Pancreatic beta cell mass PET imaging and quantification with (11C)DTBZ and (18F)FP-(+)-DTBZ in rodent models of diabetes.

摘要

PURPOSE: The aim of this study is to compare the utility of two positron emission tomography (PET) imaging ligands ((+)-[(11)C]dihydrotetrabenazine ([(11)C]DTBZ) and the fluoropropyl analog ([(18)F]FP-(+)-DTBZ)) that target islet beta-cell vesicular monoamine transporter type II to measure pancreatic beta-cell mass (BCM). PROCEDURES: [(11)C]DTBZ or [(18)F]FP-(+)-DTBZ was injected, and serial PET images were acquired in rat models of diabetes (streptozotocin-treated and Zucker diabetic fatty) and beta-cell compensation (Zucker fatty). Radiotracer standardized uptake values (SUV) were correlated to pancreas insulin content measured biochemically and histomorphometrically. RESULTS: On a group level, a positive correlation of [(11)C]DTBZ pancreatic SUV with pancreas insulin content and BCM was observed. In the STZ diabetic model, both [(18)F]FP-(+)-DTBZ and [(11)C]DTBZ correlated positively with BCM, although only approximately 25% of uptake could be attributed to beta-cell uptake. [(18)F]FP-(+)-DTBZ displacement studies indicate that there is a substantial fraction of specific binding that is not to pancreatic islet beta cells. CONCLUSIONS: PET imaging with [(18)F]FP-(+)-DTBZ provides a noninvasive means to quantify insulin-positive BCM and may prove valuable as a diagnostic tool in assessing treatments to maintain or restore BCM.