Present and future capabilities of molecular imaging techniques to understand brain function

Abstract

This article focuses on the use of positron emitting tracers and positron emission tomography (PET) as the most specific and sensitive means for imaging molecular interactions and pathways within the human brain. The concept of the imaging science of PET is developed whereby the key components that contribute to the overall accuracy of the image of molecular activity need to be separately optimized. These include radiolabelling of tracer molecules and ligands with radioisotopes of short radioactive half-life, the search for specific radioligands and tracers, and hence the need to mine molecular databases for molecules suitable for in-vivo imaging. The sensitivity and accuracy of PET scanners need to be advanced along with improvements in the signal-to-noise ratio of the tomographic reconstruction algorithms. Finally, the models used for the analysis of serial time frames of kinetic data need to be developed, the operation of which have to be effected with the minimum of noise propagation. The future use of PET for drug discovery and development is discussed whereby it offers proof principle for assays of in-vivo expression of therapeutic molecular targets as accessed from the blood stream; tissue pharmacokinetics of novel compounds; degree of occupancy of molecular targets; and pharmacodynamic measures of drug action. The future application of PET rests heavily on drug discoverers contributing to discovering specific PET radioligands and tracers in order to provide these assays through in-vivo molecular imaging.