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.
Barret
O
O
CHU de Bordeaux, Bordeaux, France. olivier.barret@imf.u-bordeaux2.fr
Mazère
J
J
Seibyl
J
J
Allard
M
M
D000368:Aged; D001921:Brain / Q000378:metabolism; D003704:Dementia / Q000175:diagnosis; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D007700:Kinetics; D008954:Models, Biological; D010880:Piperidines / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D013764:Tetrahydronaphthalenes / Q000493:pharmacokinetics; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D050494:Vesicular Acetylcholine Transport Proteins / Q000032:analysis*
D007457:Iodine Radioisotopes; D010880:Piperidines; D019275:Radiopharmaceuticals; D013764:Tetrahydronaphthalenes; D050494:Vesicular Acetylcholine Transport Proteins; C065043:5-iodobenzovesamicol