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 Rizzo^2,3, 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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