Synthesis, radiofluorination, and hypoxia-selective studies of FRAZ: A configurational and positional analogue of the clinical hypoxia marker, [18F]-FAZA.
The current work evaluates 1-alpha-d-(2-deoxy-2-fluororibofuranosyl)-2-nitroimidazole (FRAZ), a novel azomycin nucleoside that is a potential radiosensitizer of tumor hypoxia. FRAZ is a ribose analogue of 1-alpha-d-(2-deoxy-2-fluoroarabinofuranosyl)-2-nitroimidazole ([(18)F]-FAZA), a clinically used hypoxia marker. Preliminary assessment of the cytotoxicity and hypoxia-specific in vitro binding in HCT-110 colorectal cancer cells indicate that the radiosensitization properties of FRAZ are similar to that of FAZA, with a sensitizer enhancement ratio (SER) of approximately 1.8. An automated radiosynthesis of [(18)F]-FRAZ using a commercial automated synthesis unit (ASU) was established (synthesis time approximately 32 min; radiochemical yield (decay uncorrecetd) approximately 22%) to facilitate its application in PET-based diagnosis of hypoxic tumors.
Kumar
Piyush
P
Division of Oncologic Imaging, Department of Oncology, University of Alberta, Cross Cancer Institute, 11560 University Ave., Edmonton, Canada T6G1Z2.
Naimi
Ebrahim
E
McEwan
Alexander J
AJ
Wiebe
Leonard I
LI
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D014408:Biomarkers, Tumor / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D004354:Drug Screening Assays, Antitumor; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D006801:Humans; D000860:Hypoxia; D007553:Isotope Labeling; D009593:Nitroimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049268:Positron-Emission Tomography; D012266:Ribose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D005462:Fluorine Radioisotopes; D009593:Nitroimidazoles; C498052:fluoroazomycin arabinoside; D012266:Ribose