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Direct bioluminescent imaging of ABCG2 function at the blood-brain barrier using the specific substrate D-luciferin

Monday, September 22, 2014 — Poster Session II

4:00 p.m. – 6:00 p.m.

FAES Academic Center



* FARE Award Winner


  • M Gottesman
  • M.D. Hall
  • J Bakhsheshian
  • B Wei
  • R.M. Simpson


ABC transporters play a key role in protecting the brain parenchyma by exerting their action at the blood-brain barrier (BBB). However, these transporters also block the entry of therapeutic drugs, including cancer chemotherapeutics, limiting their efficacy against primary malignancies and metastases. One of the key transporters playing this role is ABCG2. D-luciferin, the endogenous substrate of fLuc, has been shown to demonstrate decreased bioluminescence in ABCG2-expressing cells. Given that the BBB probably restricts entry of D-luciferin, we hypothesized that we can image ABCG2 function at the blood-brain barrier using bioluminescent imaging in transgenic mice expressing fLuc in the brain. We showed that among the three most prevalent efflux transporters at the blood-brain barrier, D-luciferin is a specific substrate for ABCG2. Using a mouse model expressing fLuc behind the GFAP promoter, mainly expressed in astrocytes of the brain, D-luciferin BLI signal was found to be low. However, it increased in a dose-dependent fashion with co-administration of the ABCG2 inhibitor Ko143, but not the P-gp inhibitor DCPQ. This method for directly imaging ABCG2 function at the BBB will be of use in understanding pharmacokinetic inhibition of the transporter. Utilizing this model to examine other barriers is also discussed.

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