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

Journal of Nuclear Medicine

Daniel Skovronsky¹  Michael R. Kilbourn¹  Datta E. Ponde¹  Catherine Hou¹  Eric Blankemeyer¹  Hank F. Kung¹  Brian P. Lieberman¹  Shunichi Oya¹  Mei-Ping Kung¹ 

关键词: diabetes;    beta-cell mass;    pancreas imaging;    VMAT2;   

DOI  :  10.2967/jnumed.108.051680

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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.

【 授权许可】

Unknown