PET-based molecular imaging in neuroscience

Abstract

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.

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“…These reporter genes, under control of engineered promoters and enhancers that take advantage of host-cell transcriptional machinery, are introduced into cells by using a variety of vector and nonvector methods (5). Once in the cell, reporter genes can be transcribed either constitutively or only under specific biological or cellular conditions, depending on the type of promoter used (29,30,32). Transcription and translation of reporter genes into bioactive proteins is then detected with sensitive, noninvasive instrumentation (for example, charge-coupling device cameras) by using signal-generating probes such as D-luciferin for optical imaging (30).…”

“…Although MRI has been extensively used to track cells repeatedly in vivo (37), the higher specificity of positron emission tomography (PET) ligands and the ability of PET to detect reporter genes are promising features for the development of long-term in vivo monitoring of transplanted cells. Such molecular imaging has expanded the role of PET from the research domain into clinical application for neurosciences (6,32,38). Currently, PET is being used as a clinical molecular-imaging tool in neurosurgery.…”

Molecular Medicine Successes in Neuroscience

“…In contrast to visualizing the terminal effects of disease, molecular imaging probes the molecular alterations underlying disease, providing additional biochemical or molecular information compared with histological methods and classic neuroradiological diagnostic studies (3). Early identification of treatment success or failure in neurological diseases by molecular imaging could significantly influence patient management by providing more objective decision criteria for evaluation of specific therapeutic strategies.…”

“…PET, developed to visualize biochemical and physiological phenomena in living humans and animals (2,3), is the foundation of molecular imaging. Magnetic resonance imaging (MRI), an alternative molecular imaging method, is becoming more influential in neuroscience and clinical neurology (5).…”

“…This functional and molecular imaging technique has progressed rapidly from laboratory research technique to routine clinical imaging modality. Advances in detector technology have led to considerable improvements in the spatial resolution of PET (1-2 mm), enabling investigation for the first time in small experimental animals such as mice (3). Developments in radiochemistry and tracer technology have allowed a variety of endogenously-expressed and exogenously-introduced genes to be analyzed using PET (6).…”