Abstract 3041: Molecular, histopathologic, MRI and PET findings in syngeneic oncologic mouse models

Abstract

Abstract Experimental tumors raised in rodents represent an important preclinical tool to develop innovative anticancer compounds before clinical testing. Amongst others such models include solid tumors raised in syngeneic fully immunocompetent hosts and tumors spontaneously growing in genetically engineered mice (GEM) and derivate thereof. These model platforms have gained additional value since the manipulation of the immune system to fight cancer has led to tangible benefits for cancer patients. Imaging has become important part of the basic and translational research. It enables e.g. metabolic activity, volumetric and biodistribution monitoring within same individual over time. Magnetic resonance imaging (MRI) and positron emission tomography (PET) are widely used for clinical diagnosis and disease follow up. Choosing the most suitable imaging application depends of the prioritization of features. MRI offers unprecedented soft tissue contrast, high spatial resolution and non-invasive nature renders MRI in rodents a perfect tool for preclinical work in oncological applications. Similarly to clinical setting, MRI in rodents is used for detection of the tumors, evaluation of therapeutic response and induced changes, with longitudinal follow-up for early detection of possible tumor recurrence. PET is an excellent tool to study tumor metabolism, location as well biodistribution of novel antibodies. The purpose of this work was to study molecular as well volumetric, metabolic and functional changes in syngeneic oncological mouse model using MRI, MRS and PET imaging. Our panel consists of 32 fully characterized mouse tumor models covering 12 major cancer types. We characterized those models by molecular profiling (whole exome sequencing and RNAseq), histopathological examination (tissue micro array as well as whole slide analysis of Ki67, CD31, SMA, TIL infiltration) and sensitivity towards checkpoint inhibitors. Amongst other findings we saw an enhanced activity of anti-CTLA-4 treatment in combination with anti-PD1 in 4T1 orthotopically implanted into the mammary fat pad in comparison to single agent therapy. In a follow-up study we implanted 14 mice with breast cancer cell line 4T1 orthotopically into the mammary fat pad. When tumors were palpable treatment with the checkpoint inhibitor combination started. During the course of the experiment we determined tumor volume of the primary lesion twice weekly. In addition to molecular markers, MRI, MRS and PET were applied to study changes in tumor over cancer progression. As a conclusion, several syngeneic oncological mouse models have been characterized using molecular profiling, histological techniques and in vivo imaging. These readouts provide a powerful and translational research tool together with oncological disease animal models allowing comprehensive evaluation of disease progression and treatment interventions for in vivo studies. Citation Format: Julia Schueler, Artem Shatillo, Jussi Rytkönen, Nina Zanella, Antti Nurmi, Tuulia Huhtala. Molecular, histopathologic, MRI and PET findings in syngeneic oncologic mouse models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3041.