Figure 1.

(a) Metabolic extrusion method (MEM): the pro-drug tracer crosses the BBB by passive diffusion (K₁) and within the brain rapidly undergoes enzymatic conversion (k₃) to a hydrophilic radioactive metabolite (tracer). If the passive diffusion of the tracer across the BBB is negligible, the activity of the drug efflux pump can be correlated to the clearance rate of the tracer (k₄) from the brain. (b) Metabolic conversion of [¹¹C]7m6BP to the MRP1 substrate S-[6-(7-[¹¹C]methylpurinyl)]glutathione (PSG) by GSTs in the brain.