title: In vivo optical imaging of acute myeloid leukemia by green fluorescent protein: time-domain autofluorescence decoupling, fluorophore quantification, and localization.
abstract: 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.
authors.affiliation: Institute of Medicine, Haematology Section, Haukeland University Hospital, University of Bergen, Bergen, Norway.
authors.forename: Emmet
authors.initials: E
authors.lastname: McCormack
authors.forename: David R
authors.initials: DR
authors.lastname: Micklem
authors.forename: Lars-Erik
authors.initials: LE
authors.lastname: Pindard
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Silden
authors.forename: Pascal
authors.initials: P
authors.lastname: Gallant
authors.forename: Alexandre
authors.initials: A
authors.lastname: Belenkov
authors.forename: James B
authors.initials: JB
authors.lastname: Lorens
authors.forename: Bjørn Tore
authors.initials: BT
authors.lastname: Gjertsen
mesh_terms: D000208:Acute Disease; D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D042241:Early Diagnosis; D005456:Fluorescent Dyes / Q000032:analysis*; D049452:Green Fluorescent Proteins / Q000032:analysis* / Q000235:genetics; D006801:Humans; D007951:Leukemia, Myeloid / Q000175:diagnosis* / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009367:Neoplasm Staging; D055095:Optics and Photonics / Q000295:instrumentation; D013997:Time Factors; D014183:Transplantation, Heterologous; D051598:Whole Body Imaging / Q000295:instrumentation / Q000379:methods*
chemical_list: D005456:Fluorescent Dyes; D049452:Green Fluorescent Proteins