Combined injection of 18F-fluorodeoxyglucose and 3′-Deoxy-3′-[18F]fluorothymidine PET achieves more complete identification of viable lung cancer cells in mice and patients than individual radiopharmaceutical: A proof-of-concept study

PURPOSE: The objective is to validate the combination of 3′-deoxy-3′-[18F]fluorothymidine (18F-FLT) and 18F-fluorodeoxyglucose (18F-FDG) as a “novel” positron emission tomography (PET) tracer for better visualization of cancer cell components in solid cancers than individual radiopharmaceutical. METHODS: Nude mice with subcutaneous xenografts of human non-small cell lung cancer A549 and HTB177 cells and patients with lung cancer were included. In ex vivo study, intratumoral radioactivity of 18F-FDG, 18F-FLT, and the cocktail of 18F-FDG and 18F-FLT detected by autoradiography was compared with hypoxia (by pimonidazole) and proliferation (by bromodeoxyuridine) in tumor section. In in vivo study, first, 18F-FDG PET and 18F-FLT PET were conducted in the same subjects (mice and patients) 10 to 14 hours apart. Second, PET scan was also performed 1 hour after one tracer injection; subsequently, the other was administered and followed the second PET scan in the mouse. Finally, 18F-FDG and 18F-FLT cocktail PET scan was also performed in the mouse. RESULTS: When injected individually, 18F-FDG highly accumulated in hypoxic zones and high 18F-FLT in proliferative cancer cells. In case of cocktail injection, high radioactivity correlated with hypoxic regions and highly proliferative and normoxic regions. PET detected that intratumoral distribution of 18F-FDG and 18F-FLT was generally mismatched in both rodents and patients. Combination of 18F-FLT and 18F-FDG appeared to map more cancer tissue than single-tracer PET. CONCLUSIONS: Combination of 18F-FDG and 18F-FLT PET imaging would give a more accurate representation of total viable tumor tissue than either tracer alone and would be a powerful imaging strategy for cancer management.