In vivo imaging of endogenous pancreatic β-cell mass in healthy and type 1 diabetic subjects using 18F-fluoropropyl-dihydrotetrabenazine and PET.

Abstract

UNLABELLED:

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 (18)F-fluoropropyl-dihydrotetrabenazine ((18)F-FP-(+)-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 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 (18)F-FP-(+)-DTBZ PET.

• Authors: Marc D Normandin, Kitt F Petersen, Yu-Shin Ding, Shu-Fei Lin, Sarita Naik, Krista Fowles, Daniel M Skovronsky, Kevan C Herold, Timothy J McCarthy, Roberto A Calle, Richard E Carson, Judith L Treadway, Gary W Cline
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 53 Issue 6 Pg. 908-16 (Jun 2012) ISSN: 1535-5667 [Electronic] United States
• PMID: 22573821 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Fluorine Radioisotopes
• florbenazine F 18
• Tetrabenazine

Topics

• Adolescent
• Adult
• Animals
• Diabetes Mellitus, Type 1 (diagnostic imaging)
• Female
• Fluorine Radioisotopes
• Humans
• Insulin-Secreting Cells (diagnostic imaging, physiology)
• Macaca mulatta
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Positron-Emission Tomography (methods)
• Tetrabenazine (analogs & derivatives)