^(99)Tc^m-Ap4A显像探测动脉粥样硬化斑块的动物实验研究

Experimental study of ^(99)Tc^m-Ap4A in detection of atherosclerotic plaques

目的 探讨应用二磷酸腺苷 (ADP)的类似物99Tcm 四磷酸二腺苷 (Ap4A)显像探测动脉粥样硬化斑块的可行性。方法 采用酒石酸亚锡还原99TcmO- 4 标记Ap4A ,柱层析纯化 ,纸层析鉴定放射化学纯度。观察99Tcm Ap4A在昆明小鼠体内的生物分布并测定动脉粥样硬化模型家兔病灶斑块 血液、病灶斑块 无斑块动脉壁的放射性比值 ,进行腹主动脉宏观放射自显影及正常家兔及动脉粥样硬化家兔体外体内显像。结果 99Tcm Ap4A的放射化学纯度为 85 %～ 91%。99Tcm Ap4A在小鼠血液内清除迅速。注射99Tcm Ap4A后 30min粥样硬化组靶 血比值达 3.17± 1.2 7,靶 非靶比值为 5 2 3± 1.87。粥样硬化组自显影胶片上的曝光黑影与肉眼可见的动脉粥样硬化斑块有良好的一致性。体外显像 :正常家兔组腹主动脉未显影 ,粥样硬化组腹主动脉放射性浓聚清晰可见。体内显像 :粥样硬化组家兔的腹主动脉在注射99Tcm Ap4A后 15～ 30min与正常家兔组相比放射性浓聚明显增强 ,并持续到注药后 3h。结论 99Tcm Ap4A是一种有潜力的可快速显示动脉粥样硬化斑块形成的显像剂。

Objective To study 99Tcm labeled diadenosine tetraphosphate (Ap4A),a compound can bind on P 2 purine receptors on atherosclerotic lesions, for imaging experimental atherosclerotic plaques in New Zealand White (NZW) rabbits. Methods Twenty male NZW rabbits were submitted immune-injury and fed with high cholesterol diet for more than 2 months. To label the 99Tcm to Ap4A, stannous tartrate solution was used. 99Tcm-Ap4A was purified on a Sephadex G-25 column and tested for radiochemistry purity on thin layer chromatography. A biodistribution study was carried out on KM mice. Thirty minutes after intravenous injection of 7.4 MBq 99Tcm-Ap4A, 5 normal NZW rabbits and 5 NZW rabbits with atherosclerotic lesions were sacrificed; their abdominal aortas were removed and covered with X-ray films. Exposed for 24 h in refrigerator, the films were developed and fixed. In another 5 NZW rabbits with atherosclerotic lesions, blood samples, atherosclerotic plaques and normal aortic wall samples were removed. Lesion to blood (target /blood, T/B), lesion to normal (target/non-target, T/NT) radioactivity ratios were calculated. 74 MBq 99Tcm-Ap4A was injected into marginal ear veins of 5 atherosclerotic and 5 normal NZW rabbits. Simultaneously in vivo images were recorded for more than 4 h. In another group, 30 min after 99Tcm-Ap4A administration, the animals were sacrificed and their abdominal aortas were removed. The abdominal aortas were placed on the face of SPECT and image acquisition was performed. Results The radiochemistry purity of 99Tcm-Ap4A was 85% to 91%. Biodistribution study revealed the clearance of 99Tcm-Ap4A from blood was rapid. Thirty min after 99Tcm-Ap4A administration, T/B ratio was 3.17±1.27, T/NT ratio was 5.23±1.87.On the radioautography film shadows of atherosclerotic plaques were clearly visible. The atherosclerotic plaques on the aorta samples also can be seen on ex vivo images. Atherosclerotic abdominal aortas and lesions were clearly visible on in vivo images 15 min to 3 h after 99Tcm-Ap4A administration. Conclusion 99Tcm-Ap4A has the potential of clinical use for rapid noninvasive detection of plaque formation.