Labeling of Pancreatic Islets With Iron Oxide Nanoparticles for In Vivo Detection With Magnetic Resonance

Abstract

In vitro labeling of pancreatic islets with iron nanoparticles enables their direct posttransplant visualization by magnetic resonance; however, there is still a discrepancy in the fate of iron nanoparticles. This study was performed to detail the labeling process, consequently to improve the labeling efficacy and to confirm safety for islet cells. The islets were visible on T2*-weighted magnetic resonance images as hypointense spots immediately after 1-hr cultivation. Although at this time already the sufficient superparamagnetic effect was achieved, most of the particles were deposed in islet macrophages and only later were they found in endosomes of endocrine islet cells. The iron content depended on length of culture period. The labeled islets showed an intact ultrastructure, responded normally to glucose stimulation in vitro, and were able to treat experimental diabetes. For purpose of subsequent magnetic resonance imaging, a 24-hr culture with ferucarbotran leads to sufficient labeling with no apparent adverse effect on beta cell morphology or function.

Monitoring the survival of islet transplants by MRI using a novel technique for their automated detection and quantification

“…Several additional MRI studies have reported that MRI is useful for the detection and monitoring of transplanted islets labeled with SPIO agents and the impact of labeling PI with SPIO has been tested extensively [9][10][11][12]26,[31][32][33][34]. These studies have shown that islet viability, insulin secretion, apoptosis levels and the islet structure as observed by electron and light microscopy are not affected by SPIO labeling at the levels required for detection by MRI.…”

Benefits of PEGylation in the early post-transplant period of intraportal islet transplantation as assessed by magnetic resonance imaging of labeled islets

“…19 The mechanism of cellular uptake of SPIO in islets is known as fluid-phase endocytosis. 17,20,21 Because labeling with ferucarbotran preceded the PEGylation process in this study, it is reasonable to assume that surface modification with PEG did not affect the uptake process of SPIO. To determine if PEGylation could affect the translocation of SPIO from intracellular to extracellular space during the early post-transplant period, we collected histological data 1 wk after transplantation.…”

“…21 Preliminary experiments demonstrated superior labeling efficacy when isolated islets were allowed to culture in labeling medium for 48 vs. 24 h.…”

Positive contrast visualization of SPIO-labeled pancreatic islets using echo-dephased steady-state free precession

“…shortening contrast agents based on super-paramagnetic iron oxide (SPIO) nanoparticles [2,3,[5][6][7][8] are used. In our study, a commercially available SPIO contrast agent (Resovist®, Schering AG, Berlin, Germany) based on carbodextran-coated iron-oxide nanoparticles, widely studied experimentally and also approved for human use [8], was used.…”