1607448-71-4Relevant academic research and scientific papers
Radiosyntheses and in vivo evaluation of carbon-11 PET tracers for PDE10A in the brain of rodent and nonhuman primate
Fan, Jinda,Zhang, Xiang,Li, Junfeng,Jin, Hongjun,Padakanti, Prashanth K.,Jones, Lynne A.,Flores, Hubert P.,Su, Yi,Perlmutter, Joel S.,Tu, Zhude
, p. 2648 - 2654 (2014/05/06)
The radiosyntheses and in vivo evaluation of four carbon-11 labeled quinoline group-containing radioligands are reported here. Radiolabeling of [11C]1-4 was achieved by alkylation of their corresponding desmethyl precursors with [11C]CH3I. Preliminary biodistribution evaluation in Sprague-Dawley rats demonstrated that [11C]1 and [ 11C]2 had high striatal accumulation (at peak time) for [ 11C]1 and [11C]2 were 6.0-fold and 4.5-fold at 60 min, respectively. Following MP-10 pretreatment, striatal uptake in rats of [ 11C]1 and [11C]2 was reduced, suggesting that the tracers bind specifically to PDE10A. MicroPET studies of [11C]1 and [ 11C]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 [11C]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 [11C]1 had a very favorable metabolic stability. Our preclinical investigations suggest that [ 11C]1 is a promising candidate for quantification of PDE10A in vivo using PET.
