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

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 β-cell vesicular monoamine transporter type II to measure pancreatic β-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 β-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 ∼25% of uptake could be attributed to β-cell uptake. [ 18 F]FP-(+)-DTBZ displacement studies indicate that there is a substantial fraction of specific binding that is not to pancreatic islet β 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.