Combined Injection of (18)F-Fluorodeoxyglucose and 3'-Deoxy-3'-[(18)F]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'-[(18)F]fluorothymidine ((18)F-FLT) and (18)F-fluorodeoxyglucose ((18)F-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 (18)F-FDG, (18)F-FLT, and the cocktail of (18)F-FDG and (18)F-FLT detected by autoradiography was compared with hypoxia (by pimonidazole) and proliferation (by bromodeoxyuridine) in tumor section. In in vivo study, first, (18)F-FDG PET and (18)F-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, (18)F-FDG and (18)F-FLT cocktail PET scan was also performed in the mouse.

Results: When injected individually, (18)F-FDG highly accumulated in hypoxic zones and high (18)F-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 (18)F-FDG and (18)F-FLT was generally mismatched in both rodents and patients. Combination of (18)F-FLT and (18)F-FDG appeared to map more cancer tissue than single-tracer PET.

Conclusions: Combination of (18)F-FDG and (18)F-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.