Cited by 142Nanoplatforms for cancer theranosticsMolecular Sensors and Ion DetectionOptical Imaging and Spectroscopy Techniques

AND-gate contrast agents for enhanced fluorescence-guided surgery

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Widen, John C., Tholen, Martina, Yim, Joshua J., Antaris, Alexander, Casey, Kerriann M., Rogalla, Stephan, Klaassen, Alwin, Sorger, Jonathan +1 more·2020·Nature Biomedical Engineering

Abstract

Surgical resection of tumours requires precisely locating and defining the margins between lesions and normal tissue. However, this is made difficult by irregular margin borders. Although molecularly targeted optical contrast agents can be used to define tumour margins during surgery in real time, the selectivity of the contrast agents is often limited by the target being expressed in both healthy and tumour tissues. Here, we show that AND-gate optical imaging probes that require the processing of two substrates by multiple tumour-specific enzymes produce a fluorescent signal with significantly improved specificity and sensitivity to tumour tissue. We evaluated the performance of the probes in mouse models of mammary tumours and of metastatic lung cancer, as well as during fluorescence-guided robotic surgery. Imaging probes that rely on multivariate activation to selectively target complex patterns of enzymatic activity should be useful in disease detection, treatment and monitoring.

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Authors
Widen, J. C., Tholen, M., Yim, J. J., Antaris, A., Casey, K. M., Rogalla, S., Klaassen, A., Sorger, J., & Bogyo, M.
Affiliations
  • Stanford Medicine (US)
  • Intuitive Surgical (United States) (US)
Corresponding author
Bogyo, Matthew
Venue
Nature Biomedical Engineering
Published
2020-09-28
Volume
5
Issue
3
Pages
264-277
ISSN
2157-846X (ISSN-L)
OpenAlex
W3089876537
Cited by
142
References
5
Citations by year
2026: 15 · 2025: 23 · 2024: 23 · 2023: 27 · 2022: 28 · 2021: 26
FWCI
6.36
Type
journal article
Language
en
Open access
Locations
  • Nature Biomedical Engineering (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • American Cancer Society (PF-19-105-01-CCE)
  • National Science Foundation (DGE-114747)
  • U.S. Department of Health & Human Services | National Institutes of Health (R01 EB026285)
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
  • Physical Sciences › Chemistry › Spectroscopy › Molecular Sensors and Ion Detection
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Optical Imaging and Spectroscopy Techniques
Keywords
optical contrast agents, fluorescence-guided surgery, tumour margin delineation, imaging agents, mammary tumors, metastatic lung cancer, robotic surgery, metastasis detection
MeSH terms
RAW 264.7 Cells, Animals, Cell Line, Contrast Media, Disease Models, Animal, Female, Fluorescence, Fluorescent Dyes, Lung Neoplasms, Male, Mice, Inbred BALB C, Mammary Neoplasms, Animal, Surgery, Computer-Assisted, Mice, Optical Imaging

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