Noninvasive Imaging of Activated Complement in Ischemia-Reperfusion Injury Post-Cardiac Transplant Publisher Pubmed



Sharifpaghaleh E^{1, 2, 3} ; Yap ML¹ ; Meader LL² ; Chuamsaamarkkee K¹ ; Kampmeier F¹ ; Badar A¹ ; Smith RA² ; Sacks S² ; Mullen GE^{1, 2} Show Affiliations
Source: American Journal of Transplantation Published:2015

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 99mTc-recombinant complement receptor 2 (99mTc-rCR2) in murine models of cardiac transplantation following the induction of IRI and compared to 99mTc-rCR2 in C3-/- mice or with the irrelevant protein 99mTc-prostate-specific membrane antigen antibody fragment (PSMA). Significant uptake with 99mTc-rCR2 was observed as compared to C3-/- or 99mTc-PSMA. In addition, the transplanted heart to muscle ratio of 99mTc-rCR2 was significantly higher than 99mTc-PSMA or C3-/-. The results were confirmed by histology and autoradiography. 99mTc-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. The authors describe SPECT/CT imaging of activated complement post-ischemia reperfusion injury in mouse cardiac transplant grafts. See the supporting video at amjtransplant.com/videos. © 2015 The Authors. American Journal of Transplantation Published by Wiley Periodicals Inc. on behalf of American Society of Transplant Surgeons.