Noncompartmental and compartmental modeling of the kinetics of carbon-11 labeled pyrilamine in the human brain.

The kinetic pattern of a 11C-labeled histamine H1 receptor antagonist, [11C]pyrilamine, was investigated in the human brain by factor analysis of dynamic PET studies. Tissue time activity curves were also processed by compartment model curve fitting preceded by deconvolution analysis. Factor analysis revealed two statistically significant and physiologically meaningful kinetic patterns: one for specific and another for nonspecific binding of the radioligand. From these two factors a compartment model containing two tissue compartments (one for specific binding and another for nonspecific binding and free ligand) was constructed. The two-compartment model was also supported by the impulse response function, which was obtained by deconvolution and showed two components. The factor image constructed from factor two demonstrated a distribution pattern characteristic for brain regions rich (frontal, parietal, and temporal lobes) or poor (occipital lobe and cerebellum) in H1 receptors. Blockade of H1 receptors with unlabeled pyrilamine, diphenhydramine, or hydroxyzine caused a significant reduction of this factor. Blockade produced no significant changes in factor one representing nonspecific binding. We conclude that the kinetics of [11C]pyrilamine in the brain can be described by two tissue compartments, one related to the distribution of the H1 receptors. Factor analysis of dynamic studies can be used to locally separate these two compartments, for identification of regions rich and poor in H1 receptors and for noninvasive quantitative investigation of the effects of H1 receptor blockers such as pyrilamine, diphenhydramine, or hydroxyzine.