Pancreatic Beta Cell Mass PET Imaging and Quantification with [11C]DTBZ and [18F]FP-(+)-DTBZ in Rodent Models of Diabetes

The aim of this study is to compare the utility of two positron emission tomography (PET) imaging ligands ((+)-[C-11]dihydrotetrabenazine ([C-11]DTBZ) and the fluoropropyl analog ([F-18]FP-(+)-DTBZ)) that target islet beta-cell vesicular monoamine transporter type II to measure pancreatic beta-cell mass (BCM). [C-11]DTBZ or [F-18]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. On a group level, a positive correlation of [C-11]DTBZ pancreatic SUV with pancreas insulin content and BCM was observed. In the STZ diabetic model, both [F-18]FP-(+)-DTBZ and [C-11]DTBZ correlated positively with BCM, although only similar to 25% of uptake could be attributed to beta-cell uptake. [F-18]FP-(+)-DTBZ displacement studies indicate that there is a substantial fraction of specific binding that is not to pancreatic islet beta cells. PET imaging with [F-18]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.