Abstract
1695
Objectives Superiority of neither 18F-FLT nor 18F-FDG PET/CT is conclusive in the management of lung cancer. In this study, we examined intratumoral distribution of 18F-FLT and 18F-FDG by micro-PET in mouse xenografts of human non-small cell lung cancer (NSCLC) cells, and correlated this with intratumoral distribution of cellular proliferation and hypoxia.
Methods NSCLC A549 and HTB177 cells were injected into the right and the left legs, respectively, of 5 nude mice to generate subcutaneous tumors. Animals were intravenously injected 18F-FLT and cellular proliferation marker bromodeoxyuridine. After overnight fasting, same animals were intravenously administered 18F-FDG together with the hypoxia marker pimonidazole. MicroPET scans were performed 1hr after each tracer injection. Intratumoral distribution of 18F-FLT and 18F-FDG on PET was compared with the distributions of bromodeoxyuridine and pimonidazole in frozen tumor sections visualized by immunofluorescent microscopy.
Results In 10 tumors, regions with high 18F-FLT activity generally showed low 18F-FDG concentration, where had large percentage of cancer cells high bromodeoxyuridine binding but a little pimonidazole retention. Regions showed high 18F-FDG concentration had low 18F-FLT activity, where contained larger fraction of positive pimonidazole and negative bromodeoxyuridine binding cancer cells. Necrotic zones had mild 18F-FLT and 18F-FDG activity.
Conclusions This pilot study suggests NSCLC A549 and HTB177 tumors manifest non-uniform 18F-FLT and 18F-FDG activities, and there is a mismatch of 18F-FLT and 18F-FDG activity areas within tumors. These tumors contain both proliferative and hypoxic cells simultaneously, 18F-FLT accumulated in proliferating, whereas 18F-FDG in hypoxic and non-proliferative cancer cells.
Research Support Kentucky Lung Cancer Research Program Grant cycle 9 (XF Li