title: In vivo Toll-like receptor 5 (TLR5) imaging with radiolabeled anti-TLR5 monoclonal antibody in rapamycin-treated mouse allogeneic skin transplantation model.
abstract: BACKGROUND
  In organ transplantation, increasing evidence, both in experimental and human studies, indicates that Toll-like receptor (TLR) activation is involved in the innate immune recognition of allograft. TLR5, the only protein recognition receptor of TLRs, is indicated potentially to be the immune regulation target. This study was designed to determine whether TLR5 could be a biomarker for in vivo allograft visualization, after immunosuppressant rapamycin treatment, using radiolabeled sodium iodide ((131) I)-anti-TLR5 monoclonal antibody (mAb).
  
  
  METHODS
  BALB/c mice were transplanted with C57BL/6 skin, with/without rapamycin treatment (the rapamycin-treated group and the phosphate buffered saline [PBS]-rejection group, respectively). In vivo dynamic whole-body phosphor-autoradiography and ex vivo biodistribution studies were conducted after (131) I-anti-TLR5 mAb injection.
  
  
  RESULTS
  Dynamic phosphor-autoradiography imaging showed clear graft localization from 12 h onward. At 72 h after injection, graft uptake quantified from images was higher for the rapamycin-treated group (26,448 ± 904 digital light units [DLU]/mm(2) ), compared with the PBS-treated allo-rejection group (9176 ± 576 DLU/mm(2) ). Treatment with anti-TLR5 mAb inhibited graft uptake. Organ biodistribution study reflected the same tendency, and (131) I-anti-TLR5 mAb uptake reached a maximum of 12.05 ± 1.86 %ID/g (percent injected dose per gram) at 1 h, and graft-to-native skin ratio reached 8.10 ± 0.10 %ID/g at 72 h after injection in rapamycin-treated grafts.
  
  
  CONCLUSIONS
  Radiolabeled anti-TLR5 mAb showed higher uptake in allo-treated grafts compared with allo-rejection grafts, which was proved by non-invasive dynamic phosphor-autoradiography imaging, and invasive ex vivo biodistribution. Radiolabeled anti-TLR5 mAb is a new tracer for non-invasive in vivo imaging of TLR5 in rapamycin-treated allograft.
authors.affiliation: Key Laboratory for Experimental Teratology of the Ministry of Education and Institute of Experimental Nuclear Medicine, School of Medicine, Shandong University, Jinan, Shandong, China.
authors.forename: H
authors.initials: H
authors.lastname: Sun
authors.forename: Y
authors.initials: Y
authors.lastname: Zhan
authors.forename: T
authors.initials: T
authors.lastname: Liang
authors.forename: C
authors.initials: C
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Song
authors.forename: J
authors.initials: J
authors.lastname: Han
authors.forename: G
authors.initials: G
authors.lastname: Hou
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D001345:Autoradiography / Q000379:methods; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D020123:Sirolimus / Q000494:pharmacology*; D016038:Skin Transplantation; D014018:Tissue Distribution; D051198:Toll-Like Receptor 5 / Q000276:immunology* / Q000378:metabolism; D014184:Transplantation, Homologous
chemical_list: D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D051198:Toll-Like Receptor 5; D020123:Sirolimus
keywords: TLR5; Toll-like receptor; allogeneic transplantation; phosphor-autoradiography; rapamycin