Continuous Delivery of D-Luciferin by Implanted Micro-osmotic Pumps Enables True Real-Time Bioluminescence Imaging of Luciferase Activity in Vivo

Bioluminescence imaging (BLI) of luciferase reporters in small animal models offers an attractive approach to monitor regulation of gene expression, signal transduction, and protein-protein interactions, as well as following tumor progression, cell engraftment, infectious pathogens, and target-speci...

Full description

Saved in:
Bibliographic Details
Main Authors: Shimon Gross, Ute Abraham, Julie L. Prior, Erik D. Herzog, David Piwnica-Worms
Format: Article
Language:English
Published: SAGE Publishing 2007-03-01
Series:Molecular Imaging
Online Access:https://doi.org/10.2310/7290.2007.00009
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832544567034904576
author Shimon Gross
Ute Abraham
Julie L. Prior
Erik D. Herzog
David Piwnica-Worms
author_facet Shimon Gross
Ute Abraham
Julie L. Prior
Erik D. Herzog
David Piwnica-Worms
author_sort Shimon Gross
collection DOAJ
description Bioluminescence imaging (BLI) of luciferase reporters in small animal models offers an attractive approach to monitor regulation of gene expression, signal transduction, and protein-protein interactions, as well as following tumor progression, cell engraftment, infectious pathogens, and target-specific drug action. Conventional BLI can be repeated within the same animal after bolus reinjections of a bioluminescent substrate. However, intervals between image acquisitions are governed by substrate pharmacokinetics and excretion, therefore restricting temporal resolution of reinjection protocols to the order of hours, limiting analyses of processes in vivo with short time constants. To eliminate these constraints, we examined use of implanted micro-osmotic pumps for continuous, long-term delivery of bioluminescent substrates. Pump-assisted d -luciferin delivery enabled BLI for ⩾ 7 days from a variety of luciferase reporters. Pumps allowed direct repetitive imaging at < 5-minute intervals of the pharmacodynamics of proteasome- and IKK-inhibiting drugs in mice bearing tumors stably expressing ubiquitin-firefly luciferase or IκBα-firefly luciferase fusion reporters. Circadian oscillations in the olfactory bulbs of transgenic rats expressing firefly luciferase under the control of the period1 promoter also were temporally resolved over the course of several days. We conclude that implanted pumps provide reliable, prolonged substrate delivery for high temporal resolution BLI, traversing complications of repetitive substrate injections.
format Article
id doaj-art-aa31967bc3ec42899b80b5c9c1fe9e6a
institution Kabale University
issn 1536-0121
language English
publishDate 2007-03-01
publisher SAGE Publishing
record_format Article
series Molecular Imaging
spelling doaj-art-aa31967bc3ec42899b80b5c9c1fe9e6a2025-02-03T10:08:10ZengSAGE PublishingMolecular Imaging1536-01212007-03-01610.2310/7290.2007.0000910.2310_7290.2007.00009Continuous Delivery of D-Luciferin by Implanted Micro-osmotic Pumps Enables True Real-Time Bioluminescence Imaging of Luciferase Activity in VivoShimon GrossUte AbrahamJulie L. PriorErik D. HerzogDavid Piwnica-WormsBioluminescence imaging (BLI) of luciferase reporters in small animal models offers an attractive approach to monitor regulation of gene expression, signal transduction, and protein-protein interactions, as well as following tumor progression, cell engraftment, infectious pathogens, and target-specific drug action. Conventional BLI can be repeated within the same animal after bolus reinjections of a bioluminescent substrate. However, intervals between image acquisitions are governed by substrate pharmacokinetics and excretion, therefore restricting temporal resolution of reinjection protocols to the order of hours, limiting analyses of processes in vivo with short time constants. To eliminate these constraints, we examined use of implanted micro-osmotic pumps for continuous, long-term delivery of bioluminescent substrates. Pump-assisted d -luciferin delivery enabled BLI for ⩾ 7 days from a variety of luciferase reporters. Pumps allowed direct repetitive imaging at < 5-minute intervals of the pharmacodynamics of proteasome- and IKK-inhibiting drugs in mice bearing tumors stably expressing ubiquitin-firefly luciferase or IκBα-firefly luciferase fusion reporters. Circadian oscillations in the olfactory bulbs of transgenic rats expressing firefly luciferase under the control of the period1 promoter also were temporally resolved over the course of several days. We conclude that implanted pumps provide reliable, prolonged substrate delivery for high temporal resolution BLI, traversing complications of repetitive substrate injections.https://doi.org/10.2310/7290.2007.00009
spellingShingle Shimon Gross
Ute Abraham
Julie L. Prior
Erik D. Herzog
David Piwnica-Worms
Continuous Delivery of D-Luciferin by Implanted Micro-osmotic Pumps Enables True Real-Time Bioluminescence Imaging of Luciferase Activity in Vivo
Molecular Imaging
title Continuous Delivery of D-Luciferin by Implanted Micro-osmotic Pumps Enables True Real-Time Bioluminescence Imaging of Luciferase Activity in Vivo
title_full Continuous Delivery of D-Luciferin by Implanted Micro-osmotic Pumps Enables True Real-Time Bioluminescence Imaging of Luciferase Activity in Vivo
title_fullStr Continuous Delivery of D-Luciferin by Implanted Micro-osmotic Pumps Enables True Real-Time Bioluminescence Imaging of Luciferase Activity in Vivo
title_full_unstemmed Continuous Delivery of D-Luciferin by Implanted Micro-osmotic Pumps Enables True Real-Time Bioluminescence Imaging of Luciferase Activity in Vivo
title_short Continuous Delivery of D-Luciferin by Implanted Micro-osmotic Pumps Enables True Real-Time Bioluminescence Imaging of Luciferase Activity in Vivo
title_sort continuous delivery of d luciferin by implanted micro osmotic pumps enables true real time bioluminescence imaging of luciferase activity in vivo
url https://doi.org/10.2310/7290.2007.00009
work_keys_str_mv AT shimongross continuousdeliveryofdluciferinbyimplantedmicroosmoticpumpsenablestruerealtimebioluminescenceimagingofluciferaseactivityinvivo
AT uteabraham continuousdeliveryofdluciferinbyimplantedmicroosmoticpumpsenablestruerealtimebioluminescenceimagingofluciferaseactivityinvivo
AT julielprior continuousdeliveryofdluciferinbyimplantedmicroosmoticpumpsenablestruerealtimebioluminescenceimagingofluciferaseactivityinvivo
AT erikdherzog continuousdeliveryofdluciferinbyimplantedmicroosmoticpumpsenablestruerealtimebioluminescenceimagingofluciferaseactivityinvivo
AT davidpiwnicaworms continuousdeliveryofdluciferinbyimplantedmicroosmoticpumpsenablestruerealtimebioluminescenceimagingofluciferaseactivityinvivo