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ObjectiveTo evaluate the effectiveness of a new tracer (S)-1-(4-(6-(dimethylamino)quinoxalin-2-yl)phenoxy)-3-fluoropropan-2-ol ([18F]-S16), in distinguishing patients with AD from HCs.MethodsPaired [18F]-S16 and [18F]-THK5317 scans were acquired in five patients with AD, six HCs, one subject with a semantic variant of primary progressive aphasia (sv-PPA) and one subject with probable progressive supranuclear palsy (PSP). Dynamic PET scanning was performed over 90 min after injection of the tracers. Standardized uptake values (SUV) and cortical-to-cerebellum standardized uptake value ratios (SUVRs) were used for tau deposition semi-quantization. A voxel-based analysis was employed to assess the uptake difference between populations.Results[18F]-S16 exhibited excellent blood-brain-barrier penetration. AD patients showed increased cortical [18F]-THK5317 and [18F]-S16 binding. Compared to HCs, AD patients showed significantly increased cortical [18F]-S16 uptake in the bilateral occipital cortex, posterior cingulated cortex/precuneus, and lateral frontal cortex. Notable [18F]-S16 uptake was observed in the basal ganglia and brainstem compared to the neocortex. A substantial [18F]-S16 signal was detected in the basal ganglia and midbrain in a patient with probable PSP and in the bilateral anterior temporal cortex in a sv-PPA patient.Conclusion[18F]-S16 might be of help to detect tau protein in vivo.

Background: The goal of this study was to report a fully automated radiosynthetic procedure of a novel tau tracer [18F]-S16 and its safety, biodistribution, and dosimetry in healthy volunteers as well as the potential utility of [18F]-S16 positron emission tomography (PET) in Alzheimer’s disease (AD).Methods: The automated radiosynthesis of [18F]-S16 was performed on a GE Tracerlab FX2 N module. For the biodistribution and dosimetry study, healthy volunteers underwent a series of PET scans acquired at 10, 60, 120, and 240 min post-injection. The biodistribution and safety were assessed. For the AD study, both AD and healthy controls (HCs) underwent dynamic [18F]-S16 and static [18F]-FDG PET imaging. [18F]-S16 binding was assessed quantitatively using standardized uptake value ratios (SUVRs) measured at different regions of interest (ROIs). [18F]-S16 SUVRs were compared between the AD patients and HCs using the Mann–Whitney U-test. In AD patients with all cortical ROIs, Spearman rank-correlation analysis was used to calculate the voxel-wise correlations between [18F]-S16 and [18F]-FDG.Results: The automated radiosynthesis of [18F]-S16 was finished within 45 min, with a radiochemical yield of 30 ± 5% (n = 8, non-decay-corrected). The radiochemical purity was greater than 98%, and the specific activity was calculated to be 1,047 ± 450 GBq/μmol (n = 5), and [18F]-S16 was stable in vitro. In the healthy volunteer study, no adverse effect was observed within 24 h post-injection, and no defluorination was observed in vivo. The radiotracer could pass through the blood–brain barrier easily and was rapidly cleared from the circulation and excreted through the hepatic system. The whole-body mean effective dose was 15.3 ± 0.3 μSv/MBq. In AD patients, [18F]-S16 accumulation was identified as involving the parietal, temporal, precuneus, posterior cingulate, and frontal lobes. No specific [18F]-S16 cerebral uptake was identified in HCs. The SUVR of AD patients was significantly higher than that of HCs. No specific binding uptake was found in the choroid plexus, venous sinus, and white matter. A significant correlation was found between [18F]-S16 binding and hypometabolism across neocortical regions.Conclusion: [18F]-S16 could be synthesized automatically, and it showed favorable biodistribution and safety in humans. [18F]-S16 PET indicated a high image quality for imaging tau deposition in AD and distinguishing AD from HCs.

Purpose: This prospective trial aimed to evaluate the safety, dosimetry, and biodistribution of a novel theranostic probe 68Ga-DOTA-DiPSMA. Also, we have performed the first preliminary application with 68Ga-DOTA-DiPSMA in prostate cancer (PCa) patients.Methods: Five healthy volunteers and ten PCa patients were injected with an intravenous bolus of 68Ga-DOTA-DiPSMA. They received serial whole-body PET scans from the time of injection up to 60 min post-injection, with a second PET/CT scanning at 120 min post-injection. In PCa patients, low-dose CT scan and whole-body PET were performed with 2 min per bed position in 40 min post-injection. Absorbed organ doses and effective doses were calculated using OLINDA/EXM. Normal organ uptake and tumor lesion uptake were measured. A lesion-by-lesion analysis was performed.Results: 68Ga-DOTA-DiPSMA administration was safe and well-tolerated. The kidneys received the highest absorbed dose (114.46 ± 29.28 μSv/MBq), followed by the urinary bladder wall (100.82 ± 46.22 μSv/MBq) in accordance with the expected Prostate-Specific Membrane Antigen (PSMA) renal excretion of the tracer. The mean effective dose was 19.46 ± 1.73 μSv/MBq. The SUVmax of 68Ga-DOTA-DiPSMA PET/CT for PCa lesions, bone metastases, and lymph node metastases was 4.41 ± 2.72, 2.95 ± 1.11, and 3.26 ± 1.20, respectively.Conclusion: Injection of 68Ga-DOTA-DiPSMA is safe and associated with low absorbed and effective doses. 68Ga-DOTA-DiPSMA shows favorable kinetics and imaging characteristics in patients who warrant further head-to-head comparison to validate 68Ga-DOTA-DiPSMA as an alternative for gallium-68-labeled PSMA clinical PET. Low nonspecific uptake in normal organs of 68Ga-DOTA-DiPSMA indicates potential radioligand therapy (RLT) application when labeled with 177Lu, 90Y, or 225Ac.

Breast cancer is the most common malignancy among women. Inorganic pyrophosphatase 1 (PPA1) is a multifunctional protein involved in the development of several tumors. However, the role of PPA1 in breast cancer progression remains unclear. In this study, we found that PPA1 was highly expressed in breast cancer compared to its levels in normal breast tissue and that it was correlated with breast cancer clinicopathological characteristics, as well as poor survival in breast cancer patients. Silencing PPA1 restrained breast cancer proliferation and metastasis by regulating Slug-mediated epithelial-mesenchymal transition (EMT). Opposite results were observed following PPA1 overexpression. In addition, investigation of the underlying mechanism demonstrated that PPA1 ablation led to decrease phosphatidylinositol 3 kinase (PI3K) phosphorylation levels and attenuate phosphorylated AKT and glycogen synthase kinase-3 β (GSK3β), while ectopic PPA1 expression had the opposite effects. Moreover, PI3K inhibitors suppress the signaling pathways mediating the effects of PPA1 on breast cancer, resulting in tumor growth and metastasis suppression in vitro and in vivo. In summary, our results verify that PPA1 can act as an activator of PI3K/AKT/GSK3β/Slug-mediated breast cancer progression and that it is a potential therapeutic target for the inhibition of tumor progression.

Objective: To evaluate the effectiveness of a new tracer (S)-1-(4-(6-(dimethylamino)quinoxalin-2-yl)phenoxy)-3-fluoropropan-2-ol ([18F]-S16), in distinguishing patients with AD from HCs. Methods: Paired [18F]-S16 and [18F]-THK5317 scans were acquired in five patients with AD, six HCs, one subject with a semantic variant of primary progressive aphasia (sv-PPA) and one subject with probable progressive supranuclear palsy (PSP). Dynamic PET scanning was performed over 90 min after injection of the tracers. Standardized uptake values (SUV) and cortical-to-cerebellum standardized uptake value ratios (SUVRs) were used for tau deposition semi-quantization. A voxel-based analysis was employed to assess the uptake difference between populations. Results: [18F]-S16 exhibited excellent blood-brain-barrier penetration. AD patients showed increased cortical [18F]-THK5317 and [18F]-S16 binding. Compared to HCs, AD patients showed significantly increased cortical [18F]-S16 uptake in the bilateral occipital cortex, posterior cingulated cortex/precuneus, and lateral frontal cortex. Notable [18F]-S16 uptake was observed in the basal ganglia and brainstem compared to the neocortex. A substantial [18F]-S16 signal was detected in the basal ganglia and midbrain in a patient with probable PSP and in the bilateral anterior temporal cortex in a sv-PPA patient. Conclusion: [18F]-S16 might be of help to detect tau protein in vivo. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) and vascular dementia (VaD) are the most common cause of dementia. Cerebral ischemia is a major risk factor for development of dementia. 123I-FPCIT SPECT (DaTScan) is a complementary tool in the differential diagnoses of patients with incomplete or uncertain Parkinsonism. Additional application of DaTScan enables the categorization of Parkinsonian disease with dementia (PDD), and its differentiation from pure AD, and may further contribute to change the therapeutic decision. The aim of this study was to analyze the vascular contribution towards dementia and mild cognitive impairment (MCI). We evaluated the utility of DaTScan for the early diagnosis of dementia in patients with and without a clinical vascular component, and the association between neuropsychological function, vascular component and dopaminergic function on DaTScan. One-hundred and five patients with MCI or the initial phases of dementia were studied prospectively. We developed an initial assessment using neurologic examination, blood tests, cognitive function tests, structural neuroimaging and DaTScan. The vascular component was later quantified in two ways: clinically, according to the Framingham Risk Score (FRS) and by structural neuroimaging using Wahlund Scale Total Score (WSTS). Early diagnosis of dementia was associated with an abnormal DaTScan. A significant association was found between a high WSTS and an abnormal DaTScan (p < 0.01). Mixed AD was the group with the highest vascular component, followed by the VaD group, while MCI and pure AD showed similar WSTS. No significant associations were found between neuropsychological impairment and DaTScan independently of associated vascular component. DaTScan seems to be a good tool to discriminate, in a first clinical assessment, patients with MCI from those with established dementia. There was bigger general vascular affectation observable in MRI or CT in patients with abnormal dopaminergic uptake seen on DaTScan. [ABSTRACT FROM AUTHOR]