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Review
. 2008 Jun;13(2):163-73.
doi: 10.1007/s10741-007-9068-4.

Noninvasive imaging of apoptosis in cardiovascular disease

Affiliations
Review

Noninvasive imaging of apoptosis in cardiovascular disease

Ethan Chauncey Korngold et al. Heart Fail Rev. 2008 Jun.

Abstract

Recent advances in molecular imaging have permitted the noninvasive imaging of apoptosis, a critical process underlying the pathogenesis of many diseases of the cardiovascular system including atherosclerotic vascular disease, myocardial ischemia and reperfusion injury, chronic heart failure, myocarditis, and cardiac allograft rejection. Multiple molecular targets including phosphatidylserine, phosphatidylinositol 3-kinase, and caspases have been targeted by a variety of imaging agents and modalities such as nuclear scintigraphy, PET, MRI, and fluorescent and bioluminescent imaging. Translationally, methods utilizing radiolabeled annexin V have proven promising in several clinical trials of ischemia-reperfusion injury and cardiac allograft rejection. New approaches using novel molecular imaging agents show great potential for the ability to image apoptosis in the research and clinical setting. Ultimately the ability to detect apoptosis noninvasively would help to identify patients for emerging anti-apoptotic therapies and guide clinical management with the aim of maximal myocardial preservation.

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Figures

Fig. 1
Fig. 1
Pathways of apoptosis. Apoptosis in cardiomyocytes can be mediated by mitochondria (blue shaded area), in a pathway initiated by the release of cytochrome c into the cytosol, or through the death-receptor pathway. The net result of both these pathways is to activate caspase-3, the final effector enzyme of apoptosis. Reproduced with permission from Ref. [11]
Fig. 2
Fig. 2
In vivo imaging of cardiomyocyte apoptosis in mice by MRI. Apoptosis was induced by transient coronary ligation, following which reperfusion was established. The annexin V-labeled magnetofluorescent nanoparticle, AnxCLIO-Cy5.5, was injected at 2 mg Fe/kg into the tail vein of the mice upon coronary reperfusion. Accumulation of the probe in the hypokinetic anterolateral wall produced strong negative contrast enhancement (arrows). No evidence of probe accumulation was seen when the mice where injected with the unlabeled CLIO-Cy5.5 probe. Reproduced with permission from Ref. [32]
Fig. 3
Fig. 3
Imaging of cardiomyocyte apoptosis in acute myocardial infarction with 99mTc-annexin V. Combination of acute 99mTc-MIBI (left 2 columns) and 99mTc annexin V uptake (right 2 columns) in area at risk on day 1 in a patient presenting with acute MI. 99mTc-MIBI perfusion defects in anteroseptal and apical region (open arrows) correlate well with 99mTc-annexin V activity (grey arrows). Adapted and reproduced with permission from Ref. [21]
Fig. 4
Fig. 4
Diffuse myocardial uptake of 99mTc-annexin V in cardiac allograft rejection. SPECT imaging 3 h after intravenous injection of radiolabeled annexin V demonstrated diffuse myocardial uptake of radiotracer, suggesting extensive apoptosis in the myocardium and transplant rejection. Reproduced with permission from Ref. [20]

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