DEVELOPMENT OF NEW MARKERS FOR HYPOXIC CELLS - [I-131]IODOMISONIDAZOLE AND [I-131]IODOERYTHRONITROIMIDAZOLE

This study was aimed at developing Ligands to evaluate tumor hypoxia b y planar scintigraphy. Two 2-nitroimidazole analogues were developed a s precursor compounds to image hypoxic tumors. Both tosylmisonidazole (Ts MISO) and tosylerythronitroimidazole (Ts ETNIM) were labeled with I-131. The biodistribution and autoradiographic evaluations by planar scintigraphy of I-131-IMISO and I-131-IETNIM were conducted at 1, 2 an d 4 hours after administration to rats bearing 13762 breast tumors. Bi odistribution of I-131-IMISO was also evaluated in Madison lung tumor- bearing mice. Intratumoral oxygen tension was measured by the Eppendor f system. Biodistribution showed similar tumor/blood and tumor/muscle count density ratios for both compounds. The thyroid uptake of both an alogues was increased with time, suggesting in vivo deiodination proba bly occurred. Autoradiographs of I-131-IMISO and I-131-IETNIM revealed good visualization of the neoplasms. The tumor oxygen tension was 3-6 mmHg as compared to the normal tissue oxygenation of 30-40mmHg. The f indings indicate that these analogues can localize in the hypoxic regi on of solid tumors and may assist with quantitation of the hypoxic fra ction of tumor for proper selection and evaluation of appropriate radi otherapy and chemotherapy.