title: Heptamethine carbocyanine dye-mediated near-infrared imaging of canine and human cancers through the HIF-1α/OATPs signaling axis.
abstract: Near-infrared (NIR) fluorescence imaging agents are promising tools for noninvasive cancer imaging. This study explored the specific uptake and retention of a NIR heptamethine carbocyanine MHI-148 dye by canine cancer cells and tissues and human prostate cancer (PCa) specimens and also the dye uptake mechanisms. The accumulation of MHI-148 was detected specifically in canine cancer cells and tissues and freshly harvested human PCa tissues xenografted in mice by NIR fluorescence microscopy and whole-body NIR optical imaging. Specific dye uptake in canine spontaneous tumors was further confirmed by PET imaging. Higher hypoxia-inducible factor-1α (HIF-1α) and organic anion-transporting polypeptide (OATP) protein and mRNA expression was demonstrated by multiplex quantum dots labeling and qPCR in tumors over that of normal tissues. Treating cancer cells with HIF-1α stabilizers activated HIF-1α downstream target genes, induced OATP superfamily gene expression and enhanced cellular uptake and retention of NIR dyes. Moreover, silencing HIF-1α by siRNA significantly decreased OATP mRNA expression and blocked NIR dye uptake in cancer cells. Together, these results demonstrated the preferential uptake of NIR dyes by canine and human cancer cells and tissues via the HIF-1α/OATPs signaling axis, which provides insights into future application of these dyes for cancer detection and treatment.
authors.affiliation: Laboratory Animal Center, the Fourth Military Medical University, Xi'an, Shaanxi 710032, China. Uro-Oncology Research Program, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Changhong
authors.initials: C
authors.lastname: Shi
authors.affiliation: Uro-Oncology Research Program, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Jason Boyang
authors.initials: JB
authors.lastname: Wu
authors.affiliation: Uro-Oncology Research Program, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Gina C-Y
authors.initials: GC
authors.lastname: Chu
authors.affiliation: Uro-Oncology Research Program, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Qinlong
authors.initials: Q
authors.lastname: Li
authors.affiliation: Uro-Oncology Research Program, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Ruoxiang
authors.initials: R
authors.lastname: Wang
authors.affiliation: Laboratory Animal Center, the Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Caiqin
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Radiology, the University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Hyung L
authors.initials: HL
authors.lastname: Kim
authors.affiliation: Department of Nuclear Medicine, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Uro-Oncology Research Program, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Haiyen E
authors.initials: HE
authors.lastname: Zhau
authors.affiliation: Department of Radiology, the University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Pan
authors.affiliation: Uro-Oncology Research Program, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Leland W K
authors.initials: LW
authors.lastname: Chung
mesh_terms: D000818:Animals; D002232:Carbocyanines / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging / Q000379:methods; D004285:Dogs; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D064593:Heterografts; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D027361:Organic Anion Transporters / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D019265:Spectroscopy, Near-Infrared / Q000379:methods
chemical_list: D002232:Carbocyanines; D005456:Fluorescent Dyes; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D027361:Organic Anion Transporters