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Multicompartmental study of fluorine-18 altanserin binding to brain 5HT2 receptors in humans using positron emission tomography.

Serotoninergic type 2 (5HT2) receptors have been implicated in the regulation of many brain functions in humans and may play a role in several neurological and psychiatric diseases. Fluorine-18 altanserin has been proposed as a new radiotracer for the study of 5HT2 receptors by PET because of its high affinity for 5HT2 receptors (Ki: 0.13 nM) and its good specificity in in vitro studies. Dynamic PET studies were carried out in 12 healthy volunteers after intravenous injection of 0.1 mCi/kg [18F]altanserin. Ninety minutes after injection, we observed mainly cortical binding. Basal ganglia and cerebellum showed very low uptake and the frontal cortex to cerebellum ratio was about 3. To evaluate the quantitative distribution of this ligand in the brain, we used two different methods of data analysis: a four-compartment model was used to achieve quantitative evaluation of rate constants (K1 and k2 through k6) by non-linear regression, and a multiple-time graphical analysis technique for reversible binding was employed for the measurement of k1/k2 and k3/k4 ratios. Using both methods, we found significant differences in binding capacity (estimated by k3/k4 = Bmax/Kd) between regions, the values increasing as follows: occipital, limbic, parietal, frontal and temporal cortex. After correction of values obtained by the graphical method for the existence of non-specific binding, results generated by the two methods were consistent.[1]

References

  1. Multicompartmental study of fluorine-18 altanserin binding to brain 5HT2 receptors in humans using positron emission tomography. Biver, F., Goldman, S., Luxen, A., Monclus, M., Forestini, M., Mendlewicz, J., Lotstra, F. European journal of nuclear medicine. (1994) [Pubmed]
 
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