title: The Drug Excipient Cyclodextrin Interacts With d-Luciferin and Interferes With Bioluminescence Imaging.
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.
authors.affiliation: Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Jeyan S
authors.initials: JS
authors.lastname: Kumar
authors.affiliation: Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Miller Jenkins
authors.affiliation: Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA mgottesman@nih.gov.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Gottesman
authors.affiliation: 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.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Hall
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D052160:Benzothiazoles / Q000378:metabolism*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005079:Excipients / Q000008:administration & dosage* / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D008163:Luminescent Measurements / Q000379:methods*; D013058:Mass Spectrometry; D051379:Mice; D008954:Models, Biological; D011485:Protein Binding; D047392:beta-Cyclodextrins / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D052160:Benzothiazoles; C532924:D-luciferin; D005079:Excipients; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin
keywords: bioluminescence; cyclodextrin; d-luciferin; drug carriers; drug transporters