Multimodal Chelation Platform for Near-Infrared Fluorescence/Nuclear Imaging
Multimodal Chelation Platform for Near-Infrared Fluorescence/Nuclear Imaging
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DOI：
10.1021/jm300906g
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发表时间：
2013-01-24
影响因子：
7.3
通讯作者：
Azhdarinia, Ali
中科院分区：
文献类型：
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作者：
Ghosh, Sukhen C.;Ghosh, Pradip;Azhdarinia, Ali
含有核和近红外荧光对比的双标记化合物有可能通过将全身诊断成像结果扩展到手术室来分子引导癌症的手术切除。为了简化基于抗体的试剂的双标记过程，我们设计了一种多模态螯合（MMC）支架，其将放射性金属螯合剂和荧光染料结合成单个部分。三种染料衍生的MMC化合物的合成和放射性标记。IRDye 800 CW偶联物4具有良好的光学性质，并显示出体内快速清除。使用4，制备靶向MMC的上皮细胞粘附分子（EpCAM）-免疫缀合物并用Cu-64双标记。MMC结合后证实了体外结合活性。多模式成像研究显示，与非靶向Cu-64-4相比，Cu-64-7在前列腺癌模型中蓄积。需要在不同的EpCAM表达细胞系中进行进一步评估，以及使用其他单克隆抗体应用MMC双标记方法。
Dual-labeled compounds containing nuclear and near-infrared fluorescence contrast have the potential to molecularly guide surgical resection of cancer by extending whole-body diagnostic imaging findings into the surgical suite. To simplify the dual labeling process for antibody-based agents, we designed a multimodality chelation (MMC) scaffold which combined a radiometal chelating agent and fluorescent dye into a single moiety. Three dye-derivatized MMC compounds were synthesized and radiolabeled. The IRDye 800CW conjugate, 4, had favorable optical properties and showed rapid clearance in vivo. Using 4, an epithelial cell adhesion molecule (EpCAM) targeting MMC-immunoconjugate was prepared and dual-labeled with Cu-64. In vitro binding activity was confirmed after MMC conjugation. Multimodal imaging studies showed accumulation of Cu-64-7 compared to nontargeted Cu-64-4 in a prostate cancer model. Further evaluation in different EpCAM-expressing cell lines is warranted as well as application of the MMC dual labeling approach with other monoclonal antibodies.