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PET probes targeting fibroblasts are frequently used for varying applications in oncology. In recent years, the clinical spectrum has been expanded towards cardiovascular medicine, e.g., after myocardial infarction, in aortic stenosis or as a non-invasive read-out of atherosclerosis. We herein provide a brief overview of the current status of this PET radiotracer in the context of cardiovascular disease, including translational and clinical evidence. In addition, we will also briefly discuss future applications, e.g., the use of fibroblast-targeting PET to investigate bilateral organ function along the cardiorenal axis. [ABSTRACT FROM AUTHOR]

Prostate-specific membrane antigen (PSMA)-targeted PET agents have revolutionized the care of patients with prostate cancer, supplanting traditional methods of imaging prostate cancer, and improving the selection and delivery of therapies. This has led to a rapid expansion in both the number of PSMA PET scans performed and the imaging specialists required to interpret those scans. To aid those imagers and clinicians who are new to the interpretation of PSMA PET, this review provides an overview of the interpretation of PSMA PET/CT imaging and pearls for overcoming commonly encountered pitfalls. We discuss the physiologic distribution of the clinically available PSMA-targeted radiotracers, the commonly encountered patterns of prostate cancer spread, as well as the benign and malignant mimics of prostate cancer. Additionally, we review the standardized PSMA PET reporting systems and the role of PSMA in selecting appropriate patients for PSMA-targeted therapies. [ABSTRACT FROM AUTHOR]

Prostate-specific membrane antigen (PSMA) PET/CT has been widely integrated into the management of prostate cancer (PCa) patients with biochemical recurrence, is increasingly used for initial staging in high-risk patients prior to surgery or to identify candidates for PSMA-targeted radioligand therapy (RLT). To date, monitoring response in PCa patients in prospective studies remains the domain of conventional imaging, such as magnetic resonance/CT or bone scintigraphy. With the increasing use of PSMA-targeted PET/CT in PCa, however, varying criteria based on molecular imaging have been established to define progressive disease, including "PSMA PET Progression Criteria," "Response evaluation criteria in PSMA PET/CT (RECIP 1.0)" or consensus statements of respective societies. In the present review, we will discuss the current status of PSMA PET/CT for response monitoring, focusing on PSMA RLT with [177Lu]Lu-labeled PSMA ligands, along with a head-to-head comparison of recently published response criteria. [ABSTRACT FROM AUTHOR]

Renal scintigraphy is a centerpiece of nuclear medicine and is also commonly applied for (peri-)acute care. In this regard, referrals by the treating physician include: I.) acute obstructions caused by gradual and infiltrative tumor growth or renal off-target effects under anti-tumor treatment, II.) functional issues in infants, for example, structural abnormalities such as duplex kidneys or uroliths in adults, which can also trigger III.) Infections of renal parenchyma. Renal radionuclide imaging is also requested due to IV.) acute trauma to the abdomen, for example, to assess renal scarring or upon further follow-up after reconstructive surgery. We will discuss clinical applications of (peri-)acute renal scintigraphy, along with future prospects on the use of more advanced nuclear imaging techniques such as renal positron emission tomography. [ABSTRACT FROM AUTHOR]

For molecular imaging of atherosclerotic vessel wall activity, tracer kinetic analysis may yield improved contrast versus blood, more robust quantitative parameters, and more reliable characterization of systems biology. The authors introduce a novel dynamic whole-body positron emission tomography (PET) protocol that is enabled by rapid continuous camera table motion, followed by reconstruction of parametric data sets using voxel-based Patlak graphical analysis. Twenty-five subjects were prospectively enrolled and underwent dynamic PET up to 90 minutes after injection of 2-[18F]fluoro-2-deoxy-D-glucose (FDG). Two sets of images were generated: 1) the established standard of static standardized uptake value (SUV) images; and 2) parametric images of the metabolic rate of FDG (MR FDG) using the Patlak plot–derived influx rate. Arterial wall signal was measured and compared using the volume-of-interest technique, and its association with hematopoietic and lymphoid organ signal and atherosclerotic risk factors was explored. Parametric MR FDG images provided excellent arterial wall visualization, with elimination of blood-pool activity, and enhanced focus detectability and reader confidence. Target-to-background ratio (TBR) from MR FDG images was significantly higher compared with SUV images (2.6 ± 0.8 vs 1.4 ± 0.2; P < 0.0001), confirming improved arterial wall contrast. On MR FDG images, arterial wall signal showed improved correlation with hematopoietic and lymphoid organ activity (spleen P = 0.0009; lymph nodes P = 0.0055; and bone marrow P = 0.0202) and increased with the number of atherosclerotic risk factors (r = 0.49; P = 0.0138), where signal from SUV images (SUV max P = 0.9754; TBR max P = 0.8760) did not. Absolute quantification of MR FDG is feasible for arterial wall using dynamic whole-body PET imaging. Parametric images provide superior arterial wall contrast, and they might be better suited to explore the relationship between arterial wall activity, systemic organ networks, and cardiovascular risk. This novel methodology may serve as a platform for future diagnostic and therapeutic clinical studies targeting the biology of arterial wall disease. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: IQ·SPECT is a recently introduced collimator design for myocardial perfusion imaging (MPI). Little data exist on use of this collimator type in obese patients, particularly Class 2 or 3 [body mass index (BMI) > 35 kg/m2]. Methods: Two consecutive rest–stress MPI scans were prospectively acquired using a conventional collimator and IQ·SPECT (acquisition times of 20 and 7 minutes, respectively) in 20 patients with a BMI of >30 kg/m2. Assigned by two blinded, independent readers, image quality (on a 5-point scale) and metrics of myocardial perfusion [summed stress score (SSS), summed rest score (SRS) and summed difference score (SDS)] were compared. Software-based left ventricular ejection fraction (EF) was also correlated. Results: Mean BMI was 39.6 ± 7.6 kg/m2. Class 2 or 3 obesity was present in 12 patients (BMI, 44.1 ± 6.8 kg/m2). Gated/non-gated images from IQ·SPECT revealed fair to good quality scores (median ≥ 3.25), which were inferior to the conventional collimator (median ≥ 4.0; P ≤ 0.01). Significant correlative indices were achieved when comparing IQ·SPECT and conventional collimators for EF values (r = 0.86, P < 0.01), SSS (r = 0.75, P < 0.0001) and SRS (r = 0.60, P < 0.005), but not for SDS (r = 0.15). Conclusion: IQ·SPECT was comparable to conventional SPECT in obese patients. The reduced acquisition time of IQ·SPECT may allow for improved throughput with no loss in diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Sodium-glucose cotransporters (SGLTs) play a crucial role in glucose regulation and are essential therapeutic targets for diabetes management. Recent advancements have leveraged SGLT-targeted PET imaging to examine these transporters' roles in both health and disease. This review highlights recent innovations in PET imaging targeting SGLTs, with a particular focus on SGLT-specific radiotracers, such as alpha-methyl-4-deoxy-4-18F-fluoro- d -glucopyranoside (Me-4FDG). It emphasizes the advantages of these radiotracers over conventional 18F-2-fluoro-2-deoxy- d -glucose (2-FDG) imaging, especially in assessing SGLT activity. Additionally, the review addresses their potential in evaluating the pharmacodynamics of SGLT inhibitors, investigating metabolic changes in diabetes, and staging cancers. SGLT-targeted PET imaging offers promising improvements in diagnostic accuracy and therapeutic planning. The findings underscore the physiological and pathological significance of SGLTs, indicating that this imaging approach could shape future diagnostic and therapeutic strategies in metabolic and oncologic fields. [Display omitted] [ABSTRACT FROM AUTHOR]

Diuretic scintigraphy includes single-photon emitting radiotracers for planar and single photon emission computed tomography (SPECT) imaging as well as agents for positron emission tomography (PET). These radiotracers provide split-renal functional parameters, including glomerular filtration rate, effective renal plasma flow, tubular function, and/or renal blood flow. Beyond measuring kidney function, the tracer principle also allows for the assessment of various pathophysiological processes in the renal parenchyma, for example ongoing inflammation, activation of angiotensin II type 1 receptor in patients with renovascular hypertension, deterioration of mitochondrial complex I following acute or chronic kidney injury, or characterization of indeterminate renal masses. Providing a whole-body read-out, PET also enables the assessment of kidney-organ interactions, for example cardiorenal crosstalk after primary cardiac injury. This manuscript provides an overview of established clinical applications for single-photon-emitting and PET radiotracers for renal radionuclide imaging. Future perspectives in the field will also be highlighted, such as introduction of PET-guided strategies for drug dose optimization and the recent introduction of radiotracers targeting fibroblast activation protein inhibition, which may allow differentiation between acute inflammatory vs chronic fibrosis in the kidneys. [ABSTRACT FROM AUTHOR]

See related article, https://doi.org/10.1007/s12350-022-03064-8 As a chaperone crucially involved in protein folding,[1] Sigma-1 receptor (Sig-1R) has been extensively investigated in the context of neurogenerative disorders, such as Parkinson's or Alzheimer Disease.[1]-[3] In recent years, it has also gained interest within the cardiovascular community, as it exerts cardioprotective effects against a.) apoptosis, b.) hypertrophy and c.) maladjusted endoplasmic reticulum stress response.[1] In this regard, a Sig-1R I in-vivo i molecular imaging approach may not only provide further insights into cardiac ischemia post-myocardial infarction,[4] but also in the context of hypertrophy-related vascular injury.[1],[5] In the present study, Wakabayashi and coworkers focused on myocardial ischemic burden and the targeting of Sig-1R using the SPECT probe I-125-iodophenyl-piperidino-cyclopentanol (125I-OI5V).[6] Left coronary occlusion (LCA) was conducted over varying time frames of 10 to 30 min, followed by release of the snare, thereby allowing for reperfusion. Of note, such TAC models have just been recently successfully investigated using the most commonly used PET radiotracer 18F-FDG.[12] Taken together, with its chaperone activity involved in protein folding, a direct I in-vivo i visualization of Sig1-R may be of interest in various clinical scenarios, in particular if Sig-1R drugs providing cardioprotective effects would become available. [Extracted from the article]

Functional expression of gap junction proteins can be obtained conveniently with the paired oocyte cell-cell channel assay. So far all gap junction proteins (connexins), with the exception of one, have been found to make functional channels either by themselves or as hybrid channels (two hemichannels of different connexin composition). Connexin33 (cx33) appears not to follow this rule. Expression of cx33 in oocytes does not yield functional channels, and attempts to identify another connexin with which cx33 can form hybrid channels have failed so far. The observation was made that cx33 inhibits functional expression of other connexins in a connexin-specific way. While expression of cx32 remains unaffected by coinjection into oocytes of cx33 mRNA together with cx32 mRNA, junctional conductance obtained with cx43 is marginally reduced whereas coinjection of cx33 mRNA at equimolar concentrations almost completely abolishes functional cx37 expression. The fact that testis is the only tissue found to express significant levels of cx33 mRNA together with cx37 and cx43 suggests a possible functional role for an inhibitory connexin. A model is proposed where cx33 limits a cell's capability to make functional channels by allowing formation of heterotypic channels with other cells while formation of homotypic channels is disallowed. Such a mechanism would permit asynchronous maturation of germ cells while at the same time allowing communication between germ cells and Sertoli cells.

Polarization of oocyte gap junction proteins is described by several studies using an exogenous protein. Results indicate that oocytes achieve higher conductances when paired at their vegetal poles than when paired at their animal poles. This asymmetry involves the action of the ooyctes's connexin protein, which can cause changes in the membrane potential. It has not been tested whether connexin molecules are inserted randomly or preferentially into the plasma membrane.

Will (18)F flurpiridaz replace (82)rubidium as the most commonly used perfusion tracer for PET myocardial perfusion imaging? 1:CAS:528:DyaL1MXmtVyqsrg%3D. 10.1161/01.RES.65.4.1157 15 Ghotbi AA, Kjaer A, Hasbak P. Review: Comparison of PET rubidium-82 with conventional SPECT myocardial perfusion imaging. [Extracted from the article]

10.1124/jpet.113.206458 15 Werner RA, Chen X, Rowe SP, Lapa C, Javadi MS, Higuchi T. Recent paradigm shifts in molecular cardiac imaging-Establishing precision cardiology through novel (18)F-labeled PET radiotracers. Funding A KAKENHI grant (JP15K21774) has been provided for Dr. T. Higuchi from the Japan Society for the Promotion of Science (JSPS). [Extracted from the article]

As a scintigraphic approach evaluating cardiac nerve integrity, 123I-metaiodobenzylguanidine (123I-mIBG) has been recently Food and Drug Administration approved. A great deal of progress has been made by the prospective ADMIRE-HF trial, which primarily demonstrated the association of denervated myocardium assessed by 123I-mIBG and cardiac events. However, apart from risk stratification, myocardial nerve function evaluated by molecular imaging should also be expanded to other clinical contexts, in particular to guide the referring cardiologist in selecting appropriate candidates for specific therapeutic interventions. In the present issue of the Journal of Nuclear Cardiology®, the use of 123I-mIBG for identifying cardiomyopathy patients, which would most likely not benefit from ICD due to low risk of arrhythmias, is described. If we aim to deliver on the promise of cardiac innervation imaging as a powerful tool for risk stratification in a manner similar to nuclear oncology, studies such as the one reviewed here may imply an important step to lay the proper groundwork for a more widespread adoption in clinical practice. [ABSTRACT FROM AUTHOR]

Recent years have witnessed an expanded use of single-photon emission CT and PET for a wide range of clinical applications, including imaging of brain abnormalities. As a result, molecular brain imaging is now being more extensively utilized in criminal cases, in particular in the sentencing phase of a trial. This perspective aims to provide a brief overview for the practicing radiologist of this expanded use of single-photon emission CT and PET in criminal cases and will discuss the role of radiology in this field. [ABSTRACT FROM AUTHOR]

The continuing adoption of prostate specific membrane antigen (PSMA)-targeted PET for prostate cancer molecular imaging requires imagers and clinicians alike to be aware of the increasing number of potential interpretive pitfalls that have been reported. This review summarizes and illustrates the spectrum of benign and malignant nonprostatic conditions with high PSMA-radiotracer uptake that may be mistaken for sites of prostate cancer and also discusses potential false negatives. We discuss the recent literature on the effect of androgen deprivation therapy on lesion detection. Furthermore, we briefly review the recently proposed structured reporting systems for the standardized interpretation of PSMA-targeted PET that can guide both imaging specialists and referring clinicians in the appropriate interpretation and work-up of pitfalls. [ABSTRACT FROM AUTHOR]

However, in cardiac 123I-mIBG scans conducted 3 weeks after MI, the statin group showed significantly higher delayed HMR (along with a reduced washout rate), reflecting improved cardiac nerve integrity, compared to the non-statin group. A propensity-matched analysis was conducted to correct for selection bias, and 30 individuals with ST-segment elevation MI (STEMI) treated with statin therapy were compared to 30 MI patients without statin therapy. However, future studies may investigate whether SNS molecular imaging of the heart may hold the potential to identify treatment responders of novel and expensive lipid-lowering medication, preferably in subjects which are intolerant to current statin treatment. [Extracted from the article]

Funding This work was funded by the German Research Foundation (DFG), through the PRACTIS - Clinician Scientist Program of Hannover Medical School (ME 3696/3-1, RAW) the research group KFO311 (FMB) and REBIRTH cluster of excellence ("Förderung aus Mitteln des Niedersächsischen Vorab", RAW). Machine learning predicts per-vessel early coronary revascularization after fast myocardial perfusion SPECT: Results from multicentre REFINE SPECT registry. Interestingly, the ML-derived risk prediction model showed that risk for ArE was markedly elevated at the intermediate range of SPECT-derived heart-to-mediastinum ratio (HMR) in younger subjects with less severe HF. [Extracted from the article]

Introduction Peptide receptor radionuclide therapy (PRRT) is a treatment option for both iodine-refractory differentiated and advanced medullary thyroid cancer (TC). It requires over-expression of somatostatin receptor subtype II (SSTR) that can be non-invasively assessed by positron emission tomography (PET). Assessment of tumor heterogeneity is increasingly used as a tool for prognostication prediction. We investigated the potential of SSTR-PET to assess intraindividual tumor heterogeneity and thereby treatment response prior to PRRT. Methods 12 patients with progressive radioiodine-refractory differentiated (1 papillary, 1 oxyphilic, 2 oncocytic, 4 follicular) or medullary (n = 4) TC were enrolled. SSTR-PET was performed at baseline. Conventional PET parameters and heterogeneity parameters were analyzed regarding their potential to predict progression-free (PFS, mean, 221 days) and overall survival (OS, mean, 450 days). Parameters of a subgroup of lesions (n = 23) were also correlated with morphological response according to modified RECIST criteria. Results In patient-based analysis, all conventional parameters failed to predict PFS. Several textural parameters showed a significant capability to assess PFS. Thereby, “Grey level non uniformity” had the highest area under the curve (AUC, 0.93) in Receiver operating characteristics analysis followed by “Contrast” (AUC, 0.89). In lesion-based analysis, only “Entropy” revealed potential to evaluate disease progression. OS could not be assessed by any parameter investigated. Conclusions Tumor heterogeneity seems to be a predictor of response to PRRT in patients with iodine-refractory differentiated/advanced medullary thyroid cancer and outperforms conventional PET parameters like standardized uptake value. In a “theranostic” approach, assessment of textural parameters may help in selecting patients who might benefit from PRRT. [ABSTRACT FROM AUTHOR]

Background Acute myocarditis as well as post-ischemic myocardial inflammation are generally associated with a profound activation of the immune system. Current established imaging techniques such as cardiac MRI reliably demonstrate signs of acute myocardial injury. However, detection of mediating cells such as macrophages is currently limited to experimental settings. We aimed to investigate the feasibility of somatostatin receptor (SSTR) based positron emission tomography/computed tomography (PET/CT) for detecting inflammatory lesions in patients after acute myocardial infarction or acute peri-/myocarditis. Methods 12 patients with active peri-/myocarditis (n = 6) or sub-acute myocardial infarction (n = 6) underwent SSTR-PET/CT and cardiac MRI within 3-10 days after onset of symptoms. The AHA 17-segment model of the left myocardium was used for visual localization of inflamed myocardium for both imaging modalities. Tracer uptake of infarcted/inflamed myocardium was assessed as mean and maximum standardized uptake value (SUVmean and SUVmax) and compared with both remote myocardium and left ventricular (LV) cavity. Results SSTR-PET/CT revealed areas with increased cardiac tracer uptake in all patients. In the 17-segment model, PET/CT yielded 55 and MRI 47 positive segments. Overall, concordance of the 2 modalities was 85.3% (174/204 segments analyzed). In 9.3% (19/204), more positive segments were identified by PET/CT, whereas in 5.4% (11/204), MRI detected more positive segments. Conclusions The imaging patterns of SSTR-directed radiotracers and MRI in vivo show a close spatial relation of macrophage concentration and structural changes. This suggests the possibility of a new potential biomarker that predicts cardiac remodeling and, hence, progression towards heart failure. Prospective trials are warranted. [ABSTRACT FROM AUTHOR]

Purpose: We tested a novel multi-parametric (mp) whole body (WB)-MRI evaluation algorithm for medullary lesions in comparison to positron emission tomography (PET) radiotracers 18F-fluorodeoxyglucose (18F-FDG) and 11C-methionine (11C-MET).Methods and Materials: This retrospective single-center study included 44 MM patients, who received both 18F-FDG-PET and WB-MRI within ten days. MRI classified focal lesions as vital when showing 1) significant diffusion-restriction, 2) a fat fraction (FF) less than 20 % and 3) homogenous hypointensity on T2-weighted images. On a lesion-by-lesion level the findings were compared to 18F-FDG PET by using a 5-point scoring system (analogous to the Deauville score [DS]). In 24/44 (55 %) patients additional comparison to 11C-MET PET was available.Results: Among two radiologists, an excellent inter-observer reliability for mpWB-MRI in a total of 84 medullary lesions was observed (ICC = 1, k = 1, p <.01). 16/17 (94.1 %) MRI-classified vital lesions had a DS of 4 or 5 on either 18F-FDG-PET or 11C-MET-PET. MRI-rated non-vital lesions correlated with PET-based DS ≤ 3. When results of mpWB-MRI were compared to 18F-FDG, a fair inter-observer agreement was recorded (ICC = 0.52, k = 0.53, p <.01), while for 11C-MET, an excellent concordance rate was achieved (ICC = 0.81, k = 0.79, p <.01).Conclusion: The proposed mpWB-MRI interpretation algorithm allowed to assess tumor activity of myeloma lesions with high inter-observer reproducibility. We observed a substantial concordance between the mpWB-MRI classification of lesions and PET assessment based on a semi-automatically calculated 5-point scoring system analogous to the Deauville scores. [ABSTRACT FROM AUTHOR]