Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston , Houston, Texas 77030, USA.
J Med Chem. 2013 Jan 24;56(2):406-16. doi: 10.1021/jm300906g. Epub 2013 Jan 8.
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 (64)Cu. In vitro binding activity was confirmed after MMC conjugation. Multimodal imaging studies showed higher tumor accumulation of (64)Cu-7 compared to nontargeted (64)Cu-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.
双标记化合物包含核和近红外荧光对比有可能通过将全身诊断成像结果扩展到手术套房来指导癌症的手术切除。为了简化基于抗体的试剂的双重标记过程，我们设计了一种多模态螯合（MMC）支架，将放射性金属螯合剂和荧光染料结合成单一部分。合成并放射性标记了三种染料衍生的 MMC 化合物。IRDye 800CW 缀合物 4 具有良好的光学性质，体内清除迅速。使用 4，制备了靶向上皮细胞黏附分子（EpCAM）的 MMC-免疫缀合物，并与（64）Cu 双重标记。在 MMC 缀合后确认了结合活性的体外研究。多模态成像研究表明，在前列腺癌模型中，（64）Cu-7 的肿瘤积累高于非靶向（64）Cu-4。还需要在不同的 EpCAM 表达细胞系中进行进一步评估，以及应用 MMC 双重标记方法与其他单克隆抗体。
