Drug-induced perturbations in the in vivo distribution of oncological radiotracers—I. 5-fluoro-6- 3H-2′-deoxyuridine influenced by nitrobenzylthioinosine 5′-phosphate (NBMPR-P)

Abstract

Nitrobenzylthioinosine 5′-monophosphate (NBMPR-P), a water-soluble form of the nucleoside transport inhibitor nitrobenzylthioinosine (NBMPR) was administered by i.v. injection to normal mice and BDF 1 mice with implanted Lewis Lung carcinomas. Tritiated 5-Fluoro-2′-deoxyuridine ( 3H-FUdR) was injected either alone (control), 10 min before (I + 10), 10 min (I − 10) after, 60 min (I − 60) after, or simultaneously (I = 0) with the transport inhibitor. Tissue distributions of tritium were determined after intervals of 1, 2 and 4 h. The per cent of injected radioactivity (% dose) in liver was increased by all NBMPR-P protocols. Kidney radioactivity was similarly affected, with maximum increases (from 9.3 ± 3.4 to 24.1 ± 5.2% of the injected dose/g) after 1 h in the I − 60 animals. No statistically significant changes in the distribution of radioactivity in tumor, spleen, marrow or blood were induced by doses of NBMPR-P. Elevated levels of tritium radioactivity in blood were accompanied by similar increases in renal and hepatic radioactivity. The apparent increase in the tumor uptake of 3H-FUdR (from 1.4 ± 0.2 to 5.7 ± 2.3% dose/g) was not statistically significant at the 95% confidence limit. In general, NBMPR-P induced a relative tumor-sparing effect and at the same time increased uptake of 3H-FUdR by the liver and kidney, or delayed its clearance from these organs. There was no evidence to suggest that any advantage would be gained by using NBMPR-P treatment in conjunction with radiolabelled FUdR for tumor diagnosis. The data also indicate that the therapeutic ratio for FUdR would be smaller when used with NBMPR-P than when used alone.