MRI of transplanted pancreatic islets

Abstract

A promising treatment method for type 1 diabetes mellitus is transplantation of pancreatic islets containing ␤-cells. The aim of this study was to develop an MR technique to monitor the distribution and fate of transplanted pancreatic islets in an animal model. Twenty-five hundred purified and magnetically labeled islets were transplanted through the portal vein into the liver of experimental rats. The animals were scanned using a MR 4.7-T scanner. The labeled pancreatic islets were clearly visualized in the liver in both diabetic and healthy rats as hypointense areas on T 2 *-weighted MR images during the entire measurement period. Transmission electron microscopy confirmed the presence of iron-oxide nanoparticles inside the cells of the pancreatic islets. A significant decrease in blood glucose levels in diabetic rats was observed; normal glycemia was reached 1 week after transplantation. This study, therefore, represents a promising step toward possible clinical application in human medicine.

Cytosolic Delivery of Nanolabels Prevents Their Asymmetric Inheritance and Enables Extended Quantitative in Vivo Cell Imaging

“…1a. Cells are first incubated with plasmonic NPs, such as gold NPs (AuNPs), for [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] min. During that time the AuNP can adsorb to the cells and are internalized just below the plasma membrane by endocytic uptake (see TEM images in Figure S1).…”

“…In addition, several cell types such as T-cells have difficulties in internalizing extracellular compounds through endocytosis 23 . In other cases, problems may arise for cells that have a limited life span in culture, such as pancreatic islets, as efficient cell labelling through endocytic uptake is a rather slow process 24 . A second problem is that entrapment of contrast agents in the acidic endolysosomes may lead to increased cytotoxicity, for instance by creating reactive groups on the NP surface or by leaching of toxic metal ions, such as Cd 2+ in case of QDs [25][26][27] .…”

Noninvasive Imaging of Islet Transplants with 111In-Exendin-3 SPECT/CT

“…Targeting GLP-1R specifically expressed on the b-cells of the pancreatic islets offers an attractive alternative to methods using islets prelabeled with ultrasmall superparamagnetic iron oxide particles as described by Evgenov et al (7) and others (6,(16)(17)(18). Targeting a receptor, such as GLP-1R, may potentially offer higher specificity and does not require prelabeling of islets.…”

“…Although feasibility has been proven in preclinical transplantation models, these methods require transfection of b-cells or the use of transgenic animals and are therefore relatively difficult to translate to humans. In several studies, pancreatic islets prelabeled with iron oxide contrast agents were transplanted, allowing monitoring with MRI (6,7). These methods can show the presence of islets, but it remains a matter of debate to which degree the presence of iron oxide contrast agents represents viable and functional islets.…”

Imaging the pancreas: from ex vivo to non-invasive technology

“…One example, performed in a mouse model of type 1 diabetes, is the use of monocrystalline iron oxide nanoparticles to follow the alterations in the microvasculature that accompany insulitis by MRI [6]. The MRI modality has been most successful, however, when applied to the non-invasive monitoring of transplanted islets [7][8][9]. For this purpose, it appears possible that technologies such as MRI and PET could be applied in clinical settings in the near future.…”