Armstrong, GR, Khot, MI orcid.org/0000-0002-5062-2284, Portal, C et al. (7 more authors) (2022) A novel fluorescent c-met targeted imaging agent for intra-operative colonic tumour mapping: Translation from the laboratory into a clinical trial. Surgical Oncology, 40. 101679. ISSN 0960-7404
Abstract
Background
The c-Met protein is overexpressed in many gastrointestinal cancers. We explored EMI-137, a novel c-Met targeting fluorescent probe, for application in fluorescence-guided colon surgery, in HT-29 colorectal cancer (CRC) cell line and an in vivo murine model.
Methods
HT-29 SiRNA transfection confirmed specificity of EMI-137 for c-Met. A HT-29 CRC xenograft model was developed in BALB/c mice, EMI-137 was injected and biodistribution analysed through in vivo fluorescent imaging. Nine patients, received a single intravenous EMI-137 bolus (0.13 mg/kg), 1–3 h before laparoscopic-assisted colon cancer surgery (NCT03360461). Tumour and LN fluorescence was assessed intraoperatively and correlated with c-Met expression in eight samples by immunohistochemistry.
Findings
c-Met expression HT-29 cells was silenced and imaged with EMI-137. Strong EMI-137 uptake in tumour xenografts was observed up to 6 h post-administration. At clinical trial, no serious adverse events related to EMI-137 were reported. Marked background fluorescence was observed in all participants, 4/9 showed increased tumour fluorescence over background; 5/9 had histological LN metastases; no fluorescent LN were detected intraoperatively. All primary tumours (8/8) and malignant LN (15/15) exhibited high c-Met protein expression.
Interpretation
EMI-137, binds specifically to the human c-Met protein, is safe, and with further refinement, shows potential for application in fluorescence-guided surgery.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Keywords: | CRC, Colorectal cancer, SiRNA, Short Interfering Ribonucleic Acid, IHC, Immunohistochemistry, LN, Lymph Node, nM, Nanomolar |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Inst of Biomed & Clin Sciences (LIBACS) (Leeds) > Trans Anaesthetics & Surgical Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 24 Nov 2021 17:08 |
Last Modified: | 25 Feb 2025 15:03 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.suronc.2021.101679 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:180818 |