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

J Cereb Blood Flow Metab. 2008 Sep;28(9):1624-34. doi: 10.1038/jcbfm.2008.53. Epub 2008 May 28.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Brain / metabolism
  • Dementia / diagnosis
  • Humans
  • Iodine Radioisotopes / pharmacokinetics*
  • Kinetics
  • Models, Biological
  • Piperidines / pharmacokinetics
  • Radiopharmaceuticals / pharmacokinetics*
  • Tetrahydronaphthalenes / pharmacokinetics
  • Tomography, Emission-Computed, Single-Photon / methods*
  • Vesicular Acetylcholine Transport Proteins / analysis*

Substances

  • Iodine Radioisotopes
  • Piperidines
  • Radiopharmaceuticals
  • Tetrahydronaphthalenes
  • Vesicular Acetylcholine Transport Proteins
  • 5-iodobenzovesamicol