Tumor retention of 5-fluorouracil following irradiation observed using 19F nuclear magnetic resonance spectroscopy.
OBJECTIVE
The combination of 5-fluorouracil (5FU) and radiation results in improved tumor control in a variety of gastrointestinal cancers. We propose the enhancement is related to radiation potentiating the antitumor effects of 5FU. To better understand the mechanism of the 5FU-radiation interaction, 19F nuclear magnetic resonance (NMR) spectroscopy experiments were performed to observed the tumor clearance and metabolism of 5FU.


METHODS
Experiments were performed on 10 3-6-week-old female (Nu/Nu) athymic nude mice. Flank tumors measuring approximately 1.0 cm in diameter 3 weeks following a subcutaneous injection of 1 x 10(6) human colon adenocarcinoma (HT-29) cells were studied. In our first group, all animals received an intravenous bolus injection of 5FU (100 mg/kg) immediately before spectroscopic analysis. Animals in the second group were first treated with a single tumor radiation dose of 10 Gy just before the 5FU injection and subsequent spectroscopy. Spectroscopic analysis was performed with a 2.0-T NMR spectroscopy system.


RESULTS
The tumor retention of 5FU was prolonged in animals receiving radiation before the drug infusion. The tumor clearance rate of the 5FU for nonirradiated animals was 0.0178 +/- 0.0082/min vs. 0.0055 +/- 0.0027/min for irradiated animals, reflecting a threefold reduction in drug clearance in the irradiated tumors. The difference was significant at p < 0.005.


CONCLUSIONS
Our preliminary experiments suggest the enhanced cytotoxicity seen with concurrent 5FU and radiation is related to prolonged tumor retention of 5FU induced by radiation. This is consistent with the hypothesis that radiation is potentiating the cytotoxic effects of 5FU.
Blackstock
A W
AW
Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, USA.
Kwock
L
L
Branch
C
C
Zeman
E M
EM
Tepper
J E
JE
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics*; D005260:Female; D005472:Fluorouracil / Q000493:pharmacokinetics*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000378:metabolism* / Q000532:radiotherapy*; D051381:Rats; D012680:Sensitivity and Specificity; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil