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 Mice¹

The distribution of 5-[¹⁸F]fluorouracil has been compared in two variants of the same tumor in C57BL × 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.