Small-animal PET evaluation of [11C]MC113 as a PET tracer for P-glycoprotein

Background The radiolabelled inhibitor of the multidrug efflux transporter P-glycoprotein (P-gp) [C]elacridar was developed as a positron emission tomography (PET) tracer to assess expression levels of P-gp at the blood-brain barrier (BBB) [1]. [C]Elacridar was shown to interact specifically with P-gp at the rodent BBB, but its brain PET signal was very low, which was possibly caused by transport of [C]elacridar by P-gp [1]. In an attempt to gain a better understanding of the required properties of an effective P-gp PET tracer we evaluated C-labelled MC113, a structural analogue of elacridar, which was characterised as an unambiguous non-transported P-gp inhibitor and which possesses lower molecular weight, lower lipophilicity and higher potency for P-gp inhibition than elacridar (EC50 for inhibition of [ H]vinblastine transport in Caco-2 cell monolayers: 0.6 μM vs. 2.0 μM for elacridar) [2].