Michael G. Tal, MD Boaz Hirshberg, MD Ziv Neeman, MD David Bunnell, MD S. Soleimanpour, MD John Bacher Noelle Patterson Richard Chang, MD David M. Harlan, MD Index terms: Animals Diabetes mellitus Experimental study Pancreas, interventional procedures, 770.1264 Pancreas, transplantation Published online 10.1148/radiol.2301021413 Radiology 2004; 230:163–168 1 From the Department of Diagnostic Imaging, Yale University School of Medicine, PO Box 208042, New Ha- ven, CT 06520-8042 (M.G.T.); and the Transplantation and Autoimmu- nity Branch, National Institute of Dia- betes and Digestive and Kidney Dis- eases (B.H., D.B., S.S., N.P., D.M.H.); Radiology Department, Warren Grant Magnuson Clinical Center (Z.N., R.C.); and Surgery Service, Veterinary Resources Program, Office of Research Services (J.B.), Department of Health and Human Services, National Insti- tutes of Health, Bethesda, Md. From the 2002 RSNA scientific assembly. Re- ceived October 31, 2002; revision re- quested January 13, 2003; final revi- sion received May 12; accepted May 20. Address correspondence to M.G.T. (e-mail: michael.tal@yale.edu). Author contributions: Guarantors of integrity of entire study, M.G.T., B.H.; study concepts, M.G.T., B.H.; study design, B.H., D.M.H.; liter- ature research, B.H.; experimental studies, M.G.T., B.H., Z.N., J.B., R.C., D.M.H.; data acquisition, M.G.T., B.H., D.B.; data analysis/interpreta- tion, B.H., M.G.T.; statistical analysis, B.H.; manuscript preparation, M.G.T., B.H.; manuscript definition of intellec- tual content, M.G.T.; manuscript edit- ing, M.G.T., B.H., D.M.H.; manuscript revision/review and manuscript final version approval, all authors © RSNA, 2004 Induction of Diabetes in Nonhuman Primates by Means of Temporary Arterial Embolization and Selective Arterial Injection of Streptozotocin 1 PURPOSE: To develop and assess a technique for induction of C peptide–negative diabetes in adult nonhuman primates in preparation for preclinical investigation of type 1 diabetes treatments. MATERIALS AND METHODS: First, temporary embolization of the hepatic and gastric arteries was performed in 14 adult nonhuman primates (six cynomolgus, five rhesus, and three pigtail macaques). After embolization was confirmed with angiog- raphy, streptozotocin was injected at a dose of 50 –70 mg/kg into the celiac artery and branches supplying the pancreas. The macaques then were given intravenous injections of arginine and glucose, and blood levels of insulin and C peptide were measured with an enzyme-linked immunosorbent assay to determine whether diabetes had been induced. RESULTS: All but one of the macaques developed persistent long-term C peptide– negative diabetes after the streptozotocin injection. One macaque did not develop diabetes after the initial injection and was given a second dose of streoptozotocin, which did induce diabetes. None of the macaques showed any symptoms of hepatic or renal injury, and only one died (of gastric dilatation 5 days after the procedure). CONCLUSION: Streptozotocin injection after temporary embolization of the he- patic and gastric arteries is a safe and reproducible method for inducing C peptide– negative diabetes in adult nonhuman primates in preparation for preclinical inves- tigation of type 1 diabetes treatments. © RSNA, 2004 Pancreatic islet transplantation may one day enable the restoration of normal insulin produc- tion in patients with type 1 diabetes mellitus (1), but there are persistent and severe obstacles to the development and application of this therapy (2,3). To make islet transplantation viable in the clinical setting, investigators must first identify a replenishable source of islet cells, safer ways of infusing the cells into recipients, and better methods for preventing posttransplanta- tion loss of infused cells. Experimental research in animal models is key for solving these problems. Outcomes in rodent transplant models, however, do not reliably predict those in larger mammals such as humans and nonhuman primates (4,5). Although nonhuman pri- mate studies are difficult and expensive, they are highly relevant because of the phylogenetic relationship between humans and nonhuman primate species (6) and because many of the immunomodulatory agents (eg, antibodies and receptor fusion proteins) that are specific for human epitopes cross react with the corresponding primate epitopes (3,4,7). The further development of islet transplantation therapy would benefit from a reliable and safe way of inducing insulinopenic diabetes in the adult nonhuman primate model (4,5,8–10). To our knowledge, the spontaneous development of type 1 diabetes mellitus has not been reported in nonhuman primates (11,12). Methods previously used to induce 163 R adiology