A model for prediction of chemotherapy response to 5-fluorouracil based on the differential distribution of 5-[18F]fluorouracil in sensitive versus resistant lymphocytic leukemia in mice.
The distribution of 5-[18F]fluorouracil has been compared in two variants of the same tumor in c57bL X DBA/2 F1 mice: solid L1210 lymphocytic leukemia tumor susceptible to 5-fluorouracil treatment and the same tumor, made resistant to the drug over a 34-generation span. Significant differences in 5-[18F]fluorouracil distribution were observed, most notably in the tumor:blood ratios at 12 hr postinjection. The drug-responsive tumor showed a 20:1 concentration ratio, whereas the drug-resistant tumor only had a 4:1 concentration ratio. We postulate that these differences, observed here in this animal tumor model, may be a reflection of similar ratio differences in humans. This technique may allow, by noninvasive quantification of tumor:blood ratios following administration of 5-[18F]fluorouracil to man, the differentiation of those human tumors that are likely to respond to drug therapy from those in which the response will be minimal or nil.
D000818:Animals; D004351:Drug Resistance; D005260:Female; D005472:Fluorouracil / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*; D007939:Leukemia L1210 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA
D005472:Fluorouracil