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

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Abstract

Purpose

The aim of this study is to compare the utility of two positron emission tomography (PET) imaging ligands ((+)-[11C]dihydrotetrabenazine ([11C]DTBZ) and the fluoropropyl analog ([18F]FP-(+)-DTBZ)) that target islet β-cell vesicular monoamine transporter type II to measure pancreatic β-cell mass (BCM).

Procedures

[11C]DTBZ or [18F]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 [11C]DTBZ pancreatic SUV with pancreas insulin content and BCM was observed. In the STZ diabetic model, both [18F]FP-(+)-DTBZ and [11C]DTBZ correlated positively with BCM, although only ∼25% of uptake could be attributed to β-cell uptake. [18F]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 [18F]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.

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Acknowledgments

The authors acknowledge the excellent work of the staff of the Yale PET Center and Tim Mulnix, PhD for the rat holder and technical assistance critical to the success of these studies. These studies were supported by the Yale-Pfizer Bioimaging Alliance and the Juvenile Diabetes Research Foundation (1 37-2009-29). This publication was also made possible by CTSA Grant Number UL1 RR024139 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH.

Conflicts of Interest/Disclosures

Walter C. Soeller owns shares in Pfizer, Inc. and Judith L. Treadway is an employee and shareholder of Pfizer, Inc.

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Authors and Affiliations

  1. Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, USA

    Tarun Singhal, Yu-Shin Ding, David Weinzimmer, Marc D. Normandin, David Labaree, Jim Ropchan, Nabeel Nabulsi, Shu-fei Lin, Yiyun Huang & Richard E. Carson

  2. Department of Internal Medicine, Yale University School of Medicine, P. O. Box 208020, New Haven, CT, 06520-8020, USA

    Gary W. Cline

  3. Pfizer Global R&D, Groton, CT, USA

    Marc B. Skaddan, Walter C. Soeller & Judith L. Treadway

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  1. Tarun Singhal
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Correspondence to Gary W. Cline.

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Singhal, T., Ding, YS., Weinzimmer, D. et al. Pancreatic Beta Cell Mass PET Imaging and Quantification with [11C]DTBZ and [18F]FP-(+)-DTBZ in Rodent Models of Diabetes. Mol Imaging Biol 13, 973–984 (2011). https://doi.org/10.1007/s11307-010-0406-x

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