Dataset Information

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-[(18)F]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.

SUBMITTER: Kimes AS

PROVIDER: S-EPMC2386978 | biostudies-literature | 2008 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Kimes Alane S AS Chefer Svetlana I SI Matochik John A JA Contoreggi Carlo S CS Vaupel D Bruce DB Stein Elliot A EA Mukhin Alexey G AG

NeuroImage 20070919 2

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-[(18)F]F-A85380 (2FA). Seven volunteers underwe ...[more]

PMID: 17962044

Similar Datasets

Project description:The positron emission tomography (PET) radioligand (-)-[(18)F]flubatine is specific to ?4?2(?) nicotinic acetylcholine receptors (nAChRs) and has promise for future investigation of the acetylcholine system in neuropathologies such as Alzheimer's disease, schizophrenia, and substance use disorders. The two goals of this work were to develop a simplified method for ?4?2(?) nAChR quantification with bolus plus constant infusion (B/I) (-)-[(18)F]flubatine administration, and to assess the radioligand's sensitivity to acetylcholine fluctuations in humans. Healthy human subjects were imaged following either bolus injection (n=8) or B/I (n=4) administration of (-)-[(18)F]flubatine. The metabolite-corrected input function in arterial blood was measured. Free-fraction corrected distribution volumes (VT/fP) were estimated with modeling and graphical analysis techniques. Next, sensitivity to acetylcholine was assessed in two ways: 1. A bolus injection paradigm with two scans (n=6), baseline (scan 1) and physostigmine challenge (scan 2; 1.5mg over 60min beginning 5min prior to radiotracer injection); 2. A single scan B/I paradigm (n=7) lasting up to 240min with 1.5mg physostigmine administered over 60min beginning at 125min of radiotracer infusion. Changes in VT/fP were measured. Baseline VT/fP values were 33.8±3.3mL/cm(3) in thalamus, 12.9±1.6mL/cm(3) in cerebellum, and ranged from 9.8 to 12.5mL/cm(3) in other gray matter regions. The B/I paradigm with equilibrium analysis at 120min yielded comparable VT/fP values with compartment modeling analysis of bolus data in extrathalamic gray matter regions (regional means <4% different). Changes in VT/fP following physostigmine administration were small and most pronounced in cortical regions, ranging from 0.8 to 4.6% in the two-scan paradigm and 2.8 to 6.5% with the B/I paradigm. These results demonstrate the use of B/I administration for accurate quantification of (-)-[(18)F]flubatine VT/fP in 120min, and suggest possible sensitivity of (-)-[(18)F]flubatine binding to physostigmine-induced changes in acetylcholine levels.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure