Non‐invasive imaging of allogeneic transplanted skin graft by 131 I‐anti‐TLR5 mAb

Although 18 F‐fluorodeoxyglucose ( 18 F‐ FDG ) uptake can be used for the non‐invasive detection and monitoring of allograft rejection by activated leucocytes, this non‐specific accumulation is easily impaired by immunosuppressants. Our aim was to evaluate a 131 I‐radiolabelled anti‐Toll‐like receptor 5 ( TLR 5) mAb for non‐invasive in vivo graft visualization and quantification in allogeneic transplantation mice model, compared with the non‐specific radiotracer 18 F‐ FDG under using of immunosuppressant. Labelling, binding, and stability studies were performed. BALB /c mice transplanted with C57 BL /6 skin grafts, with or without rapamycin treatment (named as allo‐treated group or allo‐rejection group), were injected with 131 I‐anti‐ TLR 5 mAb, 18 F‐ FDG , or mouse isotype 131 I‐IgG, respectively. Whole‐body phosphor‐autoradiography and ex vivo biodistribution studies were obtained. Whole‐body phosphor‐autoradiography showed 131 I‐anti‐ TLR 5 mAb uptake into organs that were well perfused with blood at 1 hr and showed clear graft images from 12 hrs onwards. The 131 I‐anti‐ TLR 5 mAb had significantly higher graft uptake and target‐to‐non‐target ratio in the allo‐treated group, as determined by semi‐quantification of phosphor‐autoradiography images; these results were consistent with ex vivo biodistribution studies. However, high 18 F‐ FDG uptake was not observed in the allo‐treated group. The highest allograft‐skin‐to‐native‐skin ratio (A:N) of 131 I‐anti‐ TLR 5 mAb uptake was significantly higher than the ratio for 18 F‐ FDG (7.68 versus 1.16, respectively). 131 I‐anti‐ TLR 5 mAb uptake in the grafts significantly correlated with TLR 5 expression in the allograft area. The accumulation of 131 I‐IgG was comparable in both groups. We conclude that radiolabelled anti‐ TLR 5 mAb is capable of detecting allograft with high target specificity after treatment with the immunosuppressive drug rapamycin.