Synthesis and in Vitro/in Vivo Pharmacological Evaluation of [11C]-Thioabp, a Novel Radiotracer for Imaging Mglur5 with PET

We have designed a novel positron emission tomography (PET) radiotracer, [C-11]-ThioABP, a thiazole based derivative for imaging the metabotropic glutamate receptor subtype 5 (mGluR5), and prepared the hydroxy oxime precursor 4 in a 15% overall yield. [C-11]-ThioABP was radiosynthesized in the Veenstra module and obtained in a decay corrected radiochemical yield of 40% and specific activity of 80-250 GBq mu mol(-1) at the end of synthesis. ThioABP exhibited excellent binding affinity (K-i) in vitro of 1.9 +/- 0.9 nM and [C-11]-ThioABP showed an optimal log D-7.4 of 2.4. The autoradiographic studies on rat brain slices revealed specific binding to mGluR5. In vivo evaluation of [C-11]-ThioABP including a displacement study with MMPEP in a dynamic PET scan showed a specificity of [C-11]-ThioABP for mGluR5. Radio-TLC metabolite studies showed a good metabolic stability of [C-11]-ThioABP in vivo. The comparison of biological properties of [C-11]-ThioABP and [C-11]-ABP688 revealed similarity between these two compounds.