4′-[Methyl-11C]-Thiothymidine PET/CT for Proliferation Imaging in Non-Small Cell Lung Cancer

A new tracer, 4'-[methyl-C-11]-thiothymidine (C-11-4DST), has been developed as an in vivo cell proliferation marker based on the DNA incorporation method. This study evaluated the potential of C-11-4DST PET/CT for imaging proliferation in non small cell lung cancer (NSCLC), compared with F-18-FDG PET/CT. Methods: Eighteen patients with lung lesions were examined by PET/CT using C-11-4DST and F-18-FDG. We constructed decay-corrected time-activity curves of 9 major regions as the mean standardized uptake value. We then compared the maximum standardized uptake value (SUVmax) of lung tumors on both C-11-4DST and F-18-FDG PET/CT with the Ki-67 index of cellular proliferation and with CD31-positive vessels as a marker of angiogenesis in surgical pathology. Results: NSCLC was pathologically confirmed in 19 lesions of 18 patients. Physiologic accumulation of C-11-4DST was high in liver, kidney, and bone marrow and low in aorta, brain, lung, and myocardium. Biodistribution of C-11-4DST was almost stable by 20 min after injection of C-11-4DST. Mean C-11-4DST SUVmax for lung cancer was 2.9 +/- 1.0 (range, 1.5-4.7), significantly different from mean F-18-FDG SUVmax, which was 6.2 +/- 4.5 (range, 0.9-17.3; P < 0.001). The correlation coefficient between SUVmax and Ki-67 index was higher with C-11-4DST (r = 0.82) than with F-18-FDG (r = 0.71). The correlation coefficient between SUVmax and CD31 was low with both C-11-4DST (r = 0.21) and F-18-FDG (r = 0.21), showing no significant difference between the tracers. Conclusion: A higher correlation with proliferation of lung tumors was seen for C-11-4DST than for F-18-FDG. C-11-4DST PET/CT may allow noninvasive imaging of DNA synthesis in NSCLC.