Synthesis, radiolabeling, and biodistribution of putative metabolites of iodoazomycin arabinoside

Scintigraphic evaluation of patients with advanced oncological disease showed uptake of radioactivity in the brain following administration of the hypoxic imaging agent 123I-iodoazomycin arabinoside ( 123I-IAZA). Three proposed metabolites of IAZA—methyl 5-deoxy-5-iodo-D-arabinofuranoside, methyl 2,3-di- O-acetyl-5-deoxy-5-iodo-α-D-arabinofuranoside, and 1-(5-deoxy-5-iodo-α-D-arabinofuranosyl)-2-aminoimidazole (IAIA)—were synthesized, radiolabeled with 125I, and investigated in normal and tumor-bearing murine models for their contribution to this unusual phenomenon. The three compounds were readily radiolabeled by melt or solvent exchange procedures. Biodistribution data indicated rapid blood clearance, rapid excretion, and little tissue accumulation in the brain. IAIA showed significant tumor to blood ratios at 4 h (4.3:1) and liver to blood ratios at 24 h (30:1).