title: Kinetic analyses of [123I]IBZM SPECT for quantification of striatal dopamine D2 receptor binding: a critical evaluation of the single-scan approach.
abstract: BACKGROUND
  Dopamine-D2 receptor imaging with single-photon emission computed tomography (SPECT) and [(123)I]IBZM is of great interest for basic and applied neurosciences. However, the use of kinetic analyses for quantification of dynamic [(123)I]IBZM SPECT and the validity of the commonly employed single-scan pseudo-equilibrium analysis (PsEA) have not been appropriately investigated. The present study addresses these shortcomings.
  
  
  METHODS
  Ten movement disorder patients underwent dynamic SPECT (142 min) after single-bolus [(123)I]IBZM injection. Kinetic analyses comprise: simplified reference tissue model (SRTM), multi-linear reference tissue model (MRTM), their two-parameter versions (SRTM2/MRTM2) and non-invasive graphical analysis (NIGA). Simplified single-scan analyses were performed at peak time of specific binding (peak-equilibrium analysis, PEA) and during pseudo-equilibrium (PsEA).
  
  
  RESULTS
  SRTM and MRTM are compromised by the high noise level of dynamic SPECT. SRTM2 and MRTM2 yielded reliable binding potential estimates that agreed excellently (mean difference=-0.1+/-1.0%, R(2)>0.99). Concordance between SRTM/MRTM and SRTM2/MRTM2 was high in cases in which SRTM/MRTM provided reliable results (SRTM2 or MRTM2 vs. SRTM: 3.7+/-5.0%, R(2)=0.88). NIGA was affected by a negative bias (-9.1+/-6.3%, R(2)=0.75; MRTM2 as reference) or high variability (-1.2+/-7.4%, R(2)=0.71) for analyses without and with inclusion of the k(2)'-term, respectively. PsEA showed a positive bias and low correlation in comparison with SRTM2/MRTM2 (7.6+/-10.8%, R(2)=0.59), which was considerably improved for PEA (-2.7+/-7.6%, R(2)=0.72). MRTM2 provided parametric images with minimal bias suited for voxel-wise statistical analyses.
  
  
  CONCLUSIONS
  MRTM2 and SRTM2 can be reliably applied to dynamic [(123)I]IBZM SPECT. PEA is a suitable method for clinical routine, while our results discourage the use of PsEA (current clinical standard).
authors.affiliation: Department of Nuclear Medicine, University Hospital Aachen, Aachen, Germany. pmeyer@ukaachen.de
authors.forename: Philipp T
authors.initials: PT
authors.lastname: Meyer
authors.forename: Bernhard
authors.initials: B
authors.lastname: Sattler
authors.forename: Oliver H
authors.initials: OH
authors.lastname: Winz
authors.forename: Rico
authors.initials: R
authors.lastname: Fundke
authors.forename: Christian
authors.initials: C
authors.lastname: Oehlwein
authors.forename: Kai
authors.initials: K
authors.lastname: Kendziorra
authors.forename: Swen
authors.initials: S
authors.lastname: Hesse
authors.forename: Wolfgang M
authors.initials: WM
authors.lastname: Schaefer
authors.forename: Osama
authors.initials: O
authors.lastname: Sabri
mesh_terms: D000328:Adult; D000368:Aged; D001549:Benzamides / Q000493:pharmacokinetics*; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009069:Movement Disorders / Q000000981:diagnostic imaging / Q000378:metabolism*; D011485:Protein Binding; D011759:Pyrrolidines / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D001549:Benzamides; D011759:Pyrrolidines; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide