Potential of Noninvasive Serial Assessment of Acute Renal Allograft Rejection by ¹⁸F-FDG PET to Monitor Treatment Efficiency

Abstract

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.

Cancer cells metabolically "fertilize" the tumor microenvironment with hydrogen peroxide, driving the Warburg effect

“…[14][15][16][17][18][19][20][21] Similarly, PET is also now used to detect inflammation 78 that is due to both infectious diseases, such as fever of unknown origin (FUO) and bacteremic foci, [79][80][81] and non-infectious diseases, such as graft rejection in liver and renal transplants. [82][83][84][85] We have recently shown that inflammatory cytokines induce autophagy in cancer-associated fibroblasts, consistent with a shift toward aerobic glycolysis under inflammatory conditions. 7 Interestingly, PET glucose avidity and elevated serum inflammatory markers both correlate with poor prognosis in breast cancers.…”

PET with 18F-FDG–Labeled T Lymphocytes for Diagnosis of Acute Rat Renal Allograft Rejection

“…Moreover, 18 F-FDG PET can be applied for the early evaluation of immunosuppressive treatment response and might assist in the differential diagnosis of AR, ATN, and acute CSA toxicity (8).…”

“…Image Acquisition: PET Image acquisition of nonfasting subjects was performed as described before (8,9). In short, T-cell infiltration was calculated from a whole-body acquisition of 20 min at 1 and 2 h after injection of 30 · 10 6 ex vivo 18 F-FDG-labeled human T cells (1-2 MBq of 18 F-FDG) in 300 mL of 0.9% NaCl solution into a tail vein.…”

“…Nuclear imaging approaches including SPECT and PET have the advantages of high intrinsic sensitivity, excellent tissue penetration, and a wide range of clinically available molecular imaging probes (7). Recently, we have established 18 F-FDG PET as an entirely image-based method to assess and to monitor acute renal rejection (8,9). However, potential drawbacks in applying 18 F-FDG PET to the clinical setting should be noted.…”

Have we forgotten imaging prior to and after kidney transplantation?

“…Citation rates show a similar trend, with a surge for all included publications, but a lower rate for publications combining imaging and KTX. Studies focusing on PET/CT for the diagnosis of acute allograft rejection showed significant associations in both acute rat renal allograft models and a clinical study, while the sensitivity remained too low for clinical applications [11][12][13][14].…”