Influence of bioluminescence imaging dynamics by dluciferin uptake and efflux mechanisms

Yimao Zhang, Mrudula Pullambhatla, John Laterra, Martin G. Pomper

Research output: Contribution to journalArticlepeer-review

Abstract

Bioluminescence imaging (BLI) detects light generated by luciferase-mediated oxidation of substrate and is used widely for evaluating transgene expression in cell-based assays and in vivo in relevant preclinical models. The most commonly used luciferase for in vivo applications is firefly luciferase (fLuc), for which D-luciferin serves as the substrate. We demonstrated previously that the expression of the ABCG2 efflux transporter can significantly reduce BLI signal output and that HhAntag-691 can inhibit the efflux of Dluciferin, thereby enhancing BLI signal. Here we show that an HhAntag-691-sensitive uptake mechanism facilitates the intracellular concentration of D-luciferin and that the BLI dynamics of different cell lines are coregulated by this uptake mechanism in conjunction with ABCG2-mediated efflux. After administration of D-luciferin, the HhAntag-691-sensitive uptake mechanism generates a rapid increase in BLI signal that decreases over time, whereas ABCG2-mediated efflux stably reduces signal output. We implicate SLC22A4 (OCTN1), a member of the organic cation/zwitterion uptake transporter family, as one potential mediator of the HhAntag-691-sensitive D-luciferin uptake. These findings provide insight into mechanisms that contribute to the cellular uptake kinetics and in vivo biodistribution of D-luciferin.

Original languageEnglish (US)
Pages (from-to)499-506
Number of pages8
JournalMolecular imaging
Volume11
Issue number6
DOIs
StatePublished - Nov 2012

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Biomedical Engineering
  • Radiology Nuclear Medicine and imaging
  • Condensed Matter Physics

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