In Vivo Imaging of Endogenous Pancreatic β-Cell Mass in Healthy and Type 1 Diabetic Subjects Using 18F-Fluoropropyl-Dihydrotetrabenazine and PET
| Autor: | Yu-Shin Ding, Gary W. Cline, Judith L. Treadway, Sarita Naik, Kitt Falk Petersen, Shu-fei Lin, Marc D. Normandin, Kevan C. Herold, Daniel Skovronsky, Roberto A. Calle, Krista Fowles, Timothy J. McCarthy, Richard E. Carson |
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| Rok vydání: | 2012 |
| Předmět: |
Volume of distribution
medicine.medical_specialty Type 1 diabetes Chemistry Insulin medicine.medical_treatment Binding potential Standardized uptake value medicine.disease Dihydrotetrabenazine chemistry.chemical_compound medicine.anatomical_structure Endocrinology Internal medicine Diabetes mellitus medicine Radiology Nuclear Medicine and imaging Pancreas |
| Zdroj: | Journal of Nuclear Medicine. 53:908-916 |
| ISSN: | 2159-662X 0161-5505 |
| Popis: | The ability to noninvasively measure endogenous pancreatic b-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 inb-cells and represents a promising target for BCM imaging. Methods: We evaluated the VMAT2 radiotracer 18F-fluoropropyl-dihydrotetrabenazine ( 18 F-FP-(1)-DTBZ, also known as 18 F-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 b-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 b-cell density and aggregate BCM can be performed clinically with 18 F-FP-(1)-DTBZ PET. |
| Databáze: | OpenAIRE |
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