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• W2124327561 abstract "Phosphodiesterase 10A (PDE10A) is an intracellular enzyme responsible for the breakdown of cyclic nucleotides which are important secondary messengers in the central nervous system. Inhibition of PDE10A has been identified as a potential therapeutic target for treatment of various neuropsychiatric disorders. To assist the drug development program, we have identified a selective PDE10A PET tracer, [11C]AMG 7980, for imaging PDE10A distribution using positron emission tomography. [11C]AMG 7980 was prepared in a one-pot, two-step reaction. Dynamic PET scans were performed in non-human primates following a bolus or bolus plus constant infusion tracer injection paradigm. Regions-of-interest were defined on individuals’ MRIs and transferred to the co-registered PET images. Data were analyzed using Logan graphical analysis with metabolite-corrected input function, the simplified reference tissue model (SRTM) method and occupancy plots. A benchmark PDE10A inhibitor was used to demonstrate PDE10A-specific binding. [11C]AMG 7980 was prepared with a mean specific activity of 99 ± 74 GBq/μmol (n = 10) and a synthesis time of 45 min. Specific binding of the tracer was localized to the striatum and globus pallidus (GP) and low in other brain regions. Thalamus was used as the reference tissue to derive binding potentials (BPND). The BPND for caudate, putamen, and GP were 0.23, 0.65, 0.51, respectively by the graphical method, and 0.42, 0.76, and 0.75 from the SRTM method. A dose dependent decrease of BPND was observed with the pre-treatment of a PDE10A inhibitor. A bolus plus infusion injection paradigm yielded similar results. [11C]AMG 7980 has been successfully used for imaging PDE10A in non-human primate brain. Despite the fast brain kinetics it can be used to measure target occupancy of PDE10A inhibitors in non-human primates and potentially applicable to humans." @default.
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• W2124327561 date "2014-04-01" @default.
• W2124327561 modified "2023-10-09" @default.
• W2124327561 title "Initial characterization of a PDE10A selective positron emission tomography tracer [11C]AMG 7980 in non-human primates" @default.
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• W2124327561 doi "https://doi.org/10.1016/j.nucmedbio.2014.01.007" @default.
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