Imagerie moléculaire du transporteur vésiculaire de l’acétylcholine (VACh) par le [ 123I]-5-iodobenzovézamicol dans la démence de type Alzheimer (DTA)

Abstract

Alzheimer's disease (AD) is characterized by a premature decline of cholinergic neurons. The 5-IBVM is an analogue of the vesamicol that binds to the presynaptic vesicular acetylcholine transporter (VAChT). The exploration of this target should be useful to make an early diagnosis of AD. Our first aim was to propose a method of non invasive VAChT quantification according to 5-IBVM kinetic. 5-IBVM was injected to four AD patients (age = 77 ± 3.9 years and MMSE = 24.5 ± 1.02) were included in this methodological study. The single-photon emission computed tomography (SPECT) images were obtained at five, 20, 35 and 50 minutes, at then at three, five and 22 hours after intravenous injection of 5-IBVM (185MBq). The time activity curves were obtained after SPECT images coregistration on a MRI masque. Specific volume of interest (SPE = SPEcific) were manually drawn on striatum, pons, thalamus and para-hippocampic gyrus including hippocampus; reference volumes of interest (REF = REFerence) were drawn on frontal and occipital cerebral cortex. On the basis of uptake kinetic, two modelisation approaches were considered: transient equilibrium model for reversible ligand (binding potential (BP) = (SPE − REF)/REF) and Patlak graphical analysis for irreversible tracers (slope given by K i/DV ref where K i is the influx contant and DV ref is the distribution volume of the reference region). We observed an inflection or a stady state of the activity curves in the different regions studied between 250 and 1400 minutes, what seems to confirm that the tracer is little reversible. BP values obtained at 21 hours with occipital areas as reference and K i/DV ref values were respectively 4.62 ± 0.42 and 0.07 ± 0.01. The SPE classification according to BP and K i/DV ref values were similar to the classification according to the compartmental analysis (Kuhl 1994). The transient equilibrium model with late acquisition seems the more suitable because IBVM kinetic and practical simplicity of performing in clinical routine.