TY - JOUR T1 - F-18(+)FP-DTBZ: An investigational PET ligand for measuring beta cell mass in the pancreas JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 114P LP - 114P VL - 48 IS - supplement 2 AU - Mei-Ping Kung AU - Brian Lieberman AU - Catherine Hou AU - Datta Ponde AU - Rajesh Goswami AU - Daniel Skovronsky AU - Shaoping Deng AU - James Markmann AU - Hank Kung Y1 - 2007/05/01 UR - http://jnm.snmjournals.org/content/48/supplement_2/114P.2.abstract N2 - 386 Objectives: Vesicular monoamine transporter 2 (VMAT2), in addition to its presence in CNS, is highly expressed in the beta cells of the pancreatic islets. Recently, C-11-DTBZ, a selective VMAT2 imaging agent, has been reported as a promising probe to measure beta cell mass in diabetes. In order to generate a widely applicable probe, we have recently developed a F-18 labeled ligand, 9-fluoropropyl (+)dihydrotetrabenazine, (+)FP-DTBZ showing excellent in vitro and in vivo properties for targeting VMAT2. In this study, we tested whether F-18(+)FP-DTBZ could be useful as a potential imaging agent for quantitation of pancreatic beta cell mass in vivo. Methods: F-18(+)FP-DTBZ was labeled according to the method described previously. Organ distribution was carried out in normal Sprague-Dawley rats. Uptake of F-18(+)FP-DTBZ in pancreas of normal and streptozotocin (STZ)-treated mice was measured and correlated with blood glucose concentrations in mice. Human islets and exocrine pancreas tissues were purified and homogenates were prepared for in vitro binding study with F-18(+)FP-DTBZ. Results: The in vivo biodistribution of F-18(+)FP-DTBZ in rats showed the highest uptake in the pancreas (5% dose/g at 30 min post-injection) among all peripheral organs. In vivo competition experiments led to a significant reduction (30–40% blockade) when mice were pretreated or co-treated with cold (unlabeled) (+)DTBZ (2mg/Kg or 3.8 mg/Kg respectively). F-18(+)FP-DTBZ uptake in the pancreas was decreased by 30-40% in STZ-treated mice (a mouse model of diabetes) and was consistent with the results reported for C-11-DTBZ. Initial in vitro binding study of F-18(+)FP-DTBZ with homogenates of purified human islet cells was found to be specific and saturable. Conclusions: The preliminary data observed with F-18(+)-FP-DTBZ indicate that this F-18 tracer for VMAT2 is potentially useful for quantitative measurement of beta cell mass and may have applications for studying the pathogenesis of diabetes and evaluating potential disease modifying therapies. ER -