O-[18F]fluoromethyl-L-tyrosine is a potential tracer for monitoring tumour response to chemotherapy using PET:: an initial comparative in vivo study with deoxyglucose and thymidine

Purpose: To compare the utility of a new artificial amino acid, O-[(18)supercript stopF]fluoromethyl-L-tyrosine ([F-18]FMT), for monitoring cancer chemotherapy with deoxyglucose and thymidine. Methods: [F-18]FMT, [C-14]deoxyglucose ([(14)supercript stopC]DG) and [6-H-3]thymidine ([H-3]Thd) were applied in this study. A 2.5 mg/kg dose of mitomycin (MMC) was administered to AH272 rat hepatoma-bearing Donryu rats. Tumour uptake of each tracer was measured just before (baseline) and on days 1, 3, 5 and 7 after the MMC administration, 1 h after a mixture of [F-18]FMT, [C-14]DG and [H-3]Thd had been injected, and was shown as DURs (% injected dose/gram tissue normalised for the rat body weight). Dual-tracer macroautoradiographs with [F-18]FMT and [C-14]DG were also prepared. Results: The tumour uptake for each tracer decreased earlier than did the tumour size. DURs (mean +/- SD) at baseline and on days 1, 3, 5 and 7 were as follows: [F-18]FMT: 4.68 +/- 0.72, 3.34 +/- 0.66, 3.13 +/- 0.72, 3.42 +/- 0.45, 3.01 +/- 0.32; [C-14]DG: 3.26 +/- 0.40, 3.09 +/- 0.55, 3.01 +/- 0.97, 2.28 +/- 0.35, 1.70 +/- 0.72; and [H-3]Thd: 2.23 +/- 0.46, 1.54 +/- 0.45, 1.28 +/- 0.37, 1.35 +/- 0.20, 0.94 +/- 0.12. Decrease in [F-18]FMT uptake compared with baseline was significant from day 1 (p < 0.01), and the decrease in [H-3]Thd uptake was also significant on day 1 (p < 0.05) and days 3-7 (p < 0.01). However, decrease in [C-14]DG uptake was only significant from day 5 (p < 0.01). Macroautoradiography suggested that the influence of inflammatory cells on the accumulation of [F-18]FMT in tumours is smaller than that on the accumulation of [C-14]DG. Conclusion: [F-18]FMT uptake shows a rapid and sensitive response to chemotherapy, comparable to that of [H-3]Thd, suggesting that it may be applied as a powerful tracer for monitoring of proliferative activity after cancer chemotherapy using PET.