Fonnes Tina, Strand Elin, Fasmer Kristine E, Berg Hege F, Espedal Heidi, Sortland Kristina, Stefansson Ingunn, Bjørge Line, Haldorsen Ingfrid S, Krakstad Camilla, McCormack Emmet
Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway.
Department of Obstetrics and Gynecology, Haukeland University Hospital, 5021 Bergen, Norway.
Cancers (Basel). 2020 Feb 6;12(2):370. doi: 10.3390/cancers12020370.
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.
对临床相关的临床前动物模型进行成像对于子宫内膜癌个性化治疗策略的开发至关重要。尽管反映异质分子亚型的原位患者来源异种移植(PDX)被认为是最相关的临床前模型,但其在治疗开发中的应用因缺乏合适的成像方式而受到限制。在此,我们描述了一种靶向上皮细胞粘附分子(EpCAM)的近红外荧光标记单克隆抗体的分子成像,作为一种用于可视化原位子宫内膜癌PDX的体内成像方式。应用这种近红外探针(EpCAM-AF680)能够对原位PDX的发育进行时空可视化以及对纵向治疗进行监测。值得注意的是,EpCAM-AF680有助于对代表该疾病不同亚型的多个PDX模型进行成像。因此,EpCAM-AF680与原位PDX模型的联合应用创建了一个用于识别和验证子宫内膜癌新靶向治疗方法及相应反应预测标志物的先进临床前平台。