Synthesis of [¹²³I]iodine labelled imidazo[1,2-b] pyridazines as potential probes for the study of peripheral benzodiazepine receptors using SPECT

The pyridazines 3-acetamidomethyl-6-chloro-2-(4′-iodophenyl) imidazo[1,2-b]pyridazine 1 (IC₅₀ = 1.6 nM) and 3-benzanfidomethyl-6- iodo-2-(4′-t-butylphenyl)imidazo[1,2-b] pyridazine 2 (IC₅₀ = 4.2 nM), are high affinity and selective ligands for the Peripheral Benzodiazepine Receptors (PBR) compared to the Central Benzodiazepine counterparts. The [¹²³I]1 and [¹²³I]2 labelled analogues of these compounds were subsequently synthesised for the potential study of the PBR in vivo using SPECT. Radioiodination of [¹²³I]1 was achieved by iododestannylation of the corresponding tributyl tin precursor with Na[ ¹²³I] in the presence of peracetic acid or chloramine-T and the product isolated by C-18 RP HPLC. Radioiodination of [¹²³I]2 was achieved by copper assisted bromine [¹²³I]iodine exchange of the corresponding bromo precursor in the presence of acetic acid and sodium bisulfate as reducing agent at 200 °C. Purification of the crude products were achieved by semi-preparative C-18 RP HPLC to give the products in radiochemical yields > 90%. The products were obtained in > 97% chemical and radiochemical purity and with specific activities > 180 GBq/μmol.