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Neuroimage. 2017 Feb 15;147:461-472. doi: 10.1016/j.neuroimage.2016.12.050. Epub 2016 Dec 21.

A single-scan protocol for absolute D2/3 receptor quantification with [123I]IBZM SPECT.

Author information

1
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.
2
Vulnerability Biomarkers Unit, Division of Adult Psychiatry, Department of Mental Health and Psychiatry, University Hospitals of Geneva, Switzerland.
3
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.
4
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.

Abstract

PURPOSE:

Molecular imaging of the D2/3 receptor 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 appKd is 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 Bavail and appKd separately, 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" BPND estimation methods are also validated against the results of the 3T-7k.

METHODS:

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 D2 receptor 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.

RESULTS:

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 Bavail by 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 appKd was observed. BPND derived from SRTM, LNIGA and SUR correlated well with the Bavail values from the 3T-7k (r=0.84, r=0.84 and r=0.83, respectively, p<0.0001 for all correlations).

CONCLUSION:

A partial saturation protocol permits the non-invasive and time-efficient estimation of Bavail and appKd separately. 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.

KEYWORDS:

D(2/3) receptor; Rat; SPECT; [(123)I]IBZM

[Indexed for MEDLINE]

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