title: Molecular imaging of human tumor cells that naturally overexpress type 2 cannabinoid receptors using a quinolone-based near-infrared fluorescent probe.
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.
authors.affiliation: University of Pittsburgh, Molecular Imaging Laboratory, Department of Radiology, Pittsburgh, Pennsylvania 15219bShanghai Jiao Tong University School of Medicine, Ruijin Hospital, Department of Radiology, Shanghai 200025, China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Wu
authors.affiliation: University of Pittsburgh, Molecular Imaging Laboratory, Department of Radiology, Pittsburgh, Pennsylvania 15219.
authors.forename: Pin
authors.initials: P
authors.lastname: Shao
authors.affiliation: University of Pittsburgh, Molecular Imaging Laboratory, Department of Radiology, Pittsburgh, Pennsylvania 15219cXi'an Jiaotong University, The First Hospital of Medical School, Department of Diagnostic Radiology, Xi'an, Shaanxi 710061, China.
authors.forename: Shaojuan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: University of Pittsburgh, Molecular Imaging Laboratory, Department of Radiology, Pittsburgh, Pennsylvania 15219.
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Ling
authors.affiliation: University of Pittsburgh, Molecular Imaging Laboratory, Department of Radiology, Pittsburgh, Pennsylvania 15219dUniversity of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15232, United StateseUniversity of Pittsburgh, Department of Bioengineering.
authors.forename: Mingfeng
authors.initials: M
authors.lastname: Bai
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D005456:Fluorescent Dyes / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D057054:Molecular Imaging / Q000379:methods*; D015335:Molecular Probes / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D015363:Quinolones / Q000737:chemistry*; D043885:Receptor, Cannabinoid, CB2 / Q000032:analysis* / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D005456:Fluorescent Dyes; D015335:Molecular Probes; D015363:Quinolones; D043885:Receptor, Cannabinoid, CB2