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Molecular Imaging of Apoptosis in IschemiaReperfusion Injury With RadiolabeledDuramycin Targeting Phosphatidylethanolamine: Effective Target Uptake and Reduced Nontarget Organ Radiation Burden. JACC. Cardiovascular imaging Kawai, H., Chaudhry, F., Shekhar, A., Petrov, A., Nakahara, T., Tanimoto, T., Kim, D., Chen, J., Lebeche, D., Blankenberg, F. G., Pak, K. Y., Kolodgie, F. D., Virmani, R., Sengupta, P., Narula, N., Hajjar, R. J., Strauss, H. W., Narula, J. 2018

Abstract

OBJECTIVES: The purpose of this study was to evaluate the feasibility of imaging apoptosis in experimental ischemia-reperfusion model by technetium-99m (99mTc)-labeled Duramycin, and compare it to an established tracer, 99mTc-labeled Annexin-V, which has a relative disadvantage of high radiation burden to nontarget organs.BACKGROUND: During apoptosis, the cell membrane phospholipids-phosphatidylserine (PS) and phosphatidylethanolamine (PE) are exposed and can be targeted by Annexin-V and Duramycin, respectively, for invivo imaging. Identification of a reversible cell death process should permit therapeutic intervention to help reduce myocyte loss and left ventricle dysfunction.METHODS: In a 40-min left coronary artery ischemia-reperfusion model in 17 rabbits, 7 mCi of 99mTc-labeled Duramycin (n= 10), 99mTc-linear Duramycin (a negative tracer control; n= 3), or 99mTc-Annexin-V (a positive tracer-control; n= 4) were intravenously administered 30 min after reperfusion. Of the 10 Duramycin group animals, 4 animals were treatedwith an antiapoptotic agent, minocycline at the time of reperfusion. Invivo and exvivo micro-single-photon emission computed tomography (muSPECT) and micro-computed tomography (muCT) imaging was performed 3 h after reperfusion, followed by quantitative assessment of tracer uptake and pathological characterization. Fluorescent Duramycin and Annexin-V were injected in 4 rats to visualize colocalization in infarct areas in a 40-min left coronary artery occlusion and 30-min reperfusion model.RESULTS: Intense uptake of Duramycin and Annexin-V was observed in the apical (infarcted) areas. The percent injected dose per gram uptake of Duramycin in apical region (0.751 ± 0.262%) was significantly higher than remote area in same animals (0.045 ± 0.029%; p< 0.01). Duramycin uptake was insignificantly lower than Annexin-V uptake (1.23 ± 0.304%; p > 0.01) but demonstrated substantially lower radiation burden to kidneys (0.358 ± 0.210% vs. 1.58 ± 0.316%, respectively; p< 0.001). Fluorescence studies with Duramycin and Annexin V showed colocalization in infarct areas. Minocycline treatment substantially resolved Duramycin uptake (0.354% ± 0.0624%; p< 0.01).CONCLUSIONS: Duramycin is similarly effective in imaging apoptotic cell death as Annexin-V with lower nontarget organ radiation. Clinical feasibility of apoptosis imaging with a PE-seeking tracer should be tested.

View details for DOI 10.1016/j.jcmg.2017.11.037

View details for PubMedID 29454770