PET probes for imaging pancreatic islet cells

Purpose: PET can detect very low concentrations of the probes at subpicomolar range in the target tissue with high sensitivity. The development of PET probes for imaging pancreatic islet cells depends on several key elements: the amount of target receptors in the beta cells; the target specificity and the target tissue delivery. This review summarized the latest developments of PET probes which are targeting proteins including GLP-1, VMAT2, GPR44, antigen, glucokinase and reporter genes in the beta cell for imaging pancreatic islet cells. Methods: A survey of the literature was performed to select the articles focusing on the development of PET probes for proteins targeting in the beta cell. Since PET probe development for imaging pancreatic islet cells is a narrow research field, the literature survey comprised of those articles published from 1993 when first probe C-11 DTBZ was synthesized to 2017 in English journals. In-111 SPECT probes are included for comparison study. Results: A selection of 97 papers were identified following the literature review. The probes covered tritium-3-, carbon-11-, fluorine-18-, gallium-68-, copper-64- and indium-111 (for SPECT)-labeled radioligands. The PET imaging studies with the probes have been evaluated for in vitro, ex vivo, preclinical and clinical applications. Some issues of targeting probes have been addressed to develop ideal non-invasive PET probes for imaging pancreatic islet cells. From the literature, a number of new probes have been developed in recent years to improve their biological profile such as higher specific binding to target with lower nonspecific binding to surrounding tissue, or optimal residence time in the subjects. Conclusion: PET imaging modality for imaging pancreatic islet cell especially beta cell provided high resolution, high sensitivity, and accurate quantification through the biodistribution, pharmacokinetics and target binding of tracers. The demand for new PET probes for preclinical and clinical investigations is increasing. This review gives comprehensive overview of noteworthy probes which are proteins targeting in beta cell. The review provides some future research directions for this emerging field.