ArticleClinical cancer research : an official journal of the American Association for Cancer Research2022
A Cathepsin-Targeted Quenched Activity-Based Probe Facilitates Enhanced Detection of Human Tumors during Resection.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 42 citations in OpenAlex.
- Phase 2 Dose-Ranging Trial of VGT-309 for Molecular Imaging of Cancer during Pulmonary Resection.European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery · 2025Trial
- A Phase 2 Multicenter Clinical Trial of Intraoperative Molecular Imaging of Lung Cancer with a pH-Activatable Nanoprobe.Molecular imaging and biology · 2024Trial
- A single-chip, dual-gain color-NIR camera for fluorescence-guided lung and breast cancer surgery.Light, science & applications · 2026Article
- Phase II Multicenter Clinical Trial of Intraoperative Molecular Imaging with Abenacianine During Lung Cancer Surgery.Annals of surgical oncology · 2026Article
- Clinical fluorescent probes: mechanisms, advantages and inspirations.Chemical science · 2026Review
- Intraoperative Molecular Imaging in Thoracic Oncology: Expanding the Observable Disease Space.Cancers · 2026Review
- Translation of Intraoperative Molecular Imaging for Clinical Use.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2026Review
- A "turn-off" photoacoustic contrast for urokinase-type plasminogen activator activity.npj biomedical innovations · 2026Article
- Near-Infrared Imaging in Small Animal Surgical Oncology: Current Applications and Future Directions.Animals : an open access journal from MDPI · 2026Review
- Near-Infrared Imaging Using a Cathepsin-Targeted, Quenched Activity-Based Probe Identifies Naturally Occurring Canine Appendicular Osteosarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Considerations for the use of targeted fluorescence contrast agents to detect circulating cancer cell populations with diffuseJournal of biomedical optics · 2026Article
- Targeted near-infrared imaging utilizing a cathepsin-activated fluorophore for the intraoperative detection of canine insulinoma.PloS one · 2026Article
- Chemical probes for enzyme imaging: challenges in design, synthesis and biomedical applications.Chemical science · 2025Review
- Granzyme B-Targeting Quenched Activity-Based Probes for Assessing Tumor Response to Immunotherapy.Journal of the American Chemical Society · 2025Article
- Ex vivo fluorescence-guided resection margin assessment in breast cancer surgery using a topically applied, cathepsin-activatable imaging agent.Pharmacological research · 2024Article
- In Vivo Labeling and Detection of Circulating Tumor Cells in Mice Using OTL38.Molecular imaging and biology · 2024Article
- Review on endobronchial therapies-current status and future.Annals of translational medicine · 2024Review
- Polymer-Tethered Quenched Fluorescent Probes for Enhanced Imaging of Tumor-Associated Proteases.ACS sensors · 2024Article
- Polymer-tethered quenched fluorescent probes for enhanced imaging of tumor associated proteases.bioRxiv : the preprint server for biology · 2024Article
- Ruthenium-Cathepsin Inhibitor Conjugates for Green Light-Activated Photodynamic Therapy and Photochemotherapy.Inorganic chemistry · 2024Article
Corrections and comments
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Authors and funding
20 authors at 5 institutions in 2 countries.
Funding
Abstract
purposeFluorescence-guided surgery using tumor-targeted contrast agents has been developed to improve the completeness of oncologic resections. Quenched activity-based probes that fluoresce after covalently binding to tumor-specific enzymes have been proposed to improve specificity, but none have been tested in humans. Here, we report the successful clinical translation of a cathepsin activity-based probe (VGT-309) for fluorescence-guided surgery. EXPERIMENTAL
designWe optimized the specificity, dosing, and timing of VGT-309 in preclinical models of lung cancer. To evaluate clinical feasibility, we conducted a canine study of VGT-309 during pulmonary tumor resection. We then conducted a randomized, double-blind, dose-escalation study in healthy human volunteers receiving VGT-309 to evaluate safety. Finally, we tested VGT-309 in humans undergoing lung cancer surgery.
resultsIn preclinical models, we found highly specific tumor cell labeling that was blocked by a broad spectrum cathepsin inhibitor. When evaluating VGT-309 for guidance during resection of canine tumors, we found that the probe selectively labeled tumors and demonstrated high tumor-to-background ratio (TBR; range: 2.15-3.71). In the Phase I human study, we found that VGT-309 was safe at all doses studied. In the ongoing Phase II trial, we report two cases in which VGT-309 localized visually occult, non-palpable tumors (TBRs = 2.83 and 7.18) in real time to illustrate its successful clinical translation and potential to improve surgical management.
conclusionsThis first-in-human study demonstrates the safety and feasibility of VGT-309 to label human pulmonary tumors during resection. These results may be generalizable to other cancers due to cathepsin overexpression in many solid tumors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.