Design of new 18F-labelled radiopharmaceuticals for brain tumor imaging

Glioblastoma multiforme is the most aggressive type of primary brain tumor with a median overall survival (OS) of about 12 months. Brain metastases are the most common form of brain tumors and significantly outnumber primary brain tumors, with the majority originating from lung cancer, especially non–small cell lung cancer (NSCLC). Despite aggressive treatment, their prognosis is also poor with a median OS of approximately 7 months after diagnosis. Treatment of those tumors remains one of the most challenging tasks in clinical oncology. Although new molecular pathways in tumor biology are being constantly discovered, translation of basic science achievements into clinical practice is rather slow. Major obstacles in resistance to therapy are heterogeneity of brain tumors, multiple genetic alterations, and their diffuse, infiltrative behaviour. Hence identifying and investigating pathways related to tumor etiology and growth is highly important. Positron emission tomography (PET) offers the potential to identify key signaling pathways in brain tumors involving neurotransmitters and -modulators and to discover drugs which may be used for their therapy.
One of the most important prerequisites for PET is the development and evaluation of radiolabelled ligands in order to investigate brain functions in living human subjects. Fluorine-18 is currently the most favorable radionuclide that is routinely used for radiolabeling because of its half-life of 109.8 min. The use of PET radioligands provides brain images of transport, metabolic and neurotransmission processes on the molecular level. PET is currently the most sensitive and specific method for this type of studies. Through integration of chemical/radiochemical, pharmaceutical/radiopharmaceutical, biochemical and radiopharmacological basic research, computational chemistry and with the aid of nuclear medicine diagnostic new approaches in brain tumor treatment will be made available. The presentation will focus on the strategy of radiotracer development bridging from basic science to biomedical application focusing on targets of major importance for the mentioned tumors such as cannabinoid, sigma and nicotinic alpha7 receptors.