Quantification of nicotinic acetylcholine receptors in the human brain with PET: Bolus plus infusion administration of 2-[ 18F]F-A85380

Abstract

Quantitative analysis of most positron emission tomography (PET) data requires arterial blood sampling and dynamic scanning when the radioligand is administered as a bolus injection. Less invasive studies can be accomplished if the radioligand is administered as a bolus plus constant infusion (B/I). The purpose of the current study was to evaluate a B/I paradigm for quantifying high affinity nicotinic acetylcholine receptors (nAChRs) with PET and 2-[ 18F]F-A85380 (2FA). Seven volunteers underwent a study in which 2FA was administered as a bolus injection and another study in which the 2FA was administered by B/I (Kbolus = 500 min). We evaluated the feasibility of using scans of a 2 h duration starting 6 h after the start of the 2FA administration and data from venous blood. Radioactivity in the brain and in arterial and venous plasma reached steady state by 6 h. Volumes of distribution ( V T) calculated from the ratio of radioactivity in the brain areas of interest to the radioactivity corresponding to unbound, unmetabolized 2FA in venous plasma at steady state in the B/I studies were very similar to those calculated from time activity curves of unbound, unmetabolized 2FA in arterial plasma and regional brain radioactivity from 8-h dynamic scans after bolus administration of 2FA. The results of repeated PET studies with 2FA showed a high reproducibility of V T measurements. We conclude that B/I methodology will be useful for clinical and research studies of brain nAChRs.