Liu Min, Zheng Yumin, Avcibasi Ugur, Liu Shuang
Department of Radiation Medicine and Protection, Medical College, Soochow University, China; School of Health Sciences, Purdue University, IN, 47907, USA.
Department of Nuclear Medicine, China-Japan Friendship Hospital, Beijing, 100037, China.
Nucl Med Biol. 2016 Nov;43(11):732-741. doi: 10.1016/j.nucmedbio.2016.05.001. Epub 2016 May 9.
In this study, novel Tc(III)-azide complexes [Tc(N)(CDO)(CDOH)B-R] (Tc-ISboroxime-N: R=IS; Tc-MPboroxime-N: R=MP; Tc-PAboroxime-N: R=PA; Tc-PYboroxime-N: R=PY; and Tc-Uboroxime-N: R=5U) were evaluated as heart imaging agents.
Complexes [Tc(N)(CDO)(CDOH)B-R] (R=IS, MP, PA, PY and 5U) were prepared by ligand exchange between NaN and [TcCl(CDO)(CDOH)B-R]. Biodistribution and imaging studies were carried out in Sprague-Dawley rats. Image quantification was performed to compare their initial heart uptake and myocardial retention.
Tc-ISboroxime-N, Tc-PYboroxime-N and Tc-Uboroxime-N were prepared with high RCP (93-98%) while the RCP of Tc-MPboroxime-N and Tc-PAboroxime-N was 80-85%. The myocardial retention curves of Tc-ISboroxime-N, Tc-PYboroxime-N and Tc-Uboroxime-N were best fitted to the bi-exponential decay function. The half-time of the fast component was 1.6±0.4min for Tc-ISboroxime-N, 0.7±0.1min for Tc-PYboroxime-N and 0.9±0.4min for Tc-Uboroxime-N. The 2-min heart uptake from biodistribution studies followed the ranking order of Tc-ISboroxime-N (3.60±0.68%ID/g)>Tc-PYboroxime-N (2.35±0.37%ID/g)≫Tc-Uboroxime-N (1.29±0.06%ID/g). Tc-ISboroxime-N had the highest 2-min heart uptake among Tc radiotracers revaluated in SD rats. High quality SPECT images were obtained with the right and left ventricular walls being clearly delineated. The best image acquisition window was 0-5min for Tc-ISboroxime-N.
Both azide coligand and boronate caps had significant impact on the heart uptake and myocardial retention of complexes [Tc(N)(CDO)(CDOH)B-R]. Among the radiotracers evaluated in SD rats, Tc-ISboroxime-N has the highest initial heart uptake with the heart retention comparable to that of Tc-Teboroxime. Tc-ISboroxime-N is a promising alternative to Tc-Teboroxime for SPECT MPI.
在本研究中，新型三价锝叠氮配合物[Tc(N)(CDO)(CDOH)B-R]（Tc-异硫氰酸苯酯硼酸肟-N：R = IS；Tc-甲氧基苯硼酸肟-N：R = MP；Tc-对氨基苯硼酸肟-N：R = PA；Tc-吡啶硼酸肟-N：R = PY；以及Tc-尿嘧啶硼酸肟-N：R = 5U）被评估为心脏显像剂。
通过NaN与[TcCl(CDO)(CDOH)B-R]之间的配体交换制备配合物[Tc(N)(CDO)(CDOH)B-R]（R = IS、MP、PA、PY和5U）。在Sprague-Dawley大鼠中进行生物分布和显像研究。进行图像定量以比较它们的初始心脏摄取和心肌滞留情况。
Tc-异硫氰酸苯酯硼酸肟-N、Tc-吡啶硼酸肟-N和Tc-尿嘧啶硼酸肟-N的放射性化学纯度（RCP）较高（93 - 98%），而Tc-甲氧基苯硼酸肟-N和Tc-对氨基苯硼酸肟-N的RCP为80 - 85%。Tc-异硫氰酸苯酯硼酸肟-N、Tc-吡啶硼酸肟-N和Tc-尿嘧啶硼酸肟-N的心肌滞留曲线最适合双指数衰减函数。快速成分的半衰期对于Tc-异硫氰酸苯酯硼酸肟-N为1.6±0.4分钟，对于Tc-吡啶硼酸肟-N为0.7±0.1分钟，对于Tc-尿嘧啶硼酸肟-N为0.9±0.4分钟。生物分布研究中2分钟时的心脏摄取情况按以下顺序排列：Tc-异硫氰酸苯酯硼酸肟-N（3.60±0.68%ID/g）>Tc-吡啶硼酸肟-N（2.35±0.37%ID/g）≫Tc-尿嘧啶硼酸肟-N（1.29±0.06%ID/g）。在SD大鼠中重新评估的锝放射性示踪剂中，Tc-异硫氰酸苯酯硼酸肟-N的2分钟心脏摄取量最高。获得了高质量的SPECT图像，左右心室壁清晰可辨。对于Tc-异硫氰酸苯酯硼酸肟-N，最佳图像采集窗口为0 - 5分钟。
叠氮共配体和硼酸酯帽对配合物[Tc(N)(CDO)(CDOH)B-R]的心脏摄取和心肌滞留都有显著影响。在SD大鼠中评估的放射性示踪剂中，Tc-异硫氰酸苯酯硼酸肟-N具有最高的初始心脏摄取量，其心脏滞留情况与Tc-替硼酸肟相当。对于SPECT心肌灌注显像，Tc-异硫氰酸苯酯硼酸肟-N是Tc-替硼酸肟的一个有前景的替代物。
