The blood-brain barrier (BBB) permeabilities of 11 compounds were measured both in vitro with a newly developed coculturebased model of human BBB and in vivo with positron emission tomography (PET -ureas, and -amides). The in vitro BBB model, a new coculture system of primary human brain endothelial cells and astrocytes, was used to measure the permeability coefficient for each compound. Dynamic PET studies were performed in rats with the same compounds, and a twocompartment model analysis was used to calculate their in vivo permeability coefficients. The 11 derivatives differed in their degree of BBB passage and transport mechanism. The analysis of PET data showed a significant cerebral uptake for six derivatives, for which the in vitro evaluation indicated active influx or free diffusion. Five derivatives displayed low in vivo cerebral uptake, in agreement with the observation of an in vitro active efflux. Overall, there was a remarkable correlation between the in vitro and in vivo permeability coefficients (r ϭ 0.99). This double study proves a close correlationship between the assessment of the BBB passage in vitro and in vivo. The in vitro model of human BBB offers the possibility of subtle discrimination of various BBB permeability degrees and transport mechanisms. Conversely, small animal PET imaging appears suitable to screen directly in vivo brain targeting of drugs or radiopharmaceutical candidates.In mammals, the presence of tight junctions connecting the endothelial cells of the brain vessels creates a blood-brain barrier (BBB) that limits, to a considerable extent, the delivery of systemically administered drugs to the central nervous system (CNS). In addition, specific metabolizing enzymes and efflux pumps located within the endothelial cells actively degrade or reject exogenous molecules out of the brain (Schinkel et al

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