Molecular imaging of β-cells: diabetes and beyond

Abstract

Since diabetes is becoming a global epidemic, there is a great need to develop early β-cell specific diagnostic techniques for this disorder. There are two types of diabetes (i.e., type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM)). In T1DM, the destruction of pancreatic βcells leads to reduced insulin production or even absolute insulin deficiency, which consequently results in hyperglycemia. Actually, a central issue in the pathophysiology of all types of diabetes is the relative reduction of β-cell mass (BCM) and/or impairment of the function of individual βcells. In the past two decades, scientists have been trying to develop imaging techniques for noninvasive measurement of the viability and mass of pancreatic β-cells. Despite intense scientific efforts, only two tracers for positron emission tomography (PET) and one contrast agent for magnetic resonance (MR) imaging are currently under clinical evaluation. β-cell specific imaging probes may also allow us to precisely and specifically visualize transplanted β-cells and to improve transplantation outcomes, as transplantation of pancreatic islets has shown promise in treating T1DM. In addition, some of these probes can be applied to the preoperative detection of hidden insulinomas as well. In the present review, we primarily summarize potential tracers under development for imaging β-cells with a focus on tracers for PET, SPECT, MRI, and optical imaging. We will discuss the advantages and limitations of the various imaging probes and extend an outlook on future developments in the field. ☆ This review is part of the Advanced Drug Delivery Reviews theme issue on "Imaging and Therapy of Diabetes: State of the Art".

PET Imaging of Pancreatic Dopamine D2 and D3 Receptor Density with 11C-(+)-PHNO in Type 1 Diabetes

“…With these factors in mind, total BCM must include measurement of functional b-cells and nonfunctional b-cells (viable cells that do not secrete insulin). The ability to quantify this total BCM in vivo in T1DM patients, combined with functional measures, would provide more accurate evaluation of disease progression and efficacy of therapies, such as islet transplantation or pharmacologic intervention (6). However, an in vivo clinical tool to measure total BCM, without residual binding on other cells besides b-cells, has remained elusive.…”

<p>Islet Transplantation Imaging in vivo</p>

“…11 Third, SPIO is biodegradable and is easily affected by the surrounding internal environments. 12 The Küpffer cells in the liver decompose SPIO quickly, affecting the signal observation of the labeled islets. Fourth, many factors may cause loss of SPIO signal in transplanted islet cells, eg, immune rejection, ischemia and inflammation in the liver after islets transplantation.…”

“…15 Although Resovist is approved for clinical use as a liver-imaging agent 16 and it has been proved that porcine islets can safely and efficiently be labeled with Resovist to monitor kidney capsules of diabetic mice ( Figure 1A), 17 it has not been applied further because of its instability in clinical trials. 12 To solve this problem, SPIO has been further modified, with the conjugation of lipofectamine, poly-L-lysine, polyethyleneimine, 18 protamine sulfate, 19 and dendron guanidine 20 to improve its cell-penetrating ability. Jung et al labeled transplanted islets under the left kidney capsule of nude mice with stable heparin-SPIO to monitor transplanted islet mass by MRI in vivo for 30 days, while treating type 1 diabetes.…”

Elucidating the Relationship Between Diabetes Mellitus and Parkinson’s Disease Using 18F-FP-(+)-DTBZ, a Positron-Emission Tomography Probe for Vesicular Monoamine Transporter 2

“…Great efforts have been devoted to improving the diagnostic accuracy of DM/BCM determination using highly β-cell-specific molecular imaging probes. Considering the necessity of tracking dynamic changes in BCM over time, PET imaging seems to be a feasible method for accessing BCM ( Wei et al, 2019 ). Moreover, VMAT2 is one of the β-cell biomarkers, and the binding of VMAT2 with specific radioactive probe substances is well correlated with the amount of insulin secretion observed after a glucose challenge ( Naganawa et al, 2018 ).…”