On the Safety of 5-[125I]IODO-2'-Deoxyuridlne: Preclinical evaluation in swine

Abstract

To increase tumor incorporation and minimize hepatic degradation of radio-IUdR, compartmental administration routes are being considered as an alternative to intravenous (i. v.) injections. Although there are significant data on the biodistribution and some reports on radiotoxicity of i. v.-administered ¹²⁵IUdR, similar results for other routes of delivery are not available. We have undertaken a series of experiments intended to examine radiation effects of ¹²⁵IUdR after intravesical (3 swine; eight 3 mCi doses at 4-day intervals), intracarotid (3 swine; two 10 mCi doses at 2-week intervals), and intra-aortic (5 swine, single dose of 10 mCi) administration in a swine model. Liver, renal functions, and complete blood counts were monitored throughout the duration of the experiment. Pharmacokinetics, systemic distribution of radioactivity and metabolites were measured. The normal tissue ¹²⁵IUdR uptake and histology were determined after necropsy. No adverse systemic effects were identified. Clinical observations, laboratory data, and necropsy results were within normal range.