Tc-99m-labeled RGD-conjugated alpha-melanocyte stimulating hormone hybrid peptides with reduced renal uptake.
Tc-99m-labeled RGD-conjugated alpha-melanocyte stimulating hormone hybrid peptides with reduced renal uptake.
复制标题
DOI：
10.1007/s00726-014-1911-z
复制
发表时间：
2015-04
期刊：
影响因子：
3.5
通讯作者：
Miao, Yubin
中科院分区：
文献类型：
--
作者：
Yang, Jianquan;Hu, Chien-An A.;Miao, Yubin
本研究的目的是研究用中性连接体替代带正电荷的Lys或Arg连接体是否可以减少肾脏对Arg- gly - asp （RGD）共轭α-促黑素细胞激素（α-MSH）杂交肽的摄取。RGD主题{循环(Arg-Gly-Asp-dTyr-Asp)}是耦合(d-Phe7 Cys3 4 10日,Arg11]α-MSH3-13 {(Arg11) CCMSH}通过中性β阿拉巴马州或Ahx {aminohexanoic酸}链接器(取代赖氨酸或参数链接器)来生成小说RGD -βAla (Arg11) CCMSH和RGD-Ahx——(Arg11) CCMSH混合肽。测定了RGD-β ala -(Arg11)和RGD- ahx -(Arg11)CCMSH在B16/F1黑色素瘤细胞中的受体结合亲和力和细胞毒性。测定99mTc-RGD-β ala -(Arg11)CCMSH和99mTc-RGD- ahx -(Arg11)CCMSH在B16/F1黑色素瘤C57小鼠中的靶向性和成像特性。RGD-βAla-(Arg11)CCMSH和RGD-Ahx-(Arg11)CCMSH保留了纳米摩尔受体结合亲和性和显著的细胞毒性。RGD-β ala -(Arg11)CCMSH和RGD- ahx -(Arg11)CCMSH的受体结合亲和力分别为0.8 nM和1.3 nM。用0.1µM RGD-β ala -(Arg11)CCMSH和RGD- ahx -(Arg11)CCMSH孵育3小时后，与未处理的对照细胞相比，B16/F1细胞的存活率分别降低了71%和67%。在注射后2小时，用βAla或Ahx连接体替代Arg连接体可使99mTc-RGD-βAla-(Arg11)CCMSH和99mTc-RGD-Ahx-(Arg11)CCMSH的非特异性肾摄取分别减少62%和61%。在注射后0.5、2、4和24 h， 99mTc-RGD-β ala -(Arg11)CCMSH的黑色素瘤摄取率高于99mTc-RGD- ahx -(Arg11)CCMSH。99mTc-RGD-β ala -(Arg11)CCMSH的肿瘤对肾脏摄取率的提高，证明了188 - re -labeled RGD-β ala -(Arg11)CCMSH作为一种新的MC1受体靶向治疗肽在未来治疗黑色素瘤的进一步评估。
The purpose of this study was to examine whether the replacement of the positively-charged Lys or Arg linker with a neutral linker could reduce the renal uptake of Arg-Gly-Asp (RGD)-conjugated alpha-melanocyte stimulating hormone (α-MSH) hybrid peptide. The RGD motif {cyclic(Arg-Gly-Asp-dTyr-Asp)} was coupled to [Cys3,4,10, d-Phe7, Arg11]α-MSH3–13 {(Arg11)CCMSH} through the neutral βAla or Ahx {aminohexanoic acid} linker (replacing the Lys or Arg linker) to generate novel RGD-βAla-(Arg11)CCMSH and RGD-Ahx-(Arg11)CCMSH hybrid peptides. The receptor binding affinity and cytotoxicity of RGD-βAla-(Arg11)CCMSH and RGD-Ahx-(Arg11)CCMSH were determined in B16/F1 melanoma cells. The melanoma targeting and imaging properties of 99mTc-RGD-βAla-(Arg11)CCMSH and 99mTc-RGD-Ahx-(Arg11)CCMSH were determined in B16/F1 melanoma-bearing C57 mice. The replacement of the Lys or Arg linker with the βAla or Ahx linker retained nanomolar receptor binding affinities and remarkable cytotoxicity of RGD-βAla-(Arg11)CCMSH and RGD-Ahx-(Arg11)CCMSH. The receptor binding affinities of RGD-βAla-(Arg11)CCMSH and RGD-Ahx-(Arg11)CCMSH were 0.8 and 1.3 nM. Three-hour incubation with 0.1 µM of RGD-βAla-(Arg11)CCMSH and RGD-Ahx-(Arg11)CCMSH decreased the survival percentages of B16/F1 cells by 71 and 67% as compared to the untreated control cells five days post the treatment. The replacement of the Arg linker with the βAla or Ahx linker reduced the non-specific renal uptake of 99mTc-RGD-βAla-(Arg11)CCMSH and 99mTc-RGD-Ahx-(Arg11)CCMSH by 62% and 61% at 2 h post-injection. 99mTc-RGD-βAla-(Arg11)CCMSH displayed higher melanoma uptake than 99mTc-RGD-Ahx-(Arg11)CCMSH at 0.5, 2, 4 and 24 h post-injection. Enhanced tumor to kidney uptake ratio of 99mTc-RGD-βAla-(Arg11)CCMSH warranted the further evaluation of 188Re-labeled RGD-βAla-(Arg11)CCMSH as a novel MC1 receptor-targeting therapeutic peptide for melanoma treatment in the future.
登录
查看更多内容
影响因子：
9.3
作者：
Gotthardt, Martin;van Eerd-Vismale, Julliette;Boerman, Otto
通讯作者：
Boerman, Otto
影响因子：
3
作者：
Christensen, EI;Birn, H;Moestrup, SK
通讯作者：
Moestrup, SK
影响因子：
7.3
作者：
Cheng, Z;Chen, JQ;Jurisson, SS
通讯作者：
Jurisson, SS
影响因子：
4.7
作者：
Miao, YB;Whitener, D;Quinn, TP
通讯作者：
Quinn, TP
影响因子：
11.5
作者：
Miao, YB;Hylarides, M;Quinn, TP
通讯作者：
Quinn, TP