Armstrong, Gemma R., Khot, Mohammed I., Portal, Christophe, West, Nick P., Perry, Sarah L., Maisey, Tom I., Tiernan, Jim P., Hughes, Thomas A ORCID: https://orcid.org/0000-0003-1169-3386, Tolan, Damian J. and Jayne, David G. (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).

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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.

Item Type:	Article
Status:	Published
DOI:	https://doi.org/10.1016/j.suronc.2021.101679
Subjects:	Q Science > Q Science (General)
School/Department:	School of Science, Technology and Health
URI:	https://ray.yorksj.ac.uk/id/eprint/8720

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