Abstract
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.
Highlights
Endometrial carcinoma is a malignancy originating in the uterine mucosa, and is currently the 6th most common cancer in females worldwide [1]
In order to identify an optimal target for Near-infrared fluorescence (NIRF) imaging of xenograft models, selected cell surface proteins (EpCAM, activated leukocyte cell adhesion molecule (ALCAM), insulin-like growth factor
Results demonstrated that all cell lines analyzed presented with positive populations to all antigens in the following order; Epithelial cell adhesion molecule (EpCAM), Activated leukocyte cell adhesion molecule (ALCAM), L1 cell adhesion molecule (L1CAM) and IGF1Rα (Table S1)
Summary
Endometrial carcinoma is a malignancy originating in the uterine mucosa, and is currently the 6th most common cancer in females worldwide [1]. 15–20% of patients will experience recurrence [2,3], Cancers 2020, 12, 370; doi:10.3390/cancers12020370 www.mdpi.com/journal/cancers. Cancers 2020, 12, 370 which carries a poor prognosis (3 year survival of 8% and 14% for pelvic and distant recurrence, respectively [4]). These patients, and patients that present with advanced disease at time of diagnosis, usually receive adjuvant chemotherapy. With rising incidence of endometrial carcinoma in North America and Europe (up to 19 cases per 100,000), there is a critical unmet need to develop novel therapeutics for the anticipated increase in number of recurrent patients [6]
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