Synthesis of substituted [123I]imidazo[1,2-α]pyridines as potential probes for the study of the peripheral benzodiazepine receptors using SPECT

Abstract

The imidazo[1,2-α]pyridines [N,N´-dimethyl-6-chloro-(4´zf-iodophenyl)imidazo[1,2-α]pyridine-3-acetamide 1, [N,N´l-6-chloro-(4´-iodophenyl)imidazo[1,2-α]pyridine-3-acetamide 2, and [N-methyl-6-chloro-(4´-iodophenyl)imidazo[1,2-α]pyridine-3-acetamide 3, are high affinity and selective ligands for the Peripheral Benzodiazepine Receptors (PBR). The [123I]1-3 labelled analogues of these compounds were subsequently synthesised for the potential study of the PBR in vivo using SPECT. Radioiodination was achieved by iododestannylation reactions of the corresponding tributyl tin precursors with Na[123I] in the presence of peracetic acid, chloramine-T or Iodogen. Purification of the crude product was achieved by semipreparative C-18 RP HPLC to give the products in radiochemical yields of 40-85%. The products were obtained in >97% chemical and radiochemical purity and with specific activities >80 GBq/μmol.