Molecular platform for design and synthesis of targeted dual-modality imaging probes.
Molecular platform for design and synthesis of targeted dual-modality imaging probes.
复制标题
设计和合成目标双模式成像探针的分子平台。
DOI：
10.1021/acs.bioconjchem.5b00028
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发表时间：
2015-03-18
影响因子：
4.7
通讯作者：
Sun, Xiankai
中科院分区：
文献类型：
--
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
我们报告了一个多功能的树突状结构为基础的平台，建设有针对性的双模态成像探针。该平台含有多个拷贝的1，4，7，10-四氮杂环十二烷-1，4，7，10-四乙酸（DOTA），其从1，4，7-三氮杂环壬烷-N，N′，N″-三乙酸（NOTA）核心分支出来。NOTA和DOTA部分的特定配位化学分别提供68/67 Ga 3+和Gd 3+到共同分子支架中的特定负载。该平台还含有三个氨基，当通过目标靶向载体进一步功能化时，其可以增强PET/MRI或SPECT/MRI（PET：正电子发射断层扫描; SPECT：单光子发射计算机断层扫描; MRI：磁共振成像）的靶向双模态成像。为了验证这一设计概念，合成了具有六个外围Gd-DOTA单元和一个中心处的Ga-NOTA核心的钆络合物，其离子T1弛豫率/钆原子在20 MHz下测量为15.99 mM-1 s-1。此外，当用67 Ga标记时，该抑制剂证明了其预期的体内稳定性、组织分布和药代动力学特征。当与模型靶向肽序列缀合时，三价构建体能够通过PET和MRI经由单剂量注射使小鼠异种移植物模型中的肿瘤可视化。
We report a versatile dendritic structure based platform for construction of targeted dual-modality imaging probes. The platform contains multiple copies of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) branching out from a 1,4,7-triazacyclononane-N,N′,N″-triacetic acid (NOTA) core. The specific coordination chemistries of the NOTA and DOTA moieties offer specific loading of 68/67Ga3+ and Gd3+, respectively, into a common molecular scaffold. The platform also contains three amino groups which can potentiate targeted dual-modality imaging of PET/MRI or SPECT/MRI (PET: positron emission tomography; SPECT: single photon emission computed tomography; MRI: magnetic resonance imaging) when further functionalized by targeting vectors of interest. To validate this design concept, a bimetallic complex was synthesized with six peripheral Gd-DOTA units and one Ga-NOTA core at the center, whose ion T1 relaxivity per gadolinium atom was measured to be 15.99 mM–1 s–1 at 20 MHz. Further, the bimetallic agent demonstrated its anticipated in vivo stability, tissue distribution, and pharmacokinetic profile when labeled with 67Ga. When conjugated with a model targeting peptide sequence, the trivalent construct was able to visualize tumors in a mouse xenograft model by both PET and MRI via a single dose injection.
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影响因子：
3.3
作者：
BRASCH, RC
通讯作者：
BRASCH, RC
影响因子：
2.9
作者：
Langereis, S;de Lussanet, QG;Backes, WH
通讯作者：
Backes, WH
影响因子：
4.6
作者：
KUMAR, K;CHANG, CA;TWEEDLE, MF
通讯作者：
TWEEDLE, MF
影响因子：
4.7
作者：
Duarte, MG;Gil, MH;Geraldes, CFGC
通讯作者：
Geraldes, CFGC
DOI：
10.1016/j.ejpb.2008.09.017
发表时间：
2009-06-01
影响因子：
4.9
作者：
Hak, Sjoerd;Sanders, Honorius M. H. F.;Nicolay, Klaas
通讯作者：
Nicolay, Klaas