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Abstract #0223

Multimodal ASL/PET/mRNA-expression analysis reveals CBF changes after single dose of antipsychotics depend on dopamine D2 receptor density profiles.

Pierluigi Selvaggi1, Mattia Veronese1, Peter C. T. Hawkins1, Ottavia Dipasquale1, Gaia Rizzo2,3, Juergen Dukart4, Fabio Sambataro5, Alessandro Bertolino6, Steven C.R. Williams1, Federico E Turkheimer1, and Mitul A. Mehta1

1Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom, 2Imanova Ltd., Centre for Imaging Sciences, Hammersmith Hospital, London, United Kingdom, 3Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK, London, United Kingdom, 4Translational Medicine Neuroscience and Biomarkers, F. Hoffmann-La Roche Ltd, Basel, Switzerland, 5Department of Experimental and Clinical Medical Sciences, University of Udine, Udine, Italy, 6Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari Aldo Moro, Bari, Italy

In this study, we tested whether CBF changes after acute administration of antipsychotics in healthy volunteers are associated with receptor distribution profiles of one of their main targets, namely the dopamine D2 receptor. Receptor distribution profiles were extracted from an in-house [18F]Fallypride template and from the Human Allen Brain Atlas. Results show that changes in CBF measures are directly proportional to dopamine D2 receptor levels as indexed by PET maps and mRNA expression levels. Overall the present study shows evidence that CBF is ultimately a functional marker which can be adopted in drug challenges to inform the drug development process.

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