Journal
AMERICAN JOURNAL OF TRANSPLANTATION
Volume 15, Issue 9, Pages 2483-2490Publisher
WILEY-BLACKWELL
DOI: 10.1111/ajt.13299
Keywords
animal models: murine; complement biology; diagnostic techniques and imaging; heart (allograft) function; dysfunction; ischemia reperfusion injury (IRI)
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Funding
- King's College London, Medical Research Council Centre of Transplantation, Division of Imaging Sciences
- Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre (BRC) award
- St. Thomas' National Health Service (NHS) Foundation Trust
- King's College London and King's College Hospital NHS Foundation Trust
- British Heart Foundation
- British Heart Foundation [PG/11/111/29270] Funding Source: researchfish
- Medical Research Council [MR/J006742/1, G0600892] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0510-10142] Funding Source: researchfish
- MRC [G0600892] Funding Source: UKRI
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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 Tc-99m-recombinant complement receptor 2 (Tc-99m-rCR2) in murine models of cardiac transplantation following the induction of IRI and compared to Tc-99m-rCR2 in C3(-/-) mice or with the irrelevant protein Tc-99m-prostate-specific membrane antigen antibody fragment (PSMA). Significant uptake with Tc-99m-rCR2 was observed as compared to C3(-/-) or Tc-99m-PSMA. In addition, the transplanted heart to muscle ratio of Tc-99m-rCR2 was significantly higher than Tc-99m-PSMA or C3(-/-). The results were confirmed by histology and autoradiography. Tc-99m-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.
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