Imaging proliferation in lung tumors with PET: 18F-FLT versus 18F-FDG.
Recently, the thymidine analog 3'-deoxy-3'-(18)F-fluorothymidine (FLT) was suggested for imaging tumoral proliferation. In this prospective study, we examined whether (18)F-FLT better determines proliferative activity in newly diagnosed lung nodules than does (18)F-FDG.


METHODS
Twenty-six patients with pulmonary nodules on chest CT were examined with PET and the tracers (18)F-FDG and (18)F-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 (18)F-FLT and (18)F-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 (18)F-FDG uptake was 4.1 (median, 4.4; SD, 3.0; range, 1.0-10.6), and mean (18)F-FLT uptake was 1.8 (median, 1.2; SD, 2.0; range, 0.8-6.4). Statistical analysis revealed a significantly higher uptake of (18)F-FDG than of (18)F-FLT (Mann-Whitney U test, P < 0.05). (18)F-FLT SUV correlated better with proliferation index (P < 0.0001; r = 0.92) than did (18)F-FDG SUV (P < 0.001; r = 0.59). With the exception of 1 carcinoma in situ, all malignant tumors showed increased (18)F-FDG PET uptake. (18)F-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 (18)F-FLT uptake was related exclusively to malignant tumors. By contrast, (18)F-FDG PET was false-positive in 4 of 8 patients with benign lesions.


CONCLUSIONS
(18)F-FLT uptake correlates better with proliferation of lung tumors than does uptake of (18)F-FDG and might be more useful as a selective biomarker for tumor proliferation.
Buck
Andreas K
AK
Department of Nuclear Medicine, University of Ulm, Ulm, Germany. andreas.buck@medizin.uni-ulm.de
Halter
Gisela
G
Schirrmeister
Holger
H
Kotzerke
Jörg
J
Wurziger
Imke
I
Glatting
Gerhard
G
Mattfeldt
Torsten
T
Neumaier
Bernd
B
Reske
Sven N
SN
Hetzel
Martin
M
D000328:Adult; D000368:Aged; D015224:Dideoxynucleosides / Q000493:pharmacokinetics*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D003074:Solitary Pulmonary Nodule / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000378:metabolism*; D013223:Statistics as Topic; D014055:Tomography, Emission-Computed / Q000379:methods
D015224:Dideoxynucleosides; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C002854:alovudine