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分别选用Tricine和EDDA作为协同配体制备了99Tcm-HYNIC-β-Ala-BBN(7-14)NH2,并比较了两种标记物的体外稳定性和体内生物分布。ITLC和HPLC分析结果表明,两种标记物的标记率均大于95%,经Sep-Pak C-18柱纯化后,其放化纯度均大于99%。在生理盐水和牛血清体系中,两种标记物均保持良好的稳定性,但在半胱氨酸体系中,99Tcm-HYNIC(EDDA)-β-Ala-BBN(7-14)NH2具有更好的稳定性,37℃下孵育24 h,其放化纯度仍大于95%;而在相同条件下,99Tcm-HYNIC(Tricine)-β-Ala-BBN(7-14)NH2的放化纯度已低于90%。血液清除实验表明,99Tcm-HYNIC(EDDA)-β-Ala-BBN(7-14)NH2和99Tcm-HYNIC(Tricine)-β-Ala-BBN(7-14)NH2均符合二室代谢模型,其分布相半衰期分别为0.27 min和1.55 min,消除相半衰期分别为18.1 min和29.7 min。生物分布数据显示,99Tcm-HYNIC(Tricine)-β-Ala-BBN(7-14)NH2每个时间点所有脏器中的放射性摄取均高于99Tcm-HYNIC(EDDA)-β-Ala-BBN(7-14)NH2;两者在肾脏中的摄取均较高,99Tcm-HYNIC(Tricine)-β-Ala-BBN(7-14)NH2在肝脏和肠中的放射性摄取显著高于99Tcm-HYNIC(EDDA)-β-Ala-BBN(7-14)NH2,说明99Tcm-HYNIC(EDDA)-β-Ala-BBN(7-14)NH2主要通过肾脏排泄,而99Tcm-HYNIC(Tricine)-β-Ala-BBN(7-14)NH2既通过肾脏排泄,同时也有相当一部分标记物通过肝胆排泄。以上实验数据表明,99Tcm-HYNIC(EDDA)-β-Ala-BBN(7-14)NH2具有更好的化学和生物学性质,值得进一步研究。
The 99Tcm-HYNIC-β-Ala-BBN (7-14) NH2 was selected by using Tricine and EDDA as synergistic ligands respectively. The in vitro stability and in vivo biodistribution of the two markers were compared. The results of ITLC and HPLC analysis showed that the labeling rates of the two markers were more than 95%, and their radiochemical purity was over 99% after purification by Sep-Pak C-18 column. Both of the two markers retained good stability in physiological saline and bovine serum systems, but 99Tcm-HYNIC (EDDA) -β-Ala-BBN (7-14) NH2 had better The radiochemical purity of 99Tcm-HYNIC (Tricine) -β-Ala-BBN (7-14) NH2 was lower than 95% under the same conditions after incubation at 37 ℃ for 24 h 90%. Blood clearance experiments showed that both 99Tcm-HYNIC (EDDA) -β-Ala-BBN (7-14) NH2 and 99Tcm-HYNIC (Tricine) -β-Ala-BBN The distribution half-lives were 0.27 min and 1.55 min, respectively. The elimination half-lives were 18.1 min and 29.7 min, respectively. The biodistribution data showed that the uptake of 99Tcm-HYNIC (Tricine) -β-Ala-BBN (7-14) NH2 in all organs at each time point was higher than that of 99Tcm-HYNIC (EDDA) (P <0.05). The uptake of 99 Tcm-HYNIC (Tricine) -β-Ala-BBN (7-14) NH2 in the liver and intestine was significantly higher than that of 99 Tcm-HYNIC (EDDA) -β-Ala-BBN (7-14) NH2, indicating that 99Tcm-HYNIC (EDDA) -β-Ala- -BBN (7-14) NH2 excretion both through the kidneys, but also a considerable portion of markers excreted through the liver and gallbladder. The above experimental data show that 99Tcm-HYNIC (EDDA) -β-Ala-BBN (7-14) NH2 has better chemical and biological properties, worth further study.