Evaluation of radiobromine-labeled 5-bromo-4\u27-thio-2\u27-deoxyuridine uptake in ACHN cells after treatment with 5-fluorouracil: comparison with 3H-FLT uptake.
Objectives: We have recently developed the radiobromine-labeled 5-bromo 4\u27-thio-2\u27-deoxyuridine (BTdU) as an imaigng agent for tumor proliferation. The aim of this study was to evaluate the potential usefulness of radiobromine-labeled BTdU as an imaging agent for detecting the early therapeutic effects of 5-fluorouracil (5-FU) compared with 3H-FLT uptake. \nMethods: The radiolabeling of BTdU with 77Br was achieved by a destannylation reaction of tributylstannyl precursor. 3H-FLT was commerically available. The cells of human renal cacinoma cell line, ACHN, were treated with various concentrations of 5-FU (0.01-300 µM). At 36 hr after 5-FU addition, double tracer cell uptake studies were performed. 2.0x10-2 MBq of 77Br-BTdU and 3.7x10-2 MBq of 3H-FLT were simaltaneously added to the cells and incubated for 15min, 30min, 60min. After 3 times washing, cells were lysed, and then the radioactivity and protein content were measured. \nResults: The radiochemical yield of 77Br-BTdU was about 40% and the radiochemical purity was more than 99%. Uptakes of 77Br-BTdU and 3H-FLT were increased with time. There was not significant differences between the uptake of 77Br-BTdU and that of 3H-FLT in control group at 60min (77Br-BTdU: 18.5 +- 2.0,3H-FLT: 20.3 +- 2.7 %ID/mg protein). Compared with control the uptake of 77Br-BTdU was significantlty decreased from 0.3 µM of 5-FU (One-way ANOVA with a post hoc Dunnett\u27s Multiple Comparison Test). However, the uptake of 3H-FLT was significantly decreased from 300 µM of 5-FU. These results suggest that 77Br-BTdU could detect the earlier effect of 5-FU compared with 3H-FLT. \nConclusions: Radiobromine-labeled BTdU is potentially useful as an imaging agent for detecting the early therapeutic effects of anticancer therapy with 5-FU in patients with renal cell carcinomaSNM 2011 Annual Meetin
