In vivo evaluation of radiobromine-labeled 5-bromo-4'-thio-2'-deoxyuridine as an imaging agent for tumor proliferation

Objectives We have recently developed the radiobromine-labeled 5-bromo 4'-thio-2'-deoxyuridine (BTdU) as an imaigng agent for tumor proliferation and reported that this agent had basic characteristics in vitro. The aim of this study was to evaluate in vivo characteristics of radiobromine-labeled BTdU for tumor proliferation imaging.

Methods The radiolabeling of BTdU with ⁷⁷Br was achieved by a destannylation reaction of tributylstannyl precursor. In vivo biodistribution and tissue fractionation experiments in normal mice and tumor (L-M cells)-bearing mice were carried out.

Results The radiochemical yield of ⁷⁷Br-BTdU was about 40% and the radiochemical purity was more than 99%. In biodistribution experiments, the uptake of ⁷⁷Br-BTdU in proliferating organs was high (spleen: 13 ± 4.8, small intestine: 4.5 ± 1.0 %ID/g at 6 hr) and that in non-proliferating organs was low (muscle: 0.21 ± 0.04, liver: 0.55 ± 0.10 %ID/g at 6 hr). Although the percentages of radioactivity in DNA fraction were about 20 % in non-proliferating organs at 24 hr, those in DNA fraction were about 80% in proliferating organs at 24 hr. These results show that ⁷⁷Br-BTdU has basic characteristics as an agent for proliferation imaging. In tumor-bearing mice, the uptake of ⁷⁷Br-BTdU in tumor was higher than that in blood and muscle at 3 hr after injection (tumor: 5.7 ± 1.0, blood: 1.1 ± 0.3, muscle: 0.26 ± 0.04 %ID/g). The ratio of tumor-to-muscle was more than 20 at 3 hr. In tumor fractionation experiments, more than 70% of radioactivity existed in DNA fraction at 3 hr. These results show that ⁷⁷Br-BTdU has suitable characteristics for tumor proliferation imaging.

Conclusions Radiobromine-labeled BTdU is potentially useful as an imaging agent for tumor proliferation with PET