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 correlatedwith 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.