Abstract
This review highlights the added value of PET imaging in Central Nervous System (CNS) tumors, which is a tool that has rapidly evolved from a merely diagnostic setting to multimodal molecular diagnostics and the guidance of targeted therapy. PET is the method of choice for studying target expression and target binding behind the assumedly intact blood–brain barrier. Today, a variety of diagnostic PET tracers can be used for the primary staging of CNS tumors and to determine the effect of therapy. Additionally, theranostic PET tracers are increasingly used in the context of pharmaceutical and radiopharmaceutical drug development and application. In this approach, a single targeted drug is used for PET diagnosis, upon the coupling of a PET radionuclide, as well as for targeted (nuclide) therapy. Theranostic PET tracers have the potential to serve as a non-invasive whole body navigator in the selection of the most effective drug candidates and their most optimal dose and administration route, together with the potential to serve as a predictive biomarker in the selection of patients who are most likely to benefit from treatment. PET imaging supports the transition from trial and error medicine to predictive, preventive, and personalized medicine, hopefully leading to improved quality of life for patients and more cost-effective care.
Highlights
Since the emerge of molecular biology in the 1930s, the discipline has undergone significant changes, which can be largely attributed to the description of DNA as a double-helical structure in 1953, the accomplishment of the Human Genome Project in 2003, and the rapid development of advanced diagnostic technologies
Companion diagnostics are a prerequisite for receiving the corresponding therapeutic product, which is exemplified by the human epidermal growth factor receptor 2 (HER2) gene expression assessment by immunohistochemistry (IHC) in patients with breast cancer to determine whether they are eligible for trastuzumab treatment [4]
Receptor tyrosine kinases (RTKs) consist of an extracellular domain, which can be targeted with monoclonal antibody-based inhibitory drugs, while the intracellular signal cascades can be inhibited by small molecule tyrosine kinase inhibitors (TKIs) via competition with adenosine triphosphate (ATP) [132]
Summary
Since the emerge of molecular biology in the 1930s, the discipline has undergone significant changes, which can be largely attributed to the description of DNA as a double-helical structure in 1953, the accomplishment of the Human Genome Project in 2003, and the rapid development of advanced diagnostic technologies. Companion diagnostics are a prerequisite for receiving the corresponding therapeutic product, which is exemplified by the human epidermal growth factor receptor 2 (HER2) gene expression assessment by immunohistochemistry (IHC) in patients with breast cancer to determine whether they are eligible for trastuzumab treatment [4] This is in opposition to complementary diagnostics, for which the FDA recently presented a draft definition being: “tests that identify a biomarker-defined subset of patients that respond well to a drug and aid risk/benefit assessments, but that are not a prerequisite for receiving the drug” [4]. Tumor material is generally obtained only once or twice during the disease course, at time of diagnosis and/or disease progression, or in very few cases from post-mortem autopsy These limitations impede a thorough analysis of both spatial and temporal heterogeneity and treatment effects over time, which may lead to misclassification and reduce the chance of developing therapies that are able to outwit all (adapting) carcinogenic mechanisms. We appreciate these developments at multiple levels, with special consideration for the added value in the challenging field of neuro-oncology, where PET imaging can serve as a sensitive diagnostic tool enabling non-invasive studies of tumor characteristics at multiple sites over time, but can serve as an in vivo theranostic tool guiding drug development and drug delivery studies by display of target expression and target binding behind the assumedly intact blood–brain barrier (BBB) [9,10]
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