Figure 1.

Translational positron emission tomography (PET) imaging of the P-glycoprotein-mediated interaction between (R)-[¹¹C]verapamil and tariquidar at the mouse (C57BL/6, upper row) and human blood–brain barrier (lower row). Left, magnetic resonance imaging-coregistered PET summation images (0–60 min) at baseline and, right, at 2 h (mouse) or 1 h (human) after i.v. administration of tariquidar (mouse: 15 mg/kg over 1 min, human: 8 mg/kg over 160 min) are shown. Tariquidar plasma concentrations at the end of the PET scan were similar in the shown mouse (1,297 ng/ml) and the human volunteer (1,241 ng/ml). In mice, a 4.9-fold and in humans, a 2.0-fold increase relative to baseline in the brain-to-plasma ratio of (R)-[¹¹C]verapamil at 60 min after injection (K_p,brain) was observed. Mean baseline K_p,brain values before tariquidar administration were 0.43 ± 0.05 (n = 6) for mice and 0.55 ± 0.06 (n = 6) for humans. Radioactivity concentration is normalized to injected dose per kilogram body weight and expressed as a standardized uptake value.