Potential of noninvasive serial assessment of acute renal allograft rejection by 18F-FDG PET to monitor treatment efficiency.
We propose (18)F-FDG PET as a method to monitor acute rejection of allogeneic renal transplants in a rat model.


METHODS
Allogeneically transplanted (aTX) rats (binephrectomized Lewis-brown Norway to Lewis) served as the renal transplant model. aTX rats treated with cyclosporine A (CSA) served as a therapy monitoring group. Healthy control rats, rats with acute CSA nephrotoxicity, rats with acute tubular necrosis, syngeneically transplanted (sTX) rats, and aTX rats treated with CSA since postoperative day 0 served as controls. After surgery, renal glucose metabolism was assessed in vivo serially up to postoperative day 7 by performing small-animal PET 3 h after intravenous injection of 30 MBq of (18)F-FDG. Mean radioactivity (cps/mm(3) of tissue) was measured and the percentage injected dose calculated. Results were confirmed by histologic, functional, and autoradiographic analysis.


RESULTS
Renal (18)F-FDG uptake was significantly elevated at postoperative day 4 in aTX rats, when compared with control, sTX, acute tubular necrosis, or CSA-treated rats (P < 0.05). In vivo (18)F-FDG uptake correlated with the results of autoradiography and with inflammatory infiltrates observed on histologic examination. Notably, (18)F-FDG PET assessed the response to therapy 48 h earlier than the time at which serum creatinine decreased and when histologic examination still showed signs of allograft rejection. In aTX rats, the CSA-susceptible graft infiltrate was dominated by activated cytotoxic T cells and monocytes/macrophages.


CONCLUSIONS
(18)F-FDG PET is an option to noninvasively assess early response to therapy in rat renal allograft rejection.
Reuter
Stefan
S
Department of Medicine D, Experimental Nephrology, University of Münster, Münster, Germany. sreuter@uni-muenster.de
Schnöckel
Uta
U
Edemir
Bayram
B
Schröter
Rita
R
Kentrup
Dominik
D
Pavenstädt
Hermann
H
Schober
Otmar
O
Schlatter
Eberhard
E
Gabriëls
Gert
G
Schäfers
Michael
M
D000208:Acute Disease; D000818:Animals; D005240:Feasibility Studies; D019788:Fluorodeoxyglucose F18; D006084:Graft Rejection / Q000000981:diagnostic imaging* / Q000209:etiology*; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000000981:diagnostic imaging*; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D011379:Prognosis; D019275:Radiopharmaceuticals; D051381:Rats; D011917:Rats, Inbred Lew; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18