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F-18 (+)-Epoxide FP-DTBZ: A new PET ligand for measuring beta cell mass in the pancreas

¹ Radiology, University of Pennsylvania, Philadelphia, Pennsylvania; ² Avid Radiopharmaceuticals, Inc., Philadelphia, Pennsylvania; ³ Radiology, University of Michigan, Ann Arbor, Michigan

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Objectives: Vesicular monoamine transporter 2 (VMAT2) is highly expressed in the beta cells of the pancreatic islets. We have recently reported a F-18 9-fluoropropyl-(+)dihydrotetrabenazine, (+)FP-DTBZ showing excellent in vitro and in vivo properties for imaging pancreatic beta cell mass. To improve the beta cell selectivity we report F-18 epoxide derivative of DTBZ (at the C2 position) as a new improved imaging agent for beta cell mass.

Methods: Both F-18 and F-19 (+) and (-)-epoxide FP-DTBZ were prepared. Organ distribution was carried out in normal rats. Uptake of F-18 (+)-epoxide FP-DTBZ in pancreas of normal rats was measured and correlated with blocking study using cold (+)-DTBZ or (+)FP-DTBZ.

Results: In vitro binding study of VMAT2 using rat brain striatum showed a Ki value of 0.08 and 30 nM for the (+) and (-)-epoxide FP-DTBZ. The in vivo biodistribution of F-18 (+)-epoxide FP-DTBZ in rats showed the highest uptake in the pancreas (2.85 % dose/g at 30 min post-injection). In vivo competition experiments with cold (+)-DTBZ led to a significant reduction (62 % blockade) when rats were pretreated with (+)DTBZ (3.3 mg/kg). The inactive isomer, F-18(-)-epoxide FP-DTBZ, showed a significantly lower pancreas uptake (0.22 % dose/g at 30 min post-injection). Blocking study of the inactive isomer showed no change in pancreas uptake.

Conclusions: The preliminary data observed with F-18(+)-epoxide FP-DTBZ indicate that this F-18 tracer for VMAT2 has high selective uptake and it may be potentially useful for imaging beta cell mass.

Research Support: Supported by a grant from Avid Radiopharmaceuticals, Inc.

This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Lieberman, B. Articles by Kung, H. PubMed Articles by Lieberman, B. Articles by Kung, H.