EC50 images, a novel endpoint from PET target occupancy studies, reveal spatial variation in apparent drug affinity

• Published in: European journal of nuclear medicine and molecular imaging Vol. 49; no. 4; pp. 1232 - 1241
• Main Authors: de Laat, Bart, Hoye, Jocelyn, Liu, Heather, Morris, Evan D.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.03.2022; Springer Nature B.V
• Subjects: Affinity; Brain; Cardiology; Drug development; Drug dosages; Flumazenil; Image filters; Imaging; Medicine; Medicine & Public Health; Miscellanea; Neuroimaging; Nuclear Medicine; Occupancy; Oncology; Original Article; Orthopedics; Positron emission; Positron emission tomography; Radiology; Regional development; Spatial variations; Tomography; γ-Aminobutyric acid A receptors; Lassen plot filter; Simulations; model; Model selection; Dose selection

Purpose We recently introduced voxel-level images of drug occupancy from PET via our “Lassen plot filter.” Occupancy images revealed clear dependence of 11 C-flumazenil displacement on dose of GABAa inhibitor, CVL-865, but with different scales in different brain regions. We hypothesized that region...