Development of a novel hypoxia marker:[18F]FRP-170, and its clinical application.

Abstract

Purpose: 2-Nitroimidazole nucleoside analog, RP-170 was developed as a potential radiosensitizer by POLA Corporation. We succeeded in synthesizing [18F] labeled fluoroRP-170 ([18F]FRP-170). A purpose of this study is to investigate the potential of this new drug as a new hypoxia marker. Materials and Methods: WHT/Ht albino mice bearing the squamous cell carcinoma (sqcc) or fibrosarcoma in the both axillas were used. Biodistribution and the tumor-to-blood(T/B)ratios of [18F]FRP-170 were investigated 120 hours after iv injection. Double-tracer autoradiography(DARG) for tumors was also performed with [14C]IAP and [18F]FRP-170. [14C]IAP was used as a tracer of blood flow. Patients: 16 patients with lung cancer and recurrent esophageal cancer were injected 185 MBq of [18F]FRP-170, and PET images (Siemens ECAT EXACT HR+) were obtained 120 min after injection. Results: The uptake rates of various tissues except for liver and kidney were less than that of tumors. The T/B ratios were 1.97(1.36-2.9) for sqcc and 2.50 (1.72-3.60) for fibrosarcoma. DARG with [18F]FRP-170 and [14C]IAP revealed that the distribution of [18F]FRP-170 was just reversed to the distribution of [14C]IAP. Obvious uptakes of [18F]FRP-170 were found in the most of 16 patients with lung cancer and recurrent esophageal cancers. Their tumor/muscle ratio were approximately 1.25 to 2.14. Conclusions: [18F]FRP170 surely showed tumor image in anywhere except for liver and kidney. We conclude that [18F]FRP-170 is a promising new hypoxia marker in cancer patients.