Molecular Imaging of Apoptosis in Ischemia Reperfusion Injury With Radiolabeled Duramycin Targeting Phosphatidylethanolamine
| Autor: | Hideki Kawai, Artiom Petrov, Aditya Shekhar, Takashi Tanimoto, Takehiro Nakahara, Frank D. Kolodgie, Jiqiu Chen, Partho P. Sengupta, Renu Virmani, Jagat Narula, Harry Strauss, Koon Y. Pak, Djamel Lebeche, Francis G. Blankenberg, Farhan Chaudhry, Navneet Narula, Roger J. Hajjar, Dongbin Kim |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Programmed cell death Necrosis business.industry Ischemia 030204 cardiovascular system & hematology Pharmacology medicine.disease 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Left coronary artery Apoptosis medicine.artery Percent Injected Dose Medicine Radiology Nuclear Medicine and imaging Myocardial infarction medicine.symptom Cardiology and Cardiovascular Medicine business Reperfusion injury |
| Zdroj: | JACC: Cardiovascular Imaging. 11:1823-1833 |
| ISSN: | 1936-878X |
| DOI: | 10.1016/j.jcmg.2017.11.037 |
| Popis: | 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 in vivo 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 treated with an antiapoptotic agent, minocycline at the time of reperfusion. In vivo and ex vivo micro–single-photon emission computed tomography (μSPECT) and micro-computed tomography (μCT) 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) but demonstrated substantially lower radiation burden to kidneys (0.358 ± 0.210% vs. 1.58 ± 0.316%, respectively; p 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. |
| Databáze: | OpenAIRE |
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