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

Abstract

To compare the utility of a new artificial amino acid, O-[18F]fluoromethyl-L-tyrosine ([18F]FMT), for monitoring cancer chemotherapy with deoxyglucose and thymidine. [18F]FMT, [14C]deoxyglucose ([14C]DG) and [6-3H]thymidine ([3H]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 [18F]FMT, [14C]DG and [3H]Thd had been injected, and was shown as DURs (% injected dose/gram tissue normalised for the rat body weight). Dual-tracer macroautoradiographs with [18F]FMT and [14C]DG were also prepared. 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: [18F]FMT: 4.68+/-0.72, 3.34+/-0.66, 3.13+/-0.72, 3.42+/-0.45, 3.01+/-0.32; [14C]DG: 3.26+/-0.40, 3.09+/-0.55, 3.01+/-0.97, 2.28+/-0.35, 1.70+/-0.72; and [3H]Thd: 2.23+/-0.46, 1.54+/-0.45, 1.28+/-0.37, 1.35+/-0.20, 0.94+/-0.12. Decrease in [18F]FMT uptake compared with baseline was significant from day 1 (p<0.01), and the decrease in [3H]Thd uptake was also significant on day 1 (p<0.05) and days 3-7 (p<0.01). However, decrease in [14C]DG uptake was only significant from day 5 (p<0.01). Macroautoradiography suggested that the influence of inflammatory cells on the accumulation of [18F]FMT in tumours is smaller than that on the accumulation of [14C]DG. [18F]FMT uptake shows a rapid and sensitive response to chemotherapy, comparable to that of [3H]Thd, suggesting that it may be applied as a powerful tracer for monitoring of proliferative activity after cancer chemotherapy using PET.