We have synthesized a potent fluorinated PDE7 inhibitor, [18F]MICA-003 (PDE7 IC50 = 17 nM) and the corresponding tosylate precursor for radiolabeling. [18F]MICA-003 was injected in C57BL/6 J mice (n = 5) and in vivo images were acquired by μPET imaging. Radiometabolite analysis in plasma and brain was performed to determine the stability of the radioligand.
[18F]MICA-003 was synthesized by direct fluorination of the tosylate and produced in high decay corrected radiochemical yield (40%), high radiochemical purity (> 98%) and high specific activity (86–497 GBq/μmol). μPET imaging revealed that [18F]MICA-003 crosses the blood brain barrier and has a homogenous distribution over the brain which washes out after the initial peak uptake. [18F]MICA-003 was quickly metabolized in plasma with 8.9% ± 0.59% of intact [18F]MICA-003 remaining at 5 min post injection. We observed the formation of three distinct radiometabolites of which the main radiometabolite was also detected in the brain in a proportion of 25.7 ± 2.57% at this same time point.
We have described the synthesis and in vivo evaluation of a novel radioligand for PDE7 imaging. Despite high uptake in the brain and favorable kinetics in vivo, the presence of a brain penetrant radiometabolite makes [18F]MICA-003 unfavorable for the accurate quantification of PDE7 and more stable spiroquinazolinones analogs are in development.