Translational Molecular Imaging of Diabetes

Abstract

Diabetes mellitus contributes to significant morbidity and mortality worldwide. Translational medicine and research facilitate the transition of in vitro and experimental animal research to human applications. Molecular imaging is one of the powerful tools for translational research in diabetes, which accelerates transition of laboratory hypotheses into the clinic. These imaging tools are also instrumental for furthering our understanding about the causes that trigger diabetes and facilitate its progression. Imaging of therapeutic response is yet another avenue that can be explored in our attempt to find a cure for this disease. In this review we briefly summarize molecular imaging studies that show promise for clinical translation. Emphasis is placed on imaging of endogenous and transplanted beta cell mass, including application of various imaging modalities and approaches. Finally, the review attempts to define the future role of these non-invasive imaging techniques in diabetes research and clinical care.

GLP-1R–Targeting Magnetic Nanoparticles for Pancreatic Islet Imaging

“…Although monitoring autoantibody titers and C-peptide concentrations could provide useful information for diabetes treatment ( 3 ), a noninvasive method of directly monitoring the disease progression by quantifying β-cell mass and/or function would provide unprecedented advantages for disease treatment. Various imaging methods allowing for β-cell visualization have been developed ( 4 ). However, despite intense research efforts, only one tracer (dihydrotetrabenazine) for positron emission tomography has been developed and is currently under clinical evaluation ( 5 ).…”

Poly(4-Styrenesulfonic Acid-co-maleic Anhydride)-Coated NaGdF4:Yb,Tb,Nd Nanoparticles with Luminescence and Magnetic Properties for Imaging of Pancreatic Islets and β-Cells

“…To reverse diabetes, the islet cell transplantation has emerged as a promising alternative to traditional insulin therapy, which is potentially equally effective but much safer than whole pancreas transplantation, reducing severe hypoglycemic episodes and hemoglobin levels. However, in diabetes diagnostics, it is difficult to quantify the mass of β-cells or at least provide a suitable in vivo nanoparticle-based monitoring of the transplantation in early stages to detect islet graft rejection. , Hence, different imaging modalities for in vivo pancreatic β-cell and islet visualization have been suggested, ,, including MRI, although no method is so far routinely applicable in clinical practice. To visualize pancreatic islets and β-cells, not only magnetic iron oxide nanoparticles but also other types of materials including lanthanide-based, manganese and zinc, silver, fluorine, and gold particles have been developed. − Their major drawbacks consist in the toxicity and low in vivo sensitivity and specificity due to the absence of correlation between the particle concentration and 1 H NMR signal .…”

“…However, in diabetes diagnostics, it is difficult to quantify the mass of β-cells or at least provide a suitable in vivo nanoparticle-based monitoring of the transplantation in early stages to detect islet graft rejection. , Hence, different imaging modalities for in vivo pancreatic β-cell and islet visualization have been suggested, ,, including MRI, although no method is so far routinely applicable in clinical practice. To visualize pancreatic islets and β-cells, not only magnetic iron oxide nanoparticles but also other types of materials including lanthanide-based, manganese and zinc, silver, fluorine, and gold particles have been developed. − Their major drawbacks consist in the toxicity and low in vivo sensitivity and specificity due to the absence of correlation between the particle concentration and 1 H NMR signal . To afford the correlation, paramagnetic lanthanide ions have been suggested, interacting with water protons and generating the “hypersignal” in tissues caused by the efficient MRI relaxation.…”

“…However, in diabetes diagnostics, it is difficult to quantify the mass of β-cells 14 or at least provide a suitable in vivo nanoparticle-based monitoring of the transplantation in early stages to detect islet graft rejection. 12,15 Hence, different imaging modalities for in vivo pancreatic β-cell and islet visualization have been suggested, 12,16,17 including MRI, 18 although no method is so far routinely applicable in clinical practice. To visualize pancreatic islets and β-cells, not only magnetic iron oxide nanoparticles 19 but also other types of materials including lanthanide-based, 20 manganese and zinc, 21 silver, 22 fluorine, 23 and gold particles have been developed.…”

“…24−26 Their major drawbacks consist in the toxicity and low in vivo sensitivity and specificity due to the absence of correlation between the particle concentration and 1 H NMR signal. 16 To afford the correlation, paramagnetic lanthanide ions have been suggested, interacting with water protons and generating the "hypersignal" in tissues caused by the efficient MRI relaxation. Lanthanide-containing nanoparticles are mostly based on fluorides, oxides, phosphates, and vanadates.…”