title: Noninvasive Imaging of Activated Complement in Ischemia-Reperfusion Injury Post-Cardiac Transplant.
abstract: Ischemia-reperfusion injury (IRI) is inevitable in solid organ transplantation, due to the transplanted organ being ischemic for prolonged periods prior to transplantation followed by reperfusion. The complement molecule C3 is present in the circulation and is also synthesized by tissue parenchyma in early response to IRI and the final stable fragment of activated C3, C3d, can be detected on injured tissue for several days post-IRI. Complement activation post-IRI was monitored noninvasively by single photon emission computed tomography (SPECT) and CT using (99m) Tc-recombinant complement receptor 2 ((99m) Tc-rCR2) in murine models of cardiac transplantation following the induction of IRI and compared to (99m) Tc-rCR2 in C3(-/-) mice or with the irrelevant protein (99m) Tc-prostate-specific membrane antigen antibody fragment (PSMA). Significant uptake with (99m) Tc-rCR2 was observed as compared to C3(-/-) or (99m) Tc-PSMA. In addition, the transplanted heart to muscle ratio of (99m) Tc-rCR2 was significantly higher than (99m) Tc-PSMA or C3(-/-) . The results were confirmed by histology and autoradiography. (99m) Tc-rCR2 can be used for noninvasive detection of activated complement and in future may be used to quantify the severity of transplant damage due to complement activation postreperfusion.
authors.affiliation: Division of Imaging and Biomedical Engineering, School of Medicine, King's College London, London, England.|MRC Centre for Transplantation, King's College London, London, England.|Department of Immunology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: E
authors.initials: E
authors.lastname: Sharif-Paghaleh
authors.affiliation: Division of Imaging and Biomedical Engineering, School of Medicine, King's College London, London, England.
authors.forename: M L
authors.initials: ML
authors.lastname: Yap
authors.affiliation: MRC Centre for Transplantation, King's College London, London, England.
authors.forename: L L
authors.initials: LL
authors.lastname: Meader
authors.affiliation: Division of Imaging and Biomedical Engineering, School of Medicine, King's College London, London, England.
authors.forename: K
authors.initials: K
authors.lastname: Chuamsaamarkkee
authors.affiliation: Division of Imaging and Biomedical Engineering, School of Medicine, King's College London, London, England.
authors.forename: F
authors.initials: F
authors.lastname: Kampmeier
authors.affiliation: Division of Imaging and Biomedical Engineering, School of Medicine, King's College London, London, England.
authors.forename: A
authors.initials: A
authors.lastname: Badar
authors.affiliation: MRC Centre for Transplantation, King's College London, London, England.
authors.forename: R A
authors.initials: RA
authors.lastname: Smith
authors.affiliation: MRC Centre for Transplantation, King's College London, London, England.
authors.forename: S
authors.initials: S
authors.lastname: Sacks
authors.affiliation: Division of Imaging and Biomedical Engineering, School of Medicine, King's College London, London, England.|MRC Centre for Transplantation, King's College London, London, England.
authors.forename: G E
authors.initials: GE
authors.lastname: Mullen
mesh_terms: D000818:Animals; D003167:Complement Activation / Q000276:immunology*; D015933:Complement C3d / Q000276:immunology; D005260:Female; D016027:Heart Transplantation; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015428:Myocardial Reperfusion Injury / Q000000981:diagnostic imaging* / Q000276:immunology*; D017464:Receptors, Complement 3d / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D013667:Technetium / Q000008:administration & dosage; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D014057:Tomography, X-Ray Computed / Q000379:methods*
chemical_list: D017464:Receptors, Complement 3d; D011994:Recombinant Proteins; D013667:Technetium; D015933:Complement C3d
keywords: animal models: murine; complement biology; diagnostic techniques and imaging; heart (allograft) function/dysfunction; ischemia reperfusion injury (IRI)