, limiting reirradiation options. Boron neutron capture therapy (BNCT) offers a promising alternative, selectively delivering a radical dose to tumors while sparing adjacent normal tissue. This study investigates the initial clinical outcomes and prognostic factors associated with BNCT for recurrent squamous cell carcinoma of the head and neck. This retrospective analysis investigated the initial 47 patients treated with BNCT between May 2020 and February 2021 in Japan. All patients had received radiation therapy with a median dose of 70 Gy (range, 44-176) before BNCT. Median tumor size was 11 cm3 (range, 1-117 cm3), with 23% of tumors larger than 30 cm3, and 87% of patients had prior systemic therapy. The most common prescribed dose to the pharyngeal mucosa was 15 Gy-Eq (36%), followed by 18 Gy-Eq (34%). The minimum dose given to tumor was 27.4 Gy-Eq (range, 13.3-45.2). In 23 patients, 18F-fluoro-borono-phenylalanine positron emission tomography was performed within 1 week before BNCT, and the tumor-to-blood 10B ratio was 3.5 (range, 2.0-8.7). Efficacy analysis revealed a 51% complete response rate and a 74% overall response rate. Disease-free survival rates at 1 and 2 years were 34.6% and 26.6%, respectively. Overall survival rates at 1 and 2 years were 86.1% and 66.5%, respectively. Multivariate analysis revealed that, among the patient characteristics, whether the lesion was mucosal had a significant effect on achieving complete response. This study provided valuable insights into the early integration of BNCT into routine clinical practice, highlighting its efficacy and safety. Technical improvements are needed to ensure precise dose administration. Ongoing prospective studies, such as the phase II REBIVAL study, will further elucidate the role of BNCT in recurrent head and neck cancer. [ABSTRACT FROM AUTHOR]

Striatal hyperdopaminergia is implicated in the pathoetiology of schizophrenia, but how this relates to dopaminergic midbrain activity is unclear. Neuromelanin (NM)-sensitive magnetic resonance imaging provides a marker of long-term dopamine function. We examined whether midbrain NM-sensitive magnetic resonance imaging contrast-to-noise ratio (NM-CNR) was higher in people with schizophrenia than in healthy control (HC) participants and whether this correlated with dopamine synthesis capacity. One hundred fifty-four participants (schizophrenia group: n = 74, HC group: n = 80) underwent NM-sensitive magnetic resonance imaging of the substantia nigra and ventral tegmental area (SN-VTA). A subset of the schizophrenia group (n = 38) also received [18F]-DOPA positron emission tomography to measure dopamine synthesis capacity (K i cer) in the SN-VTA and striatum. SN-VTA NM-CNR was significantly higher in patients with schizophrenia than in HC participants (effect size = 0.38, p =.019). This effect was greatest for voxels in the medial and ventral SN-VTA. In patients, SN-VTA K i cer positively correlated with SN-VTA NM-CNR (r = 0.44, p =.005) and striatal K i cer (r = 0.71, p <.001). Voxelwise analysis demonstrated that SN-VTA NM-CNR was positively associated with striatal K i cer (r = 0.53, p =.005) and that this relationship seemed strongest between the ventral SN-VTA and associative striatum in schizophrenia. Our results suggest that NM levels are higher in patients with schizophrenia than in HC individuals, particularly in midbrain regions that project to parts of the striatum that receive innervation from the limbic and association cortices. The direct relationship between measures of NM and dopamine synthesis suggests that these aspects of schizophrenia pathophysiology are linked. Our findings highlight specific mesostriatal circuits as the loci of dopamine dysfunction in schizophrenia and thus as potential therapeutic targets. [ABSTRACT FROM AUTHOR]

We sought to investigate the impact of sex on myocardial perfusion changes following chronic total coronary occlusion (CTO) percutaneous coronary intervention (PCI) as measured by [15O]H 2 O positron-emission tomography (PET) perfusion imaging. CTO PCI has been associated with an increase in myocardial perfusion, yet females are less likely to undergo revascularization. As such, data on the impact of sex on myocardial perfusion following CTO PCI is scarce. A total of 212 patients were prospectively enrolled and underwent CTO PCI combined with [15O]H 2 O PET perfusion imaging prior to and 3 months after PCI. Hyperemic myocardial blood flow (hMBF, mL·min−1·g−1) and coronary flow reserve (CFR) allocated to the CTO territory were quantitatively assessed. This study comprised 34 (16 %) females and 178 (84 %) males. HMBF at baseline did not differ between sexes. Females showed a higher increase in hMBF than males (Δ1.34 ± 0.67 vs. Δ1.06 ± 0.74, p = 0.044), whereas post-PCI hMBF was comparable (2.59 ± 0.85 in females vs. 2.28 ± 0.84 in males, p = 0.052). Female sex was independently associated with a higher increase in hMBF after correction for clinical covariates. CFR increase after revascularization was similar in females and males (Δ1.47 ± 0.99 vs. Δ1.30 ± 1.14, p = 0.711). The present study demonstrates a greater recovery of stress perfusion in females compared to males as measured by serial [15O]H 2 O PET imaging. In addition, a comparable increase in CFR was found in females and males. These results emphasize the benefit of performing CTO PCI in both sexes. What is new? • CTO PCI has been associated with an increase in myocardial perfusion, yet females are less likely to undergo revascularization. • We found a greater recovery of stress perfusion in females compared to males after CTO PCI as measured by serial [15O]H 2 O PET imaging, whereas coronary flow reserve was comparable between sexes. • The present study adds to the limited body of evidence on the impact of sex on myocardial perfusion following CTO PCI. What are the clinical implications? • Our findings suggest that recovery of myocardial perfusion following CTO PCI is achievable in both female and male patients. • These results underscore the need to adhere to current guidelines for optimal CTO management in both sexes. • Future studies with standardized preprocedural imaging are warranted to increase our understanding of the impact of sex on changes in myocardial perfusion following CTO PCI. • CTO PCI is associated with an increase in myocardial perfusion, yet females are less likely to undergo revascularization. • We found a greater recovery of stress perfusion in females after CTO PCI as measured by serial [15O]H 2 O PET imaging. • Our findings suggest that recovery of myocardial perfusion following CTO PCI is achievable in both female and male patients. • These results underscore the need to adhere to current guidelines for optimal CTO management in both sexes. • Studies with preprocedural imaging are warranted to increase our understanding of the impact of sex on MBF after CTO PCI. [ABSTRACT FROM AUTHOR]

Perineural tumour spread in head and neck cancer can be a challenging diagnosis for radiologists; head and neck anatomy is intimidating and perineural tumour spread can be subtle and difficult to detect. It results in significant morbidity for patients, can upstage disease and will frequently result in more prolonged treatment courses. This pictorial review provides a thorough examination of the imaging characteristics of perineural tumour spread in head and neck malignancy. It highlights key imaging features, from initial diagnosis to its post-therapy appearance, emphasising the clinical relevance and role of imaging in post-therapy assessment. Multi-modality imaging examples are included with a focus on magnetic resonance imaging (MRI) and positron-emission tomography (PET)/computed tomography (CT). MRI features of perineural tumour spread include intermediate T2 signal expansion of a nerve, abnormal enhancement extending along a nerve, expansion of a skull or neural foramen and loss of normal fat planes surrounding nerve pathways. 18F-fluorodeoxyglucose (FDG) PET/CT is a useful adjunct to MRI, perineural tumour spread results in abnormal FDG accumulation in a linear fashion anatomically spreading along a nerve pathway. Knowledge of these features and useful check areas will ensure that radiologists can be confident both in making the diagnosis and re-assessment post-therapy. • Perineural tumour spread results in morbidity for patients and can upstage disease. • Fat pad check areas are critical for identifying perineural tumour spread. • 18F-FDG PET/CT is a very useful adjunct to MRI in post-therapy assessment. [ABSTRACT FROM AUTHOR]

Radiomics involves the extraction of quantitative data from medical images to facilitate the diagnosis, prognosis, and staging of tumors. This study provides a comprehensive overview of the efficacy of radiomics in prognostic applications for head and neck cancer (HNC) in recent years. It undertakes a systematic review of prognostic models specific to HNC and conducts a meta-analysis to evaluate their predictive performance. This study adhered rigorously to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for literature searches. The literature databases, including PubMed, Embase, Cochrane, and Scopus were systematically searched individually. The methodological quality of the incorporated studies underwent assessment utilizing the radiomics quality score (RQS) tool. A random-effects meta-analysis employing the Harrell concordance index (C-index) was conducted to evaluate the performance of all radiomics models. Among the 388 studies retrieved, 24 studies encompassing a total of 6,978 cases were incorporated into the systematic review. Furthermore, eight studies, focusing on overall survival as an endpoint, were included in the meta-analysis. The meta-analysis revealed that the estimated random effect of the C-index for all studies utilizing radiomics alone was 0.77 (0.71–0.82), with a substantial degree of heterogeneity indicated by an I2 of 80.17%. Based on this review, prognostic modeling utilizing radiomics has demonstrated enhanced efficacy for head and neck cancers; however, there remains room for improvement in this approach. In the future, advancements are warranted in the integration of clinical parameters and multimodal features, balancing multicenter data, as well as in feature screening and model construction within this field. • Radiomics models perform well in head and neck cancer prognosis. • Clinical features may not necessarily enhance the performance of radiomics models. • Multimodal imaging contributes to the improvement of radiomics models. [ABSTRACT FROM AUTHOR]

Local recurrence remains the main cause of death in stage III-IV nonmetastatic head and neck cancer (HNC), with relapse-prone regions within high 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET)-signal gross tumor volume. We investigated if dose escalation within this subvolume combined with a 3-phase treatment adaptation could increase local (LC) and regional (RC) control at equal or minimized radiation-induced toxicity, by comparing adaptive 18F-FDG-PET voxel intensity–based dose painting by numbers (A-DPBN) with nonadaptive standard intensity modulated radiation therapy (S-IMRT). This 2-center randomized controlled phase 2 trial assigned (1:1) patients to receive A-DPBN or S-IMRT (+/–chemotherapy). Eligibility: nonmetastatic HNC of oral cavity, oro-/hypopharynx, or larynx, needing radio(chemo)therapy; T1-4N0-3 (exception: T1-2N0 glottic); KPS ≥ 70; ≥18 years; and informed consent. Primary outcomes: 1-year LC and RC. The dose prescription for A-DPBN was intercurrently adapted in 2 steps to an absolute dose-volume limit (≤1.75 cm3 can receive >84 Gy and normalized isoeffective dose >96 Gy) as a safety measure during the study course after 4/7 A-DPBN patients developed ≥G3 mucosal ulcers. Ninety-five patients were randomized (A-DPBN, 47; S-IMRT, 48). Median follow-up was 31 months (IQR, 14-48 months); 29 patients died (17 of cancer progression). A-DPBN resulted in superior LC compared with S-IMRT, with 1- and 2-year LC of 91% and 88% versus 78% and 75%, respectively (hazard ratio, 3.13; 95% CI, 1.13-8.71; P =.021). RC and overall survival were comparable between arms, as was overall grade (G) ≥3 late toxicity (36% vs 20%; P =.1). More ≥G3 late mucosal ulcers were observed in active smokers (29% vs 3%; P =.005) and alcohol users (33% vs 13%; P =.02), independent of treatment arm. Similarly, in the A-DPBN arm, significantly more patients who smoked at diagnosis developed ≥G3 (46% vs 12%; P =.005) and ≥G4 (29% vs 8%; P =.048) mucosal ulcers. One arterial blowout occurred after a G5 mucosal toxicity. A-DPBN resulted in superior 1- and 2-year LC for HNC compared with S-IMRT. This supports further exploration in multicenter phase 3 trials. It will, however, be challenging to recruit a substantial patient sample for such trials, as concerns have arisen regarding the association of late mucosal ulcers when escalating the dose in continuing smokers. [ABSTRACT FROM AUTHOR]

Positron emission tomography (PET) and magnetic resonance spectroscopy (1H-MRS) are complementary techniques that can be applied to study how proteinopathy and neurometabolism relate to cognitive deficits in preclinical stages of Alzheimer's disease (AD)—mild cognitive impairment (MCI) and late-life depression (LLD). We acquired beta-amyloid (Aβ) PET and 7 T 1H-MRS measures of GABA, glutamate, glutathione, N-acetylaspartate, N-acetylaspartylglutamate, myo-inositol, choline, and lactate in the anterior and posterior cingulate cortices (ACC, PCC) in 13 MCI and 9 LLD patients, and 13 controls. We used linear regression to examine associations between metabolites, Aβ, and cognitive scores, and whether metabolites and Aβ explained cognitive scores better than Aβ alone. In the ACC, higher Aβ was associated with lower GABA in controls but not MCI or LLD patients, but results depended upon MRS data quality control criteria. Greater variance in California Verbal Learning Test scores was better explained by a model that combined ACC glutamate and Aβ deposition than by models that only included one of these variables. These findings identify preliminary associations between Aβ, neurometabolites, and cognition. [Display omitted] • Astudy of mild cognitive impairment, late-life depression, and healthy controls. • We examined beta-amyloid (Aβ) and neurometabolites using PET and 7 T MRS. • We report novel associations between brain metabolites and Aβ. • Glu + Aβ predicts verbal learning scores better than Aβ-only models. [ABSTRACT FROM AUTHOR]

Elucidating biological mechanisms contributing to bipolar disorder (BD) is key to improved diagnosis and treatment development. With converging evidence implicating the metabotropic glutamate receptor 5 (mGlu5) in the pathology of BD, here, we therefore test the hypothesis that recently identified deficits in mGlu5 are associated with functional brain differences during emotion processing in BD. Positron emission tomography (PET) with [18F]FPEB was used to measure mGlu5 receptor availability and functional imaging (fMRI) was performed while participants completed an emotion processing task. Data were analyzed from 62 individuals (33 ± 12 years, 45 % female) who completed both PET and fMRI, including individuals with BD (n = 18), major depressive disorder (MDD: n = 20), and psychiatrically healthy comparisons (HC: n = 25). Consistent with some prior reports, the BD group displayed greater activation during fear processing relative to MDD and HC, notably in right lateralized frontal and parietal brain regions. In BD, (but not MDD or HC) lower prefrontal mGlu5 availability was associated with greater activation in bilateral pre/postcentral gyri and cuneus during fear processing. Furthermore, greater prefrontal mGlu5-related brain activity in BD was associated with difficulties in psychomotor function (r ≥ 0.904, p ≤ 0.005) and attention (r ≥ 0.809, p ≤ 0.028). The modest sample size is the primary limitation. Deficits in prefrontal mGlu5 in BD were linked to increased cortical activation during fear processing, which in turn was associated with impulsivity and attentional difficulties. These data further implicate an mGlu5-related mechanism unique to BD. More generally these data suggest integrating PET and fMRI can provide novel mechanistic insights. • Functional (fMRI) and molecular (PET) imaging performed in the same individuals with bipolar disorder (BD) and major depressive disorder (MDD). • Findings provide evidence of relationships between prefrontal mGlu5 and brain function during emotional processing that is unique to BD. • We propose a mechanism by which deficient prefrontal mGlu5 in BD contributes to alterations in clinically relevant brain function. • Understanding the role of mGlu5 in BD pathology could aid in the development of targeted, mechanistically informed treatments. [ABSTRACT FROM AUTHOR]

Medical therapy for aortic stenosis (AS) remains an elusive goal. This study sought to establish whether evogliptin, a dipeptidyl peptidase-4 inhibitor, could reduce AS progression. A total of 228 patients (age 67 ± 11 years; 33% women) with AS were randomly assigned to receive placebo (n = 75), evogliptin 5 mg (n = 77), or evogliptin 10 mg (n = 76). The primary endpoint was the 96-week change in aortic valve calcium volume (AVCV) on computed tomography. Secondary endpoints included the 48-week change in active calcification volume measured using 18F-sodium fluoride positron emission tomography (18F-NaF PET). There were no significant differences in the 96-week changes in AVCV between evogliptin 5 mg and placebo (−5.27; 95% CI: −55.36 to 44.82; P = 0.84) or evogliptin 10 mg and placebo (−18.83; 95% CI: −32.43 to 70.10; P = 0.47). In the placebo group, the increase in AVCV between 48 weeks and 96 weeks was higher than that between baseline and 48 weeks (136 mm3; 95% CI: 108–163 vs 102 mm3; 95% CI: 75–129; P = 0.0485). This increasing trend in the second half of the study was suppressed in both evogliptin groups. The 48-week change in active calcification volume on 18F-NaF PET was significantly lower in both the evogliptin 5 mg (−1,325.6; 95% CI: −2,285.9 to −365.4; P = 0.008) and 10-mg groups (−1,582.2; 95% CI: −2,610.8 to −553.5; P = 0.0038) compared with the placebo group. This exploratory study did not demonstrate the protective effect of evogliptin on AV calcification. Favorable 18F-NaF PET results and possible suppression of aortic valve calcification with longer medication use in the evogliptin groups suggest the need for larger confirmatory trials. (A Multicenter, Double-blind, Placebo-controlled, Stratified-randomized, Parallel, Therapeutic Exploratory Clinical Study to Evaluate the Efficacy and Safety of DA-1229 in Patients With Calcific Aortic Valve Disease; NCT04055883) [ABSTRACT FROM AUTHOR]

The translocator protein (TSPO) has been widely investigated as a PET-imaging biomarker of neuroinflammation and, more recently, as a therapeutic target for the treatment of neurodegenerative disease. TSPO ligands have been shown to exert neuroprotective effects in vivo and in vitro models of Alzheimer's disease (AD), by reducing toxic beta amyloid peptides, and attenuating brain atrophy. Recent transcriptomic and proteomic analyses, and the generation of TSPO-KO mice, have enabled new insights into the mechanistic function of TSPO in AD. Using a multi-omics approach in both TSPO-KO- and TSPO ligand-treated mice, we have demonstrated a key role for TSPO in microglial respiratory metabolism and phagocytosis in AD. In this review, we discuss emerging evidence for therapeutic and immunomodulatory functions of TSPO in AD, and new tools for studying TSPO in the brain. • TSPO is a candidate biomarker of neuroinflammation and potential therapeutic target for Alzheimer's disease. • TSPO is functionally implicated in cellular bioenergetics, lipid and reactive oxygen species homeostasis, and apoptosis. • These functions are thought to underlie TSPO effects on Aβ clearance, cytokine levels, oxidative stress, and neuronal loss. • Despite the promising benefits of TSPO-targeted drugs, their potential use in Alheimer's has not yet been tested. [ABSTRACT FROM AUTHOR]

Translocator protein (TSPO) is involved in several cellular mechanisms such as steroidogenesis, immunomodulation, cell proliferation and differentiation. Overexpressed in several neurodegenerative diseases and brain cancer, TSPO radioligands have been developed over the last 20 years in positron emission tomography (PET) imaging. Recently, TSPO radioligands have extended beyond their initial application due to their specific binding to activated macrophages, making them a compelling biomarker for deciphering the intricacies of the tumor microenvironment (TME). In this review, we synthesized recent progress from the evaluation of TSPO-specific PET tracers in various peripheral tumor models and highlighted the hurdles and limitations associated with heterogeneous uptake in healthy tissue and tumor regions to achieve the clinical development of such a radiotracer. • Translocator protein (TSPO) specific radioligands may be useful to explore cancer using PET imaging (Positron Emission Tomography). • TSPO is a compelling biomarker for deciphering the intricacies of the tumor microenvironment. • Recent progress from the evaluation of TSPO-specific PET tracers in various peripheral tumor models has been performed. • Hurdles and limitations associated with heterogeneous uptake in healthy tissue and tumor regions persist to achieve clinical applications. [ABSTRACT FROM AUTHOR]

Affective temperaments are assumed to have biological and neural bases. In the present study, we analyzed 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) images of healthy participants to explore the neural basis of affective temperaments. We utilized data of affective temperament measured by the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Autoquestionnaire and 18F-FDG PET images of healthy participants from two of our previous studies. A multiple regression analysis was performed to assess the association between 18F-FDG uptake and temperament scores using Statistical Parametric Mapping 12. The final sample included 62 healthy participants. Whole-brain analysis revealed a cluster of 18F-FDG uptake that was significantly and positively associated with irritable temperament scores in the right cerebellum (Crus II, VIII, and IX). After further adjustment for the other four temperament scores, whole-brain analysis revealed a cluster of 18F-FDG uptake significantly and positively associated with irritable temperament scores in the left insula and right cerebellum (Crus II, VIII, and IX). However, no significant association was found between 18F-FDG uptake and the other four temperaments (depressive, cyclothymic, hyperthymic, and anxious). The left insula and right cerebellum of the cerebrocerebellar circuit may be one of the neural bases of irritable temperament. [ABSTRACT FROM AUTHOR]

Prostate specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET-CT) is revolutionising the management of prostate cancer (PC) in primary staging and assessment of biochemical recurrence (BCR) through its higher diagnostic accuracy compared to both conventional imaging and previously available PET radiopharmaceuticals. PSMA is a transmembrane glycoprotein, highly expressed in prostate cancer, with its extracellular domain the target for PSMA PET radiopharmaceuticals. However, PSMA expression is not prostate specific and resultant PSMA uptake on PET-CT is not restricted to pathologies arising from the prostate gland. The increasing use of PSMA PET-CT has revealed PSMA uptake in a variety of non-prostatic benign and malignant diseases, which adds complexity to PET-CT interpretation and subsequent clinical management. This pictorial review will provide a thorough knowledge and understanding of the comprehensive range of PSMA avid non-prostatic benign and malignant diseases demonstrable on PSMA PET-CT, whilst highlighting the complimentary nature of other imaging modalities. • PSMA is a transmembrane glycoprotein highly expressed in prostate cancer (PC). • PSMA PET-CT is revolutionising PC management in staging and biochemical recurrence. • PSMA expression is not restricted to the prostate gland. • PSMA expression occurs in the endothelial tumour neovasculature. • PSMA uptake on PET-CT occurs in both non-prostatic benign and malignant diseases. [ABSTRACT FROM AUTHOR]

This meta-analysis aimed to evaluate the comparative diagnostic efficacy of [18F]Fluorodeoxyglucose positron emission tomography ([18F]FDG PET) and conventional imaging, MRI, and white blood cell (WBC) scintigraphy in detecting foot osteomyelitis among diabetic patients. An exhaustive search was conducted within the PubMed and Embase databases to identify publications available up until February 2024. Studies were included if they evaluated the diagnostic efficacy of [18F]FDG PET or the comparative diagnostic performance between PET and (MRI or WBC scintigraphy). Two researchers independently assessed the quality of the included studies, utilizing the Quality Assessment of Diagnostic Performance Studies (QUADAS-2) tool. Nine retrospective or prospective studies involving 605 patients were included in the meta-analysis. For [18F]FDG PET, the overall sensitivity was 0.83(95% CI: 0.69–0.94), while the overall specificity was 0.92(95% CI: 0.86–0.97). In the head-to-head comparison, no significant difference of sensitivity was found between [18F]FDG PET and MRI (0.72 vs. 0.68, P =0.81), as well as between [18F]FDG PET and WBC scintigraphy (0.57 vs. 0.66, P =0.64). In addition, specificity was also found to be no significant difference between [18F]FDG PET and MRI (0.90 vs. 0.82, P=0.27), as well as [18F]FDG PET and WBC scintigraphy (0.81 vs. 0.93, P =0.09). [18F]FDG PET demonstrates similar sensitivity and specificity to MRI and WBC scintigraphy in detecting foot osteomyelitis among diabetic patients. MRI, often cited as a primary choice in guidelines, might be preferred due to its lower cost and lower dose. Further larger sample prospective studies are needed to confirm these findings. • First meta-analysis in [18F]FDG PET and conventional imaging for osteomyelitis. • [18F]FDG PET has similar ability to MRI and WBC in foot osteomyelitis. • MRI might be preferred due to its lower cost and lower dose. [ABSTRACT FROM AUTHOR]

The objective of this study was to create and authenticate a prognostic model for lymph node metastasis (LNM) in colorectal cancer (CRC) that integrates clinical, radiomics, and deep transfer learning features. In this study, we analyzed data from 119 CRC patients who underwent F18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scanning. The patient cohort was divided into training and validation subsets in an 8:2 ratio, with an additional 33 external data points for testing. Initially, we conducted univariate analysis to screen clinical parameters. Radiomics features were extracted from manually drawn images using pyradiomics, and deep-learning features, radiomics features, and clinical features were selected using Least Absolute Shrinkage and Selection Operator (LASSO) regression and Spearman correlation coefficient. We then constructed a model by training a support vector machine (SVM), and evaluated the performance of the prediction model by comparing the area under the curve (AUC), sensitivity, and specificity. Finally, we developed nomograms combining clinical and radiological features for interpretation and analysis. The deep learning radiomics (DLR) nomogram model, which was developed by integrating deep learning, radiomics, and clinical features, exhibited excellent performance. The area under the curve was (AUC = 0.934, 95% confidence interval [CI]: 0.884–0.983) in the training cohort, (AUC = 0.902, 95% CI: 0.769–1.000) in the validation cohort, and (AUC = 0.836, 95% CI: 0.673–0.998) in the test cohort. We developed a preoperative predictive machine-learning model using deep transfer learning, radiomics, and clinical features to differentiate LNM status in CRC, aiding in treatment decision-making for patients. • Multimodal and multiparametric codiagnosis of lymph node metastases. • Deep learning applied to positron emission tomography/computed tomography (PET/CT) has undeniable advantages. • Multicenter validation. [ABSTRACT FROM AUTHOR]

Magnetization transfer ratio asymmetry (MTRasym) analysis is used for chemical exchange saturation transfer (CEST) in patients with gliomas; however, this approach has limitations. CEST imaging using a multi-pool model (MPM) may allow a more detailed assessment of gliomas; however, its mechanism remains unknown. This study aimed to assess the relationship between CEST imaging by MPM, intravoxel incoherent motion (IVIM), and 11C-methionine (11C-MET) uptake on positron emission tomography/computed tomography (PET/CT) to clarify the clinical significance of CEST imaging using MPM in gliomas. This retrospective study included 17 patients with gliomas who underwent 11C-MET PET/CT at our institution between January 2020 and January 2022. Two-dimensional axial CEST imaging was conducted using single-shot fast-spin echo acquisition at 3 T. The apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo-diffusion coefficient (D*), f, MTRasym (3.5 ppm), parameters of MPM-based CEST imaging, and tumor-to-contralateral normal brain tissue (T/N) ratio were calculated using a region-of-interest analysis. Shapiro–Wilk test, weighted kappa coefficient, and Spearman's rank correlation coefficients were used for statistical analysis. Significant correlations were found between APT_T1 and T/N ratio (ρ = 0.87, p < 0.001), APT_T2 and T/N ratio (ρ = 0.47, p < 0.05), MTRasym and T/N ratio (ρ = 0.55, p < 0.01), and T2/T1 and T/N ratio (ρ = −0.36, p < 0.05). Furthermore, significant correlations were observed between APT_T1 and ADC (ρ = −0.67, p < 0.001), APT_T1 and D (ρ = −0.70, p < 0.001), APT_T2 and D* (ρ = −0.45, p < 0.05), and T2/T1 and D (ρ = 0.39, p < 0.05). These preliminary findings indicate that MPM-based CEST imaging parameters correlate with IVIM and 11C-MET uptake on PET/CT in patients with gliomas. In particular, the new parameter APT_T1 correlated more strongly with 11C-MET uptake compared to the traditional CEST parameter MTRasym. [ABSTRACT FROM AUTHOR]

Despite longstanding interest in the central cholinergic system in schizophrenia (SCZ), cholinergic imaging studies with patients have been limited to receptors. Here, we conducted a proof-of-concept positron emission tomography study using [18F]-VAT, a new radiotracer that targets the vesicular acetylcholine transporter as a proxy measure of acetylcholine transmission capacity, in patients with SCZ and explored relationships of vesicular acetylcholine transporter with clinical symptoms and cognition. A total of 18 adult patients with SCZ or schizoaffective disorder (the SCZ group) and 14 healthy control participants underwent a positron emission tomography scan with [18F]-VAT. Distribution volume (V T) for [18F]-VAT was derived for each region of interest, and group differences in V T were assessed with 2-sample t tests. Functional significance was explored through correlations between V T and scores on the Positive and Negative Syndrome Scale and a computerized neurocognitive battery (PennCNB). No group differences in [18F]-VAT V T were observed. However, within the SCZ group, psychosis symptom severity was positively associated with V T in multiple regions of interest, with the strongest effects in the hippocampus, thalamus, midbrain, cerebellum, and cortex. In addition, in the SCZ group, working memory performance was negatively associated with V T in the substantia innominata and several cortical regions of interest including the dorsolateral prefrontal cortex. In this initial study, the severity of 2 important features of SCZ—psychosis and working memory deficit—was strongly associated with [18F]-VAT V T in several cortical and subcortical regions. These correlations provide preliminary evidence of cholinergic activity involvement in SCZ and, if replicated in larger samples, could lead to a more complete mechanistic understanding of psychosis and cognitive deficits in SCZ and the development of therapeutic targets. [ABSTRACT FROM AUTHOR]

Physiological age-related alterations in the interstitial flow in the brain, which plays an important role in waste product removal, remain unclear. Using [15O]H 2 O positron emission tomography (PET), water dynamics were evaluated in 63 healthy adult participants aged between 20 and 80 years. Interstitial flow was assessed by influx ratio (IR) and drain rate (DR), using time-activity concentration data. Participants were divided into four age groups with 15-year ranges, to evaluate age-related functional alterations. At least one of the indices declined significantly with age across all groups. A significant linear negative correlation between age and both indicators was found in the scatter plots (IR: R2 = 0.54, DR: R2 = 0.44); both indicators were predominantly lower after age 50 years. These results suggest interstitial flow decreases with age, especially after 50 years. These important findings can contribute to devising therapeutic interventions for neurological diseases characterized by abnormal accumulation of waste products, and suggest the need for taking measures to maintain interstitial flow starting around the age of 50 years. [ABSTRACT FROM AUTHOR]

The arginine-vasopressin (AVP) hormone plays a pivotal role in regulating various physiological processes, such as hormone secretion, cardiovascular modulation, and social behavior. Recent studies have highlighted the V1a receptor as a promising therapeutic target. In-depth insights into V1a receptor-related pathologies, attained through in vivo imaging and quantification in both peripheral organs and the central nervous system (CNS), could significantly advance the development of effective V1a inhibitors. To address this need, we develop a novel V1a-targeted positron emission tomography (PET) ligand, [18F]V1A-2303 ([18F] 8), which demonstrates favorable in vitro binding affinity and selectivity for the V1a receptor. Specific tracer binding in peripheral tissues was also confirmed through rigorous cell uptake studies, autoradiography, biodistribution assessments. Furthermore, [18F] 8 was employed in PET imaging and arterial blood sampling studies in healthy rhesus monkeys to assess its brain permeability and specificity, whole-body distribution, and kinetic properties. Our research indicated [18F] 8 as a valuable tool for noninvasively studying V1a receptors in peripheral organs, and as a foundational element for the development of next-generation, brain-penetrant ligands specifically designed for the CNS. This work described the synthesis and evaluation of a novel 18F-labeled vasopressin 1a receptor PET ligand, which showed peripheral binding specificity and could cross the blood‒brain barrier in non-human primates. [Display omitted] [ABSTRACT FROM AUTHOR]

Worry is a transdiagnostic symptom common to many neurocognitive disorders of aging, including early stages of Alzheimer's disease and related dementias (ADRD). Severe worry is associated with amyloid burden in cognitively intact older adults, yet the mechanisms underlying this association are not well understood. We hypothesize that this relationship involves altered brain and cardiovascular reactivity to acute stressors, a brain-body phenotype that also increases risk for cardiovascular disease. Twenty cognitively normal older adults (age 60 to 80) with varying levels of worry severity underwent positron emission tomography using Pittsburgh Compound-B and functional magnetic resonance imaging. We examined associations of worry severity and amyloid burden with cardiovascular reactivity, brain activation, and brain connectivity using a cognitive stressor task. Worry severity was not associated with global amyloid burden, but was associated with greater resting levels of cardiovascular physiology and lower systolic blood pressure reactivity. Worry severity also was associated with altered stressor-evoked activation and effective connectivity in brain circuits implicated in stress processing, emotion perception, and physiological regulation. These associations showed small to medium effect sizes. These preliminary findings introduce key components of a model that may link severe worry to ADRD risk via stressor-evoked brain-body interactions. • Examined worry, amyloid burden, and stress reactivity in a cohort of older adults. • Worry associated with greater resting blood pressure and less blood pressure reactivity. • Worry associated with altered stressor-evoked brain activation and connectivity. • Associations showed small to medium effect sizes in this pilot cohort. • Worry may relate to ADRD risk via stressor-evoked brain-body pathways. [ABSTRACT FROM AUTHOR]

In Alzheimer's disease (AD), neuropsychiatric symptoms (NPS) correlate with tau deposition in the brain. Here, we investigated the association of PET-based Braak stages with NPS and assessed whether they predict annual changes in NPS. We evaluated 231 individuals in the aging and AD continuum. Participants were assigned a Braak stage at baseline and followed for 1.97 (s.d. 0.62) years. NPS were investigated using the Mild Behavioral Impairment Checklist (MBI-C) and the Neuropsychiatric Inventory Questionnaire severity (NPI-Q-S) and distress (NPI-Q-D) scales. Multiple linear regressions (MLR) assessed the association of Braak stages with baseline NPS and the annual change in NPS scores. At baseline, stages I-II, III-IV, and V-VI were associated with higher MBI-C, NPI-Q-S, and NPI-Q-D scores. Stages V-VI were associated with a significant annual increase in MBI-C scores. These findings suggest that tau accumulation may manifest clinically with an increase in NPS, which seems to be an early event in AD pathophysiology. Moreover, PET-based Braak staging appears to be a good predictor of NPS severity progression. • Neuropsychiatric symptoms are linked to tau pathology from the early disease stages. • Neuropsychiatric symptoms increase as tau pathology becomes more severe. • Tau accumulation may precede the onset of neuropsychiatric symptoms. • PET-based Braak staging predicts future behavioral symptoms in Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Glutathione (GSH) is a brain marker for oxidative stress and has previously been associated with cerebral amyloid deposition and memory decline. However, to date, no study has examined the links among GSH, sex, age, amyloid, and Apolipoprotein E (APOE) genotype in a large non-clinical cohort of older adults. We performed APOE genotyping, magnetic resonance spectroscopy (MRS) as well as simultaneous positron emission tomography with the radiotracer Flutemetamol (Amyloid-PET), in a group of older adults. The final analysis set comprised 140 healthy older adults (mean age: 64.7 years) and 49 participants with mild cognitive impairment (mean age: 71.4 years). We recorded metabolites in the posterior cingulate cortex (PCC) by a GSH-edited MEGAPRESS sequence. Structural equation modeling revealed that higher GSH levels were associated with female sex, but neither APOE- epsilon 4 carrier status nor age showed significant associations with GSH. Conversely, older age and the presence of an APOE4 allele, but not sex, are linked to higher global amyloid load. Our results suggest that the PCC shows sex-specific GSH alterations in older adults. • PCC GSH levels may be higher in women than in men. • PCC GSH levels were unrelated to local amyloid load. • PCC GSH levels were unrelated to the presence of an APOE epsilon 4 allele. [ABSTRACT FROM AUTHOR]

Surgery is a good treatment option for drug-resistant temporal lobe epilepsy (TLE). 2-deoxy-2-(18F) fluoro-D-glucose (FDG) positron emission tomography (PET) is used to detect epileptic foci as hypometabolic lesions in presurgical evaluation. Visual field defects (VFDs) in the contralateral homonymous upper quadrant are common postoperative complications in TLE. This study aimed to quantify VFDs using pattern deviation probability plots (PDPPs) and examine the effect of hypometabolism in FDG-PET on VFDs. This study included 40 patients. Both visual fields were assessed using the Humphrey field analyzer preoperatively and 3 months and 2 years postoperatively. PDPPs with <0.5% confidence level counted in the contralateral homonymous upper quadrant. FDG-PET results were compared between groups with (15 patients) and without (24 patients) hypometabolism in the optic radiation. All 40 patients were evaluated by Humphrey field analyzer at 3 months postoperatively and 39 at 2 years postoperatively. The incidence of VFDs 3 months postoperatively was 35/40 (87.5%), and 17/40 (42.5%) patients had severe VFDs. In cases of surgery on the left temporal lobe, ipsilateral eyes appeared to be more significantly affected than contralateral eyes. VFDs were more severe in patients with FDG hypometabolism than in those without hypometabolism in posteromedial temporal and medial occipital cortex (P < 0.01); however, 85% of patients with FDG hypometabolism had a reduced VFD 2 years postoperatively. PDPP counting is useful for quantifying VFDs. Preoperative dysfunction indicated by preoperative FDG-PET in the posteromedial temporal and medial occipital cortex could enhance VFDs early after TLE surgery. [ABSTRACT FROM AUTHOR]

NCT03253744 is a phase 1 trial with the primary objective to identify the maximum tolerated dose (MTD) of salvage stereotactic body radiation therapy (SBRT) in patients with local prostate cancer recurrence after brachytherapy. Additional objectives included biochemical control and imaging response. This trial was initially designed to test 3 therapeutic dose levels (DLs): 40 Gy (DL1), 42.5 Gy (DL2), and 45 Gy (DL3) in 5 fractions. Intensity modulation was used to deliver the prescription dose to the magnetic resonance imaging and prostate-specific membrane antigen–based positron emission tomography imaging–defined gross tumor volume while simultaneously delivering 30 Gy to an elective volume defined by the prostate gland. This phase 1 trial followed a 3+3 design with a 3-patient expansion at the MTD. Toxicities were scored until trial completion at 2 years post-SBRT using Common Terminology Criteria for Adverse Events version 5.0. Escalation was halted if 2 dose limiting toxicities occurred, defined as any persistent (>4 days) grade 3 toxicity occurring within the first 3 weeks after SBRT or any grade ≥3 genitourinary (GU) or grade 4 gastrointestinal toxicity thereafter. Between August 2018 and January 2023, 9 patients underwent salvage SBRT and were observed for a median of 22 months (Q1-Q3, 20-43 months). No grade 3 to 5 adverse events related to study treatment were observed; thus, no dose limiting toxicities occurred during the observation period. Escalation was halted by amendment given excellent biochemical control in DL1 and DL2 in the setting of a high incidence of clinically significant late grade 2 GU toxicity. Therefore, the MTD was considered 42.5 Gy in 5 fractions (DL2). One- and 2-year biochemical progression-free survival were 100% and 86%, representing a single patient in the trial cohort with biochemical failure (prostate-specific antigen [PSA] nadir + 2.0) at 20 months posttreatment. The MTD of salvage SBRT for the treatment of intraprostatic radiorecurrence after brachytherapy was 42.5 Gy in 5 fractions producing an 86% 2-year biochemical progression-free survival rate, with 1 poststudy failure at 20 months. The most frequent clinically significant toxicity was late grade 2 GU toxicity. [ABSTRACT FROM AUTHOR]

Delta-like ligand 3 (DLL3) is aberrantly expressed on the surface of small-cell lung cancer (SCLC) and neuroendocrine prostate cancer cells. We assessed the safety and feasibility of the DLL3-targeted imaging tracer [89Zr]Zr-DFO-SC16.56 (composed of the anti-DLL3 antibody SC16.56 conjugated to p-SCN-Bn-deferoxamine [DFO] serving as a chelator for zirconium-89) in patients with neuroendocrine-derived cancer. We conducted an open-label, first-in-human study of immunoPET-CT imaging with [89Zr]Zr-DFO-SC16.56. The study was done at Memorial Sloan Kettering Cancer Center, New York, NY, USA. Patients aged 18 years or older with a histologically verified neuroendocrine-derived malignancy and an Eastern Cooperative Oncology Group performance status of 0–2 were eligible. An initial cohort of patients with SCLC (cohort 1) received 37–74 MBq [89Zr]Zr-DFO-SC16.56 as a single intravenous infusion at a total mass dose of 2·5 mg and had serial PET-CT scans at 1 h, day 1, day 3, and day 7 post-injection. The primary outcomes of phase 1 of the study (cohort 1) were to estimate terminal clearance half-time, determine whole organ time-integrated activity coefficients, and assess the safety of [89Zr]Zr-DFO-SC16.56. An expansion cohort of additional patients (with SCLC, neuroendocrine prostate cancer, atypical carcinoid tumours, and non-small-cell lung cancer; cohort 2) received a single infusion of [89Zr]Zr-DFO-SC16.56 at the same activity and mass dose as in the initial cohort followed by a single PET-CT scan 3–6 days later. Retrospectively collected tumour biopsy samples were assessed for DLL3 by immunohistochemistry. The primary outcome of phase 2 of the study in cohort 2 was to determine the potential association between tumour uptake of the tracer and intratumoural DLL3 protein expression, as determined by immunohistochemistry. This study is ongoing and is registered with ClinicalTrials.gov , NCT04199741. Between Feb 11, 2020, and Jan 30, 2023, 12 (67%) men and six (33%) women were enrolled, with a median age of 64 years (range 23–81). Cohort 1 included three patients and cohort 2 included 15 additional patients. Imaging of the three patients with SCLC in cohort 1 showed strong tumour-specific uptake of [89Zr]Zr-DFO-SC16.56 at day 3 and day 7 post-injection. Serum clearance was biphasic with an estimated terminal clearance half-time of 119 h (SD 31). The highest mean absorbed dose was observed in the liver (1·83 mGy/MBq [SD 0·36]), and the mean effective dose was 0·49 mSv/MBq (SD 0·10). In cohort 2, a single immunoPET-CT scan on day 3–6 post-administration could delineate DLL3-avid tumours in 12 (80%) of 15 patients. Tumoural uptake varied between and within patients, and across anatomical sites, with a wide range in maximum standardised uptake value (from 3·3 to 66·7). Tumour uptake by [89Zr]Zr-DFO-SC16.56 was congruent with DLL3 immunohistochemistry in 15 (94%) of 16 patients with evaluable tissue. Two patients with non-avid DLL3 SCLC and neuroendocrine prostate cancer by PET scan showed the lowest DLL3 expression by tumour immunohistochemistry. One (6%) of 18 patients had a grade 1 allergic reaction; no grade 2 or worse adverse events were noted in either cohort. DLL3 PET-CT imaging of patients with neuroendocrine cancers is safe and feasible. These results show the potential utility of [89Zr]Zr-DFO-SC16.56 for non-invasive in-vivo detection of DLL3-expressing malignancies. National Institutes of Health, Prostate Cancer Foundation, and Scannell Foundation. [ABSTRACT FROM AUTHOR]

• Endometriosis diagnosis is delayed on average by 6–7 years and requires invasive surgery. • PET imaging has shown potential as a non-invasive technique for detection of endometriosis. • Systematic review of the literature found 18F-FDG PET does not consistently identify endometriotic lesions. • Other existing PET tracers with biological plausibility in the detection of endometriosis warrant further investigation. Despite the profound impact of endometriosis worldwide, delays in diagnosis and suboptimal surveillance techniques are well-recognised issues. Case studies have reported incidental uptake of 18F-FDG PET tracer in endometriotic lesions. However, the utility of PET imaging as a non-invasive diagnostic tool for endometriosis is currently unclear. The purpose of this systematic review was to summarise the existing evidence and determine the value of available PET scanning techniques in the detection and monitoring of endometriosis. MEDLINE, EMBASE, CENTRAL, SCOPUS and Web of Science were searched from conception to 05/03/23. Eligible studies included participants with a history of known or suspected endometriosis who underwent a PET scan for any indication. All PET tracers and protocols were eligible. Outcomes included correlation of PET tracer uptake with the presence of endometriosis seen at laparoscopy or confirmed on histology, sensitivity of tracer uptake, specificity of tracer uptake, site of lesions with tracer uptake, stage of lesions with tracer uptake, SUV max of endometriosis lesions and adverse reactions to PET imaging. The protocol for this review was registered with PROSPERO (ID: CRD42023405260). Eight studies describing 110 participants were eligible for inclusion. Six studies assessed 18F-FDG with combined PET-CT, one study assessed 18F-FDG PET alone, and the remaining study assessed PET-CT with an alternative tracer, 68Ga-DOTATATE. For 18F-FDG imaging, the correlation of PET avidity with lesions or sites of endometriosis ranged from 0-55 %. Pre-operative 68Ga-DOTATATE PET-CT detected endometriosis in 33 % of cases. All included studies were cohort studies, six were assessed to have low risk of bias, one with moderate risk and one with high risk of bias. Overall, 18F-FDG PET scanning does not appear to consistently identify endometriotic lesions, and therefore its reliability and usefulness in endometriosis diagnosis is limited. The utility of 68Ga-DOTATATE PET-CT remains uncertain. Findings are constrained by limited available evidence reporting outcomes of PET imaging for endometriosis. Other existing PET tracers with biological plausibility in the detection or monitoring of endometriosis warrant further investigation. [ABSTRACT FROM AUTHOR]

The evidence in the field of diagnosis, staging, and treatment of localised prostate cancer (PCa) is evolving rapidly. The 2024 European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Urological Pathology (ISUP)-International Society of Geriatric Oncology (SIOG) guidelines on PCa summarise the most recent findings and advice for their use in clinical practice. These PCa guidelines reflect the multidisciplinary nature of PCa management. The European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Urological Pathology (ISUP)-International Society of Geriatric Oncology (SIOG) guidelines provide recommendations for the management of clinically localised prostate cancer (PCa). This paper aims to present a summary of the 2024 version of the EAU-EANM-ESTRO-ESUR-ISUP-SIOG guidelines on the screening, diagnosis, and treatment of clinically localised PCa. The panel performed a literature review of all new data published in English, covering the time frame between May 2020 and 2023. The guidelines were updated, and a strength rating for each recommendation was added based on a systematic review of the evidence. A risk-adapted strategy for identifying men who may develop PCa is advised, generally commencing at 50 yr of age and based on individualised life expectancy. The use of multiparametric magnetic resonance imaging in order to avoid unnecessary biopsies is recommended. When a biopsy is considered, a combination of targeted and regional biopsies should be performed. Prostate-specific membrane antigen positron emission tomography imaging is the most sensitive technique for identifying metastatic spread. Active surveillance is the appropriate management for men with low-risk PCa, as well as for selected favourable intermediate-risk patients with International Society of Urological Pathology grade group 2 lesions. Local therapies are addressed, as well as the management of persistent prostate-specific antigen after surgery. A recommendation to consider hypofractionation in intermediate-risk patients is provided. Patients with cN1 PCa should be offered a local treatment combined with long-term intensified hormonal treatment. The evidence in the field of diagnosis, staging, and treatment of localised PCa is evolving rapidly. These PCa guidelines reflect the multidisciplinary nature of PCa management. This article is the summary of the guidelines for "curable" prostate cancer. Prostate cancer is "found" through a multistep risk-based screening process. The objective is to find as many men as possible with a curable cancer. Prostate cancer is curable if it resides in the prostate; it is then classified into low-, intermediary-, and high-risk localised and locally advanced prostate cancer. These risk classes are the basis of the treatments. Low-risk prostate cancer is treated with "active surveillance", a treatment with excellent prognosis. For low-intermediary-risk active surveillance should also be discussed as an option. In other cases, active treatments, surgery, or radiation treatment should be discussed along with the potential side effects to allow shared decision-making. [ABSTRACT FROM AUTHOR]

Inconsistencies between Alzheimer's disease (AD) clinical trials and prevention studies using omega-3 (n-3) polyunsaturated fatty acid (PUFA) supplementation can be largely attributed to differences in age, environmental factors, genetic factors, baseline n-3/n-6 intake, and disease stage. Changes in docosahexaenoic acid (DHA) brain uptake throughout AD progression are influenced by the apolipoprotein E ε4 (APOE4) allele and lifestyle factors, such as DHA intake or exercise, and can be monitored by DHA positron emission tomography (PET) brain imaging. APOE4 carriers are more susceptible to blood–brain barrier dysfunction, oxidative stress, neuroinflammation, and fatty acid oxidation with aging compared to noncarriers. We hypothesize that increasing n-3 PUFA intake provides APOE4 carriers with the highest potential for protection against AD dementia when implemented early in life, many years before the onset of cognitive decline. During the AD dementia phase, alternative strategies targeting neuroinflammation and PUFA metabolism may offer potential benefits. Omega-3 (n-3) polyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid (DHA), have important roles in human nutrition and brain health by promoting neuronal functions, maintaining inflammatory homeostasis, and providing structural integrity. As Alzheimer's disease (AD) pathology progresses, DHA metabolism in the brain becomes dysregulated, the timing and extent of which may be influenced by the apolipoprotein E ε4 (APOE4) allele. Here, we discuss how maintaining adequate DHA intake early in life may slow the progression to AD dementia in cognitively normal individuals with APOE4 , how recent advances in DHA brain imaging could offer insights leading to more personalized preventive strategies, and how alternative strategies targeting PUFA metabolism pathways may be more effective in mitigating disease progression in patients with existing AD dementia. [ABSTRACT FROM AUTHOR]

• What is the primary question addressed by this study? What is the relationship between apathy, obtained by both self and study partner report, and in vivo Alzheimer's disease (AD) pathology in community-dwelling older adults during the earliest stages of AD? • What is the main finding of this study? Higher study partner-reported participant apathy, but not self-reported apathy, is cross-sectionally associated with cortical amyloid-β and temporal lobe tau. Findings held when we controlled for depressive symptoms and were observed starting in the preclinical stage of Alzheimer's disease (AD). • What is the meaning of the finding? Our findings suggest that AD-pathology-associated apathy in older adults may arise in preclinical AD, at the transition to cognitive impairment, and best be captured by study partner or collateral report. We examined relationships between apathy (self and study-partner-reported) and markers of Alzheimer's disease (AD) in older adults. The study utilized a well-characterized sample of participants from the Harvard Aging Brain Study (HABS), a longitudinal cohort study. Participants were cognitively unimpaired without clinically significant neuropsychiatric symptoms at HABS baseline. The dependent variables, apathy evaluation scale-self (AES-S) and informant (AES-I), were administered cross-sectionally between years 6–9 and compared to the independent variables, amyloid and tau PET neuroimaging, from the same year. Community-dwelling participants assessed at research visits in an academic medical center. Participants (n = 170) completed assessments within 1.5 years of their neuroimaging visit. At the time of apathy assessment, N = 156 were cognitively unimpaired and 14 had progressed to mild cognitive impairment (n = 8) or dementia (n = 6). We utilized linear regression models to assess cross-sectional associations of AES-S and AES-I with AD PET imaging measures (beta-amyloid (Pittsburgh Compound B) and tau (Flortaucipir)), covarying for age, sex, education, and the time between PET scan-apathy assessment. AES-I was significantly associated with beta-amyloid and temporal lobe tau, and the associations were retained after further adjusting for depressive symptoms. The associations between AES-S and AD biomarkers were not significant. In an exploratory subgroup analysis of cognitively unimpaired individuals with elevated Aβ, we observed an association between AES-I and inferior temporal tau. Study-partner-reported, but not self-reported, apathy in older adults is associated with AD pathology, and we observed this relationship starting from the preclinical stage. Our findings highlight the importance of collateral information in capturing AD-related apathy. [ABSTRACT FROM AUTHOR]

To study in vivo the bioactivity of biodegradable magnesium implants and other possible biomaterials, we are proposing a previously unexplored application of PET-CT imaging, using available tracers to follow soft tissue and bone remodelling and immune response in the presence of orthopaedic implants. Female Wistar rats received either implants (Ti6Al7Nb titanium or WE43 magnesium) or corresponding transcortical sham defects into the diaphyseal area of the femurs. Inflammatory response was followed with [18F]FDG and osteogenesis with [18F]NaF, over the period of 1.5 months after surgery. An additional pilot study with [68Ga]NODAGA-RGD tracer specific to α v β 3 integrin expression was performed to follow the angiogenesis for one month. [18F]FDG tracer uptake peaked on day 3 before declining in all groups, with Mg and Ti groups exhibiting overall higher uptake compared to sham. This suggests increased cellular activity and tissue response in the presence of Mg during the initial weeks, with Ti showing a subsequent increase in tracer uptake on day 45, indicating a foreign body reaction. [18F]NaF uptake demonstrated the superior osteogenic potential of Mg compared to Ti, with peak uptake on day 7 for all groups. [68Ga]NODAGA-RGD pilot study revealed differences in tracer uptake trends between groups, particularly the prolonged expression of α v β 3 integrin in the presence of implants. Based on the observed differences in the uptake trends of radiotracers depending on implant material, we suggest that PET-CT is a suitable modality for long-term in vivo assessment of orthopaedic biomaterial biocompatibility and underlying tissue reactions. The study explores the novel use of positron emission tomography for the assessment of the influence that biomaterials have on the surrounding tissues. Previous related studies have mostly focused on material-related effects such as implant-associated infections or to follow the osseointegration in prosthetics, but the use of PET to evaluate the materials has not been reported before. The approach tests the feasibility of using repeated PET-CT imaging to follow the tissue response over time, potentially improving the methodology for adopting new biomaterials for clinical use. [Display omitted] [ABSTRACT FROM AUTHOR]

Positron Emission Tomography (PET) image reconstruction remains a pivotal area in PET technology, critically influencing clinical diagnostic outcomes. Addressing the need for enhanced image quality, this study introduces a novel algorithm for PET image reconstruction. This algorithm integrates a penalty mechanism, morphological filtering, and the Maximum Likelihood Expectation Maximization (MLEM) algorithm, aiming to improve reconstructed image quality significantly. The operational process of the algorithm within each iteration encompasses two primary phases. Initially, image reconstruction is accomplished via the MLEM algorithm, followed by the application of a morphological filter to attenuate noise in the reconstructed image. Simulation experiments demonstrate that this algorithm effectively mitigates noise while preserving crucial details, such as image edges. Notably, this method presents the dual benefits of straightforward parameter configuration and ease of implementation. The results indicate a substantial enhancement in noise suppression and fine structure preservation in the reconstructed images, marking a significant advancement in PET image reconstruction techniques. [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) holds promise for neuropsychiatric conditions where imbalance in network activity contributes to symptoms. Treatment-resistant Combat post-traumatic stress disorder (TR-PTSD) is a highly morbid condition and 50% of PTSD sufferers fail to recover despite psychotherapy or pharmacotherapy. Reminder-triggered symptoms may arise from inadequate top-down ventromedial prefrontal cortex (vmPFC) control of amygdala reactivity. Here, we report long-term data on two TR-PTSD participants from an investigation utilizing high-frequency amygdala DBS. The two combat veterans were implanted bilaterally with quadripolar electrodes targeting the basolateral amygdala. Following a randomized staggered onset, patients received stimulation with adjustments based on PTSD symptom severity for four years while psychiatric and neuropsychiatric symptoms, neuropsychological performance, and electroencephalography were systematically monitored. Evaluation of vmPFC-Amygdala network engagement was assessed with 18FDG positron emission tomography (PET). CAPS-IV scores varied over time, but improved 55% from 119 at baseline to 53 at 4-year study endpoint in participant 1; and 44%, from 68 to 38 in participant 2. Thereafter, during 5 and 1.5 years of subsequent clinical care respectively, long-term bilateral amygdala DBS was associated with additional, clinically significant symptomatic and functional improvement. There were no serious stimulation-related adverse psychiatric, neuropsychiatric, neuropsychological, neurological, or neurosurgical effects. In one subject, symptomatic improvement was associated with an intensity-dependent reduction in amygdala theta frequency power. In our two participants, FDG-PET findings were inconclusive regarding the hypothesized mechanism of suppression of amygdala hyperactivity. Our findings encourage further research to confirm and extend our preliminary observations. • There are limited treatment options for treatment-resistant combat PTSD (TR-PTSD) • Functional neuroimaging implicates amygdala hyperactivity • Two veterans with severe combat TR-PTSD received amygdala DBS for 9 and 5.5 years • Stimulation resulted in no seizures, neuropsychological or psychiatric impairments • Significant clinical and functional improvements were observed [ABSTRACT FROM AUTHOR]

• Transcranial magnetic stimulation is an objective biomarker of upper motor neuron dysfunction in motor neuron disease (MND). • Cortical hyperexcitability is mediated by cortical disinhibition and increased facilitation. • Neuroimaging biomarkers of upper motor neuron dysfunction in MND exhibit utility. Identifying upper motor neuron (UMN) dysfunction is fundamental to the diagnosis and understanding of disease pathogenesis in motor neuron disease (MND). The clinical assessment of UMN dysfunction may be difficult, particularly in the setting of severe muscle weakness. From a physiological perspective, transcranial magnetic stimulation (TMS) techniques provide objective biomarkers of UMN dysfunction in MND and may also be useful to interrogate cortical and network function. Single, paired- and triple pulse TMS techniques have yielded novel diagnostic and prognostic biomarkers in MND, and have provided important pathogenic insights, particularly pertaining to site of disease onset. Cortical hyperexcitability, as heralded by reduced short interval intracortical inhibition (SICI) and increased short interval intracortical facilitation, has been associated with the onset of lower motor neuron degeneration, along with patterns of disease spread, development of specific clinical features such as the split hand phenomenon, and may provide an indication about the rate of disease progression. Additionally, reduction of SICI has emerged as a potential diagnostic aid in MND. The triple stimulation technique (TST) was shown to enhance the diagnostic utility of conventional TMS measures in detecting UMN dysfunction in MND. Separately, sophisticated brain imaging techniques have uncovered novel biomarkers of neurodegeneration that have bene associated with progression. The present review will discuss the utility of TMS and brain neuroimaging derived biomarkers of UMN dysfunction in MND, focusing on recently developed TMS techniques and advanced neuroimaging modalities that interrogate structural and functional integrity of the corticomotoneuronal system, with an emphasis on pathogenic, diagnostic, and prognostic utility. [ABSTRACT FROM AUTHOR]

Depression is a chronic psychiatric disorder related to diminished dopaminergic neurotransmission. Deep brain stimulation (DBS) has shown effectiveness in treating patients with treatment-refractory depression (TRD). This study aimed to evaluate the effect of DBS on dopamine D2 receptor binding in patients with TRD. Six patients with TRD were treated with bed nucleus of the stria terminalis (BNST)-nucleus accumbens (NAc) DBS were recruited. Ultra-high sensitivity [11C]raclopride dynamic total-body positron emission tomography (PET) imaging was used to assess the brain D2 receptor binding. Each patient underwent a [11C]raclopride PET scan for 60-min under DBS OFF and DBS ON, respectively. A simplified reference tissue model was used to generate parametric images of binding potential (BP ND) with the cerebellum as reference tissue. Depression and anxiety symptoms improved after 3–6 months of DBS treatment. Compared with two-day-nonstimulated conditions, one-day BNST-NAc DBS decreased [11C]raclopride BP ND in the amygdala (15.9 %, p < 0.01), caudate nucleus (15.4 %, p < 0.0001) and substantia nigra (10.8 %, p < 0.01). This study was limited to the small sample size and lack of a healthy control group. Chronic BNST-NAc DBS improved depression and anxiety symptoms, and short-term stimulation decreased D2 receptor binding in the amygdala, caudate nucleus, and substantia nigra. The findings suggest that DBS relieves depression and anxiety symptoms possibly by regulating the dopaminergic system. • BNST-NAc DBS can improve the depressive and anxiety symptoms of TRD patients. • BNST-NAc DBS decreased dopamine D2 receptor binding in the amygdala, caudate, and substantia nigra. • BNST-NAc DBS improves clinical symptoms of TRD patients potentially by compensating for the defective dopaminergic system. [ABSTRACT FROM AUTHOR]

Radiology has seen tremendous evolution in the last few decades. At the same time, oncology has made great strides in diagnosing and treating cancer. Distant metastases of neoplasms are being encountered more often in light of longer patient survival due to better therapeutic strategies and diagnostic methods. Brain metastasis (BM) is a dismal manifestation of systemic cancer. In the present scenario, magnetic resonance imaging (MRI), computed tomography (CT) and positron emission tomography (PET) are playing a big role in providing molecular information about cancer. Lately, molecular imaging has emerged as a stirring arena of dynamic imaging techniques that have enabled clinicians and scientists to noninvasively visualize and understand biological processes at the cellular and molecular levels. This knowledge has impacted etiopathogenesis, detection, personalized treatment, drug development, and our understanding of carcinogenesis. This article offers insight into the molecular biology underlying brain metastasis, its pathogenesis, imaging protocols, and algorithms. It also discusses disease-specific molecular imaging features, focusing on common tumors that spread to the brain, such as lung, breast, colorectal cancer, melanoma, and renal cell carcinoma. Additionally, it covers various targeted treatment options, criteria for assessing treatment response, and the role of artificial intelligence in diagnosing, managing, and predicting prognosis for patients with brain metastases. [ABSTRACT FROM AUTHOR]

To study prostate specific membrane antigen – positron emission tomography (Ga68PSMA-PETCT) based patterns of relapse at biochemical failure (BCF) after prostate-only radiotherapy (PORT) in high-risk (HR) prostate cancer and its implications on pelvic contouring recommendations. Patients with clinico-radiological high-risk node-negative prostate cancer treated with curative PORT and androgen deprivation therapy (ADT), either within the POP-RT randomised trial or off trial, who underwent a Ga68PSMA-PETCT upon BCF were included. Patterns of regional and distant recurrence on Ga68PSMA-PETCT were studied. Pelvic nodal recurrences were mapped with reference to the superior border of pubic symphysis. Pelvic lymph nodal caudal border (PLN cb) recommendations in the published contouring guidelines (RTOG cb , GETUG cb , PIVOTAL cb , NRG cb , GFRU cb) were evaluated. Of the total 262 patients screened, 68 eligible patients were included (POP-RT trial 35 patients; off-trial 33 patients). Median follow-up was 91 months (IQR, 72–117) and median time to BCF was 65 months (IQR, 49–83). Regional and distant recurrence was seen in 31 (46%) and 31 (46%) patients, respectively. Of the nodal recurrences, nearly half (46%, 14/31) had no distant metastases and 64% (20/31) had a failure in the common iliac nodal region. The lower-most nodal recurrence was 20 mm cranial to the top of pubic symphysis (RTOG cb , GETUG cb , GFRU cb) and 10 mm cranial to the PIVOTAL cb. The PLN cb recommended by NRG guideline (NRG cb) had an inter-patient variability of 32 mm, ranging from 16 mm above to 16 mm below the top of pubic symphysis, and the lower most nodal recurrence ranged from 4 mm to 36 mm cranial to NRG cb. Pelvic failures accounted for a major proportion of recurrences after prostate-only radiotherapy, with the caudal most nodal recurrence being 20 mm cranial to the top of pubic symphysis. This could have implications in defining the caudal border of contouring recommendations. • Roughly half of men with localised HRCaP have pelvic failures post prostate-only RT. • Pelvic nodal lower-border definition lacks consensus across existing guidelines. • Caudal-most nodal failure was mapped 20 mm superior to the top of pubic symphysis. [ABSTRACT FROM AUTHOR]

In this prospective randomized controlled trial of prostate-specific membrane antigen positron emission tomography (PSMA-PET)-based salvage radiotherapy for patients with biochemical recurrence after radical prostatectomy (n = 103 in the PSMA-PET arm; n = 90 in the control arm), the information from PSMA-PET imaging influenced major treatment management decisions in 33% of patients. Both imaging and several prognostic factors inform the planning of salvage radiotherapy (SRT). Prostate-specific membrane antigen positron emission tomography (PSMA-PET) can localize disease unseen by other imaging modalities. The main objective of the study was to evaluate the impact of PSMA-PET on biochemical recurrence–free survival rate after SRT. This prospective randomized, controlled, phase 3 clinical trial randomized 193 patients with biochemical recurrence of prostate cancer after radical prostatectomy to proceed with SRT (control arm, n = 90) or undergo a PSMA-PET/computed tomography (CT) scan prior to SRT planning (investigational arm, n = 103) from June 2018 to August 2020. Any other approved imaging modalities were allowed in both arms (including fluciclovine-PET). This is a secondary endpoint analysis: impact of PSMA-PET on SRT planning. Case-report forms were sent to referring radiation oncologists to collect the management plans before randomization and after completion of SRT. The relative frequency (%) of management changes within each arm were compared using chi-square and Fisher's exact tests. The delivered SRT plan was available in 178/193 patients (92.2%;76/90 control [84.4%] and 102/103 PSMA-PET [99%]). Median prostate-specific antigen levels at enrollment was 0.30 ng/ml (interquartile range [IQR] 0.19–0.91) in the control arm and 0.23 ng/ml (IQR 0.15–0.54) in the PSMA-PET arm. Fluciclovine-PET was used in 33/76 (43%) in the control arm. PSMA-PET localized recurrence(s) in 38/102 (37%): nine of 102 (9%) outside of the pelvis (M1), 16/102 (16%) in the pelvic LNs (N1, with or without local recurrence), and 13/102 (13%) in the prostate fossa only. There was a 23% difference (95% confidence interval [CI] 9–35%, p = 0.002) of frequency of major changes between the control arm (22% [17/76]) and the PSMA-PET intervention arm (45%[46/102]). Of the major changes in the intervention group, 33/46 (72%) were deemed related to PSMA-PET. There was a 17.6% difference (95% CI 5.4–28.5%, p = 0.005) of treatment escalation frequency between the control arm (nine of 76 [12%]) and the intervention arm (30/102 [29%]). Treatment de-escalation occurred in the control and intervention arms in eight of 76 (10.5%) and 12/102 (11.8%) patients, and mixed changes in zero of 76 (0%) and four of 102 (3.9%) patients, respectively. In this prospective randomized phase 3 study, PSMA-PET findings provided information that initiated major management changes to SRT planning in 33/102 (33%) patients. The final readout of the primary endpoint planned in 2025 may provide evidence on whether these changes result in improved outcomes. Prostate-specific membrane antigen positron emission tomography leads to management changes in one-third of patients receiving salvage radiotherapy for post-radical prostatectomy biochemical recurrence of prostate cancer. [ABSTRACT FROM AUTHOR]

• PET is applied to the diagnosis of PD, AD, and drug dependence. • PET imaging emerges as a crucial tool for detecting brain biomarkers. • This article also indicates the limitations that specificity and sensitivity of PET imaging agents need to be further improved. • The article provides a forward-looking perspective in the future development directions of PET imaging. Brain disorders are a series of conditions with damage or loss of neurons, such as Parkinson's disease (PD), Alzheimer's disease (AD), or drug dependence. These individuals have gradual deterioration of cognitive, motor, and other central nervous system functions affected. This degenerative trajectory is intricately associated with dysregulations in neurotransmitter systems. Positron Emission Tomography (PET) imaging, employing radiopharmaceuticals and molecular imaging techniques, emerges as a crucial tool for detecting brain biomarkers. It offers invaluable insights for early diagnosis and distinguishing brain disorders. This article comprehensively reviews the application and progress of conventional and novel PET imaging agents in diagnosing brain disorders. Furthermore, it conducts a thorough analysis on merits and limitations. The article also provides a forward-looking perspective in the future development directions of PET imaging agents for diagnosing brain disorders and proposes potential innovative strategies. It aims to furnish clinicians and researchers with an all-encompassing overview of the latest advancements and forthcoming trends in the utilization of PET imaging for diagnosing brain disorders. [ABSTRACT FROM AUTHOR]

• Myocardial flow reserve (MFR) on positron emission tomography longitudinally declines over time after heart transplantation and is prognostic for adverse post-transplant events. • Cardiometabolic risk factors, allograft rejection and cytomegalovirus infection are associated with reduced MFR and, therefore, the development and progression of cardiac allograft vasculopathy. • The use of moderate- to high-intensity statin therapy is associated with a higher MFR, and escalation of statin intensity may reduce the incidence of cardiac allograft vasculopathy. Positron emission tomography (PET) myocardial flow reserve (MFR) is a noninvasive method of detecting cardiac allograft vasculopathy in recipients of heart transplants (HTs). There are limited data on longitudinal change and predictors of MFR following HT. We conducted a retrospective analysis of HT recipients undergoing PET myocardial perfusion imaging at an academic center. Multivariable linear and Cox regression models were constructed to identify longitudinal trends, predictors and the prognostic value of MFR after HT. Of HT recipients, 183 underwent 658 PET studies. The average MFR was 2.34 ± 0.70. MFR initially increased during the first 3 years following HT (+ 0.12 per year; P = 0.01) before beginning to decline at an annual rate of -0.06 per year (P < 0.001). MFR declines preceding acute rejection and improves after treatment. Treatment with mammalian target of rapamycin (mTOR) inhibitors (37.2%) slowed the rate of annual MFR decline (P = 0.03). Higher-intensity statin therapy was associated with improved MFR. Longer time post-transplant (P < 0.001), hypertension (P < 0.001), chronic kidney disease (P < 0.001), diabetes mellitus (P = 0.038), antibody-mediated rejection (P = 0.040), and cytomegalovirus infection (P = 0.034) were associated with reduced MFR. Reduced MFR (HR: 7.6, 95% CI: 4.4–13.4; P < 0.001) and PET-defined ischemia (HR: 2.3, 95% CI: 1.4–3.9; P < 0.001) were associated with a higher risk of the composite outcome of mortality, retransplantation, heart failure hospitalization, acute coronary syndrome, or revascularization. MFR declines after the third post-transplant year and is prognostic for cardiovascular events. Cardiometabolic risk-factor modification and treatment with higher-intensity statin therapy and mechanistic target of rapamycin inhibitors are associated with a higher MFR. [Display omitted] [ABSTRACT FROM AUTHOR]

Among patients with obstructive coronary artery disease (CAD) on coronary computed tomography angiography (CTA), downstream positron emission tomography (PET) perfusion imaging can be performed to assess the presence of myocardial ischemia. A novel artificial-intelligence-guided quantitative computed tomography ischemia algorithm (AI-QCT ischemia) aims to predict ischemia directly from coronary CTA images. We aimed to study the prognostic value of AI-QCT ischemia among patients with obstructive CAD on coronary CTA and normal or abnormal downstream PET perfusion. AI-QCT ischemia was calculated by blinded analysts among patients from the retrospective coronary CTA cohort at Turku University Hospital, Finland, with obstructive CAD on initial visual reading (diameter stenosis ≥50%) being referred for downstream 15O-H 2 O-PET adenosine stress perfusion imaging. All coronary arteries with their side branches were assessed by AI-QCT ischemia. Absolute stress myocardial blood flow ≤2.3 ​ml/g/min in ≥2 adjacent segments was considered abnormal. The primary endpoint was death, myocardial infarction, or unstable angina pectoris. The median follow-up was 6.2 [IQR 4.4–8.3] years. 662 of 768 (86%) patients had conclusive AI-QCT ischemia result. In patients with normal 15O-H 2 O-PET perfusion, an abnormal AI-QCT ischemia result (n ​= ​147/331) vs. normal AI-QCT ischemia result (n ​= ​184/331) was associated with a significantly higher crude and adjusted rates of the primary endpoint (adjusted HR 2.47, 95% CI 1.17–5.21, p ​= ​0.018). This did not pertain to patients with abnormal 15O-H 2 O-PET perfusion (abnormal AI-QCT ischemia result (n ​= ​269/331) vs. normal AI-QCT ischemia result (n ​= ​62/331); adjusted HR 1.09, 95% CI 0.58–2.02, p ​= ​0.794) (p-interaction ​= ​0.039). Among patients with obstructive CAD on coronary CTA referred for downstream 15O-H 2 O-PET perfusion imaging, AI-QCT ischemia showed incremental prognostic value among patients with preserved perfusion by 15O-H 2 O-PET imaging, but not among those with reduced perfusion. [ABSTRACT FROM AUTHOR]

Total coronary atherosclerotic plaque activity across the entire coronary arterial tree is associated with patient-level clinical outcomes. We aimed to investigate whether vessel-level coronary atherosclerotic plaque activity is associated with vessel-level myocardial infarction. In this secondary analysis of an international multicenter study of patients with recent myocardial infarction and multivessel coronary artery disease, we assessed vessel-level coronary atherosclerotic plaque activity using coronary 18F-sodium fluoride positron emission tomography to identify vessel-level myocardial infarction. Increased 18F-sodium fluoride uptake was found in 679 of 2,094 coronary arteries and 414 of 691 patients. Myocardial infarction occurred in 24 (4%) vessels with increased coronary atherosclerotic plaque activity and in 25 (2%) vessels without increased coronary atherosclerotic plaque activity (HR: 2.08; 95% CI: 1.16-3.72; P = 0.013). This association was not demonstrable in those treated with coronary revascularization (HR: 1.02; 95% CI: 0.47-2.25) but was notable in untreated vessels (HR: 3.86; 95% CI: 1.63-9.10; P interaction = 0.024). Increased coronary atherosclerotic plaque activity in multiple coronary arteries was associated with heightened patient-level risk of cardiac death or myocardial infarction (HR: 2.43; 95% CI: 1.37-4.30; P = 0.002) as well as first (HR: 2.19; 95% CI: 1.18-4.06; P = 0.013) and total (HR: 2.50; 95% CI: 1.42-4.39; P = 0.002) myocardial infarctions. In patients with recent myocardial infarction and multivessel coronary artery disease, coronary atherosclerotic plaque activity prognosticates individual coronary arteries and patients at risk for myocardial infarction. [Display omitted] [ABSTRACT FROM AUTHOR]

To clarify the relationships between 11C-methionine (MET) positron emission tomography (PET) metrics and the histology, genetics, and prognosis of adult-type diffuse glioma (ADG) based on the World Health Organization (WHO) 2021 classification. A total of 125 newly diagnosed patients with ADG were enrolled. We compared the maximum standardized uptake value (SUVmax), tumor-to-normal background ratio (TNR), metabolic tumor volume (MTV), and total lesion methionine uptake (TLMU) to the histology and genetics of the patients with ADG. We also evaluated the prognoses of the 93 surgically treated patients. The patients with isocitrate dehydrogenase wild ADG showed significantly higher MET-PET metrics (P < 0.05 for all parameters), significantly shorter overall survival and progression-free survival (P < 0.0001 for both) than those of the patients with isocitrate dehydrogenase mutant (IDHm) ADG. In the IDHm ADG group, the SUVmax, MTV, and TLMU values were significantly higher in patients with IDHm grade (G) 4 astrocytoma than patients with IDHm G2/3 astrocytoma (P < 0.05 for all), but not than patients with G2–3 oligodendroglioma. The progression-free survival was significantly shorter in the patients with G4 astrocytoma versus the patients with G2/3 astrocytoma and G3 oligodendroglioma (P < 0.05 for both). The SUVmax and TNR values were significantly higher in recurrent patients than nonrecurrent patients (P < 0.01 for both), but no significant differences were found in MTV or TLMU values. MET-PET metrics well reflect the histological subtype, WHO grade and prognosis of ADG based on the 2021 WHO classification, with the exception of oligodendroglial tumors. Volumetric parameters were not significantly associated with recurrence, unlike the SUVmax and TNR. [Display omitted] [ABSTRACT FROM AUTHOR]

• Total body CT is frequently used as a diagnostic tool for FUO workup instead of FDG-PET/CT. • FDG-PET/CT is associated with higher cost and radiation exposure and lower availability. • Our results showed that total body CT achieves diagnostic rate of 40.2 % in medical patients. • In subgroup identified by elevated CRP and WBC and low hemoglobin diagnostic yield reaches 55 %. Total body computerized tomography (TBCT) is frequently used as a diagnostic tool for fever of unknown origin (FUO) workup instead of a recommended fluorodeoxyglucose positron emission tomography FDG-PET/CT. We have assessed the TBCT diagnostic yield on a large, unselected cohort of patients with FUO. We performed a single-center retrospective cohort study, examining all patients hospitalized in internal medicine between 2012 and 2019 with a documented fever and three negative blood cultures who subsequently had a total-body CT performed. After manually reviewing, we included 408 who met the criteria of FUO. We defined a positive study as a scan that led to the documented final diagnosis. A total of 164 patients (40.2 %) had a positive TBCT result. The majority of positive CT findings were of infectious etiologies (58.5 %), followed by neoplasms (22.8 %) and inflammatory disorders (14.0 %), with the chest (43.9 %) and abdomen (29.8 %) most affected. Using a logistic regression model, a positive scan results were associated with an elevated CRP (p <0.001). Decision tree analysis showed that 55 % of scans of patients with an elevated CRP (>6 mg/dL), low hemoglobin and high leucocyte count (>18000/ml) were positive. Patients without an elevated CRP had a positive scan in only 26 % of tests, and those with also an elevated albumin (>4 gr/dL) and low CRP had positive scan in only 11 % of cases. TBCT has a clinically significant yield under specific clinical scenarios in medical patients with FUO- reaching 55 % in patients with an elevated CRP and leukocyte count and low hemoglobin. It is reasonable to proceed to TTBCT when FDG-PET/CT is unavailable and in well-defined clinical situations. [ABSTRACT FROM AUTHOR]

Our main goal of this meta-analytical analysis was to evaluate the diagnostic effectiveness of prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) against multiparametric magnetic resonance imaging (mpMRI) in the context of identifying biochemical recurrence in patients with prostate cancer (PCa). A thorough search covering articles published until March 2023 was carried out across major databases such as PubMed, Embase, and Web of Science. Studies examining the direct comparison of PSMA PET/CT and mpMRI in patients with PCa suffering biochemical recurrence were included in the inclusion criteria. Using the renowned Quality Assessment of Diagnostic Performance Studies-2 technique, each study's methodological rigor was assessed. We analyzed data from six eligible studies involving 290 patients in total. The combined data showed that for PSMA PET/CT and mpMRI, respectively, the pooled overall detection rates for recurrent PCa after definitive treatment were 0.69 (95% confidence interval [CI]: 0.45–0.89) and 0.70 (95% CI: 0.44–0.91). The detection rates for local recurrence were specifically 0.52 (95% CI: 0.39–0.65) and 0.62 (95% CI: 0.31–0.89), while they were 0.50 (95% CI: 0.26–0.74) and 0.32 (95% CI: 0.18–0.48) for lymph node metastasis. Notably, there was no discernible difference between the two imaging modalities in terms of the overall detection rate (P = 0.95). The detection rates for local recurrence and lymph node metastasis did not differ statistically significantly (P = 0.55, 0.23). The performance of PSMA PET/CT and mpMRI in identifying biochemical recurrence in PCa appears to be comparable. However, the meta-analysis' findings came from research with modest sample sizes. In this context, more extensive research should be conducted in the future. • Pooled detection rates for recurrent prostate cancer (PCa): 0.69 with prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT), 0.70 with multiparametric magnetic resonance imaging (mpMRI). • PSMA PET/CT and mpMRI perform equally in detecting PCa recurrence. • This article is a head-to-head comparative meta-analysis. [ABSTRACT FROM AUTHOR]

To evaluate the diagnostic performance of 2-[18F]-fluoro-2-deoxy- d -glucose (18F-FDG) positron-emission tomography (PET)/computed tomography (CT) in TA diagnosis and Takayasu arteritis (TA) activity assessment. This retrospective study included patients with TA diagnosed according to the American College of Rheumatology (ACR) criteria and undergoing 18F-FDG PET/CT imaging from October 2010 to July 2022. TA activity was assessed through 18F-FDG PET/CT (maximum standard uptake value [SUVmax], vascular SUVmax/mean standard uptake value [SUVmean] of liver (SUV ratio), and PET vascular activity score [PETVAS]) using physician global assessment (PGA) as the reference standard, and the results of these assessments were compared against the clinical activity scores (National Institutes of Health [NIH] and Indian Aortitis Disease Activity [ITAS-A] scores), acute-phase reactants (APR), and white blood cell and platelet counts. Twenty 18F-FDG PET/CT examinations from 19 patients were included in the study, nine were performed in the active phase and 11 in the inactive phase. The involved vessels showed segmental and tubular FDG uptake in the active group. The average SUVmax, SUV ratio, and PETVAS was 6.3 ± 2.7 (range 3.4–12), 4.2 ± 1.7 (range 2.1–7.5), and 22.7 ± 11.2 (range 6–39), respectively, in the active group and 1.7 ± 0.9 (0.9–3.1), 1.1 ± 0.6 (range 0.6–2.4), and 3.5 ± 5.5 (range 0–18), respectively, in the inactive group. The sensitivity, specificity of SUVmax, SUV ratio, and PETVAS for TA activity assessment were 100%, 100%; 100%, 90.9%; and 88.9, 90.9%, respectively. After ROC curve analysis, a new SUVmax cut-off was obtained. Based on the new cut-off value, SUVmax 3.3 and SUV ratio 1.9 had a more perfect assessment performance. 18F-FDG PET/CT is an alternative imaging technique for TA. • 18F-FDG PET/CT has advantages in TAK activity assessment. • Arterial SUVmax and SUV target/background ratio are important parameters for TAK activity assessment. • 18F-FDG PET/CT allows for a more accurate classification of TAK. • PET/CT can better evaluate TAK efficacy [ABSTRACT FROM AUTHOR]

18F-fluoroestradiol (FES) positron emission tomography (PET)/computed tomography (CT) is considered an accurate diagnostic tool to determine whole-body endocrine responsiveness. In the endocrine therapy (ET)-FES trial, we evaluated 18F-FES PET/CT as a predictive tool in estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (MBC). Eligible patients underwent an 18F-FES PET/CT at baseline. Patients with standardized uptake value (SUV) ≥ 2 received single-agent ET until progressive disease; patients with SUV < 2 were randomized to single-agent ET (arm A) or chemotherapy (ChT) (arm B). The primary objective was to compare the activity of first-line ET versus ChT in patients with 18F-FES SUV < 2. Overall, 147 patients were enrolled; 117 presented with 18F-FES SUV ≥ 2 and received ET; 30 patients with SUV < 2 were randomized to ET or ChT. After a median follow-up of 62.4 months, 104 patients (73.2%) had disease progression and 53 died (37.3%). Median progression-free survival (PFS) was 12.4 months [95% confidence interval (CI) 3.1-59.6 months] in patients with SUV < 2 randomized to arm A versus 23.0 months (95% CI 7.7-30.0 months) in arm B, [hazard (HR) = 0.71, 95% CI 0.3-1.7 months]; median PFS was 18.0 months (95% CI 11.2-23.1 months) in patients with SUV ≥ 2 treated with ET. Median overall survival (OS) was 28.2 months (95% CI 14.2 months-not estimable) in patients with SUV < 2 randomized to ET (arm A) versus 52.8 months (95% CI 16.2 months-not estimable) in arm B (ChT). Median OS was not reached in patients with SUV ≥ 2. 60-month OS rate was 41.6% (95% CI 10.4% to 71.1%) in arm A, 42.0% (95% CI 14.0% to 68.2%) in arm B, and 59.6% (95% CI 48.6% to 69.0%) in patients with SUV ≥ 2. In patients with SUV ≥ 2, 60-month OS rate was 72.6% if treated with aromatase inhibitors (AIs) versus 40.6% in case of fulvestrant or tamoxifen (P < 0.005). The ET-FES trial demonstrated that ER+/HER2− MBC patients are a heterogeneous population, with different levels of endocrine responsiveness based on 18F-FES CT/PET SUV. • 18F-FES PET/CT may be used as a predictive tool of efficacy of ET to assess overall endocrine sensitivity. • Endocrine-sensitive patients (SUVmax ≥ 2) treated with single-agent ET have a prolonged OS. • In endocrine-sensitive patients, PFS and OS related to the use of AI were significantly higher than ER-directed agents. • 18F-FES PET/CT can be used as a valid alternative to biopsy. [ABSTRACT FROM AUTHOR]