[Correlation of 3'-deoxy-3'-18F-fluorothymidine uptake to cell proliferation in lung carcinoma xenografts]

Abstract

Background & objective: 3'-Deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) has been described recently as a new positron emission tomography (PET) tracer for imaging tumor cell proliferation. This study was to investigate the biodistribution and PET imaging of (18)F-FLT in a murine model of lung cancer, and to explore the correlation of (18)F-FLT uptake to cell proliferation of lung cancer.

Methods: A total of 48 T739 mice bearing lung adeno-carcinoma were randomized into (18)F-FLT group and 2-(18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG) group according to the radioactive tracers. Each group was also divided into 3 subgroups: (A) untreated controls, (B) 1 day after treatment of cisplatin, (C) 2 days after treatment of cisplatin. Each subgroup contained 8 mice. All mice were injected with (18)F-FLT or (18)F-FDG through the tail veins. The biodistribution of (18)F-FLT and (18)F-FDG in tumor tissue was measured with well-gamma detector 60 min after injection; the PET imaging of mice was performed. Tumor cell proliferation was determined by immunohistochemical examination of proliferating cell nuclear antigen (PCNA).

Results: In both subgroups A, the PET images of the tracers in tumor were clear. Considerable radioactive uptake of tumor was observed; the T/NT ratios of tumor/blood, tumor/muscle and tumor/lung were all above 2.0. The positive rate of PCNA was reduced significantly in (18)F-FLT group after treatment of cisplatin [(90.3+/-3.9)% (A) vs. (65.5+/-9.2)% (B) and (47.4+/-7.2)% (C), P<0.01], and in (18)F-FDG group [(91.2+/-3.5)% (A) vs. (67.8+/-8.2)% (B) and (45.9+/-9.1)% (C), P<0.01]. Tumor uptake of (18)F-FLT was decreased rapidly after treatment [(1.25+/-0.19) %ID/g (A) vs. (0.82+/-0.19) %ID/g (B) and (0.37+/-0.17) %ID/g (C), P<0.01]; tumor uptake of (18)F-FDG was decreased slightly after treatment [(8.83+/-1.73)%ID/g (A) vs. (7.88+/-1.78)% ID/g (B) and (7.45+/-1.67)%ID/g (C), P>0.05]. The PET imaging confirmed that tumor (18)F-FLT retention was suppressed after treatment. Tumor uptake of (18)F-FLT was correlated to the positive rate of PCNA (r=0.930, P<0.001), but tumor uptake of (18)F-FDG did not (r=-0.136, P=0.538).

Conclusions: The uptake of (18)F-FLT in lung malignant tissues is higher than that in normal tissues, therefore, the tumor could be imaged clearly with PET. The correlation of tumor uptake of (18)F-FLT to PCNA expression is more obvious than that of (18)F-FDG. (18)F-FLT is a promising PET tracer for reflecting cell proliferation in lung carcinoma.