Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Contrast Media Mol Imaging. 2012 Nov-Dec;7(6):516-24. doi: 10.1002/cmmi.1484.
Image-guided surgery using optical imaging requires the availability of large quantities of clinical-grade fluorophores. We describe the cGMP-compatible synthesis of the zwitterionic heptamethine indocyanine near-infrared fluorophore ZW800-1 at the 10 g scale (~1000 patient doses) using facile and efficient solvent purification, and without the need for column chromatography. ZW800-1 has >90% yield at the final step and >99% purity as measured by fluorescence and evaporative light scatter detection. We describe an analytical framework for qualifying impurities, as well as a detailed analysis of counterion identities. Finally, we report the unique in vivo properties of ZW800-1 in large animals approaching the size of humans, thus laying the foundation for rapid clinical translation of these methods.
基于光学成像的影像引导手术需要大量临床级别的荧光染料。我们描述了在符合 cGMP 要求的条件下，以 10 克规模（~1000 个患者剂量），通过简便、高效的溶剂纯化，且无需柱层析，合成两性离子七甲川花菁近红外荧光染料 ZW800-1 的方法。终产物的收率大于 90%，荧光和蒸发光散射检测的纯度大于 99%。我们描述了一种用于鉴定杂质的分析框架，以及对反离子身份的详细分析。最后，我们在接近人体大小的大型动物中报告了 ZW800-1 的独特体内特性，从而为这些方法的快速临床转化奠定了基础。
