In Vivo Optical Imaging of Acute Myeloid Leukemia by Green Fluorescent Protein: Time-Domain Autofluorescence Decoupling, Fluorophore Quantification, and Localization

Human xenografts of acute myeloid leukemia (AML) in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice result in disease states of diffuse, nonpalpable tissue infiltrates exhibiting a variable disease course, with some animals not developing a disease phenotype. Thus, disease staging...

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Main Authors: Emmet McCormack, David R. Micklem, Lars-Erik Pindard, Elisabeth Silden, Pascal Gallant, Alexandre Belenkov, James B. Lorens, Bjørn Tore Gjertsen
Format: Article
Language:English
Published: SAGE Publishing 2007-05-01
Series:Molecular Imaging
Online Access:https://doi.org/10.2310/7290.2007.00016
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author Emmet McCormack
David R. Micklem
Lars-Erik Pindard
Elisabeth Silden
Pascal Gallant
Alexandre Belenkov
James B. Lorens
Bjørn Tore Gjertsen
author_facet Emmet McCormack
David R. Micklem
Lars-Erik Pindard
Elisabeth Silden
Pascal Gallant
Alexandre Belenkov
James B. Lorens
Bjørn Tore Gjertsen
author_sort Emmet McCormack
collection DOAJ
description Human xenografts of acute myeloid leukemia (AML) in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice result in disease states of diffuse, nonpalpable tissue infiltrates exhibiting a variable disease course, with some animals not developing a disease phenotype. Thus, disease staging and, more critically, quantification of preclinical therapeutic effect in these models are particularly difficult. In this study, we present the generation of a green fluorescent protein (GFP)-labeled human leukemic cell line, NB4, and validate the potential of a time-domain imager fitted with a 470 nm picosecond pulsed laser diode to decouple GFP fluorescence from autofluorescence on the basis of fluorescence lifetime and thus determine the depth and relative concentration of GFP inclusions in phantoms of homogeneous and heterogeneous optical properties. Subsequently, we developed an optical imageable human xenograft model of NB4-GFP AML and illustrate early disease detection, depth discrimination of leukemic infiltrates, and longitudinal monitoring of disease course employing time-domain optical imaging. We conclude that early disease detection through use of time-domain imaging in this initially slowly progressing AML xenograft model permits accurate disease staging and should aid in future preclinical development of therapeutics for AML.
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publishDate 2007-05-01
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series Molecular Imaging
spelling doaj-art-aa1824d8ed1d442f84931d5c01d4a8cc2025-01-02T02:58:14ZengSAGE PublishingMolecular Imaging1536-01212007-05-01610.2310/7290.2007.0001610.2310_7290.2007.00016In Vivo Optical Imaging of Acute Myeloid Leukemia by Green Fluorescent Protein: Time-Domain Autofluorescence Decoupling, Fluorophore Quantification, and LocalizationEmmet McCormackDavid R. MicklemLars-Erik PindardElisabeth SildenPascal GallantAlexandre BelenkovJames B. LorensBjørn Tore GjertsenHuman xenografts of acute myeloid leukemia (AML) in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice result in disease states of diffuse, nonpalpable tissue infiltrates exhibiting a variable disease course, with some animals not developing a disease phenotype. Thus, disease staging and, more critically, quantification of preclinical therapeutic effect in these models are particularly difficult. In this study, we present the generation of a green fluorescent protein (GFP)-labeled human leukemic cell line, NB4, and validate the potential of a time-domain imager fitted with a 470 nm picosecond pulsed laser diode to decouple GFP fluorescence from autofluorescence on the basis of fluorescence lifetime and thus determine the depth and relative concentration of GFP inclusions in phantoms of homogeneous and heterogeneous optical properties. Subsequently, we developed an optical imageable human xenograft model of NB4-GFP AML and illustrate early disease detection, depth discrimination of leukemic infiltrates, and longitudinal monitoring of disease course employing time-domain optical imaging. We conclude that early disease detection through use of time-domain imaging in this initially slowly progressing AML xenograft model permits accurate disease staging and should aid in future preclinical development of therapeutics for AML.https://doi.org/10.2310/7290.2007.00016
spellingShingle Emmet McCormack
David R. Micklem
Lars-Erik Pindard
Elisabeth Silden
Pascal Gallant
Alexandre Belenkov
James B. Lorens
Bjørn Tore Gjertsen
In Vivo Optical Imaging of Acute Myeloid Leukemia by Green Fluorescent Protein: Time-Domain Autofluorescence Decoupling, Fluorophore Quantification, and Localization
Molecular Imaging
title In Vivo Optical Imaging of Acute Myeloid Leukemia by Green Fluorescent Protein: Time-Domain Autofluorescence Decoupling, Fluorophore Quantification, and Localization
title_full In Vivo Optical Imaging of Acute Myeloid Leukemia by Green Fluorescent Protein: Time-Domain Autofluorescence Decoupling, Fluorophore Quantification, and Localization
title_fullStr In Vivo Optical Imaging of Acute Myeloid Leukemia by Green Fluorescent Protein: Time-Domain Autofluorescence Decoupling, Fluorophore Quantification, and Localization
title_full_unstemmed In Vivo Optical Imaging of Acute Myeloid Leukemia by Green Fluorescent Protein: Time-Domain Autofluorescence Decoupling, Fluorophore Quantification, and Localization
title_short In Vivo Optical Imaging of Acute Myeloid Leukemia by Green Fluorescent Protein: Time-Domain Autofluorescence Decoupling, Fluorophore Quantification, and Localization
title_sort in vivo optical imaging of acute myeloid leukemia by green fluorescent protein time domain autofluorescence decoupling fluorophore quantification and localization
url https://doi.org/10.2310/7290.2007.00016
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