Purpose: During acute rejection episodes large amounts of immune cells infiltrate renal grafts, leading to inflammation accompanied by an increased glucose metabolism.

Given these circumstances we could already show that the uptake of radioactive labeled glucose can be used to non-invasively assess renal allograft rejection in vivo using positron emission tomography (PET).

In late 2013 it was shown that local alterations in tissue glucose uptake can be assessed by magnetic resonance imaging (MRI) using glucose chemical exchange saturation transfer (glucoCEST). We herein propose glucoCEST-MRI as a method for early detection of renal allograft rejection.

Methods: Adult, uni-nephrectomized, allogeneically kidney transplanted rats (Brown Norway to Lewis) without immunosuppression after surgery served as the renal transplant model. glucoCEST MRI was performed four days after transplantation, a time point at which the renal graft usually shows marked signs of acute cellular rejection. MRI images were acquired at 9.4 T on a Bruker BioSpec94/20 using a 72 mm volume coil and a RARE sequence. To guarantee constant blood glucose levels during MRI measurements, the animals received two time-displaced glucose boluses i.p..

Results: To assess kidney rejection by glucoCEST MRI, a glucose infusion protocol was successfully developed and validated. Blood glucose level was kept constantly above 120 mg/dL duringMRI measurements. In vivo glucoCEST contrast was calculated and compared to the native kidney. The renal allograft undergoing rejection showed increased CEST-contrast in the pelvis (native: 0.077 ± 0.039, transplanted: 0.149 ± 0.054, p: 0.043) and the cortex (native: 0.026 ± 0.011, transplanted: 0.060 ± 0.027, p: 0.033, n=6).

Conclusion: We propose glucoCEST MRI as a new option for noninvasive diagnosis of acute renal rejection. Moreover, glucoCEST MRI is able to identify and differentiate zones of renal inflammation in vivo.

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