BackgroundAt present, renal grafts are the most common solid organ transplants world-wide. Given the importance of renal transplantation and the limitation of available donor kidneys, detailed analysis of factors that affect transplant survival are important. Despite the introduction of new and effective immunosuppressive drugs, acute cellular graft rejection (AR) is still a major risk for graft survival. Nowadays, AR can only be definitively by renal biopsy. However, biopsies carry a risk of renal transplant injury and loss. Most important, they can not be performed in patients taking anticoagulant drugs.Methodology/Principal FindingsWe present a non-invasive, entirely image-based method to assess AR in an allogeneic rat renal transplantation model using small animal positron emission tomography (PET) and 18F-fluorodeoxyglucose (FDG). 3 h after i.v. injection of 30 MBq FDG into adult uni-nephrectomized, allogeneically transplanted rats, tissue radioactivity of renal parenchyma was assessed in vivo by a small animal PET-scanner (post operative day (POD) 1,2,4, and 7) and post mortem dissection. The mean radioactivity (cps/mm3 tissue) as well as the percent injected dose (%ID) was compared between graft and native reference kidney. Results were confirmed by histological and autoradiographic analysis. Healthy rats, rats with acute CSA nephrotoxicity, with acute tubular necrosis, and syngeneically transplanted rats served as controls. FDG-uptake was significantly elevated only in allogeneic grafts from POD 1 on when compared to the native kidney (%ID graft POD 1: 0.54±0.06; POD 2: 0.58±0.12; POD 4: 0.81±0.06; POD 7: 0.77±0.1; CTR: 0.22±0.01, n = 3–28). Renal FDG-uptake in vivo correlated with the results obtained by micro-autoradiography and the degree of inflammatory infiltrates observed in histology.Conclusions/SignificanceWe propose that graft FDG-PET imaging is a new option to non-invasively, specifically, early detect, and follow-up acute renal rejection. This method is potentially useful to improve post-transplant rejection monitoring.

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 Lewisbrown 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. Conclusion: 18 F-FDG PET is an option to noninvasively assess early response to therapy in rat renal allograft rejection.

BACKGROUND The American Joint Committee on Cancer and the Union Internationale Contre le Cancer have acknowledged routine laboratory parameters, such as serum calcium, alkaline phosphatase, hemoglobin, and the erythrocyte sedimentation rate (ESR), as predictors of survival in patients with renal cell carcinoma. The predictive value of these parameters compared with proliferation markers, such as Ki‐67, proliferating cell nuclear antigen (PCNA), topoisomerase II‐α, and p100, has not been determined. METHODS Forty‐eight consecutive patients who underwent nephrectomy for nonmetastatic renal cell carcinoma between 1990 and 1994 were observed up to 120 months postoperatively. Ten of 48 patients developed tumor progression 6–69 months after surgery. Routine preoperative laboratory parameters as well as tumor‐specific data were assessed. Findings were compared with tumor proliferation indices, which were obtained by immunohistochemical staining for nuclear antigens Ki‐67, PCNA, topoisomerase II‐α, and p100 in paraffin embedded tumor tissue. RESULTS Univariate and multivariate statistical analyses demonstrated superiority of routine laboratory values compared with tumor proliferation indices in predicting progression‐free survival and disease‐specific death. The best predictor after tumor size and symptomatic presentation was ESR (P < 0.0001), with ESR values > 70 mm at 2 hours indicating a significantly poorer prognosis. Only the proliferation marker Ki‐67 reached univariate significance at a threshold of 7%. CONCLUSIONS Routine laboratory parameters, such as alkaline phosphatase, lactate dehydrogenase, thrombocyte count, and especially ESR, provided superior long‐term prognostic information for patients with nonmetastatic renal cell carcinoma compared with the molecular tumor proliferation markers Ki‐67, PCNA, topoisomerase II‐α, and p100. Cancer 2004. © 2004 American Cancer Society.

(18)F-PET is able to noninvasively assess renal function in rats and provides a significant potential for serial studies in different experimental scenarios.