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J Nucl Med. 1996 Jan;37(1):95-104.

Estimation of neocortical serotonin-2 receptor binding potential by single-dose fluorine-18-setoperone kinetic PET data analysis.

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  • 1CYCERON, INSERM U320, Centre François Baclesse, Caen, France.

Abstract

Because it satisfies most of the characteristics required to quantify in vivo neocortical serotonin-2 (5HT2) receptors, 18F-setoperone was selected for use in PET estimation of the neocortical 5HT2 binding parameters in baboons according to a single-dose paradigm.

METHODS:

The neocortical binding potential (i.e., Bmax/KD or the k3/k4 ratio) was assessed by three different methods, with the cerebellum taken as the reference structure in all instances. Method 1 was based on a Logan-Patlak graphical analysis of both cerebellar and neocortical data, which allows estimation of the neocortical k3'/k4 ratio; it required a separate estimation of k5 and k6 from classical nonlinear least-squares (NLSQ) three-compartment modeling of cerebellar data. Method 2 was an original combination of a four-compartment Logan-Patlak procedure for neocortical data and an NLSQ three-compartment procedure for cerebellar data, allowing the neocortical k3/k4 ratio to be obtained directly. In Method 3, an NLSQ three-compartment procedure was applied to cerebellar data and an NLSQ four-compartment procedure to neocortical data, allowing separate determinations of k3 and k4 for the neocortex and, in turn, the k3/k4 ratio.

RESULTS:

In all three methods, the arterial plasma input function was corrected for the presence of 18F-metabolites, and the vascular fraction was either fitted or fixed. Statistical analysis showed no significant difference among the k3/k4 values obtained from the three methods. Method 3 was the least stable because of an occasional poor NLSQ four-compartment fit on neocortical data. Method 2 provided the least cumbersome estimate of the k3/k4 ratio and was found easy and accurate for generating parametric maps of the 5HT2 binding potential.

CONCLUSION:

This method might be useful in clinical investigations to provide quantitative assessment of receptor binding potential. In semiquantitative investigations, the neocortical-to-cerebellum pseudoequilibrium ratio may be adequate, as suggested by the significant correlations with measured k3/k4 ratios found here.

PMID:
8544011
[PubMed - indexed for MEDLINE]
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