99mTc-nebivolol as a novel heart imaging radiopharmaceutical for myocardial infarction assessment
99mTc-nebivolol as a novel heart imaging radiopharmaceutical for myocardial infarction assessment
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DOI：
10.1007/s10967-012-2168-1
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发表时间：
2013-02-01
影响因子：
1.6
通讯作者：
Motaleb, M. A.
中科院分区：
文献类型：
--
作者：
Sakr, T. M.;Moustapha, M. E.;Motaleb, M. A.
心肌β受体的非侵入性定量可能成为慢性心力衰竭和心血管疾病的独立预后标志物。本研究的目的是研制一种新的放射性药物，用于在易感患者的早期阶段检测心肌梗死，这需要开发高心肌亲和力的放射性药物，能够在体内建立准确的心脏β(1)-肾上腺素能受体的定量。这是通过奈比洛尔作为心脏选择性试剂与作为诊断核医学中最有用的放射性核素之一的~(99m)Tcm直接络合而实现的。对影响放化产率的因素如奈比洛尔用量、氯化亚锡用量、反应时间和反应混合物的pH值进行了优化。结果表明，放化产率为95+/-A2.87%，并用高效液相色谱分离了放射性标记化合物。体外研究表明，所形成的络合物在体内最长稳定时间为24小时，在体内的摄取为4.55+/-A 0.23%ID/g器官，而从白化小鼠体内的清除似乎是通过肝胆和肾清除途径进行的。预先给予冷奈比洛尔的小鼠心脏摄取率降至1.1+/-A 0.02%，进一步证实了这种放射性示踪剂用于评估心肌β(1)-肾上腺素能受体的高度特异性和选择性。
Non-invasive quantification of myocardial beta-receptors could become an independent prognostic marker for chronic heart failure and cardiovascular disorders. The aim of this study was to formulate a novel radiopharmaceutical for the detection of myocardial infarction at early stages in susceptible patients, which requires the development of high myocardium affinity radiopharmaceuticals able to establish an accurate in vivo quantification of cardiac beta(1)-adrenoceptors. This was attained by the direct complexation of nebivolol as a cardioselective agent with technetium-99m as one of the most useful radionuclides in diagnostic nuclear medicine. Factors affecting the radiochemical yield such as nebivolol amount, stannous chloride amount, reaction time and pH of the reaction mixture were optimized. The results showed that the radiochemical yield was 95 +/- A 2.87 % and the radiolabeled compound was separated by high performance liquid chromatography. In vitro studies showed that the formed complex was stable for up to 24 h. In vivo uptake of Tc-99m-nebivolol in the heart was 4.55 +/- A 0.23 % ID/g organ at 0.5 h post injection, whereas the clearance from Albino mice appeared to proceed via the hepatobiliary and renal clearance pathways. Predosing mice with cold nebivolol reduced the heart uptake to 1.1 +/- A 0.02 % and further confirmed the high specificity and selectivity of this radiotracer for the assessment of the myocardial beta(1)-adrenoceptors.