Importance of the blood-brain barrier for neuroimaging studies

The blood-brain barrier (BBB) is a control system to preserve homeostasis in the nervous system, facilitating the entry of necessary metabolites, but blocking the entry or facilitating the removal of unnecessary metabolites or toxic substances. For any solute the efficacy of the exclusion or transport is determined by the morphological and functional characteristics of the brain capillaries and by the biochemical and biophysical characteristics of the solute. This applies also for radiotracers which are used for brain imaging. Several transport routes across the BBB exist. Therfore, the transport of radiotracers depends on the functional status of the brain endothelium. Studies were performed to investigate the expression and function of various transport systems at the BBB, such as ABC transporters, aquaporins, glucose, amino acid, choline and serotonin transporters. The influence of drugs, hormones and brain development on transport processes has been explored. Our main findins are: (1) The brain uptake of certain ^99m/99Tc-labelled radiotracers is reduced by the presence of drug efflux transporters, e.g: P-glycoprotein. (2) Peptide hormones selectively alter the water permeability and the transport of neutral amino acids at the BBB. (3) The BBB transport of neutral amino acids decreases during development. (4) The transport of basic drugs from blood to brain is partly mediated by the BBB choline transporter. (5) The transport of the PET radiotracer [¹¹C]McN5652 is mediated by the serotonin transporter at the BBB but of no relevance for human PET studies. It is concluded that the transport of radiotracers across the BBB does not solely depend on the lipophilicity of the compounds. Active and regulated efflux systems need to be considered. For many radiotracers specific transport systems exist, which underlie developmental changes and physiological regulation. Nutrient transporter, e. g. for glucose, amino acids and choline, are of special importance.