Abstract
BackgroundOrthotopic endometrial cancer models provide a unique tool for studies of tumour growth and metastatic spread. Novel preclinical imaging methods also have the potential to quantify functional tumour characteristics in vivo, with potential relevance for monitoring response to therapy.MethodsAfter orthotopic injection with luc-expressing endometrial cancer cells, eleven mice developed disease detected by weekly bioluminescence imaging (BLI). In parallel the same mice underwent positron emission tomography–computed tomography (PET-CT) and magnetic resonance imaging (MRI) employing 18F-fluorodeoxyglocose (18F-FDG) or 18F- fluorothymidine (18F-FLT) and contrast reagent, respectively. The mice were sacrificed when moribund, and post-mortem examination included macroscopic and microscopic examination for validation of growth of primary uterine tumours and metastases. PET-CT was also performed on a patient derived model (PDX) generated from a patient with grade 3 endometrioid endometrial cancer.ResultsIncreased BLI signal during tumour growth was accompanied by increasing metabolic tumour volume (MTV) and increasing MTV x mean standard uptake value of the tumour (SUVmean) in 18F-FDG and 18F-FLT PET-CT, and MRI conspicuously depicted the uterine tumour. At necropsy 82% (9/11) of the mice developed metastases detected by the applied imaging methods. 18F-FDG PET proved to be a good imaging method for detection of patient derived tumour tissue.ConclusionsWe demonstrate that all imaging modalities enable monitoring of tumour growth and metastatic spread in an orthotopic mouse model of endometrial carcinoma. Both PET tracers, 18F-FDG and 18F-FLT, appear to be equally feasible for detecting tumour development and represent, together with MRI, promising imaging tools for monitoring of patient-derived xenograft (PDX) cancer models.
Highlights
Endometrial cancer is the most common pelvic gynaecologic malignancy in industrialized countries, and the incidence is increasing [1]
Increased bioluminescence imaging (BLI) signal during tumour growth was accompanied by increasing metabolic tumour volume (MTV) and increasing MTV x mean standard uptake value of the tumour (SUVmean) in 18F-FDG and 18F- fluorothymidine (18F-FLT) positron emission tomography–computed tomography (PET-CT), and magnetic resonance imaging (MRI) conspicuously depicted the uterine tumour
We demonstrate that all imaging modalities enable monitoring of tumour growth and metastatic spread in an orthotopic mouse model of endometrial carcinoma
Summary
Endometrial cancer is the most common pelvic gynaecologic malignancy in industrialized countries, and the incidence is increasing [1]. For endometrial cancer, subcutaneous xenograft models have long been employed to explore effect of new treatments [5]. This model enables monitoring of tumour growth by visual inspection and palpation to monitor tumour growth. Orthotopic xenograft models, whereby molecularly defined cancer cell lines or primary patient cells are surgically implanted into the organ of origin, induce disease that more accurately reflect human metastatic patterns and response to therapeutics. Orthotopic endometrial cancer models have been successfully developed [6,7,8] This has provided a valuable research platform for studies of molecular and cellular mechanisms underlying tumour growth and metastatic spread in endometrial cancer [8,9,10,11,12,13]. Novel preclinical imaging methods have the potential to quantify functional tumour characteristics in vivo, with potential relevance for monitoring response to therapy.
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