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). 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.

目的本研究的目的是评估用tech 99m（^99m Tc）标记的杜拉霉素在实验性缺血/再灌注模型中进行细胞凋亡成像的可行性，并将其与已建立的示踪剂^99m Tc标记的Annexin-V进行比较。高辐射负荷对非目标器官的相对不利。

背景技术在细胞凋亡过程中，细胞膜磷脂-磷脂酰丝氨酸（PS）和磷脂酰乙醇胺（PE）暴露在外，可被Annexin-V和Duramycin分别靶向以进行体内成像。鉴定可逆性细胞死亡过程应允许治疗干预，以帮助减少心肌细胞丢失和左心室功能障碍。

方法：在17只兔的40分钟左冠状动脉缺血再灌注模型中，^99m Tc标记的杜拉霉素（n = 10），^99m Tc-线性杜拉霉素（示踪剂阴性； n = 3）或^99m为7 mCi。Tc-Annexin-V（示踪剂阳性对照； n = 4）在再灌注后30分钟静脉内给药。在10只杜拉霉素组动物中，在再灌注时用抗凋亡剂米诺环素治疗了4只动物。在再灌注后3 h进行体内和离体微单光子发射计算机断层扫描（μSPECT）和微计算机断层扫描（μCT）成像，然后定量评估示踪剂摄取和病理学特征。在4只大鼠中注射了荧光杜拉霉素和膜联蛋白-V，以在40分钟左冠状动脉闭塞和30分钟再灌注模型中观察梗死区域的共定位。

结果在顶端（梗塞）区域观察到大量的Duramycin和Annexin-V摄取。在相同的动物中，顶端区域每克摄取的杜拉霉素注射剂量百分比（0.751±0.262％）显着高于偏远地区（0.045±0.029％； p <0.01）。Duramycin的摄取量显着低于Annexin-V的摄取量（1.23±0.304％; p> 0.01），但对肾脏的辐射负荷却显着降低（分别为0.358±0.210％和1.58±0.316％； p <0.001）。用杜拉霉素和膜联蛋白V进行的荧光研究表明，在梗塞区域存在共定位。米诺环素治疗基本解决了杜拉霉素的摄取（0.354％±0.0624％； p <0.01）。

结论Duramycin在检测凋亡细胞死亡方面与Annexin-V类似，但具有较低的非靶器官放射水平。应当使用寻求PE的示踪剂测试细胞凋亡成像的临床可行性。