Pharmacokinetics of [F-18]FETNIM: A potential hypoxia marker for PET

F-18-labeled fluoroerythronitroimidazole (FETNIM) has been suggested as a m arker of tumor hypoxia for use with PET. Our goal was to evaluate the pharm acokinetic properties of [F-13]FETNIM in rats and analyze metabolites in hu man, dog, and rat plasma and urine. Metabolites in liver and tumor homogena tes from tumor-bearing rats, as well as the biodistribution of the tracer, were also studied. Methods: Radio-thin-layer chromatography and digital aut oradiography were used to distinguish metabolites from the parent drug in u rine and plasma from 8 patients, 3 dogs, and 18 rats, as well as in liver a nd tumor homogenates from Sprague-Dawley rats bearing 7,12-dimethylbenzanth racene-induced rat mammary carcinoma. Biodistribution of [F-18]FETNIM was a lso 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 t racer, whereas rat liver homogenates contained almost only metabolites of [ F-18]FETNIM. None of the species studied showed binding of tracer to plasma proteins. A large variation-3%-70%-In the radioactivity represented by unc hanged [F-18]FETNIM was found in rat tumor. A negative correlation was foun d between the percentage of radioactivity represented by unchanged [F-18]FE TNIM in tumor tissue and tumor uptake (percentage injected dose per gram of tissue) at later times. The highest radioactivity was seen in urine and ki dney; the lowest uptake was in fat, cerebellum, and bone matrix. In contras t to matrix, bone marrow had high uptake of 18F. The tumor-to-blood ratio r eached a maximum of 1.80 +/- 0.64 at 2 h. Conclusion: We conclude that [F-1 8]FETNIM shows low peripheral metabolism, little defluorination, and possib le metabolic trapping in hypoxic tumor tissue. These suggest a potential us e for this tracer in PET studies on hypoxia of cancer patients.