Specific biomarkers of receptors, pathways of inhibition and targeted therapies: pre-clinical developments.

A deeper understanding of the role of specific genes, proteins, pathways and networks in health and disease, coupled with the development of technologies to assay these molecules and pathways in patients, promises to revolutionise the practice of clinical medicine. Especially the discovery and development of novel drugs targeted to disease-specific alterations could benefit significantly from non-invasive imaging techniques assessing the dynamics of specific disease-related parameters. Here we review the application of imaging biomarkers in the management of patients with brain tumours, especially malignant glioma. In our other review we focused on imaging biomarkers of general biochemical and physiological processes related with tumour growth such as energy, protein, DNA and membrane metabolism, vascular function, hypoxia and cell death. In this part of the review, we will discuss the use of imaging biomarkers of specific disease-related molecular genetic alterations such as apoptosis, angiogenesis, cell membrane receptors and signalling pathways and their application in targeted therapies.

Specific biomarkers of receptors, pathways of inhibition and targeted therapies: clinical applications.

A deeper understanding of the role of specific genes, proteins, pathways and networks in health and disease, coupled with the development of technologies to assay these molecules and pathways in patients, promises to revolutionise the practice of clinical medicine. In particular, the discovery and development of novel drugs targeted to disease-specific alterations could benefit significantly from non-invasive imaging techniques assessing the dynamics of specific disease-related parameters. Here we review the application of imaging biomarkers in the management of patients with brain tumours, especially malignant glioma. This first part of the review focuses on imaging biomarkers of general biochemical and physiological processes related to tumour growth such as energy, protein, DNA and membrane metabolism, vascular function, hypoxia and cell death. These imaging biomarkers are an integral part of current clinical practice in the management of primary brain tumours. The second article of the review discusses the use of imaging biomarkers of specific disease-related molecular genetic alterations such as apoptosis, angiogenesis, cell membrane receptors and signalling pathways. Current applications of these biomarkers are mostly confined to experimental small animal research to develop and validate these novel imaging strategies with future extrapolation in the clinical setting as the primary objective.

Imaging noradrenergic influence on amyloid pathology in mouse models of Alzheimer's disease.

INTRODUCTION: Molecular imaging aims towards the non-invasive characterization of disease-specific molecular alterations in the living organism in vivo. In that, molecular imaging opens a new dimension in our understanding of disease pathogenesis, as it allows the non-invasive determination of the dynamics of changes on the molecular level. IMAGING OF AD CHARACTERISTIC CHANGES BY microPET: The imaging technology being employed includes magnetic resonance imaging (MRI) and nuclear imaging as well as optical-based imaging technologies. These imaging modalities are employed together or alone for disease phenotyping, development of imaging-guided therapeutic strategies and in basic and translational research. In this study, we review recent investigations employing positron emission tomography and MRI for phenotyping mouse models of Alzheimer's disease by imaging. We demonstrate that imaging has an important role in the characterization of mouse models of neurodegenerative diseases.

PET-based molecular imaging in neuroscience.

Positron emission tomography (PET) allows non-invasive assessment of physiological, metabolic and molecular processes in humans and animals in vivo. Advances in detector technology have led to a considerable improvement in the spatial resolution of PET (1-2 mm), enabling for the first time investigations in small experimental animals such as mice. With the developments in radiochemistry and tracer technology, a variety of endogenously expressed and exogenously introduced genes can be analysed by PET. This opens up the exciting and rapidly evolving field of molecular imaging, aiming at the non-invasive localisation of a biological process of interest in normal and diseased cells in animal models and humans in vivo. The main and most intriguing advantage of molecular imaging is the kinetic analysis of a given molecular event in the same experimental subject over time. This will allow non-invasive characterisation and "phenotyping" of animal models of human disease at various disease stages, under certain pathophysiological stimuli and after therapeutic intervention. The potential broad applications of imaging molecular events in vivo lie in the study of cell biology, biochemistry, gene/protein function and regulation, signal transduction, transcriptional regulation and characterisation of transgenic animals. Most importantly, molecular imaging will have great implications for the identification of potential molecular therapeutic targets, in the development of new treatment strategies, and in their successful implementation into clinical application. Here, the potential impact of molecular imaging by PET in applications in neuroscience research with a special focus on neurodegeneration and neuro-oncology is reviewed.