Synthesis of carbon-11-labeled imidazopyridine- and purine-thioacetamide derivatives as new potential PET tracers for imaging of nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1)

The target tracer carbon-11-labeled imidazopyridine- and purine-thioacetamide derivatives, N-(3-[11C]methoxy-4-methoxyphenyl)-2-((5-methoxy-3H-imidazo[4,5-b]pyridin-2-yl)thio)acetamide (3-[11C]4a) and N-(4-[11C]methoxy-3-methoxyphenyl)-2-((5-methoxy-3H-imidazo[4,5-b]pyridin-2-yl)thio)acetamide (4-[11C]4a); 2-((6-amino-9H-purin-8-yl)thio)-N-(3-[11C]methoxy-4-methoxyphenyl)acetamide (3-[11C]8a) and 2-((6-amino-9H-purin-8-yl)thio)-N-(4-[11C]methoxy-3-methoxyphenyl)acetamide (4-[11C]8a), were prepared by O-[11C]methylation of their corresponding precursors with [11C]CH3OTf under basic condition (2 N NaOH) and isolated by a simplified solid-phase extraction (SPE) method in 50–60% radiochemical yields based on [11C]CO2 and decay corrected to end of bombardment (EOB). The overall synthesis time from EOB was 23 min, the radiochemical purity was >99%, and the specific activity at end of synthesis (EOS) was 185–555 GBq/μmol.

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