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Imaging Islets Labeled With Magnetic Nanoparticles at 1.5 Tesla

¹ Department of Transplantation, Robarts Research Institute, London, Ontario, Canada
² Imaging Research Laboratories, Robarts Research Institute, London, Ontario, Canada
³ Human Islet Transplantation Program, London Health Sciences Centre, London, Ontario, Canada
⁴ Department of Pathology, London Health Sciences Centre, London, Ontario, Canada
⁵ Department of Medical Biophysics and Medicine, University of Western Ontario, Lawson Health Research Institute, London, Ontario, Canada

Address correspondence and reprint requests to Dr. David J.G. White, FRCPath, PhD, Novartis/Stiller Professor of Xenotransplantation, Robarts Research Institute, Room 200, SDRI Building, University of Western Ontario, 1400 Western Rd., London, Ontario, Canada N6G 2V4. E-mail: david.white{at}robarts.ca

Abbreviations: HBSS, Hanks’ balanced salt solution; ICP-MS, inductively coupled plasma mass spectrometry; ISG, insulin secretory granule; MRI, magnetic resonance imaging; PGFL, Phen Green FL; PLL, poly-L-lysine; SPIO, superparamagnetic iron oxide

We have developed a magnetic resonance imaging (MRI) technique for imaging Feridex (superparamagnetic iron oxide [SPIO])-labeled islets of Langerhans using a standard clinical 1.5-Tesla (T) scanner and employing steady-state acquisition imaging sequence (3DFIESTA). Both porcine and rat islets were labeled with SPIO by a transfection technique using a combination of poly-L-lysine and electroporation. Electron microscopy demonstrated presence of SPIO particles within the individual islet cells, including ß-cells and particles trapped between cell membranes. Our labeling method produced a transfection rate of 860 pg to 3.4 ng iron per islet, dependent on the size of the islet. The labeling procedure did not disrupt either the function or viability of the islets. In vitro 3DFIESTA magnetic resonance images of single-labeled islets corresponded with their optical images. In vivo T2*-weighted scan using 1.5 T detected as few as 200 SPIO-labeled islets transplanted under rat kidney capsule, which correlated with immunohistochemistry of the transplant for insulin and iron. Ex vivo 3DFIESTA images of kidneys containing 200, 800 or 2,000 SPIO-labeled islet isografts showed good correlation between signal loss and increasing numbers of islets. These data provide evidence that islets can be labeled with SPIO and imaged using clinically available 1.5- T MRI.

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