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Macrophage labeling by SPIO as an early marker of allograft chronic rejection in a rat model of kidney transplantation
Author(s) -
Beckmann N.,
Cannet C.,
FringeliTanner M.,
Baumann D.,
Pally C.,
Bruns C.,
Zerwes H.G.,
Andriambeloson E.,
Bigaud M.
Publication year - 2003
Publication title -
magnetic resonance in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.696
H-Index - 225
eISSN - 1522-2594
pISSN - 0740-3194
DOI - 10.1002/mrm.10387
Subject(s) - transplantation , medicine , perfusion , urology , cortex (anatomy) , kidney , renal cortex , kidney transplantation , magnetic resonance imaging , ciclosporin , pathology , nuclear medicine , radiology , biology , neuroscience
Anatomical and functional information (renography, perfusion) was obtained by MRI in a life‐supporting transplantation model, in which Lewis rats received kidneys from Fisher 344 donors. Renography and perfusion analyses were carried out with Gd‐DOTA and small particles of iron oxide (SPIO), respectively. Starting 12 weeks posttransplantation, images from grafts of untreated recipients exhibited distinctive signal attenuation in the cortex. Animals treated with cyclosporin (Sandimmune Neoral; Novartis Pharma, Basel, Switzerland) to prevent acute rejection showed a signal attenuation in the cortex at 33 weeks posttransplantation, while kidneys from rats treated additionally with everolimus (Certican; Novartis), a rapamycin derivative, had no changes in anatomical appearance. A significant negative correlation was found between the MRI cortical signal intensity and the histologically determined iron content in macrophages located in the cortex. Renography revealed a significantly reduced functionality of the kidneys of untreated controls 33 weeks after transplantation, while no significant changes in perfusion were observed in any group of rats. These results suggest the feasibility, by labeling macrophages with SPIO, of detecting signs of graft rejection significantly earlier than when changes in function occur. Monitoring early changes associated with chronic rejection can have an impact in preclinical studies by shortening the duration of the experimental period and by facilitating the investigation of novel immunomodulatory therapies for transplantation. Magn Reson Med 49:459–467, 2003. © 2003 Wiley‐Liss, Inc.