title: Near‑infrared fluorescence imaging of prostate cancer using heptamethine carbocyanine dyes.
abstract: Near‑infrared fluorescence (NIRF) imaging is an attractive novel modality for the detection of cancer. A previous study defined two organic polymethine cyanine dyes as ideal NIRF probes, IR‑783 and its derivative MHI‑148, which have excellent optical characteristics, superior biocompatibility and cancer targeting abilities. To investigate the feasibility of NIRF dye‑mediated prostate cancer imaging, dye uptake and subcellular co‑localization were investigated in PC‑3, DU‑145 and LNCaP human prostate cancer cells and RWPE‑1 normal prostate epithelial cells. Different organic anion transporting peptide (OATP) inhibitors were utilized to explore the potential role of the OATP subtype, including the nonspecific OATP inhibitor bromosulfophthalein, the OATP1 inhibitor 17β‑estradiol, the selective OATP1B1 inhibitor rifampicin and the selective OATP1B3 inhibitor cholecystokinin octapeptide. NIRF dyes were also used for the simulated detection of circulating tumor cells and the rapid detection of prostate cancer in human prostate cancer tissues and prostate cancer xenografts in mouse models. The results revealed that the cancer‑specific uptake of these organic dyes in prostate cancer cells occurred primarily via OATP1B3. A strong NIRF signal was detected in prostate cancer tissues, but not in normal tissues that were stained with IR‑783. Prostate cancer cells were recognized with particular NIR fluorescence in isolated mononuclear cell mixtures. The results of the present study demonstrated that NIRF dye‑mediated imaging is a feasible and practicable method for prostate cancer detection, although further investigative studies are required before clinical translation.
authors.affiliation: Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Jianlin
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Yi
authors.affiliation: Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yan
authors.affiliation: Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Fuli
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Weijun
authors.initials: W
authors.lastname: Qin
authors.affiliation: Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Guojun
authors.initials: G
authors.lastname: Wu
authors.affiliation: Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Shao
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 / Q000737:chemistry*; D002460:Cell Line; D004958:Estradiol / Q000737:chemistry / Q000378:metabolism; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000737:chemistry*; D006801:Humans; D027381:Liver-Specific Organic Anion Transporter 1; D008297:Male; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D009360:Neoplastic Cells, Circulating / Q000473:pathology; D027361:Organic Anion Transporters / Q000037:antagonists & inhibitors / Q000378:metabolism; D029362:Organic Anion Transporters, Sodium-Independent / Q000037:antagonists & inhibitors / Q000378:metabolism; D027701:Organic Cation Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D011467:Prostate / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D012293:Rifampin / Q000737:chemistry / Q000378:metabolism; D012844:Sincalide / Q000737:chemistry / Q000378:metabolism; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; D019265:Spectroscopy, Near-Infrared; D013448:Sulfobromophthalein / Q000737:chemistry / Q000378:metabolism; D014183:Transplantation, Heterologous
chemical_list: D002232:Carbocyanines; D005456:Fluorescent Dyes; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; D029362:Organic Anion Transporters, Sodium-Independent; D027701:Organic Cation Transport Proteins; C503999:SLCO1B1 protein, human; C421209:SLCO1B3 protein, human; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; D013448:Sulfobromophthalein; D004958:Estradiol; D012844:Sincalide; D012293:Rifampin