EpCAM as multi-tumour target for near-infrared fluorescence guided surgery

Driel, Pieter B A A van; Boonstra, Martin C.; Prevoo, H.A.J.M.; Giessen, M.V. van de; Snoeks, T; Tummers, Quirijn R.J.G.; Keereweer, Stijn; Cordfunke, Robert A.; Fish, Alexander; Eendenburg, J. D. H. Van; Lelieveldt, Boudewijn P. F.; Dijkstra, Jouke; Velde, Cornelis J.H. van de; Kuppen, Peter J.K.; Vahrmeijer, Alexander L.; Löwik, Clemens W.G.M.; Sier, Cornelis F.M.

doi:10.1186/s12885-016-2932-7

Cited by 42 publications

(26 citation statements)

References 49 publications

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“… 14 The recognition of EpCAM as one of the most promising pluripotent tumor markers has resulted in (pre)clinical testing of several EpCAM-targeted agents. 10 , 15 , 16 First-in-human studies with an EpCAM-specific fluorescent agent to visualize various tumors during surgery are planned to start soon in our institution. c-Met, the receptor of hepatocyte growth factor (HGF), is involved in tumor cell proliferation and invasion, and its enhanced expression is associated with a poorer survival.…”

Section: Introductionmentioning

confidence: 99%

Biomarker expression in rectal cancer tissue before and after neoadjuvant therapy

Boogerd¹,

Valk²,

Boonstra³

et al. 2018

OTT

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PurposeIntraoperative identification of rectal cancer (RC) can be challenging, especially because of fibrosis after treatment with preoperative chemo- and radiotherapy (CRT). Tumor-targeted fluorescence imaging can enhance the contrast between tumor and normal tissue during surgery. Promising targets for RC imaging are carcinoembryonic antigen (CEA), epithelial cell adhesion molecule (EpCAM) and the tyrosine-kinase receptor Met (c-Met). The effect of CRT on their expression determines their applicability for imaging. Therefore, we investigated whether CRT modifies expression patterns in tumors, lymph node (LN) metastases and adjacent normal rectal tissues.Patients and methodsPreoperative biopsies, primary tumor specimens and metastatic LNs were collected from 38 RC patients who did not receive CRT (cohort 1) and 34 patients who did (cohort 2). CEA, EpCAM and c-Met expression was determined using immunohistochemical staining and was semiquantified by a total immunostaining score (TIS), consisting of the percentage and intensity of stained tumor cells (0–12).ResultsIn both cohorts CEA, EpCAM and c-Met were significantly highly expressed in >60% of tumor tissues compared with adjacent normal epithelium (T/N ratio, P<0.01). EpCAM showed the most homogenous expression in tumors, whereas CEA showed the highest T/N ratio. Most importantly, CEA and EpCAM expression did not significantly change in normal or neoplastic RC tissue after CRT, whereas levels of c-Met changed (P=0.02). Tissues of eight patients with a pathological complete response after CRT showed expression of all biomarkers with TIS close to normal epithelium.ConclusionHistological evaluation shows that CEA, EpCAM and c-Met are suitable targets for RC imaging, because all three are significantly enhanced in cancer tissue from primary tumors or LN metastases compared with normal adjacent tissue. Furthermore, the expression of CEA and EpCAM is not significantly changed after CRT. These data underscore the applicability of c-Met and especially, CEA and EpCAM as targets for image-guided RC surgery, both before and after CRT.

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Section: Introductionmentioning

confidence: 99%

Biomarker expression in rectal cancer tissue before and after neoadjuvant therapy

Boogerd¹,

Valk²,

Boonstra³

et al. 2018

OTT

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“…However, extension of these modalities to the visualization of orthotopic PDX models required a more targeted approach. Previously, NIRF imaging using EpCAM antibodies have been demonstrated to detect orthotopic tumors in cell line-based xenograft models of head and neck, breast and colorectal cancer [24], as well as to visualize metastatic lymph nodes [34] and improve detection of tumor margins [35] in preclinical prostate cancer models. In the current study, we extend this approach to develop a comprehensive NIRF imaging probe EpCAM-AF680 and demonstrate its feasibility in monitoring of orthotopic endometrial carcinoma PDX models.…”

Section: Discussionmentioning

confidence: 99%

“…In vivo near-infrared fluorescent (NIRF) optical imaging using exogenous fluorescent antibodies targeting specific molecular markers has been applied to visualize tumor growth and therapeutic interventions in multiple cancer models [23][24][25]. In the current study we mined for a marker that is universally expressed in endometrial carcinoma, to serve as an imaging target for NIRF imaging of orthotopic PDX models.…”

Section: Introductionmentioning

confidence: 99%

Near-Infrared Fluorescent Imaging for Monitoring of Treatment Response in Endometrial Carcinoma Patient-Derived Xenograft Models

Fonnes

Strand

Fasmer

et al. 2020

Cancers

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Imaging of clinically relevant preclinical animal models is critical to the development of personalized therapeutic strategies for endometrial carcinoma. Although orthotopic patient-derived xenografts (PDXs) reflecting heterogeneous molecular subtypes are considered the most relevant preclinical models, their use in therapeutic development is limited by the lack of appropriate imaging modalities. Here, we describe molecular imaging of a near-infrared fluorescently labeled monoclonal antibody targeting epithelial cell adhesion molecule (EpCAM) as an in vivo imaging modality for visualization of orthotopic endometrial carcinoma PDX. Application of this near-infrared probe (EpCAM-AF680) enabled both spatio-temporal visualization of development and longitudinal therapy monitoring of orthotopic PDX. Notably, EpCAM-AF680 facilitated imaging of multiple PDX models representing different subtypes of the disease. Thus, the combined implementation of EpCAM-AF680 and orthotopic PDX models creates a state-of-the-art preclinical platform for identification and validation of new targeted therapies and corresponding response predicting markers for endometrial carcinoma.

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“…As mentioned before, using the TASC scoring system, seven potential targets for optical molecular imaging of PC of colorectal origin have been identified: CXCR4, EpCAM, EGFR, CEA, Muc1, MMPs, and VEGF‐A . The specifics of these proteins and receptors are summarized in Table . Several fluorescent imaging probes targeting these biomarkers have already been investigated in humans in a broad variety of indications.…”

Section: Potential Fluorescence Imaging Agents For Detection Of Colormentioning

confidence: 99%

Molecular fluorescence‐guided surgery of peritoneal carcinomatosis of colorectal origin: A narrative review

Hentzen

Jongh

Hemmer

et al. 2018

Journal of Surgical Oncology

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Patients with peritoneal carcinomatosis (PC) from colorectal origin may undergo cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) as a curative approach. One major prognostic factor that affects survival is completeness of cytoreduction. Molecular Fluorescence Guided Surgery (MFGS) is a novel intraoperative imaging technique that may improve tumor identification in the future, potentially preventing over‐ and under‐treatment in these patients. This narrative review outlines a chronological overview of MFGS development in patients with PC of colorectal origin.

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EpCAM as multi-tumour target for near-infrared fluorescence guided surgery

Cited by 42 publications

References 49 publications

Biomarker expression in rectal cancer tissue before and after neoadjuvant therapy

Biomarker expression in rectal cancer tissue before and after neoadjuvant therapy

Near-Infrared Fluorescent Imaging for Monitoring of Treatment Response in Endometrial Carcinoma Patient-Derived Xenograft Models

Molecular fluorescence‐guided surgery of peritoneal carcinomatosis of colorectal origin: A narrative review

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