[Correlation of 3'-deoxy-3'-18F-fluorothymidine uptake to cell proliferation in lung carcinoma xenografts].
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.
Liu
Xi
X
Department of Thoracic Surgery, General Hospital of PLA, Beijing, 100853 P. R. China. Liuyk112@vip.sina.com
Zhou
Nai-Kang
NK
Zhang
Jin-Ming
JM
Liang
Zhao-Yang
ZY
Zheng
Xin
X
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002945:Cisplatin / Q000627:therapeutic use; D015224:Dideoxynucleosides / Q000493:pharmacokinetics; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D049268:Positron-Emission Tomography; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D015224:Dideoxynucleosides; D005462:Fluorine Radioisotopes; D018809:Proliferating Cell Nuclear Antigen; D019788:Fluorodeoxyglucose F18; C002854:alovudine; D002945:Cisplatin