Imaging of Preclinical Endometrial Cancer Models for Monitoring Tumor Progression and Response to Targeted Therapy

Abstract

Endometrial cancer is the most common gynecologic malignancy in industrialized countries. Most patients are cured by surgery; however, about 15% of the patients develop recurrence with limited treatment options. Patient-derived tumor xenograft (PDX) mouse models represent useful tools for preclinical evaluation of new therapies and biomarker identification. Preclinical imaging by magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT), single-photon emission computed tomography (SPECT) and optical imaging during disease progression enables visualization and quantification of functional tumor characteristics, which may serve as imaging biomarkers guiding targeted therapies. A critical question, however, is whether the in vivo model systems mimic the disease setting in patients to such an extent that the imaging biomarkers may be translatable to the clinic. The primary objective of this review is to give an overview of current and novel preclinical imaging methods relevant for endometrial cancer animal models. Furthermore, we highlight how these advanced imaging methods depict pathogenic mechanisms important for tumor progression that represent potential targets for treatment in endometrial cancer.

Targeting CDK9: A novel biomarker in�the�treatment of endometrial cancer

“…The endoscopic single-site (LESS) surgery, 3 mm laparoscopy (MiniLPS) and percutaneous system (PSS) include the principal innovations in ultra-minimally invasive surgery introduced during the last few years. Even when reducing the port number or instrument size to reduce invasiveness, these improvements still maintain the same surgical technique, efficacy and safety of standard laparoscopy (LPS) ( 24 – 27 ). Although there exists continuous research concerning the tumorigenesis and development of endometrial cancer, it still remains unclear which signaling pathways or related molecules promote the occurrence and development of endometrial cancer.…”

Feasibility and utility of MRI and dynamic 18F-FDG-PET in an orthotopic organoid-based patient-derived mouse model of endometrial cancer

“…However, as small-animal hybrid PET-MRI scanners are becoming more common, this opens the avenue for utilizing this novel imaging platform in the future. Dynamic quantitative PET imaging requires an arterial input function (AIF) which in preclinical studies can be challenging to obtain with the gold standard of blood sampling, since mice have small blood volumes [ 6 ]. Hence, we used an image-derived input function from vena cava that allowed noninvasive and longitudinal analyses.…”

“…Previous preclinical endometrial cancer (EC) studies have mostly relied on caliper size measurements of less relevant subcutaneous models using cell lines, or endpoint-only measurements in orthotopic models [ 4 , 5 ]. Very few preclinical studies have used imaging methods mimicking those employed in the clinic [ 6 ]. We have recently developed EC organoid-based orthotopic mouse xenograft models (O-PDX) that recapitulate the histopathologic architecture, protein biomarker expression and the genetic profile of the donor tumor tissue [ 7 ].…”

New Insights into Breast and Endometrial Cancers

“…It is desirable that these examinations be performed using non-invasively collected samples such as endometrial fluid or peritoneal lavage fluid [ 16 , 20 ]. The mouse xenograft model is useful for studying the mechanism of tumor progression and the effect of drugs in vivo [ 23 ]. The exploration of biomarkers using an in vitro model and database analysis has made great progress.…”

“…The exploration of biomarkers using an in vitro model and database analysis has made great progress. With advancement, it is necessary to develop a bioimaging system that enables precise inspection [ 23 ].…”