Synthesis of radiolabeled protein disulfide isomerase (PDI) inhibitors as new potential PET agents for imaging of the enzyme PDI in neurological disorders and cancer

Carbon-11-labeled substituted β-tetrahydrocarbolines were prepared from their corresponding phenolic hydroxyl precursors with [11C]CH3OTf through O-[11C]methylation and isolated by simplified SPE in 50–60% decay corrected radiochemical yields at EOB with 185–370 GBq/μmol specific activity at EOS. A fluorine-18-labeled substituted β-tetrahydrocarboline was prepared from its corresponding halo-precursors (X=Cl, Br, I) with K[18F]F/Kryptofix 2.2.2 via the nucleophilic substitution and isolated by HPLC combined with SPE in 25–40% decay corrected radiochemical yield with 37–222 GBq/μmol specific activity at EOB.

► New substituted β-tetrahydrocarbolines were synthesized.
► New radiolabeled substituted β-tetrahydrocarbolines were synthesized.
► Simple solid-phase extraction (SPE) method was employed in radiosynthesis.