| Literature DB >> 24721831 |
Jinda Fan1, Xiang Zhang1, Junfeng Li1, Hongjun Jin1, Prashanth K Padakanti1, Lynne A Jones1, Hubert P Flores2, Yi Su2, Joel S Perlmutter3, Zhude Tu4.
Abstract
The radiosyntheses and in vivo evaluation of four carbon-11 labeled quinoline group-containing radioligands are reported here. Radiolabeling of [(11)C]1-4 was achieved by alkylation of their corresponding desmethyl precursors with [(11)C]CH3I. Preliminary biodistribution evaluation in Sprague-Dawley rats demonstrated that [(11)C]1 and [(11)C]2 had high striatal accumulation (at peak time) for [(11)C]1 and [(11)C]2 were 6.0-fold and 4.5-fold at 60 min, respectively. Following MP-10 pretreatment, striatal uptake in rats of [(11)C]1 and [(11)C]2 was reduced, suggesting that the tracers bind specifically to PDE10A. MicroPET studies of [(11)C]1 and [(11)C]2 in nonhuman primates (NHP) also showed good tracer retention in the striatum with rapid clearance from non-target brain regions. Striatal uptake (SUV) of [(11)C]1 reached 1.8 at 30 min with a 3.5-fold striatum:cerebellum ratio. In addition, HPLC analysis of solvent extracts from NHP plasma samples suggested that [(11)C]1 had a very favorable metabolic stability. Our preclinical investigations suggest that [(11)C]1 is a promising candidate for quantification of PDE10A in vivo using PET.Entities:
Keywords: CNS; Carbon-11; MP-10; PDE10A; PET imaging
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Year: 2014 PMID： 24721831 PMCID： PMC4054929 DOI： 10.1016/j.bmc.2014.03.028
Source DB: PubMed Journal: Bioorg Med Chem ISSN： 0968-0896 Impact factor: 3.641