The Drug Excipient Cyclodextrin Interacts With -Luciferin and Interferes With Bioluminescence Imaging
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 i...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2016-01-01
|
| Series: | Molecular Imaging |
| Online Access: | https://doi.org/10.1177/1536012115625225 |
| _version_ | 1826904179960971264 |
|---|---|
| author | Jeyan S. Kumar MSc Lisa M. Miller Jenkins PhD Michael M. Gottesman MD Matthew D. Hall PhD |
| author_facet | Jeyan S. Kumar MSc Lisa M. Miller Jenkins PhD Michael M. Gottesman MD Matthew D. Hall PhD |
| author_sort | Jeyan S. Kumar MSc |
| collection | DOAJ |
| description | 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 binds d -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 of d -luciferin, and mass spectrometry revealed d -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. |
| first_indexed | 2024-03-07T17:39:27Z |
| format | Article |
| id | doaj.art-eac0c95bb8fa4bb386211d0c65f28f5a |
| institution | Directory Open Access Journal |
| issn | 1536-0121 |
| language | English |
| last_indexed | 2025-02-17T08:07:21Z |
| publishDate | 2016-01-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Molecular Imaging |
| spelling | doaj.art-eac0c95bb8fa4bb386211d0c65f28f5a2025-01-03T00:10:40ZengSAGE PublishingMolecular Imaging1536-01212016-01-011510.1177/153601211562522510.1177_1536012115625225The Drug Excipient Cyclodextrin Interacts With -Luciferin and Interferes With Bioluminescence ImagingJeyan S. Kumar MSc0Lisa M. Miller Jenkins PhD1Michael M. Gottesman MD2Matthew D. Hall PhD3 Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA 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, USACyclodextrins 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 binds d -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 of d -luciferin, and mass spectrometry revealed d -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.https://doi.org/10.1177/1536012115625225 |
| spellingShingle | Jeyan S. Kumar MSc Lisa M. Miller Jenkins PhD Michael M. Gottesman MD Matthew D. Hall PhD The Drug Excipient Cyclodextrin Interacts With -Luciferin and Interferes With Bioluminescence Imaging Molecular Imaging |
| title | The Drug Excipient Cyclodextrin Interacts With -Luciferin and Interferes With Bioluminescence Imaging |
| title_full | The Drug Excipient Cyclodextrin Interacts With -Luciferin and Interferes With Bioluminescence Imaging |
| title_fullStr | The Drug Excipient Cyclodextrin Interacts With -Luciferin and Interferes With Bioluminescence Imaging |
| title_full_unstemmed | The Drug Excipient Cyclodextrin Interacts With -Luciferin and Interferes With Bioluminescence Imaging |
| title_short | The Drug Excipient Cyclodextrin Interacts With -Luciferin and Interferes With Bioluminescence Imaging |
| title_sort | drug excipient cyclodextrin interacts with luciferin and interferes with bioluminescence imaging |
| url | https://doi.org/10.1177/1536012115625225 |
| work_keys_str_mv | AT jeyanskumarmsc thedrugexcipientcyclodextrininteractswithluciferinandinterfereswithbioluminescenceimaging AT lisammillerjenkinsphd thedrugexcipientcyclodextrininteractswithluciferinandinterfereswithbioluminescenceimaging AT michaelmgottesmanmd thedrugexcipientcyclodextrininteractswithluciferinandinterfereswithbioluminescenceimaging AT matthewdhallphd thedrugexcipientcyclodextrininteractswithluciferinandinterfereswithbioluminescenceimaging AT jeyanskumarmsc drugexcipientcyclodextrininteractswithluciferinandinterfereswithbioluminescenceimaging AT lisammillerjenkinsphd drugexcipientcyclodextrininteractswithluciferinandinterfereswithbioluminescenceimaging AT michaelmgottesmanmd drugexcipientcyclodextrininteractswithluciferinandinterfereswithbioluminescenceimaging AT matthewdhallphd drugexcipientcyclodextrininteractswithluciferinandinterfereswithbioluminescenceimaging |