Allogeneic renal graft rejection in a rat model: in vivo MR imaging of the homing trait of macrophages.
OBJECTIVE
To evaluate the feasibility of MR imaging to depict the in vivo recruitment of superparamagnetic iron oxide (SPIO)-labeled macrophages and to aid diagnosis of graft rejection in kidney transplantation.


METHODS
This study was approved by the institution's committee on animal research. Eighteen male Lewis rats received a kidney transplant; 12 had an F344 rat donor and six had a Lewis rat donor. Peritoneal macrophages were harvested from thioglycollate-treated Lewis rats, cultured, and labeled with SPIO. After resuspension of macrophages in a concentration of 1 x 10(7) cells per milliliter of Hanks balanced salt solution, 5 x 10(6) of SPIO-labeled macrophages was administered through the tail vein 2 or 5 days after transplantation in each group. The transplanted kidneys were imaged on a 4.7-T MR imager 24 hours after macrophage administration. The Wilcoxon signed rank test was performed for evaluating the differences between the relative signal intensity (SI) before and after SPIO-labeled macrophage administration.


RESULTS
A low-SI zone was predominantly noted in the medulla of the transplanted kidneys, and the relative SI decreased significantly from 1.40 to 0.53 (P < .001) in the allogeneic transplants following SPIO-labeled macrophage administration 5 days after the allogeneic transplantation. In the syngeneic group, the lower-SI zone was not noted in the grafts. At histopathologic examination, the lower-SI zone corresponded to the distribution of the SPIO-labeled macrophages.


CONCLUSIONS
This study demonstrates that the homing of intravenously administered SPIO-labeled macrophages can be monitored in the allograft rejection model on in vivo MR images.
Chae
Eun Young
EY
Department of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Songpagu, Seoul, South Korea.
Song
Eun Ju
EJ
Sohn
Jin Young
JY
Kim
Sang-Tae
ST
Woo
Chul Woong
CW
Gong
Gyungyub
G
Kang
Hee Jung
HJ
Lee
Jin Seong
JS
D000818:Animals; D003287:Contrast Media / Q000493:pharmacokinetics*; D003911:Dextrans; D005240:Feasibility Studies; D052203:Ferrosoferric Oxide / Q000493:pharmacokinetics*; D006084:Graft Rejection / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D016030:Kidney Transplantation; D008264:Macrophages; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D008297:Male; D023421:Models, Animal; D051381:Rats; D011917:Rats, Inbred Lew; D018709:Statistics, Nonparametric; D014184:Transplantation, Homologous
D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; C065507:ferumoxides; D052203:Ferrosoferric Oxide