Impact of PKM linkers on biodistribution characteristics of the 99mTc-labeled cyclic RGDfK dimer
Impact of PKM linkers on biodistribution characteristics of the 99mTc-labeled cyclic RGDfK dimer
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DOI：
10.1021/bc060235l
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发表时间：
2006-11-15
影响因子：
4.7
通讯作者：
Jiang, Young
中科院分区：
文献类型：
--
作者：
Liu, Shuang;He, Zhengjie;Jiang, Young
本文报道了三种新的环状RGDfK多肽结合物HYNIC-PKM-SU016(PKM)E、K和PEG4的合成，并在体内评价了PKM连接物对其三元配体络合物[TC-99m(HYNIC-PKM-SU016)1(Tricine)(TPPTS)]在裸鼠体内的分布特征。生物分布研究结果表明，PKM连接体对放射性示踪剂整合素RV-3结合能力的影响很小。尽管它们在生理条件下具有不同的电荷，但在注射后30分钟，所有三个连接体(E、K和PEG4)都能够减少血、肾、肝和肺中标记的E[c(RGDfK)]2的摄取，并增加目标与背景(T/B)的比率。E和K可能比PEG4更有优势，这是因为相对较低的肝脏摄取率和较高的肿瘤/肝脏和肿瘤/肺比例的三元配体络合物[TC-99m(HYNIC-PKM-SU016)(Tricine)(TPPTS)](PKM)E和K)。
This report describes synthesis of three new cyclic RGDfK peptide conjugates, HYNIC-PKM-SU016 ( PKM) E, K and PEG4) and in vivo evaluation of the impact of PKM linkers on biodistribution characteristics of their ternary ligand complexes [ Tc-99m( HYNIC-PKM-SU016) 1( tricine)( TPPTS)] in athymic nude mice bearing the MDA-MB-435 human breast cancer xenografts. Results from biodistribution studies show that PKM linkers have minimal impact on the integrin Rv,3 binding capability of radiotracers. Even though they have different charges under physiological conditions, all three linkers ( E, K, and PEG4) are able to reduce the uptake of Tc-99m-labeled E[ c( RGDfK)] 2 in blood, kidneys, liver, and lungs, and increase target-to-background ( T/B) ratios at > 30 min postinjection. E and K may have advantages over PEG4 due to a combination of relatively low liver uptake and high tumor/liver and tumor/lung ratios of ternary ligand complexes [ Tc-99m( HYNIC-PKM-SU016)( tricine)( TPPTS)] ( PKM) E and K).