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

Sharif‐Paghaleh, Ehsan; Yap, May Lin; Meader, Lucy; Chuamsaamarkkee, Krisanat; Kampmeier, Florian; Badar, Adam; Smith, Richard A.; Sacks, Steven H.; Mullen, Gregory

doi:10.1111/ajt.13299

Cited by 11 publications

(11 citation statements)

References 30 publications

(50 reference statements)

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“…Generation of the cleavage product C3d following C3 activation has been associated with N1 neutrophil recruitment to damaged or stressed cells following radiotherapy, as well as in other forms of tissue injury and infection [85,86]. A radiolabeled peptide based on the natural ligand of C3d, complement receptor-2 [ 99m Tc]Tc-rCR2, has been developed for the non-invasive imaging of complement activation following ischemia-reperfusion injury (IRI) in a murine model of cardiac transplantation [87]. Higher uptake of [ 99m Tc]Tc-rCR2 was detected in the heart isografts following IRI in wild-type mice and confirmed on ex vivo biodistribution studies and histology.…”

Section: Complement Activationmentioning

confidence: 99%

Clinical Translation of Neutrophil Imaging and Its Role in Cancer

2021

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Neutrophils are the first line of defense against pathogens and abnormal cells. They regulate many biological processes such as infections and inflammation. Increasing evidence demonstrated a role for neutrophils in cancer, where different subpopulations have been found to possess both pro- or anti-tumorigenic functions in the tumor microenvironment. In this review, we discuss the phenotypic and functional diversity of neutrophils in cancer, their prognostic significance, and therapeutic relevance in human and preclinical models. Molecular imaging methods are increasingly used to probe neutrophil biology in vivo, as well as the cellular changes that occur during tumor progression and over the course of treatment. This review will discuss the role of neutrophil imaging in oncology and the lessons that can be drawn from imaging in infectious diseases and inflammatory disorders. The major factors to be considered when developing imaging techniques and biomarkers for neutrophils in cancer are reviewed. Finally, the potential clinical applications and the limitations of each method are discussed, as well as the challenges for future clinical translation.

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Section: Complement Activationmentioning

confidence: 99%

Clinical Translation of Neutrophil Imaging and Its Role in Cancer

2021

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“…In a previous study, we used a heterotopic cardiac transplant model in mice to examine the ability of 99m Tc-rCR2 to localise to global areas of myocardial IRI induced by cold ischaemia prior to implant surgery. By SPECT imaging, we found evidence of specific uptake within the injured myocardium corresponding to areas of complement deposition 23 .…”

Section: Introductionmentioning

confidence: 85%

Non-Invasive whole-body detection of complement activation using radionuclide imaging in a mouse model of myocardial ischaemia-reperfusion injury

Sharif‐Paghaleh

Yap

Puhl

et al. 2017

Sci Rep

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Complement activation is a recognised mediator of myocardial ischaemia-reperfusion-injury (IRI) and cardiomyocytes are a known source of complement proteins including the central component C3, whose activation products can mediate tissue inflammation, cell death and profibrotic signalling. We investigated the potential to detect and quantify the stable covalently bound product C3d by external body imaging, as a marker of complement activation in heart muscle in a murine model of myocardial IRI. We used single-photon-emission-computed-tomography (SPECT) in conjunction with 99mTechnecium-labelled recombinant complement receptor 2 (99mTc-rCR2), which specifically detects C3d at the site of complement activation. Compared to control imaging with an inactive CR2 mutant (99mTc-K41E CR2) or an irrelevant protein (99mTc-PSMA) or using 99mTc-rCR2 in C3-deficient mice, the use of 99mTc-rCR2 in complement-intact mice gave specific uptake in the reperfused myocardium. The heart to skeletal muscle ratio of 99mTc-rCR2 was significantly higher than in the three control groups. Histological analysis confirmed specific uptake of 99mTc-rCR2. Following therapeutic inhibition of complement C3 activation, we found reduced myocardial uptake of 99mTc-rCR2. We conclude, therefore that 99mTc-rCR2 imaging can be used for non-invasive detection of activated complement and in future could be exploited to quantify the severity of myocardial damage due to complement activation.

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“…Imaging techniques may track complement activity using conjugated CR2 with superparamagnetic iron oxide (SPIO) nanoparticles [142]. Alternatively, CR2 radiolabelled with 99mTc can be injected and followed with single-photon emission computer tomography (SPECT) imaging allowing real-time visualisation of post-ischaemic myocardial injury that may further elucidate the function of major targets [143,144].…”

Section: Biomarker Limitationmentioning

confidence: 99%

Complement—here, there and everywhere, but what about the transplanted organ?

Montero

Sacks

Smith

2016

Seminars in Immunology

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The part of the innate immune system that communicates and effectively primes the adaptive immune system was termed "complement" by Ehrlich to reflect its complementarity to antibodies having previously been described as "alexine" (i.e protective component of serum) by Buchner and Bordet. It has been established that complement is not solely produced systemically but may have origin in different tissues where it can influence organ specific functions that may affect the outcome of transplanted organs. This review looks at the role of complement in particular to kidney transplantation. We look at current literature to determine whether blockade of the peripheral or central compartments of complement production may prevent ischaemic reperfusion injury or rejection in the transplanted organ.We also review new therapeutics that have been developed to inhibit components of the complement cascade with varying degrees of success leading to an increase in our understanding of the multiple triggers of this complex system. In addition, we consider whether biomarkers in this field are effective markers of disease or treatment. Word count 169

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

Cited by 11 publications

References 30 publications

Clinical Translation of Neutrophil Imaging and Its Role in Cancer

Clinical Translation of Neutrophil Imaging and Its Role in Cancer

Non-Invasive whole-body detection of complement activation using radionuclide imaging in a mouse model of myocardial ischaemia-reperfusion injury

Complement—here, there and everywhere, but what about the transplanted organ?

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