High-precision tumor resection down to few-cell level guided by NIR-IIb molecular fluorescence imaging.

Abstract

In vivo fluorescence/luminescence imaging in the near-infrared-IIb (NIR-IIb, 1,500 to 1,700 nm) window under <1,000 nm excitation can afford subcentimeter imaging depth without any tissue autofluorescence, promising high-precision intraoperative navigation in the clinic. Here, we developed a compact imager for concurrent visible photographic and NIR-II (1,000 to 3,000 nm) fluorescence imaging for preclinical image-guided surgery. Biocompatible erbium-based rare-earth nanoparticles (ErNPs) with bright down-conversion luminescence in the NIR-IIb window were conjugated to TRC105 antibody for molecular imaging of CD105 angiogenesis markers in 4T1 murine breast tumors. Under a ∼940 ± 38 nm light-emitting diode (LED) excitation, NIR-IIb imaging of 1,500- to 1,700-nm emission afforded noninvasive tumor–to–normal tissue (T/NT) signal ratios of ∼40 before surgery and an ultrahigh intraoperative tumor-to-muscle (T/M) ratio of ∼300, resolving tumor margin unambiguously without interfering background signal from surrounding healthy tissues. High-resolution imaging resolved small numbers of residual cancer cells during surgery, allowing thorough and nonexcessive tumor removal at the few-cell level. NIR-IIb molecular imaging afforded 10-times-higher and 100-times-higher T/NT and T/M ratios, respectively, than imaging with IRDye800CW-TRC105 in the ∼900- to 1,300-nm range. The vastly improved resolution of tumor margin and diminished background open a paradigm of molecular imaging-guided surgery.

• Authors: Feifei Wang, Liangqiong Qu, Fuqiang Ren, Ani Baghdasaryan, Yingying Jiang, RuSiou Hsu, Peng Liang, Jiachen Li, Guanzhou Zhu, Zhuoran Ma, Hongjie Dai
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 119 Issue 15 Pg. e2123111119 (04 12 2022) ISSN: 1091-6490 [Electronic] United States
• PMID: 35380898 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• Fluorescent Dyes
• Erbium
• carotuximab

Topics

• Animals
• Antibodies, Monoclonal (chemistry, immunology)
• Erbium
• Fluorescence
• Fluorescent Dyes (chemistry)
• Mammary Neoplasms, Experimental (diagnostic imaging, surgery)
• Metal Nanoparticles
• Mice
• Neoplasm, Residual (diagnostic imaging)
• Optical Imaging (methods)
• Spectroscopy, Near-Infrared (methods)
• Surgery, Computer-Assisted (methods)