Abstract
Recently, the thymidine analog 3′-deoxy-3′-18F-fluorothymidine (FLT) was suggested for imaging tumoral proliferation. In this prospective study, we examined whether 18F-FLT better determines proliferative activity in newly diagnosed lung nodules than does 18F-FDG. Methods: Twenty-six patients with pulmonary nodules on chest CT were examined with PET and the tracers 18F-FDG and 18F-FLT. Tumoral uptake was determined by calculation of standardized uptake value (SUV). Within 2 wk, patients underwent resective surgery or had core biopsy. Proliferative activity was estimated by counting nuclei stained with the Ki-67–specific monoclonal antibody MIB-1 per total number of nuclei in representative tissue specimens. The correlation between the percentage of proliferating cells and the SUVs for 18F-FLT and 18F-FDG was determined using linear regression analysis. Results: Eighteen patients had malignant tumors (13 with non–small cell lung cancer [NSCLC], 1 with small cell lung cancer, and 4 with pulmonary metastases from extrapulmonary tumors); 8 had benign lesions. In all visible lesions, mean 18F-FDG uptake was 4.1 (median, 4.4; SD, 3.0; range, 1.0–10.6), and mean 18F-FLT uptake was 1.8 (median, 1.2; SD, 2.0; range, 0.8–6.4). Statistical analysis revealed a significantly higher uptake of 18F-FDG than of 18F-FLT (Mann–Whitney U test, P < 0.05). 18F-FLT SUV correlated better with proliferation index (P < 0.0001; r = 0.92) than did 18F-FDG SUV (P < 0.001; r = 0.59). With the exception of 1 carcinoma in situ, all malignant tumors showed increased 18F-FDG PET uptake. 18F-FLT PET was false-negative in the carcinoma in situ, in another NSCLC with a low proliferation index, and in a patient with lung metastases from colorectal cancer. Increased 18F-FLT uptake was related exclusively to malignant tumors. By contrast, 18F-FDG PET was false-positive in 4 of 8 patients with benign lesions. Conclusion: 18F-FLT uptake correlates better with proliferation of lung tumors than does uptake of 18F-FDG and might be more useful as a selective biomarker for tumor proliferation.
Footnotes
Received Nov. 27, 2002; revision accepted Feb. 19, 2003.
For correspondence or reprints contact: Andreas K. Buck, MD, Department of Nuclear Medicine, University of Ulm, Robert-Koch-Strasse 8, D-89081 Ulm, Germany.
E-mail: andreas.buck{at}medizin.uni-ulm.de