Targets and probes for non-invasive imaging of β-cells

Abstract

β-cells, located in the islets of the pancreas, are responsible for production and secretion of insulin and play a crucial role in blood sugar regulation. Pathologic β-cells often cause serious medical conditions affecting blood glucose level, which severely impact life quality and are life-threatening if untreated. With 347 million patients, diabetes is one of the most prevalent diseases, and will continue to be one of the largest socioeconomic challenges in the future. The diagnosis still relies mainly on indirect methods like blood sugar measurements. A non-invasive diagnostic imaging modality would allow direct evaluation of β-cell mass and would be a huge step towards personalized medicine. Hyperinsulinism is another serious condition caused by β-cells that excessively secrete insulin, like for instance β-cell hyperplasia and insulinomas. Treatment options with drugs are normally not curative, whereas curative procedures usually consist of the resection of affected regions for which, however, an exact localization of the foci is necessary. In this review, we describe potential tracers under development for targeting β-cells with focus on radiotracers for PET and SPECT imaging, which allow the non-invasive visualization of β-cells. We discuss either the advantages or limitations for the various tracers and modalities. This article concludes with an outlook on future developments and discuss the potential of new imaging probes including dual probes that utilize functionalities for both a radioactive and optical moiety as well as for theranostic applications.

Optoacoustic imaging of GLP-1 Receptor with a near-infrared exendin-4 analog

“…Compared to traditional fluorescence imaging systems, the key difference of MSOT is that its ability to use light for excitation and sound for detection enables a greater penetration depth. The development of optoacoustic imaging tools for diabetes is a valuable but unmet clinical need 7,8,25,31,43 . A handful of proof-of-concept studies in the literature have emerged to show the potential of diabetes monitoring via optoacoustic imaging, but none feature direct visualizations of ß-cells 6-9, 19, 44-46 .…”

“…One such drug, exendin-4 (exenatide), well-known for its high affinity and efficacy is an excellent agonist 4,23 . Over the past few years, several fluorescent imaging agents based on exendin-4 have been described in the literature [24][25][26][27] .…”

Multiorgan, Multimodality Imaging in Cardiometabolic Disease

“…Pancreatic fat accumulation impairs beta cell mass and function; intriguing pilot data from Lim et al using MRI-based quantification suggests that marked, short-term calorie restriction lowers pancreatic triglyceride content, normalizes beta cell function, and restores hepatic insulin sensitivity 35 . Novel molecular probes for use with nuclear imaging techniques, like single photon emission computed tomography (SPECT) and PET, show promise for noninvasive quantification of beta cell mass 36 . Glucagon-like peptide 1 receptor (GLP-1R) is a protein specifically expressed by pancreatic beta cells, and is a common target for molecular imaging probes.…”

The Use of 18f-Dopa Pet/Ct Imaging in Congenital Hyperinsulinism

“…Перспектив-ной технологией исследования является совме-щенная ПЭТ/МРТ с 18 F-ДОФА, которая позволит существенно снизить лучевую нагрузку на па-циентов с ВГИ, т.к. выполнение МРТ не со-пряжено с воздействием на организм ребенка ионизирующего излучения [53].…”