PET Imaging in Cardiac Sarcoidosis: A Narrative Review with Focus on Novel PET Tracers.
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ABSTRACT:
SUBMITTER: Saric P
PROVIDER: S-EPMC8704408 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The use of PET imaging agents in oncology, cardiovascular disease, and neurodegenerative disease shows the power of this technique in evaluating the molecular and biological characteristics of numerous diseases. These agents provide crucial information for designing therapeutic strategies for individual patients. Novel PET tracers are in continual development and many have potential use in clinical and research settings. This article discusses the potential applications of tracers in diagnostics, the biological characteristics of diseases, the ability to provide prognostic indicators, and using this information to guide treatment strategies including monitoring treatment efficacy in real time to improve outcomes and survival.
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Project description:PurposeTo compare combined cardiac fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/MRI with standard-of-care evaluation using cardiac MRI, 18F-FDG PET/CT, and SPECT perfusion imaging in suspected cardiac sarcoidosis (CS) with respect to radiation dose, imaging duration, and diagnostic test performance.Materials and methodsConsecutive patients with suspected CS undergoing clinical evaluation with cardiac 18F-FDG PET/CT and gated rest technetium 99m sestamibi SPECT perfusion imaging were prospectively recruited between November 2017 and May 2021 for parallel assessment with combined cardiac 18F-FDG PET/MRI on the same day (ClinicalTrials.gov identifier, NCT03356756). Total effective radiation dose and imaging duration were compared between approaches (combined cardiac PET/MRI vs separate cardiac MRI, PET/CT, and SPECT). MRI findings were initially interpreted without PET data, and then PET and late gadolinium enhancement images were fused and interpreted together. Final diagnosis of CS was established using Japanese Ministry of Health and Welfare guidelines.ResultsForty participants (mean age, 54 years ± 14 [SD]; 26 [65%] male participants) were included, 14 (35%) with a final diagnosis of CS. Compared with separate cardiac MRI, PET/CT, and SPECT perfusion imaging, combined cardiac PET/MRI had 52% lower total radiation dose (8.0 mSv ± 1.2 vs 16.8 mSv ± 1.6, P < .001) and 43% lower total imaging duration (122 minutes ± 15 vs 214 minutes ± 26, P < .001). Combined PET/MRI had the highest area under the curve for diagnosis of CS (0.84) with 96% specificity and 71% sensitivity for colocalized FDG uptake and late gadolinium enhancement in a pattern typical for CS.ConclusionIn the evaluation of suspected CS, combined cardiac 18F-FDG PET/MRI had a lower radiation dose, shorter imaging duration, and higher diagnostic performance compared with standard-of-care imaging.Clinical trial registration no. NCT03356756Keywords: Cardiac Sarcoidosis, 18F-FDG PET/MRI, 18F-FDG PET/CT, SPECT Perfusion Imaging, Cardiac MRI, Standard-of-Care Imaging Supplemental material is available for this article. © RSNA, 2023.
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Project description:The P2Y12 receptor (P2Y12R) is uniquely expressed on microglia in the brain, and its expression level directly depends on the microglial activation state. Therefore, P2Y12R provides a promising imaging marker for distinguishing the pro- and anti-inflammatory microglial phenotypes, both of which play crucial roles in neuroinflammatory diseases. In this study, three P2Y12R antagonists were selected from the literature, radiolabeled with carbon-11 or fluorine-18, and evaluated in healthy Wistar rats. Brain imaging was performed with and without blocking of efflux transporters P-glycoprotein and breast cancer resistance protein using tariquidar. Low brain uptake in healthy rats was observed for all tracers at baseline conditions, whereas blocking of efflux transporters resulted in a strong (6-7 fold) increase in brain uptake for both of them. Binding of the most promising tracer, [18F]3, was further evaluated by in vitro autoradiography on rat brain sections, ex vivo metabolite studies, and in vivo P2Y12R blocking studies. In vitro binding of [18F]3 on rat brain sections indicated high P2Y12R targeting with approximately 70% selective and specific binding. At 60 min post-injection, over 95% of radioactivity in the brain accounted for an intact tracer. In blood plasma, still 40% intact tracer was found, and formed metabolites did not enter the brain. A moderate P2Y12R blocking effect was observed in vivo by positron emission tomography (PET) imaging with [18F]3 (p = 0.04). To conclude, three potential P2Y12R PET tracers were obtained and analyzed for P2Y12R targeting in the brain. Unfortunately, the brain uptake appeared low. Future work will focus on the design of P2Y12R inhibitors with improved physicochemical characteristics to reduce efflux transport and increase brain penetration.
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