PT - JOURNAL ARTICLE AU - Grönroos, Tove AU - Eskola, Olli AU - Lehtiö, Kaisa AU - Minn, Heikki AU - Marjamäki, Päivi AU - Bergman, Jörgen AU - Haaparanta, Merja AU - Forsback, Sarita AU - Solin, Olof TI - Pharmacokinetics of [<sup>18</sup>F]FETNIM: A Potential Hypoxia Marker for PET DP - 2001 Sep 01 TA - Journal of Nuclear Medicine PG - 1397--1404 VI - 42 IP - 9 4099 - http://jnm.snmjournals.org/content/42/9/1397.short 4100 - http://jnm.snmjournals.org/content/42/9/1397.full SO - J Nucl Med2001 Sep 01; 42 AB - 18F-labeled fluoroerythronitroimidazole (FETNIM) has been suggested as a marker of tumor hypoxia for use with PET. Our goal was to evaluate the pharmacokinetic properties of [18F]FETNIM in rats and analyze metabolites in human, dog, and rat plasma and urine. Metabolites in liver and tumor homogenates from tumor-bearing rats, as well as the biodistribution of the tracer, were also studied. Methods: Radio–thin-layer chromatography and digital autoradiography were used to distinguish metabolites from the parent drug in urine and plasma from 8 patients, 3 dogs, and 18 rats, as well as in liver and tumor homogenates from Sprague-Dawley rats bearing 7,12-dimethylbenzanthracene–induced rat mammary carcinoma. Biodistribution of [18F]FETNIM was also studied in rats at 15, 30, 60, 120, and 240 min after tracer injection. Results: Most of the radioactivity in plasma and urine was the unchanged tracer, whereas rat liver homogenates contained almost only metabolites of [18F]FETNIM. None of the species studied showed binding of tracer to plasma proteins. A large variation—3%–70%—in the radioactivity represented by unchanged [18F]FETNIM was found in rat tumor. A negative correlation was found between the percentage of radioactivity represented by unchanged [18F]FETNIM in tumor tissue and tumor uptake (percentage injected dose per gram of tissue) at later times. The highest radioactivity was seen in urine and kidney; the lowest uptake was in fat, cerebellum, and bone matrix. In contrast to matrix, bone marrow had high uptake of 18F. The tumor-to-blood ratio reached a maximum of 1.80 ± 0.64 at 2 h. Conclusion: We conclude that [18F]FETNIM shows low peripheral metabolism, little defluorination, and possible metabolic trapping in hypoxic tumor tissue. These suggest a potential use for this tracer in PET studies on hypoxia of cancer patients.