~(99m)Tc-nebivolol as a novel heart imaging radiopharmaceutical for myocardial infarction assessment

摘要

Non-invasive quantification of myocardial β-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 β_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 ± 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 ~(99m)Tc-nebivolol in the heart was 4.55 ± 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 ± 0.02 % and further confirmed the high specificity and selectivity of this radiotracer for the assessment of the myocardial β1-adrenoceptors.