title: A small-molecule dye for NIR-II imaging.
abstract: Fluorescent imaging of biological systems in the second near-infrared window (NIR-II) can probe tissue at centimetre depths and achieve micrometre-scale resolution at depths of millimetres. Unfortunately, all current NIR-II fluorophores are excreted slowly and are largely retained within the reticuloendothelial system, making clinical translation nearly impossible. Here, we report a rapidly excreted NIR-II fluorophore (∼90% excreted through the kidneys within 24 h) based on a synthetic 970-Da organic molecule (CH1055). The fluorophore outperformed indocyanine green (ICG)-a clinically approved NIR-I dye-in resolving mouse lymphatic vasculature and sentinel lymphatic mapping near a tumour. High levels of uptake of PEGylated-CH1055 dye were observed in brain tumours in mice, suggesting that the dye was detected at a depth of ∼4 mm. The CH1055 dye also allowed targeted molecular imaging of tumours in vivo when conjugated with anti-EGFR Affibody. Moreover, a superior tumour-to-background signal ratio allowed precise image-guided tumour-removal surgery.
authors.affiliation: State Key Laboratory of Virology, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China.|Department of Chemistry, Stanford University, California 94305, USA.
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Antaris
authors.affiliation: State Key Laboratory of Virology, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China.|Molecular Imaging Program at Stanford (MIPS), Bio-X Program, and Department of Radiology, Canary Center at Stanford for Cancer Early Detection, Stanford University, California 94305-5344, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.affiliation: Molecular Imaging Program at Stanford (MIPS), Bio-X Program, and Department of Radiology, Canary Center at Stanford for Cancer Early Detection, Stanford University, California 94305-5344, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Virology, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Chemistry, Stanford University, California 94305, USA.
authors.forename: Guosong
authors.initials: G
authors.lastname: Hong
authors.affiliation: State Key Laboratory of Virology, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China.
authors.forename: Chunrong
authors.initials: C
authors.lastname: Qu
authors.affiliation: Department of Chemistry, Stanford University, California 94305, USA.
authors.forename: Shuo
authors.initials: S
authors.lastname: Diao
authors.affiliation: State Key Laboratory of Virology, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China.
authors.forename: Zixin
authors.initials: Z
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Virology, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China.
authors.forename: Xianming
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Chemistry, Stanford University, California 94305, USA.
authors.forename: Bo
authors.identifier: http://orcid.org/0000-0003-0743-4816
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Chemistry, Stanford University, California 94305, USA.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Chemistry, Stanford University, California 94305, USA.
authors.forename: Omar K
authors.initials: OK
authors.lastname: Yaghi
authors.affiliation: Department of Chemistry, Stanford University, California 94305, USA.
authors.forename: Zita R
authors.initials: ZR
authors.lastname: Alamparambil
authors.affiliation: State Key Laboratory of Virology, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China.
authors.forename: Xuechuan
authors.initials: X
authors.lastname: Hong
authors.affiliation: Molecular Imaging Program at Stanford (MIPS), Bio-X Program, and Department of Radiology, Canary Center at Stanford for Cancer Early Detection, Stanford University, California 94305-5344, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Department of Chemistry, Stanford University, California 94305, USA.
authors.forename: Hongjie
authors.initials: H
authors.lastname: Dai
mesh_terms: D000818:Animals; D001578:Benzopyrans / Q000737:chemistry / Q000494:pharmacology* / Q000652:urine; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging / Q000379:methods; D005260:Female; D005456:Fluorescent Dyes / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology* / Q000652:urine; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000473:pathology*; D010666:Phenylpropionates / Q000494:pharmacology*; D019265:Spectroscopy, Near-Infrared; D013830:Thiadiazoles / Q000494:pharmacology*
chemical_list: D001578:Benzopyrans; C000608108:CH1055; C439044:DY 630; D005456:Fluorescent Dyes; D007211:Indoles; D010666:Phenylpropionates; D013830:Thiadiazoles