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

Xiaoxia Guo; Xiaoxi Ling; Fang Du; Qingbing Wang; Wei Huang; Zhongmin Wang; Xiaoyi Ding; Mingfeng Bai; Zhiyuan Wu

doi:10.1016/j.tranon.2018.06.009

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

Transl Oncol. 2018 Oct;11(5):1065-1073. doi: 10.1016/j.tranon.2018.06.009. Epub 2018 Jul 9.

Authors

Xiaoxia Guo¹, Xiaoxi Ling², Fang Du³, Qingbing Wang¹, Wei Huang¹, Zhongmin Wang¹, Xiaoyi Ding¹, Mingfeng Bai⁴, Zhiyuan Wu⁵

Affiliations

¹ Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
² Department of Medicine, University of Pittsburgh, 3501 Fifth Ave, Pittsburgh, PA 15213, USA.
³ Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
⁴ Vanderbilt University Institute of Imaging Science (VUIIS), Vanderbilt University Medical Center, Nashville, TN 37232, USA; Center for Molecular Probes, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt-Ingram Cancer Center (VICC), Vanderbilt University Medical Center, Nashville, TN 37232, USA.
⁵ Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: [email protected].

Abstract

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.