In both type 1 and type 2 diabetes mellitus, beta-cell mass (BCM), which exclusively produces insulin, is lost. Various therapeutic strategies are being developed that target BCM to restore its function by promoting beta-cell neogenesis and regeneration or by preventing its apoptosis. To this end, it is essential to identify biomarkers of BCM. Of the various imaging platforms, radionuclide-based imaging methods using radioligands that directly target BCM appear promising. In particular, the vesicular monoamine transporter type 2 (VMAT2), which is expressed almost exclusively by beta-cells and found in close association with insulin, can be noninvasively imaged with PET and (11)C-dihydrotetrabenazine or its derivatives. Despite the major limitation that beta-cells are low in abundance (1%-2%) and dispersed throughout the pancreas, VMAT2 PET is sensitive enough to detect VMAT2 signal and to allow kinetic model-based quantification of VMAT2 binding within the pancreas. However, these techniques are still in early stages, and careful further evaluations and technical developments are needed before they can be clinically used as a valid biomarker of BCM.