Abstract
Diabetes is a chronic metabolic disease affecting over 400 million people worldwide and one of the leading causes of death, especially in developing nations. The disease is characterized by chronic hyperglycemia, caused by defects in the insulin secretion or action pathway. Current diagnostic methods measure metabolic byproducts of the disease such as glucose level, glycated hemoglobin (HbA1c), insulin or C-peptide levels, which are indicators of the beta-cell function. However, they inaccurately reflect the disease progression and provide poor longitudinal information. Beta-cell mass has been suggested as an alternative approach to study disease progression in correlation to beta-cell function, as it behaves differently in the diabetes physiopathology. Study of the beta-cell mass, however, requires highly invasive and potentially harmful procedures such as pancreatic biopsies, making diagnosis and monitoring of the disease tedious. Nuclear medical imaging techniques using radiation emitting tracers have been suggested as strong non-invasive tools for beta-cell mass. A highly sensitive and high-resolution technique, such as positron emission tomography, provides an ideal solution for the visualization of beta-cell mass, which is particularly essential for better characterization of a disease such as diabetes, and for estimating treatment effects towards regeneration of the beta-cell mass. Development of novel, validated biomarkers that are aimed at beta-cell mass imaging are thus highly necessary and would contribute to invaluable breakthroughs in the field of diabetes research and therapies. This review aims to describe the various biomarkers and radioactive probes currently available for positron emission tomography imaging of beta-cell mass, as well as highlight the need for precise quantification and visualization of the beta-cell mass for designing new therapy strategies and monitoring changes in the beta-cell mass during the progression of diabetes.
Highlights
Science for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, SE-75183 Uppsala, Sweden; Citation: Cheung, P.; Eriksson, O
The generated probe should display a signal many folds higher in endocrine islets compared to exocrine tissues, and significantly higher than the non-specific signal arising from the surrounding tissues as well as the unbound plasmatic tracer associated with organ perfusion
A glaring weakness of using VMAT2 as a target for imaging is the noted expression in pancreatic polypeptide (PP) cells of the endocrine pancreas, warranting caution when interpreting results, as the observed signal uptake of 18 F-FP-DTBZ could possibly be the result of non-specific binding [62]
Summary
The human pancreas is an elongated organ situated in the left hypochondriac and epigastric region of the abdomen with a dual exocrine and endocrine function. The majority of the pancreas is composed of exocrine cells (~98–99%), which are organized into acini, that release a mixture of digestive enzymes and bicarbonate to help with digestion. The endocrine cells (~1–2%) are organized into clusters named islets of Langerhans and dispatched heterogeneously over the pancreas. They are divided into five different cell types (alpha, beta, delta, PP, epsilon), which were discovered through histochemical and immuno-staining. Beta cells account for ~50–80% of the pancreatic endocrine cell population and are responsible for insulin production. Insulin is a hypoglycemic peptide hormone that plays a major role in maintaining proper glucose metabolism and is tightly linked to pathologies such as diabetes mellitus [1]
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