Purpose: We previously reported the feasibility of islet magnetic resonance imaging (MRI) using ferumoxytol, which is the only clinically-available ultrasmall superparamagnetic iron oxide. However, the labeling efficacy was not sufficient for its clinical use in islet transplantation. We aimed to evaluate the feasibility of islet MRI using direct linking of ferumoxytol to islet surface through PEGylation.

Method: Islets were labeled by surface modification with up to 4% PEG-heparin-ferumoxytol. We compared islet function and viability of control islets and ferumoxytol-heparin-PEGylated islets. Efficacy of labeling with ferumoxytol-heparin-PEGylation and ferumoxytol alone was assessed in both ex vivo and in vivo models.

Results: Labeling of islets with up to 2% PEG-heparin-ferumoxytol did not derange ex vivo islet viability and function. The T2* relaxation time was optimal when islets were labeled with 1 to 4% PEG-heparin-ferumoxytol. The labeling intensity in the ex vivo MRI of ferumoxytol-heparin-PEGylated islets was stronger than islets labeled with ferumoxytol alone. In syngeneic renal subcapsular islet transplantation, labeling with ferumoxytol-heparin-PEGylation showed better in vivo labeling efficacy than that of islets labeled with ferumoxytol alone. After labeling with ferumoxytol-heparin-PEGylation, there was a correlation between the total area of visualized islets and the transplanted islet mass in syngeneic mouse intraportal islet transplantation, and the visibility was also confirmed in the preliminary analysis of non-human primate intraportal islet transplantation model.

Conclusion: Direct linking of ferumoxytol to islet surface through PEGylation improved the labeling efficacy and it could be used for the islet MRI in clinical islet transplantation.


H. Lee: None. Y. Kwon: None. H. Kim: None. M.R. Haque: None. G. Kim: None. S. Jin: None. M. Lee: None. Y. Byun: None. J. Kim: None.

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