Can different intestinal transplantation scenarios alter radioactive tracer uptake in a rodent experimental model? a preliminary study

Graft rejection is one of the most common complications associated with intestinal transplantation (ITx). The current diagnosis of acute graft rejection (ACR) is made by clinical symptoms, surveillance or indicated endoscopic and confirmed by pathological findings in the intestinal mucosa. This methodology is unable to determine what occurs in all layers and along the whole length of the graft. The search for a non-invasive method for graft monitoring continues to be of much interest. Positron emission tomography (PET) is a non-invasive nuclear medicine imaging approach that allows early detection of oncological 1or infectious processes, due to an increased glycolytic metabolism. During rejection, cell populations may increase its metabolism, and therefore their capacity to uptake the radioactive tracer F-18 fluorodeoxyglucose (FDG). The aim of this preliminary study is to correlate the differences in tracer uptake in different ITx scenarios comparing to the histopathological diagnosis of ACR, to evaluate the potential utility as a noninvasive method for graft monitoring after ITx. Allogeneic heterotopic ITxs were performed in rats (Sprague Dawley as donor, Wistar as recipient); tacrolimus 0.6 mg/kg/day was administrated subcutaneously for 7 days as immunosuppressive therapy (TAC group, N=3). Controls without interventions (control, n=4) and without immunosuppressant (w/o IS, N=1) were used. Native intestines from each tacrolimus-treated animal were analyzed. The Wu’ score was used for histopathological diagnosis of ACR. The PET-scan study was performed in recipients and controls, and FDG uptake was assessed as standardized uptake value (SUV). Histopathological analysis of the graft w/o IS group showed findings compatible with moderate-severe rejection at 7 post-operation days (POD), with epithelial damage and increased mucosal infiltrate, while these same features were observed between 21 and 28 POD in the TAC group. No histological changes compatible with ACR were observed in the control samples and native intestine. The mean ± SEM SUV values were 1.9 ± 0.6, 1.8 ± 0.24, 3.97 ± 0.38 and 12.4 (in control, native, TAC 21 POD and w/o IS 7 POD groups, respectively). Conclusions: Despite exhibiting similar histopathological features of rejection, the FDG uptake in grafts from animals treated for one week with tacrolimus 0.6 mg/kg/day was reduced three-fold compared to the allogeneic group w/o IS (p<0.001), which could indicate that different underlying mechanisms are involved in the rejection process in each case. When the graft presents histological characteristics without appreciable alterations, as in the case of a control and a native intestine, FDG uptake was significantly reduced (p<0.0001). Accordingly, this preliminary study suggests that PET-scan might be a good complement when a clinical suspicious is present in order to further prescribe the endoscopy and histopathological analysis for early diagnosis of intestinal graft rejection.