Abstract 1959: Translational imaging findings in a pediatric patient-derived orthotopic xenograft brain tumor model

Abstract

Abstract Malignant brain tumors are the most common cause of solid cancer death in children. Innovative therapies are vital to improve treatment outcomes, but must be developed to enable trafficking across the blood brain barrier (BBB). For this advent, animal models provide important information prior to clinical studies. Among the different in vivo models orthotopic patient-derived xenograft (PDX) models represent the diversity seen in patient tumors and hence replicate response rates in the clinical trials better as compared to other more simplistic models. Especially in the brain tumor field, imaging has a central role in clinical diagnosis and as a prognostic factor to monitor therapy response. It enables longitudinal patient monitoring in a fully translational manner. 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 target of interest or mechanism of action. 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. In case of orthotopic brain tumor models, MRI offers the state-of-the-art quantitative volumetric tumor size analysis over disease progression. PET is an excellent tool to study tumor proliferation, metabolism, metastasis as well biodistribution of novel antibodies. The purpose of this work was to analyze volumetric, metabolic and functional changes in orthotopic PDX brain tumor model using MRI, MRS and PET imaging. During the course of the experiment, volume, perfusion within the tumor as well proliferation and metastasis were monitored. Perfusion measurement indicates angiogenesis in tumor, one hallmark of most malignant gliomas. Also, alterations in glucose and amino acid metabolism between tumor and healthy tissue has been previously identified. By direct comparison of the imaging data derived from the preclinical mouse model with similar data-sets from the donor patient the translational value of the model as well as the read-out system will be achieved. As a conclusion, translational in vivo imaging techniques were applied to study orthotopic tumor progression. 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: Tuulia Huhtala, Julia Schueler, Jussi Rytkönen, Daniela Lötsch, Dorothee Lenhard, Artem Shatillo, Kimmo Lehtimäki, Pekka Poutiainen, Diana Miszczuk, Johannes Gojol, Walter Berger. Translational imaging findings in a pediatric patient-derived orthotopic xenograft brain tumor model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1959.