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Molecular Imaging of Pancreatic Duct Adenocarcinoma Using a Type 2 Cannabinoid Receptor-Targeted Near-Infrared Fluorescent Probe

机译:胰腺导管腺癌的分子成像使用2型大麻素受体靶向的近红外荧光探针。

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摘要

Imaging probes targeting type 2 cannabinoid receptor (CB2R) overexpressed in pancreatic duct adenocarcinoma (PDAC) tissue have the potential to improve early detection and surgical outcome of PDAC. The aim of our study was to evaluate the molecular imaging potential of a CB2R-targeted near-infrared (NIR) fluorescent probe (NIR760-XLP6) for PDAC. CB2R overexpression was observed in both PDAC patient tissues and various pancreatic cancer cell lines. In vitro fluorescence imaging indicated specific binding of NIR760-XLP6 to CB2R in human PDAC PANC-1 cells. In a xenograft mouse tumor model, NIR760-XLP6 showed remarkable 50- (ex vivo) and 3.2-fold (in vivo) tumor to normal contrast enhancement with minimal liver and kidney uptake. In a PDAC lymph node metastasis model, significant signal contrast was observed in bilateral axillary lymph nodes with PDAC metastasis after injection of the probe. In conclusion, NIR760-XLP6 exhibits promising characteristics for imaging PDAC, and CB2R appears to be an attractive target for PDAC imaging.
机译:靶向在胰管腺癌(PDAC)组织中过表达的2型大麻素受体(CB2R)的成像探针具有改善PDAC的早期检测和手术结果的潜力。我们研究的目的是评估针对CB2R的PDAC的近红外(NIR)荧光探针(NIR760-XLP6)的分子成像潜力。在PDAC患者组织和各种胰腺癌细胞系中均观察到CB2R过表达。体外荧光成像表明NIR760-XLP6与人PDAC PANC-1细胞中的CB2R特异性结合。在异种移植小鼠肿瘤模型中,NIR760-XLP6显示出显着的50倍(离体)和3.2倍(体内)的肿瘤与正常对比增强,肝脏和肾脏摄取最少。在PDAC淋巴结转移模型中,注射探针后,在具有PDAC转移的双侧腋窝淋巴结中观察到明显的信号对比。总之,NIR760-XLP6在PDAC成像方面显示出令人鼓舞的特性,而CB2R似乎是PDAC成像的诱人靶标。

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