期刊
JOURNAL OF NUCLEAR MEDICINE
卷 53, 期 6, 页码 908-916出版社
SOC NUCLEAR MEDICINE INC
DOI: 10.2967/jnumed.111.100545
关键词
diabetes; pancreas; beta cell mass; PET
资金
- Yale-Pfizer Bioimaging Research Alliance
- NIH [UL1 RR024139, R01 AG-23686, T32 DA022975]
- American Diabetes Association
The ability to noninvasively measure endogenous pancreatic beta-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 beta-cells and represents a promising target for BCM imaging. Methods: We evaluated the VMAT2 radiotracer F-18-fluoropropyl-dihydrotetrabenazine (F-18-FP-(+)-DTBZ, also known as F-18-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 beta-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 beta-cell density and aggregate BCM can be performed clinically with F-18-FP-(+)-DTBZ PET.
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