Guo Xiaoxia, Ling Xiaoxi, Du Fang, Wang Qingbing, Huang Wei, Wang Zhongmin, Ding Xiaoyi, Bai Mingfeng, Wu Zhiyuan
Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Department of Medicine, University of Pittsburgh, 3501 Fifth Ave, Pittsburgh, PA 15213, USA.
Transl Oncol. 2018 Oct;11(5):1065-1073. doi: 10.1016/j.tranon.2018.06.009. Epub 2018 Jul 9.
Imaging probes targeting type 2 cannabinoid receptor (CBR) 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 CBR-targeted near-infrared (NIR) fluorescent probe (NIR760-XLP6) for PDAC. CBR 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 CBR 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 CBR appears to be an attractive target for PDAC imaging.
靶向在胰腺导管腺癌(PDAC)组织中过表达的2型大麻素受体(CBR)的成像探针,有潜力改善PDAC的早期检测和手术结果。我们研究的目的是评估一种靶向CBR的近红外(NIR)荧光探针(NIR760-XLP6)对PDAC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CBR过表达。体外荧光成像表明NIR760-XLP6与人PDAC PANC-1细胞中的CBR有特异性结合。在异种移植小鼠肿瘤模型中,NIR760-XLP6显示出显著的肿瘤与正常组织对比度增强,离体时为50倍,体内时为3.2倍,肝脏和肾脏摄取极少。在PDAC淋巴结转移模型中,注射探针后,在发生PDAC转移的双侧腋窝淋巴结中观察到显著的信号对比度。总之,NIR760-XLP6在PDAC成像方面表现出有前景的特性,并且CBR似乎是PDAC成像的一个有吸引力的靶点。