Fig. 5

The relationship between plasma ipratropium concentration and changes in organ-specific binding of [¹¹C]VC-002. Upper panels show changes in total binding (estimated using post-dosing over baseline V_T ratios) for the lungs and the pituitary gland, respectively. Lower charts show estimated changes in specific binding (i.e., target occupancy) for the two organs, respectively. The charts indicate subject- and occasion-specific data as scatter points and the results of model fitting as continuous curves. In detail, the scatter points for total binding were used to fit a model providing administration route and organ-specific parameter estimates for drug affinity (K_i), as well as organ-specific estimates of baseline-specific binding (BP_ND). The K_i in the lungs at inhalation was 1.01 nM (95% CI 0.36–2.82 nM), and in case of intravenous administration, it was 10.72 nM (95% CI 5.40–21.26 nM). These K_i values were significantly different at the 5% level (p value < 10⁻⁴). The baseline BP_ND in the lungs was 7.2 (3.6–14.4). The K_i in the pituitary at inhalation was 0.58 nM (95% CI 0.31–1.09 nM), and in case of intravenous administration, it was 1.72 nM (95% CI 0.93–3.17 nM). These K_i values were not significantly different at the 5% level (p value = 0.24). The baseline BP_ND in the pituitary gland was 21.4 (9.2–49.6)