F-18(+)FP-DTBZ: a PET ligand for imaging VMAT2 binding sites in the brain and pancreas

NUCL 2

H Kung1, MP Kung2, B Lieberman3, C Hou3, D Ponde3, R Goswami3, D Skovraonsky4, S Deng3, J Markamnn3, and M Kilborn5. (1) Department of Radiology and Pharmacology, University of Pennsylvania, 3700 Market St, Philadelphia, PA 19104, (2) Radiology, University of Pennsylvania, (3) University of Pennsylvania, (4) Avid Radiopharmaceuticals Inc, (5) University of Michigan
Vesicular monoamine transporter 2 (VMAT2) binding sites are present in the brain and beta cells of the pancreatic islets. We have prepared a F-18 labeled ligand, 9-fluoropropyl(+)dihydrotetrabenazine, (+)FP-DTBZ, showing excellent in vitro and in vivo properties for targeting VMAT2. Organ distribution of F-18(+)FP-DTBZ in normal rats displayed an excellent striatum uptake and also a high uptake in the pancreas (5% dose/g at 30 min post-injection). In vivo competition experiments led to a significantly reduction (30–40% blockade in pancreas and > 90% reduction in the striatum) 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 streptozotocin-treated mice (a mouse model of diabetes). The preliminary data suggest that this F-18 tracer is potentially useful for imaging VMAT2 binding sites in the beta cell mass and basal ganglia.
 

Molecular Imaging
9:00 AM-11:50 AM, Sunday, August 19, 2007 Boston Park Plaza -- Stuart Rm, Oral

Division of Nuclear Chemistry & Technology

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007