Mdrla/lb knockout mice

To further evaluate the potential utility of the Ga-complex as an in vivo marker of Pgp-mediated transport activity, the complexes were injected in wild-type and mdrla/lb (-/-) knoekout mice to study the drug transport across the BBB. As previously mentioned, Pgp is expressed in the luminal surfaces of brain endothelial cells preventing the entry of amphipathic compounds into the central nervous system. Therefore, the mdrla/lb (-/-) knockout mice offer an interesting model to evaluate the applicability of radiotracers for in vivo transport activity of Pgp. At 5 min after injection, the brain uptake of Ga-complex in Pgp-knockout miee was 10-fold higher compared with that in the wild-type mice. As the cerebral blood flow did not differ significantly between the wild-type and the knockout mice, differences on initial brain uptake and retention of Ga-complex were not attributed to changes in cerebral perfusion. 

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