Xiao-Feng Li1, Tao Huang2, Huijie Jiang3, Xuemei Wang4, Baozhong Shen5, Xiangcheng Wang4, Chin K Ng1, Gregory C Postel1, A Cahid Civelek1. 1. Department of Radiology, University of Louisville School of Medicine, Louisville, KY. 2. Department of Radiology, University of Louisville School of Medicine, Louisville, KY ; Department of Radiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China. 3. Department of Radiology, University of Louisville School of Medicine, Louisville, KY ; Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. 4. Department of Nuclear Medicine, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China. 5. Department of Radiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
Abstract
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.
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 humannon-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.
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