Determining hypoxic fraction in a rat glioma by uptake of radiolabeled fluoromisonidazole

The usefulness of radiolabeled nitroimidazoles for measuring hypoxia will b e clarified by defining the relationship between tracer uptake and radiobio logically hypoxic fraction. We determined the radiobiologically hypoxic fra ction from radiation response data in 36B10 rat gliomas using the paired ce ll survival curve technique and compared the values to the radiobiologicall y hypoxic fraction inferred from mathematical modeling of time-activity dat a acquired by PET imaging of [F-18]FMISO uptake. Rats breathed either air o r 10% oxygen during imaging, and timed blood samples were taken, The uptake of [H-3]FMISO by 36B10 cells in vitro provided cellular binding characteri stics of this radiopharmaceutical as a function of oxygen concentration. Th e radiobiologically hypoxic fraction determined for tumors in air-breathing rats using the paired survival curve technique was 6.1% (95% CL = 4.3-8.6% ), which agreed well with that determined by modeling FMISO time-activity d ata (7.4%; 95% CL = 2.5-17.3%). These results are consistent with the agree ment between the two techniques for measuring radiobiologically hypoxic fra ction in Chinese hamster V79 cell spheroids. In contrast, the FMISO-derived radiobiologically hypoxic fraction in rats breathing 10% oxygen was 13.1% (95% CL 7.9-8.3%), much lower than the radiobiologically hypoxic fraction o f 43% determined from the radiation response data. This discrepancy may be due to the failure of FMISO to identify hypoxic cells residing at or above an oxygen level of 2-3 mmHg that will still confer substantial protection a gainst radiation. The presence of transiently hypoxic cells in rats breathi ng reduced oxygen may also be under-reported by nitroimidazole binding, whi ch is strongly dependent on time and concentration. (C) 2000 by Radiation R esearch Society.