A small-molecule dye for NIR-II imaging

• Published in: Nature materials Vol. 15; no. 2; pp. 235 - 242
• Main Authors: Antaris, Alexander L., Chen, Hao, Cheng, Kai, Sun, Yao, Hong, Guosong, Qu, Chunrong, Diao, Shuo, Deng, Zixin, Hu, Xianming, Zhang, Bo, Zhang, Xiaodong, Yaghi, Omar K., Alamparambil, Zita R., Hong, Xuechuan, Cheng, Zhen, Dai, Hongjie
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2016; Nature Publishing Group
• Subjects: 639/624/1107/510; 639/624/399/54; 639/638/549; Animals; Benzopyrans - chemistry; Benzopyrans - pharmacology; Benzopyrans - urine; Biomaterials; Brain tumors; Carcinoma, Squamous Cell - pathology; Cell Line, Tumor; Chemical compounds; Condensed Matter Physics; Diagnostic Imaging - methods; Dyes; Female; Fluorescence; Fluorescent Dyes - pharmacology; Humans; Imaging; Indoles - chemistry; Indoles - pharmacology; Indoles - urine; Kidneys; Male; Materials Science; Medical imaging; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Molecules; Nanotechnology; Neoplasms, Experimental - pathology; Optical and Electronic Materials; Phenylpropionates - pharmacology; Spectroscopy, Near-Infrared; Surgery; Thiadiazoles - pharmacology; Translations; Tumours; Uptakes
• ISSN: 1476-1122; 1476-4660
• DOI: 10.1038/nmat4476

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. A renally cleared, water-soluble dye emitting in the near-infrared-imaging (NIR)-II window outperforms a clinically approved NIR-I dye in the in vivo imaging of tumours and their nearby blood and lymphatic vasculatures.