HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: jnumed.108.051680v1 49/7/1171    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JNM Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kung, M.-P. Articles by Kung, H. F. Search for Related Content PubMed PubMed Citation Articles by Kung, M.-P. Articles by Kung, H. F.

In Vivo Imaging of β-Cell Mass in Rats Using ¹⁸F-FP-(+)-DTBZ: A Potential PET Ligand for Studying Diabetes Mellitus

¹ Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania; ² Avid Radiopharmaceuticals, Inc., Philadelphia, Pennsylvania; ³ Department of Radiology, University of Michigan, Ann Arbor, Michigan; and ⁴ Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania

Correspondence: For correspondence or reprints contact: Hank F. Kung, Department of Radiology, University of Pennsylvania, 3700 Market St., Room 305, Philadelphia, PA 19104. E-mail: kunghf{at}sunmac.spect.upenn.edu

Recent studies on gene expression of β-cell mass (BCM) in the pancreas showed that vesicular monoamine transporter 2 (VMAT2) is highly expressed in the BCM (mainly in the islets of Langerhans). Imaging pancreatic BCM may provide an important tool for understanding the relationship between loss of insulin-secreting β-cells and onset of diabetes mellitus. In this article, 9-fluoropropyl-(+)-dihydrotetrabenazine (FP-(+)-DTBZ), which is a VMAT2 imaging agent, was evaluated as a PET agent for estimating BCM in vivo. Methods: Organ biodistribution after an intravenous injection of ¹⁸F-FP-(+)-DTBZ (active isomer) and ¹⁸F-FP-(–)-DTBZ (inactive isomer) was evaluated in normal rats. The specificity of uptake of ¹⁸F-FP-(+)-DTBZ was assessed by a pretreatment (3.8 mg of (+)-DTBZ per kilogram and 3.5 mg of FP-(+)-DTBZ per kilogram, intravenously, 5 min prior) or coadministration (2 mg of (+)-DTBZ per kilogram). PET studies were performed in normal rats. Results: The in vivo biodistribution of ¹⁸F-FP-(+)-DTBZ in rats showed the highest uptake in the pancreas (5% dose/g at 30 min after injection), whereas ¹⁸F-FP-(–)-DTBZ showed a very low pancreas uptake. Rats pretreated with FP-(+)-DTBZ displayed a 78% blockade of pancreas uptake. PET studies in normal rats demonstrated an avid pancreas uptake of ¹⁸F-FP-(+)-DTBZ. Conclusion: The preliminary data obtained with ¹⁸F-FP-(+)-DTBZ suggest that this fluorinated derivative of DTBZ shows good pancreas specificity and has the potential to be useful for quantitative measurement of VMAT2 binding sites reflecting BCM in the pancreas.

Key Words: diabetes • beta-cell mass • pancreas imaging • VMAT2

COPYRIGHT © 2008 by the Society of Nuclear Medicine, Inc.

Related articles in JNM:

This Month in JNM

JNM 2008 49: 13A-14A. [Full Text]