title: Non-invasive imaging of allogeneic transplanted skin graft by 131I-anti-TLR5 mAb.
abstract: 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 (TLR5) 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 C57BL/6 skin grafts, with or without rapamycin treatment (named as allo-treated group or allo-rejection group), were injected with (131)I-anti-TLR5 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-TLR5 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-TLR5 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-TLR5 mAb uptake was significantly higher than the ratio for (18)F-FDG (7.68 versus 1.16, respectively). (131)I-anti-TLR5 mAb uptake in the grafts significantly correlated with TLR5 expression in the allograft area. The accumulation of (131)I-IgG was comparable in both groups. We conclude that radiolabelled anti-TLR5 mAb is capable of detecting allograft with high target specificity after treatment with the immunosuppressive drug rapamycin.
authors.affiliation: Key Laboratory for Experimental Teratology of the Ministry of Education and Institute of Experimental Nuclear Medicine, School of Medicine, Shandong University, Ji'nan, Shandong, China.
authors.forename: Hukui
authors.initials: H
authors.lastname: Sun
authors.forename: Guangjie
authors.initials: G
authors.lastname: Yang
authors.forename: Ting
authors.initials: T
authors.lastname: Liang
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Song
authors.forename: Jiankui
authors.initials: J
authors.lastname: Han
authors.forename: Guihua
authors.initials: G
authors.lastname: Hou
mesh_terms: D064591:Allografts / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics; D001345:Autoradiography; D003952:Diagnostic Imaging / Q000379:methods; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D015203:Reproducibility of Results; D020123:Sirolimus / Q000494:pharmacology; D016038:Skin Transplantation / Q000379:methods*; D014018:Tissue Distribution / Q000187:drug effects; D051198:Toll-Like Receptor 5 / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D007457:Iodine Radioisotopes; D051198:Toll-Like Receptor 5; D019788:Fluorodeoxyglucose F18; D020123:Sirolimus
keywords: 131I-anti-TLR5 mAb; 18F-FDG; allo-treated; phosphor-autoradiography; rapamycin