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EJNMMI Research

, 5:69

First Online: 26 November 2015Received: 10 July 2015Accepted: 16 November 2015DOI: 10.1186-s13550-015-0146-7

Cite this article as: O’Neill, A.S.G., Terry, S.Y.A., Brown, K. et al. EJNMMI Res 2015 5: 69. doi:10.1186-s13550-015-0146-7

Abstract

BackgroundMacrophages represent a critical cell type in host defense, development and homeostasis. The ability to image non-invasively pro-inflammatory macrophage infiltrate into a transplanted organ may provide an additional tool for the monitoring of the immune response of the recipient against the donor graft. We therefore decided to image in vivo sialoadhesin Sn, Siglec 1 or CD169 using anti-Sn mAb SER-4 directly radiolabelled with Tc pertechnetate.

MethodsWe used a heterotopic heart transplantation model where allogeneic or syngeneic heart grafts were transplanted into the abdomen of recipients. In vivo nanosingle-photon emission computed tomography SPECT-CT imaging was performed 7 days post transplantation followed by biodistribution and histology.

ResultsIn wild-type mice, the majority of Tc-SER-4 monoclonal antibody cleared from the blood with a half-life of 167 min and was located predominantly on Sn tissues in the spleen, liver and bone marrow. The biodistribution in the transplantation experiments confirmed data derived from the non-invasive SPECT-CT images, with significantly higher levels of Tc-SER-4 observed in allogeneic grafts 9.4 ±2.7 %ID-g compared to syngeneic grafts 4.3 ±10.3 %ID-g p = 0.0022 or in mice which received allogeneic grafts injected with Tc-IgG isotype control 5.9 ±0.6 %ID-g p = 0.0185. The transplanted heart to blood ratio was also significantly higher in recipients with allogeneic grafts receiving Tc-SER-4 as compared to recipients with syngeneic grafts p = 0.000004 or recipients with allogeneic grafts receiving Tc-IgG isotype p = 0.000002.

ConclusionsHere, we demonstrate that imaging of Sn macrophages in inflammation may provide an important additional and non-invasive tool for the monitoring of the pathophysiology of cellular immunity in a transplant model.

KeywordsMacrophages Cardiac transplantation Preclinical imaging Sialoadhesin SER-4 AbbreviationsmAbmonoclonal antibody

MRImagnetic resonance imaging

Snsialoadhesin

SPECTsingle-photon emission computed tomography

SPIOsuperparamagnetic iron oxide

Electronic supplementary materialThe online version of this article doi:10.1186-s13550-015-0146-7 contains supplementary material, which is available to authorized users.

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Autor: Alexander S. G. O’Neill - Samantha Y. A. Terry - Kathryn Brown - Lucy Meader - Andrew M. S. Wong - Jonathan D. Coop

Fuente: https://link.springer.com/







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