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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 BDF1 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.(ABSTRACT TRUNCATED AT 250 WORDS)
AuthorsL I Wiebe, E E Knaus
JournalInternational journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology (Int J Rad Appl Instrum B) Vol. 13 Issue 3 Pg. 257-9 ( 1986) ISSN: 0883-2897 [Print] England
PMID2945804 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Thionucleotides
  • Floxuridine
  • Tritium
  • Thioinosine
  • Inosine
  • nitrobenzylthioinosine 5'-monophosphate
Topics
  • Animals
  • Floxuridine (metabolism)
  • Inosine (analogs & derivatives)
  • Lung Neoplasms (diagnostic imaging)
  • Male
  • Mice
  • Mice, Inbred Strains
  • Neoplasm Transplantation
  • Radionuclide Imaging
  • Thioinosine (analogs & derivatives, pharmacology)
  • Thionucleotides (pharmacology)
  • Tissue Distribution
  • Tritium (metabolism)

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