Department of Chemistry and Institute for Drug Discovery, Purdue University, West Lafayette, Indiana 47907, USA.
J Mater Chem B. 2022 Mar 23;10(12):2038-2046. doi: 10.1039/d1tb02651h.
Tumor-targeted fluorescent dyes have been shown to significantly improve a surgeon's ability to locate and resect occult malignant lesions, thereby enhancing a patient's chances of long term survival. Although several tumor-targeted fluorescent dyes have been developed for imaging specific subsets of human cancers, no tumor-targeted dye has been designed that can image all cancer types. Based on observations that fibroblast activation protein (FAP) is upregulated on cancer-associated fibroblasts (CAFs) that infiltrate essentially all solid tumors, we have undertaken to develop a FAP-targeted fluorescent dye that can image CAFs without accumulating in healthy cells or fibroblasts. We report here that FTL-S-S0456, a novel FAP-targeted near infrared dye that binds FAP with high affinity (∼12 nM) and specificity (>5000-fold over PREP and DPP-IV), concentrates in all seven solid tumor types examined, yielding fluorescence images with high tumor to background ratios that persist for several days. We conclude that FTL-S-S0456 constitutes an excellent ligand-targeted near infrared dye that enables intra-operative imaging of most if not all solid tumors.
肿瘤靶向荧光染料已被证明能显著提高外科医生定位和切除隐匿性恶性病变的能力，从而提高患者长期生存的机会。尽管已经开发出几种用于成像特定人类癌症亚群的肿瘤靶向荧光染料，但尚未设计出能够成像所有癌症类型的肿瘤靶向染料。基于观察到成纤维细胞激活蛋白（FAP）在浸润几乎所有实体瘤的癌相关成纤维细胞（CAFs）中上调，我们着手开发一种能够成像 CAFs 而不在健康细胞或成纤维细胞中积累的 FAP 靶向荧光染料。我们在这里报告，FTL-S-S0456，一种新型的 FAP 靶向近红外染料，与 FAP 具有高亲和力（∼12 nM）和特异性（超过 PREP 和 DPP-IV 5000 倍），在所有七种检查的实体瘤类型中浓缩，产生具有高肿瘤与背景比的荧光图像，持续数天。我们得出结论，FTL-S-S0456 构成了一种出色的配体靶向近红外染料，能够对大多数（如果不是全部）实体瘤进行术中成像。
