Radiosynthesis of [I-131]IAZGP via nucleophilic substitution and its evaluation as a hypoxia marker – Does specific activity influence hypoxia-mapping ability of the radiotracer?

Objectives a) To label the hypoxia marker IAZGP with radioiodine via nucleophilic substitution, producing the radiotracer in specific activity (SA) 300-3000 times higher (high SA IAZGP) than that of conventionally-labeled IAZGP via iodine-radioiodine exchange (low SA IAZGP) and b) to determine whether the difference in specific activity influences hypoxia-mapping ability of the radiotracer by comparing their biological behavior.

Methods High SA [¹³¹I]IAZGP was prepared by substitution of the tosyl functionality with [¹³¹I]iodide. In-vitro uptake of high and low SA [¹³¹I]IAZGP by HT29 cells was assessed in normoxic and hypoxic conditions. Their body and intra-tumor distributions were also studied by injection of the radiotracer at doses of 2.3 nmol and 1.9 μmol/kg into HT29 tumor-bearing mice.

Results The nucleophilic substitution reaction proceeded efficiently at 150ºC in acetonitrile, giving the final product in an average yield of 42% and an average SA of 30 GBq/μmol. In vitro, high SA [¹³¹I]IAZGP was incorporated into the cells with similar kinetics and oxygen dependence to low SA [¹³¹I]IAZGP. In HT29 tumor-bearing mice, biodistributions of high and low SA [¹³¹I]IAZGP were equivalent. Ex vivo autoradiography revealed heterogeneous intra-tumor localization of high SA [¹³¹I]IAZGP corresponding closely to distributions of other exogenous and endogenous hypoxia markers. Comparable microregional distribution patterns were observed with low SA [¹³¹I]IAZGP.

Conclusions These results and data in the literature, taken together, suggest that specific activity does not influence the hypoxia-labeling ability of the radiotracer.