Comparison of noninvasive quantification methods of in vivo vesicular acetylcholine transporter using [123I]-IBVM SPECT imaging.

Dementia with Lewy Body and Alzheimer's disease exhibit degeneration of the cholinergic neurons, and currently, the primary target of treatment is the cholinergic neurotransmitter system. [(123)I]-IBVM is a highly selective radioligand for in vivo visualization of the vesicular acetylcholine transporter (VAChT) using single photon emission computed tomography. This study compares different noninvasive methods using the occipital cortex as a reference region for the quantification of [(123)I]-IBVM binding in six older, healthy volunteers: two kinetic analyses based on one-tissue (1TCM) or two-tissue compartment model (2TCM), one linear and one multilinear analysis, and a simplified peak equilibrium analysis. Time-activity curves were well described by a 1TCM for all regions. The 2TCM converged reliably only in the striatum. Goodness of fit was not improved by using a 2TCM as compared with a 1TCM. The multilinear analysis gave binding potentials similar to the 1TCM while being more robust. The peak equilibrium method might prove to be a useful simplified analysis. The binding potentials obtained with reference region methods strongly correlated with results from invasive blood-sampling analysis. Noninvasive quantification of [(123)I]-IBVM data provides reliable estimates of VAChT binding, which is most valuable to study neurodegenerative diseases with specific cholinergic alteration.

In vivo SPECT imaging of vesicular acetylcholine transporter using [(123)I]-IBVM in early Alzheimer's disease.

INTRODUCTION: Little is known about cholinergic activity in the early stage of Alzheimer's disease. We investigated differences in the distribution of vesicular acetylcholine transporter, using [(123)I]-iodobenzovesamicol ([(123)I]-IBVM) and Single Photon Computed Tomography (SPECT), in early AD and age-matched controls. MATERIALS AND METHODS: Sixteen subjects (8 controls, 8 AD) underwent [(123)I]-IBVM SPECT scanning, T1-weighted anatomic scan by Magnetic Resonance (MR) imaging and Mini-Mental State Evaluation (MMSE). Image analysis, using Statistical Parametric Mapping (SPM 02), involved coregistration of each SPECT image to the MR scan, followed by a spatial normalisation to the Montreal Neurological Institute standard brain and a smoothing of each SPECT image. Group effects and correlation were assessed using two sample t-tests and linear regression respectively. Atrophy difference between the two groups was assessed by voxel-based morphometry of each MR scan using two sample t-tests. RESULTS: MMSE values were significantly different between AD and controls. Relative to controls, a significant decrease in [(123)I]-IBVM binding (47-62%) was apparent in AD subjects in cingulate cortex and parahippocampal-amygdaloïd complex. These patterns appeared to be independent of atrophied areas. CONCLUSION: These results strongly suggest that a cholinergic degeneration occurs in the early stage of AD and could be involved in the impairment of the cognitive functions. Imaging of cholinergic neurons used here could be effective in identifying potential cholinergic treatment responders.

[I131 in blood samples: management in the laboratory]. / Gestion au laboratoire d'échantillons de sang de patients traités par iode radioactif.

OBJECTIVES: Patients treated by (131)I may require blood sampling in the days following its administration. We investigated the safety of such samples in terms of radioactivity and the possible disturbance of the analyses by these "131I-spiked" samples. METHOD: 1) The radioactivity of blood samples from 131I-treated patients was measured (dose rate, surface activity, total activity) ; 2) The risk for the personnel was subsequently evaluated and ; 3) The interference of this 131I-generated radioactivity on the results of routine automated and IRMA assays was investigated. RESULTS: 1) All RA measures but two were found below the European limits ; 2) Irradiation of personnel was negligible ; 3) The faint radioactivity did not disturb any analyses. CONCLUSION: These data demonstrate the safety that results from the negligible radioactivity in these blood samples.