Molecular Imaging Reviews

Imaging of beta-cell mass and function. - 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.

Renal toxicity of radiolabeled peptides and antibody fragments: mechanisms, impact on radionuclide therapy, and strategies for prevention. - Peptide-receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogs such as octreotide is an effective therapy against neuroendocrine tumors. Other radiolabeled peptides and antibody fragments are under investigation. Most of these compounds are cleared through the kidneys and reabsorbed and partially retained in the proximal tubules, causing dose-limiting nephrotoxicity. An overview of renal handling of radiolabeled peptides and resulting nephrotoxicity is presented, and strategies to reduce nephrotoxicity are discussed. Modification of size, charge, or structure of radiolabeled peptides can alter glomerular filtration and tubular reabsorption. Coinfusion of competitive inhibitors of reabsorption also interferes with the interaction of peptides with renal endocytic receptors; coinfusion of basic amino acids is currently used for kidney protection in clinical PRRT. Furthermore, nephrotoxicity may be reduced by dose fractionation, use of radioprotectors, or use of mitigating agents. Decreasing the risk of nephrotoxicity allows for administration of higher radiation doses, increasing the effectiveness of PRRT.