Activatable Near-Infrared Fluorescent Probe for In Vivo Imaging of Fibroblast Activation Protein-alpha

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• 作者：Jinbo Li ; Kai Chen ; Hongguang Liu ; Kai Cheng ; Meng Yang ; Jiping Zhang ; Jonathan D. Cheng ; Yan Zhang ; Zhen Cheng
• 刊名：Bioconjugate Chemistry
• 出版年：2012
• 出版时间：August 15, 2012
• 年：2012
• 卷：23
• 期：8
• 页码：1704-1711
• 全文大小：383K
• 年卷期：v.23,no.8(August 15, 2012)
• ISSN：1520-4812

文摘

Fibroblast activation protein-alpha (FAP伪) is a cell surface glycoprotein which is selectively expressed by tumor-associated fibroblasts in malignant tumors but rarely on normal tissues. FAP伪 has also been reported to promote tumor growth and invasion and therefore has been of increasing interest as a promising target for designing tumor-targeted drugs and imaging agents. Although medicinal study on FAP伪 inhibitors has led to the discovery of many FAP伪-targeting inhibitors including a drug candidate in a phase II clinical trial, the development of imaging probes to monitor the expression and activity of FAP伪 in vivo has largely lagged behind. Herein, we report an activatable near-infrared (NIR) fluorescent probe (ANP_FAP) for in vivo optical imaging of FAP伪. The ANP_FAP consists of a NIR dye (Cy5.5) and a quencher dye (QSY21) which are linked together by a short peptide sequence (KGPGPNQC) specific for FAP伪 cleavage. Because of the efficient fluorescence resonance energy transfer (FRET) between Cy5.5 and QSY21 in ANP_FAP, high contrast on the NIR fluorescence signal can be achieved after the cleavage of the peptide sequence by FAP伪 both in vitro and in vivo. In vitro assay on ANP_FAP indicated the specificity of the probe to FAP伪. The in vivo optical imaging using ANP_FAP showed fast tumor uptake as well as high tumor to background contrast on U87MG tumor models with FAP伪 expression, while much lower signal and tumor contrast were observed in the C6 tumor without FAP伪 expression, demonstrating the in vivo targeting specificity of the ANP_FAP. Ex vivo imaging also demonstrated ANP_FAP had high tumor uptake at 4 h post injection. Collectively, these results indicated that ANP_FAP could serve as a useful NIR optical probe for early detection of FAP伪 expressing tumors.