Research Papers: Imaging

Molecular imaging of human tumor cells that naturally overexpress type 2 cannabinoid receptors using a quinolone-based near-infrared fluorescent probe

[+] Author Affiliations
Zhiyuan Wu

University of Pittsburgh, Molecular Imaging Laboratory, Department of Radiology, Pittsburgh, Pennsylvania 15219

Shanghai Jiao Tong University School of Medicine, Ruijin Hospital, Department of Radiology, Shanghai 200025, China

Pin Shao

University of Pittsburgh, Molecular Imaging Laboratory, Department of Radiology, Pittsburgh, Pennsylvania 15219

Shaojuan Zhang

University of Pittsburgh, Molecular Imaging Laboratory, Department of Radiology, Pittsburgh, Pennsylvania 15219

Xi’an Jiaotong University, The First Hospital of Medical School, Department of Diagnostic Radiology, Xi’an, Shaanxi 710061, China

Xiaoxi Ling

University of Pittsburgh, Molecular Imaging Laboratory, Department of Radiology, Pittsburgh, Pennsylvania 15219

Mingfeng Bai

University of Pittsburgh, Molecular Imaging Laboratory, Department of Radiology, Pittsburgh, Pennsylvania 15219

University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15232, United States

University of Pittsburgh, Department of Bioengineering, Pittsburgh, Pennsylvania 15232, United States

J. Biomed. Opt. 19(7), 076016 (Jul 18, 2014). doi:10.1117/1.JBO.19.7.076016
History: Received February 17, 2014; Revised April 24, 2014; Accepted May 1, 2014
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Abstract.  Cannabinoid CB2 receptors (CB2R) hold promise as therapeutic targets for treating diverse diseases, such as cancers, neurodegenerative diseases, pain, inflammation, osteoporosis, psychiatric disorders, addiction, and immune disorders. However, the fundamental role of CB2R in the regulation of diseases remains unclear, largely due to a lack of reliable imaging tools for the receptors. The goal of this study was to develop a CB2R-targeted molecular imaging probe and evaluate the specificity of the probe using human tumor cells that naturally overexpress CB2R. To synthesize the CB2R-targeted probe (NIR760-Q), a conjugable CB2R ligand based on the quinolone structure was first prepared, followed by bioconjugation with a near-infrared (NIR) fluorescent dye, NIR760. In vitro fluorescence imaging and competitive binding studies showed higher uptake of NIR760-Q than free NIR760 dye in Jurkat human acute T-lymphoblastic leukemia cells. In addition, the high uptake of NIR760-Q was significantly inhibited by the blocking agent, 4-quinolone-3-carboxamide, indicating specific binding of NIR760-Q to the target receptors. These results indicate that the NIR760-Q has potential in diagnostic imaging of CB2R positive cancers and elucidating the role of CB2R in the regulation of disease progression.

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© 2014 Society of Photo-Optical Instrumentation Engineers

Citation

Zhiyuan Wu ; Pin Shao ; Shaojuan Zhang ; Xiaoxi Ling and Mingfeng Bai
"Molecular imaging of human tumor cells that naturally overexpress type 2 cannabinoid receptors using a quinolone-based near-infrared fluorescent probe", J. Biomed. Opt. 19(7), 076016 (Jul 18, 2014). ; http://dx.doi.org/10.1117/1.JBO.19.7.076016


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