Quantitative Analysis of D2 Dopamine Receptor Binding in the Living Human Brain by PET

TLDR

D2 dopamine receptors in the putamen of living human subjects were characterized using the selective, high‑affinity carbon‑11‑labeled raclopride antagonist and positron emission tomography. Experiments in four healthy men showed that [11C]raclopride binding to putamen D2 receptors is saturable with a Hill coefficient near unity, maximum binding of 12–17 pmol cc⁻¹, Kd of 3.4–4.7 nM, and that clinically effective neuroleptics occupy 85–90 % of these receptors in schizophrenic patients.

Abstract

D2 dopamine receptors in the putamen of living human subjects were characterized by using the selective, high-affinity D2 dopamine receptor antagonist carbon-11-labeled raclopride and positron emission tomography. Experiments in four healthy men demonstrated saturability of [ 11 C]raclopride binding to an apparently homogeneous population of sites with Hill coefficients close to unity. In the normal putamen, maximum binding ranged from 12 to 17 picomoles per cubic centimeter and dissociation constants from 3.4 to 4.7 nanomolar. Maximum binding for human putamen at autopsy was 15 picomoles per cubic centimeter. Studies of [ 11 C]raclopride binding indicate that clinically effective doses of chemically distinct neuroleptic drugs result in 85 to 90 percent occupancy of D2 dopamine receptors in the putamen of schizophrenic patients.