VMAT2 quantitation by PET as a biomarker for beta-cell mass in health and disease.
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.
Department of Medicine of Columbia University Medical Center, New York, NY, USA.
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M
Freeby
R
R
Goland
M
M
Ichise
A
A
Maffei
R
R
Leibel
P
P
Harris
D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D050417:Insulin-Secreting Cells / Q000000981:diagnostic imaging* / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism* / Q000502:physiology
D015415:Biomarkers; D019275:Radiopharmaceuticals; D050493:Vesicular Monoamine Transport Proteins