NONCOMPARTMENTAL AND COMPARTMENTAL MODELING OF THE KINETICS OF C-11 LABELED PYRILAMINE IN THE HUMAN BRAIN

The kinetic pattern of a C-11-labeled histamine H-1 receptor antagonis t, [C-11]pyrilamine, was investigated in the human brain by factor ana lysis of dynamic PET studies. Tissue time activity curves were also pr ocessed by compartment model curve fitting preceded by deconvolution a nalysis. Factor analysis revealed two statistically significant and ph ysiologically meaningful kinetic patterns: one for specific and anothe r for nonspecific binding of the radioligand. From these two factors a compartment model containing two tissue compartments (one for specifi c binding and another for nonspecific binding and free ligand) was con structed. 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 H-1 receptors. Blockade of H-1 receptors with unlabeled pyrilamine , diphenhydramine, or hydroxyzine caused a significant reduction of th is factor. Blockade produced no significant changes in factor one repr esenting nonspecific binding. We conclude that the kinetics of [C-11]p yrilamine in the brain can be described by two tissue compartments, on e related to the distribution of the H-1 receptors. Factor analysis of dynamic studies can be used to locally separate these two compartment s, for identification of regions rich and poor in H-1 receptors and fo r noninvasive quantitative investigation of the effects of H-1 recepto r blockers such as pyrilamine, diphenhydramine, or hydroxyzine. (C) 19 93 Wiley-Liss, Inc.