In Vivo Studies of Drug BBB Transport: Translational Challenges and the Role of Brain Imaging.

ABSTRACT

Drug delivery to the brain is challenging to study due to the complexity of the barriers of the central nervous system (CNS). The present chapter describes and compares experimental methods such as microdialysis, two-photon laser scanning fluorescence microscopy and positron emission tomography (PET) that can be used for in vivo studies of drug transport across the blood-brain barrier (BBB). The selection of appropriate method is based on the research question, and the different methods will in most cases provide complementary information. Attention is also given to the fact that the BBB might undergo changes in integrity, protein expression and other morphological alterations as a result of disease. The use of animal models of human disease is therefore also discussed. Special emphasis is given to translational aspects of the different methods and readouts.