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Mol Imaging. 2016 Jan 27;15. pii: 1536012115625225. doi: 10.1177/1536012115625225. Print 2016.

The Drug Excipient Cyclodextrin Interacts With d-Luciferin and Interferes With Bioluminescence Imaging.

Author information

1
Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
2
Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA mgottesman@nih.gov.
3
Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA NCATS Chemical Genomics Center, National Institutes of Health, Rockville, MD, USA.

Abstract

Cyclodextrins are well-characterized, barrel-shaped molecules that can solubilize organic small molecules in aqueous solution via host-guest interactions. As such, cyclodextrins are used as excipients for experimental therapeutics in vivo. We observed unanticipated modifications to bioluminescence imaging (BLI) signal intensity when 2-hydroxy-propyl-β-cyclodextrin (HPCD) was coinjected as an excipient. We hypothesized that HPCD bindsd-luciferin and interferes with the BLI signal. Using luciferase-expressing cell lines, we showed that HPCD lowers the BLI signal in a concentration-dependent manner. Flow cytometry revealed that HPCD resulted in reduced cellular accumulation ofd-luciferin, and mass spectrometry revealedd-luciferin HPCD species, confirming a direct interaction. In vivo imaging using a luciferase mouse model demonstrated that HPCD reduced luciferin-mediated BLI compared to luciferin alone. The implications of using HPCD as an excipient in BLI studies are discussed.

KEYWORDS:

bioluminescence; cyclodextrin; d-luciferin; drug carriers; drug transporters

PMID:
27030398
PMCID:
PMC4982550
DOI:
10.1177/1536012115625225
[Indexed for MEDLINE]
Free PMC Article

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