Development and Evaluation of a Novel Radiotracer I-125-rIL-27 to Monitor Allotransplant Rejection by Specifically Targeting IL-27R alpha

Noninvasive monitoring of allograft rejection is beneficial for the prognosis of patients with organ transplantation. Recently, IL-27/IL-27R alpha was proved in close relation with inflammatory diseases, and I-125-anti-IL-27R alpha mAb our group developed demonstrated high accumulation in the rejection of the allograft. However, antibody imaging has limitations in the imaging background due to its large molecular weight. Therefore, we developed a novel radiotracer (iodine-125-labeled recombinant IL-27) to evaluate the advantage in the targeting and imaging of allograft rejection. In vitro specific binding of I-125-rIL-27 was determined by saturation and competitive assay. Blood clearance, biodistribution, phosphor autoradioimaging, and IL-27R alpha expression were studied on day 10 after transplantation (top period of allorejection). Our results indicated that I-125-rIL-27 could bind with IL-27R alpha specifically and selectively in vitro. The blood clearance assay demonstrated fast blood clearance with 13.20 mu l/h of I-125-rIL-27 staying in the blood after 24 h. The whole-body phosphor autoradiography and biodistribution assay indicated a higher specific uptake of I-125-rIL-27 and a clear radioimage in allograft than in syngraft at 24 h, while a similar result was obtained at 48 h in the group of I-125-anti-IL-27R alpha mAb injection. Meanwhile, a higher expression of IL-27R alpha was found in the allograft by Western blot. The accumulation of radioactivity of I-125-rIL-27 was highly correlated with the expression of IL-27R alpha in the allograft. In conclusion, I-125-rIL-27 could be a promising probe for acutely monitoring allograft rejection with high specific binding towards IL-27R alpha on allograft and low imaging background.