EC50 images reveal reproducible spatial variation in drug affinity across single- and repeat-dose occupancy studies.

Alaaddin Ibrahimy¹, Su Jin Kim², Mark E Schmidt³, Mark Slifstein⁴, Erik Mannaert³, Randolph D Andrews⁵, Dawn C Matthews⁵, Cristian C Constantinescu⁶, Graham E Searle⁷, Roger N Gunn^7,8, Eugenii A Rabiner⁹, Evan D Morris^1,2,10

¹Biomedical Engineering Department, Yale University, New Haven, CT, USA.

²Psychiatry Department, Yale University, New Haven, CT, USA.

³Johson&Johnson Innovative Medicine, Beerse, Belgium.

⁴Stony Brook University, Stony Brook, NY, USA.

⁵ADM Diagnostics Inc., Northbrook, IL, USA.

⁶Perceptive Discovery, New Haven, CT, USA.

⁷XingImaging - A Mitro Company, London, UK.

⁸Department of Brain Sciences, Imperial College London, London, UK.

⁹Perceptive Discovery, London, UK.

¹⁰Radiology Department, Yale University, New Haven, CT, USA.

PubMed PMC DOI PDF

Abstract

We investigated spatial variation in the apparent affinity of the D2 antagonist drug, JNJ-37822681, for dopamine receptors across single-dose (SD) and repeat-dose (RD) PET occupancy studies. Traditional whole-brain EC50 estimates overlook potential spatial variation in drug affinity. We reanalyzed PET occupancy data from two published studies in healthy male volunteers (SD: administering 1 dose be…

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