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Evaluation of D-¹⁸F-FMT, ¹⁸F-FDG, L-¹¹C-MET, and ¹⁸F-FLT for Monitoring the Response of Tumors to Radiotherapy in Mice

¹ Department of Clinical Pharmacology, Tokai University School of Medicine, Isehara, Kanagawa, Japan; ² Department of Radiation Oncology, Tokai University School of Medicine, Isehara, Kanagawa, Japan; ³ Central Research Laboratory, Hamamatsu Photonics KK, Hamakita, Hamamatsu, Shizuoka, Japan; ⁴ Teaching and Research Support Center, Tokai University School of Medicine, Isehara, Kanagawa, Japan; and ⁵ Department of Cell Transplantation and Regenerative Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan

Correspondence: For correspondence or reprints contact: Chieko Murayama, Department of Clinical Pharmacology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan. E-mail: patra{at}is.icc.u-tokai.ac.jp

O-¹⁸F-fluoromethyl-D-tyrosine (D-¹⁸F-FMT) is a promising novel agent for tumor imaging by PET. The aim of this study was to evaluate the potential of D-¹⁸F-FMT and the other conventional ligands used for tumor imaging, namely, ¹⁸F-FDG, L-¹¹C-methionine (L-¹¹C-MET), and 3'-deoxy-3'-¹⁸F-fluorothymidine (¹⁸F-FLT), as a PET ligand for monitoring early responses to radiotherapy in tumor-bearing mice. Methods: C3H/HeN mice inoculated with murine squamous cell carcinomas were treated with a single dose of x-ray irradiation at 2, 6, 20, or 60 Gy. Tumor uptake of each ligand was examined 1, 3, and 7 d after the irradiation. Results: Tumor uptake of D-¹⁸F-FMT was decreased on day 1 after irradiation at 6, 20, or 60 Gy, and the decrease persisted until day 7. Tumor uptake of ¹⁸F-FDG was elevated on days 1 and 3 after irradiation at 2, 6, or 20 Gy, followed by a decrease in uptake on day 7 in mice irradiated at 20 or 60 Gy. Decreased tumor uptake of L-¹¹C-MET was observed only on day 3 after the irradiation. Decreased tumor uptake of ¹⁸F-FLT was detected on day 1 after irradiation at 2, 6, 20, or 60 Gy; thereafter, the dose-dependent decrease in uptake was no longer seen. Only for D-¹⁸F-FMT were significant positive correlations found between ligand uptake at all the time points examined and tumor volume on day 14 after various doses of irradiation. Conclusion: The findings suggest that D-¹⁸F-FMT is a promising PET ligand for early-phase detection and prediction of the effects of radiation therapy.

Key Words: O-¹⁸F-fluoromethyl-D-tyrosine • D-¹⁸F-FMT • ¹⁸F-fluoro-2-deoxy-D-glucose • ¹⁸F-FDG • L-¹¹C-methionine • L-¹¹C-MET • 3'-deoxy-3'-¹⁸F-fluorothymidine • ¹⁸F-FLT • radiation therapy

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