Synthesis and evaluation of nanoglobular macrocyclic Mn(II) chelate conjugates as non-gadolinium(III) MRI contrast agents.
Synthesis and evaluation of nanoglobular macrocyclic Mn(II) chelate conjugates as non-gadolinium(III) MRI contrast agents.
复制标题
DOI：
10.1021/bc100573t
复制
发表时间：
2011-05-18
影响因子：
4.7
通讯作者：
Lu, Zheng-Rong
中科院分区：
文献类型：
--
作者：
Tan, Mingqian;Ye, Zhen;Jeong, Eun-Kee;Wu, Xueming;Parker, Dennis L.;Lu, Zheng-Rong
由于最近观察到基于Gd（III）的MRI造影剂在肾功能受损患者中的毒副作用，因此对开发替代MRI造影剂有浓厚的兴趣。在本研究中，以硅氧烷为核心的赖氨酸树状大分子作为纳米微球载体，与Mn(II)-1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸单酰胺（代2,3,4 - dota -Mn）偶联，合成非gd （III）基磁共振成像造影剂（MRI）。合成了Mn(II)-1,4,7-三氮杂环壬烷-1,4,7-三乙酸酯- ga酰胺（G3-NOTA-Mn）的第三代纳米微球缀合物并对其进行了评价。G2、G3、G4纳米微球Mn(II)-DOTA单酰胺偶联物的T1、T2弛豫度随载体数量的增加而降低。G2、G3、G4纳米球Mn(II)-DOTA缀合物在3t时的T1弛豫度分别为3.3、2.8、2.4 mM−1sec−1 / Mn（II）。3 t时，G3-NOTA-Mn的T1弛豫度为3.80 mM - 1sec - 1 / Mn（II）螯合物。纳米红球大环Mn（II）螯合物具有良好的体内稳定性，易于通过肾滤过排出体外。与MnCl2相比，该偶联物的非特异性肝脏增强效果要小得多，并且在剂量为0.03 mmol Mn/kg的MDA-MB-231乳腺肿瘤异种移植裸鼠中，对肿瘤造影剂增强成像有效。纳米球形大环锰（II）螯合物是很有前途的非钆基MRI造影剂。
Because of the recent observation of the toxic side effects of Gd(III) based MRI contrast agents in the patients with impaired renal functions, there is a strong interest on developing alternative contrast agents for MRI. In this study, lysine dendrimers with a silsesquioxane core acted as nanoglobular carriers that were conjugated to Mn(II)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate monoamide (Generation 2, 3, 4-DOTA-Mn) to synthesize non-Gd(III) based contrast agents for magnetic resonance imaging (MRI). A generation 3 nanoglobular conjugate of Mn(II)-1,4,7-triaazacyclononane-1,4,7-triacetate-GA amide (G3-NOTA-Mn) was also synthesized and evaluated. The per ion T1 and T2 relaxivities of G2, G3, G4 nanoglobular Mn(II)-DOTA monoamide conjugates decreased with increasing generation of the carriers. The T1 relaxivity of G2, G3, G4 nanoglobular Mn(II)-DOTA conjugates was 3.3, 2.8, 2.4 mM−1sec−1 per Mn(II) chelate at 3 T, respectively. The T1 relaxivity of G3-NOTA-Mn was 3.80 mM−1sec−1 per Mn(II) chelate at 3 T. The nanoglobular macrocyclic Mn(II) chelate conjugates showed good in vivo stability and were readily excreted via renal filtration. The conjugates resulted in much less non-specific liver enhancement than MnCl2 and were effective for contrast enhanced tumor imaging in nude mice bearing MDA-MB-231 breast tumor xenografts at a dose of 0.03 mmol Mn/kg. The nanoglobular macrocyclic Mn(II) chelate conjugates are promising non-gadolinium based MRI contrast agents.
登录
查看更多内容
影响因子：
6.2
作者：
Kaneshiro, Todd Lyle;Jeong, Eun-Kee;Morrell, Glen;Parker, Dennis L.;Lu, Zheng-Rong
通讯作者：
Lu, Zheng-Rong
影响因子：
4.6
作者：
Wang, Sen;Westmoreland, T. David
通讯作者：
Westmoreland, T. David
影响因子：
2.8
作者：
Tanaka, Kazuo;Kitamura, Narufumi;Chujo, Yoshiki
通讯作者：
Chujo, Yoshiki
影响因子：
4
作者：
SHUKLA, GS;CHANDRA, SV
通讯作者：
CHANDRA, SV
影响因子：
4.4
作者：
Sieber, Martin A.;Lengsfeld, Philipp;Pietsch, Hubertus
通讯作者：
Pietsch, Hubertus