Introduction: Advances in positron emission tomography (PET) imaging have provided opportunities to develop radiotracers specific for imaging insulin-producing pancreatic β-cells. However, a host of lingering questions should be addressed before these radiotracers are advocated for noninvasive quantification of β-cell mass (BCM) in vivo in the native pancreas.
Method: We provide an overview of tetrabenazine-based PET tracers developed to image and quantify BCM and discuss several theoretical, technical, and biological limitations of applying these tracers in clinical practice.
Discussion: VMAT2, a transporter protein expressed on pancreatic β-cells, has been advocated as a promising target for PET imaging tracers, such as dihydrotetrabenazine. However, the lack of radiotracer specificity for these proteins hampers their clinical application. Another important argument against their use is a striking discrepancy between radiotracer uptake and BCM in subjects with type I diabetes mellitus and healthy controls. Additionally, technical issues, such as the finite spatial resolution of PET, partial volume effects, and movement of the pancreas during respiration, impede PET imaging as a viable option for BCM quantification in the foreseeable future.
Conclusion: The assertion that BCM can be accurately quantified by tetrabenazine derived β-cell-specific radiotracers as density per unit volume of pancreatic tissue is not justifiable at this time. The fallacy of these claims can be explained by technical as well as biological facts that have been disregarded and ignored in the literature.