Modular Synthesis of Peptide-Based Single- and Multimodal Targeted Molecular Imaging Agents.
Modular Synthesis of Peptide-Based Single- and Multimodal Targeted Molecular Imaging Agents.
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DOI：
10.1021/acsabm.1c00157
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发表时间：
2021-07-19
影响因子：
4.7
通讯作者：
Ferran, Maureen C
中科院分区：
文献类型：
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作者：
Schmitthenner, Hans F;Barrett, Taylor M;Beach, Stephanie A;Heese, Lauren E;Weidman, Chelsea;Dobson, Damien E;Mahoney, Emily R;Schug, Nicholas C;Jones, Kelsea G;Durmaz, Ceyda;Otasowie, Osarhuwense;Aronow, Sean;Lee, Yin Peng;Ophardt, Henry D;Becker, Amy E;Hornak, Joseph P;Evans, Irene M;Ferran, Maureen C
一种实用的、模块化合成的靶向分子显像剂（tmia）含有用于光学分子成像（OMI）的近红外染料或用于磁共振成像（MRI）和单光子发射相关断层扫描或正电子发射断层扫描（PET）的螯合金属。在该方法中，通过将显像剂附着在受保护赖氨酸的侧链上，在合成的早期形成成像模块。这些模块可以组装以提供一组给定的单模或双模显像剂，这些显像剂可以在温和条件下在合成的最后步骤中共轭到连接剂和靶向基团。一个关键的发现是钆等金属的能力，在MRI中很有用，可以作为螯合剂1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸（DOTA）的保护基团。进一步发现La和Ce两种镧系金属可兼作保护基团和占位金属，在温和的条件下可被用于PET的金属转金属。模块化的方法可以用两种相同或不同的染料，两种相同或不同的金属，或染料和金属的混合物合成离散的靶向探针。该方法的例子是合成用于MRI-OMI、PET-OMI和PET-MRI的单模或双模成像模块，然后与寻求整合素的肽c（RGDyK）偶联。对于Gd模块，通过测量核磁共振自旋晶格弛豫度来验证其对MRI的有效性。为了验证tmia的功能成像，通过共聚焦荧光显微镜显示含有Cy5.5的双峰药物靶向A549癌细胞。
A practical, modular synthesis of targeted molecular imaging agents (TMIAs) containing near-infrared dyes for optical molecular imaging (OMI) or chelated metals for magnetic resonance imaging (MRI) and single-photon emission correlation tomography or positron emission tomography (PET) has been developed. In the method, imaging modules are formed early in the synthesis by attaching imaging agents to the side chain of protected lysines. These modules may be assembled to provide a given set of single- or dual-modal imaging agents, which may be conjugated in the last steps of the synthesis under mild conditions to linkers and targeting groups. A key discovery was the ability of a metal such as gadolinium, useful in MRI, to serve as a protecting group for the chelator, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). It was further discovered that two lanthanide metals, La and Ce, can double as protecting groups and placeholder metals, which may be transmetalated under mild conditions by metals used for PET in the final step. The modular method enabled the synthesis of discrete targeted probes with two of the same or different dyes, two same or different metals, or mixtures of dyes and metals. The approach was exemplified by the synthesis of single- or dual-modal imaging modules for MRI–OMI, PET–OMI, and PET–MRI, followed by conjugation to the integrin-seeking peptide, c(RGDyK). For Gd modules, their efficacy for MRI was verified by measuring the NMR spin–lattice relaxivity. To validate functional imaging of TMIAs, dual-modal agents containing Cy5.5 were shown to target A549 cancer cells by confocal fluorescence microscopy.
设计和合成目标双模式成像探针的分子平台。
影响因子：
4.7
作者：
Kumar, Amit;Zhang, Shanrong;Hao, Guiyang;Hassan, Gedaa;Ramezani, Saleh;Sagiyama, Koji;Lo, Su-Tang;Takahashi, Masaya;Sherry, A. Dean;Oez, Orhan K.;Kovacs, Zoltan;Sun, Xiankai
通讯作者：
Sun, Xiankai
影响因子：
2.7
作者：
Ye, Yunpeng;Akers, Walter;Xu, Baogang;Bloch, Sharon;Odonkor, Charles;Achilefu, Samuel
通讯作者：
Achilefu, Samuel