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BEHANDLING-God og treffsikker diagnostikk, behandling og rehabilitering

IMAGINE: Imaging molecular mechanisms of angiogenesis in glioma-associated neovasculature

Alternative title: IMAGINE: Avbildning av molekylære mekanismer som styrer blodårevekst i hjernetumor

Awarded: NOK 12.0 mill.

Glioblastoma is one of the deadliest forms of cancer, and there is an urgent and unmet need to improve treatment strategies. A significant challenge is that glioblastomas are heterogeneous; therefore future treatment advances must be tailored to each patients? unique and specific molecular features. Such patient-specific and personalized treatment approach requires precise and accurate imaging diagnostics. In this study, we will use advanced imaging techniques such as Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) to measure molecular features of the cancer cells and the microenvironment. More specifically, these imaging techniques will provide knowledge on a new cancer therapy at Oslo University Hospital (OUH), aiming to reduce the unwanted pressure from a growing tumor. We aim to use this knowledge to predict which patients who will be benefit from this new treatment regimen, and hopefully get one step closer to becoming truly personalized medicine. Since the start of patient recruitment in October 2020, two pilot patients have been included and scanned on PET/CT and MRI. According to study protocol, each patient underwent two PET/CT examinations; first at baseline, then 2 weeks after start of treatment. The coordination of patient logistics between departments has been successful, and we are currently in an active recruitment phase following a formal study initiation meeting in September 2021 as per good clinical practice. To ensure optimal quantitative imaging data, a phantom study has been conducted to determine the accurate reconstruction parameters for the study-specific imaging protocol. The results from this work will be orally presented at the European Association of Nuclear Medicine (EANM) annual meeting in October 2021. Also, a manuscript is currently prepared and will be submitted before the end of 2021 project period. Finally, we are currently developing methods for assessing and quantifying vasculature as observed on the MR images. This has led to a range of published works in 2021 (please refer results section)

Glioblastoma is one of the deadliest forms of cancer and the primary goal of treatment is simply to decelerate tumor growth. Still, after decades of research, standard-of-care for these brain tumors only includes surgery, radiotherapy and chemotherapy. A significant challenge of therapy is reduced penetration of anti-cancer drugs from a dysfunctional and impaired tumor vasculature. Oslo University Hospital (OUH) is currently spearheading an international effort to identify and alleviate impaired perfusion directly in brain cancer patients by targeting the abnormal physical forces of the tumor microenvironment. Using a safe and affordable anti-hypertensive medicine, an angiotensin II receptor blocker (ARB), we will remove the physical barriers of the extracellular matrix that prevent anti-cancer drugs from reaching their target. However, glioblastomas are notoriously heterogeneous, and we hypothesize that a specific physical, vascular and metabolic 'signature' is required for ARBs to have an impact on treatment. Intriguingly, the natural interplay of these mechanisms in patients may only be assessed by in vivo imaging and we therefore build on current efforts by performing a clinical imaging study using a novel Positron Emission Tomography (PET) tracer in combination with Magnetic Resonance Imaging (MRI). This study will reveal the unique and patient-specific signature of the cancers' microenvironment and bring current treatments options one step closer to becoming truly personalized medicine.


BEHANDLING-God og treffsikker diagnostikk, behandling og rehabilitering