Abstract
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Objectives: Even if cholinergic impairment has been shown in Alzheimer's and Lewy bodies dementia, little is known about cholinergic impairment in the earlier stages of the disease, which constitute a crucial step for conceiving prevention trials and optimizing the treatment efficiency. With this aim, we studied the feasibility of non-invasive cholinergic activity quantification in human brain.
Methods: A SPECT acquisition was performed over 6 hours for a group of six healthy subjects following intravenous injection of 233MBq [123I]-IBVM. The binding potential BP* was determined in several brain regions using reference region methods: two kinetic models (two compartments FRTM and one compartment SRTM), a multi-linear model (MRTM) and a graphical model (Logan non-invasive) where the reference region was the occipital cortex. The results were also compared to published data obtained by invasive blood sampling kinetic modelling (Kuhl et al., 1999).
Results: FRTM converged for all subjects only in the striatum where no significant difference was found with SRTM indicating that a one tissue compartment model might be adequate. This is also supported by a t* close to 0 for MRTM and Logan. For all regions, no real difference was found between SRTM, MRTM and Logan with however better BP* estimation accuracy obtained with MRTM. A good correlation (>0.83) was found between BP* estimated by SRTM, MRTM and Logan and the k3 quantification index used by Kuhl.
Conclusions: Non invasive estimation of BP* was found to produce results in agreement with previously published data obtained with invasive methods. A one tissue compartment modelling of IBVM pharmacokinetic is adequate. The MRTM method gives an estimation of BP* with the best accuracy. This non-invasive method will be applied in patients with cholinergic impairment.
- Society of Nuclear Medicine, Inc.