title: A single-scan protocol for absolute D2/3receptor quantification with [123I]IBZM SPECT.
abstract: Molecular imaging of the D2/3receptor is widely used in neuropsychiatric research. Non-displaceable binding potential (BPND) is a very popular quantitative index, defined as the product of the receptor concentration (Bavail) and the radiotracer affinity for the receptor (1/appKd). As the appKdis influenced by parameters such as the endogenous neurotransmitter dynamics, it often constitutes a confounding factor in research studies. A simplified method for absolute quantification of both these parameters would be of great interest in this context. Here, we describe the use of a partial saturation protocol that permits to produce an in vivo Scatchard plot and thus estimate Bavailand appKdseparately,through a single dynamic SPECT session. To validate this approach, a multi-injection protocol is used for the full kinetic modeling of [123I]IBZM using a 3-tissue compartment, 7-parameter model (3T-7k). Finally, more "classic" BPNDestimation methods are also validated against the results of the 3T-7k.
  
  
  
  Twenty-nine male rats were used. Binding parameters were estimated using the 3T-7k in a multi-injection protocol. A partial saturation protocol was applied at the region- and voxel-level and results were compared to those obtained with the 3T-7k model. The partial saturation protocol was applied after an adenovirus-mediated D2receptor striatal overexpression and in an amphetamine-induced dopamine release paradigm. The Simplified Reference Tissue Model (SRTM), the Logan's non-invasive graphical analysis (LNIGA) and a simple standardized uptake ratio (SUR) method were equally applied.
  
  
  
  The partial saturation experiments gave similar values as the 3T-7k both at the regional and voxel-level. After adenoviral-mediated D2-receptor overexpression, an increase in Bavailby approximately 18% was observed in the striatum. After amphetamine administration, a 16.93% decrease in Bavail(p<0.05) and a 39.12% increase (p<0.01) in appKdwas observed. BPNDderived from SRTM, LNIGA and SUR correlated well with the Bavailvalues from the 3T-7k (r=0.84, r=0.84 and r=0.83, respectively, p<0.0001 for all correlations).
  
  
  
  A partial saturation protocol permits the non-invasive and time-efficient estimation of Bavailand appKdseparately. Given the different biological phenomena that underlie these parameters, this method may be applied for the in-depth study of the dopaminergic system in translational molecular imaging studies. It can detect the biological variations in these parameters, dissociating the variations in receptor density (Bavail) from affinity (1/appKd), which reflects the interactions of the receptor with its endogenous ligand.
authors.affiliation: Vulnerability Biomarkers Unit, Division of Adult Psychiatry, Department of Mental Health and Psychiatry, University Hospitals of Geneva, Switzerland; Division of Addictology, Department of Mental Health and Psychiatry, University Hospitals of Geneva, Switzerland; Department of Psychiatry, University of Geneva, Switzerland.
authors.forename: Stergios
authors.initials: S
authors.lastname: Tsartsalis
authors.affiliation: Vulnerability Biomarkers Unit, Division of Adult Psychiatry, Department of Mental Health and Psychiatry, University Hospitals of Geneva, Switzerland.
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Tournier
authors.affiliation: Vulnerability Biomarkers Unit, Division of Adult Psychiatry, Department of Mental Health and Psychiatry, University Hospitals of Geneva, Switzerland.
authors.forename: Karl
authors.initials: K
authors.lastname: Aoun
authors.affiliation: Vulnerability Biomarkers Unit, Division of Adult Psychiatry, Department of Mental Health and Psychiatry, University Hospitals of Geneva, Switzerland.
authors.forename: Selim
authors.initials: S
authors.lastname: Habiby
authors.affiliation: Vulnerability Biomarkers Unit, Division of Adult Psychiatry, Department of Mental Health and Psychiatry, University Hospitals of Geneva, Switzerland.
authors.forename: Diego
authors.initials: D
authors.lastname: Pandolfo
authors.affiliation: Vulnerability Biomarkers Unit, Division of Adult Psychiatry, Department of Mental Health and Psychiatry, University Hospitals of Geneva, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Dimiziani
authors.affiliation: Vulnerability Biomarkers Unit, Division of Adult Psychiatry, Department of Mental Health and Psychiatry, University Hospitals of Geneva, Switzerland; Department of Psychiatry, University of Geneva, Switzerland.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Ginovart
authors.affiliation: Vulnerability Biomarkers Unit, Division of Adult Psychiatry, Department of Mental Health and Psychiatry, University Hospitals of Geneva, Switzerland; Department of Psychiatry, University of Geneva, Switzerland. Electronic address: Philippe.Millet@hcuge.ch.
authors.forename: Philippe
authors.initials: P
authors.lastname: Millet
mesh_terms: D000818:Animals; D001549:Benzamides / Q000493:pharmacokinetics*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000493:pharmacokinetics*; D008297:Male; D011485:Protein Binding; D011759:Pyrrolidines / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D001549:Benzamides; D018492:Dopamine Antagonists; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide
keywords: D(2/3) receptor; Rat; SPECT; [(123)I]IBZM