Small animal imaging of Glioblastoma – PET/SPECT radiotracer development and validation

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Despite decades of research in oncology, cancer often remains incurable causing an burden to the patient, health care system and economy. The cancer occurrence will increase and amplify its effects in future. Hence, intensive research in the development of advanced diagnostic approaches is needed to enhance cancer management. Multimodality imaging of tumor microenvironment is available to optimize personalized treatment. In particular glioblastoma (GBM) with its high proliferation rate is not curable and the median survival is 14.6 month. In clinical routine the use of molecular imaging techniques like PET and SPECT have shown promising results. However, there is a need of finding suitable PET/SPECT imaging targets with the potential to enhance diagnosis, staging, and treatment approaches for GBM.
Small animal PET/SPECT can be combined with other imaging techniques to follow the tumor development and treatment. Combining these techniques provides additional important information.
Using PET/SPECT, changes in the biological processes can be detected and treated at an earlier stage compared to traditional methods and hence earlier humane and scientific endpoints can be established in order to reduce the burden on the animals. (Refinement). This in turn minimizes the discomfort and amount of research animals in use (Reduction). As a tumor is a complex system, the use of live animals can not be fully avoided (Replacement). However, this combined imaging is superior to conventional diagnostics and enables the repeated use of one animal, which can serve as its own control and hence, reduce the total number of animals in use. (Reduction)
The methods are available at PETcore facility and research is being built upon them. Establishing protocols for all imaging modalities is evaluated in the FOTS application 18956, 22916 and 19743 and the brain tumor model was established under 19743.
The application’s aim is to develop and validate PET/SPECT radiotracers and protocols (already established in healthy mice. FOTS 22916) in mouse models of cancer (Cell line derived xenografts and syngeneic mouse models. Ectopic (sc implantation) and orthotopic (ic. implantation) models). The goal is to define promising radiotracer(s) to image brain tumors (glioblastoma) and evaluate targets as diagnostic tools for brain cancer imaging in these particular mouse models. This information will be used for the further planning of animal experiments for brain cancer imaging.
The animals will be monitored daily throughout the whole study by animal facility personal and 3 times/week more closely by the researcher in charge. In addition, animals will be sedated during imaging and euthanized at the end of the protocol. All imaging including ultrasound will be performed before adverse symptoms due to brain tumor growth occur. If untreatable neurological or clinical symptoms are detected, the animal will be euthanized under deep anesthesia. The use of tumor-bearing animals is unavoidable to study in vivo the complex tumor microenvironment with PET imaging.
We are applying for a maximum of 1440 athymic nude mice and 960 C57Bl/6J mice. Developed protocols from FOTS applications 18956, 22916 and 19743 will be used and data processed for intensive image driven analysis at our facility.