In Vivo Imaging of Endogenous Pancreatic β-Cell Mass in Healthy and Type 1 Diabetic Subjects Using 18F-Fluoropropyl-Dihydrotetrabenazine and PET

Journal of Nuclear Medicine

Daniel M. Skovronsky¹  Krista Fowles¹  Judith L. Treadway¹  Kitt F. Petersen¹  Gary W. Cline¹  Kevan C. Herold¹  Timothy J. McCarthy¹  Richard E. Carson¹  Sarita Naik¹  Yu-Shin Ding¹  Shu-Fei Lin¹  Roberto A. Calle¹  Marc D. Normandin¹ 

关键词: diabetes;    pancreas;    beta cell mass;    PET;   

DOI  :  10.2967/jnumed.111.100545

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

The ability to noninvasively measure endogenous pancreatic β-cell mass (BCM) would accelerate research on the pathophysiology of diabetes and revolutionize the preclinical development of new treatments, the clinical assessment of therapeutic efficacy, and the early diagnosis and subsequent monitoring of disease progression. The vesicular monoamine transporter type 2 (VMAT2) is coexpressed with insulin in β-cells and represents a promising target for BCM imaging. Methods: We evaluated the VMAT2 radiotracer 18F-fluoropropyl-dihydrotetrabenazine (18F-FP-(+)-DTBZ, also known as 18F-AV-133) for quantitative PET of BCM in healthy control subjects and patients with type 1 diabetes mellitus. Standardized uptake value was calculated as the net tracer uptake in the pancreas normalized by injected dose and body weight. Total volume of distribution, the equilibrium ratio of tracer concentration in tissue relative to plasma, was estimated by kinetic modeling with arterial input functions. Binding potential, the steady-state ratio of specific binding to nondisplaceable uptake, was calculated using the renal cortex as a reference tissue devoid of specific VMAT2 binding. Results: Mean pancreatic standardized uptake value, total volume of distribution, and binding potential were reduced by 38%, 20%, and 40%, respectively, in type 1 diabetes mellitus. The radiotracer binding parameters correlated with insulin secretion capacity as determined by arginine-stimulus tests. Group differences and correlations with β-cell function were enhanced for total pancreas binding parameters that accounted for tracer binding density and organ volume. Conclusion: These findings demonstrate that quantitative evaluation of islet β-cell density and aggregate BCM can be performed clinically with 18F-FP-(+)-DTBZ PET.

【 授权许可】

Unknown