VMAT2 quantitation by PET as a biomarker for beta-cell mass in health and disease

Abstract

The common pathology underlying both type 1 and type 2 diabetes (T1DM and T2DM) is insufficient beta-cell mass (BCM) to meet metabolic demands. An important impediment to the more rapid evaluation of interventions for both T1DM and T2DM lack of biomarkers of pancreatic BCM. A reliable means of monitoring the mass and/or function of beta-cells would enable evaluation of the progression of diabetes as well as the monitoring of pharmacologic and other interventions. Recently, we identified a biomarker of BCM that is quantifiable by positron emission tomography (PET). PET is an imaging technique which allows for non-invasive measurements of radioligand uptake and clearance, is sensitive in the pico- to nanomolar range and of which the results can be deconvoluted into measurements of receptor concentration. For BCM estimates, we have identified VMAT2 (vesicular monoamine transporter type 2) as a biomarker and [(11)C] DTBZ (dihydrotetrabenazine) as the transporter's ligand. VMAT2 is highly expressed in beta-cells of the human pancreas relative to other cells of the endocrine and exocrine pancreas. Thus measurements of [(11)C] DTBZ in the pancreas provide an indirect measurement of BCM. Here we summarize our ongoing efforts to validate the clinical utility of this non-invasive approach to real-time BCM measurements.