Molecular imaging in neurodegenerative diseases

NeuroImage 52 (2010) S9

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NeuroImage j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / y n i m g

NRM2010 Abstracts – Keynote Presentations

Keynote Lecture 1

What makes a good PET radioligand for brain imaging? Victor W. Pike Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA Positron emission tomography (PET) provides a uniquely powerful means for quantifying low density protein targets, such as enzymes, plaques, transporters and receptors, in the living human brain and therefore for investigating neuropsychiatric disorders and aiding CNS drug development, provided that suitable radioligands are available. The development of such radioligands requires considerable investment of resources, and is not unlike drug development itself, since candidate radioligands may fail at any stage of development leading through to application in human subjects. The properties sought in candidate radioligands are not necessarily those found in candidate CNS drugs. Effective PET radioligands must generally meet a set of demanding criteria that promote or ensure desirable properties, such as their amenability to labeling with a positron-emitter, ability to enter the brain, expression of high specific binding and low nonspecific binding, and lack of troublesome radiometabolites. This talk will examine traditional criteria for designing and developing PET radioligands for imaging protein targets in the brain and how these criteria can now be hardened or refined in view of accumulating experience, new methodology and new challenges. Application of these evolving criteria along with emerging technologies should bolster the development of novel PET radioligands for brain imaging. Acknowledgment: VWP is supported by the Intramural Research Program of the National Institutes of Health (NIMH). doi:10.1016/j.neuroimage.2010.04.189

Keynote Lecture 2

Molecular imaging in neurodegenerative diseases David Brooks Division of Experimental Medicine, Imperial College, London, UK Functional imaging approaches such as positron emission tomography (PET) and single photon emission computerised tomography (SPECT) sensitively demonstrate changes in metabolism, receptor availability, and transmitter fluxes in neurodegenerative disorders such as Alzheimer's, Parkinson's, and Huntington's diseases. Disease activity can now be detected at a preclinical stage in at risk subjects and the effects of putative protective and restorative therapies on neuronal function and clearance of abnormal protein aggregations, such as amyloid, can be monitored in vivo so providing proof of mechanism. It has become clear that microglial activation plays an important role in driving disease progression but also in aiding adaptation to loss of connections. TSPO radioligands now allow glial activity to be quantitated and opens the door for the use of molecular imaging as a biomarker to measure the efficacy of anti-inflammatory strategies in neurodegenerative disease. This talk will highlight some of these areas and discuss future directions. doi:10.1016/j.neuroimage.2010.04.190