title: In vivo fluorescence lifetime imaging monitors binding of specific probes to cancer biomarkers.
abstract: One of the most important factors in choosing a treatment strategy for cancer is characterization of biomarkers in cancer cells. Particularly, recent advances in Monoclonal Antibodies (MAB) as primary-specific drugs targeting tumor receptors show that their efficacy depends strongly on characterization of tumor biomarkers. Assessment of their status in individual patients would facilitate selection of an optimal treatment strategy, and the continuous monitoring of those biomarkers and their binding process to the therapy would provide a means for early evaluation of the efficacy of therapeutic intervention. In this study we have demonstrated for the first time in live animals that the fluorescence lifetime can be used to detect the binding of targeted optical probes to the extracellular receptors on tumor cells in vivo. The rationale was that fluorescence lifetime of a specific probe is sensitive to local environment and/or affinity to other molecules. We attached Near-InfraRed (NIR) fluorescent probes to Human Epidermal Growth Factor 2 (HER2/neu)-specific Affibody molecules and used our time-resolved optical system to compare the fluorescence lifetime of the optical probes that were bound and unbound to tumor cells in live mice. Our results show that the fluorescence lifetime changes in our model system delineate HER2 receptor bound from the unbound probe in vivo. Thus, this method is useful as a specific marker of the receptor binding process, which can open a new paradigm in the "image and treat" concept, especially for early evaluation of the efficacy of the therapy.
authors.affiliation: National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Yasaman
authors.initials: Y
authors.lastname: Ardeshirpour
authors.forename: Victor
authors.initials: V
authors.lastname: Chernomordik
authors.forename: Rafal
authors.initials: R
authors.lastname: Zielinski
authors.forename: Jacek
authors.initials: J
authors.lastname: Capala
authors.forename: Gary
authors.initials: G
authors.lastname: Griffiths
authors.forename: Olga
authors.initials: O
authors.lastname: Vasalatiy
authors.forename: Aleksandr V
authors.initials: AV
authors.lastname: Smirnov
authors.forename: Jay R
authors.initials: JR
authors.lastname: Knutson
authors.forename: Ilya
authors.initials: I
authors.lastname: Lyakhov
authors.forename: Samuel
authors.initials: S
authors.lastname: Achilefu
authors.forename: Amir
authors.initials: A
authors.lastname: Gandjbakhche
authors.forename: Moinuddin
authors.initials: M
authors.lastname: Hassan
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D000939:Epitopes / Q000737:chemistry; D005260:Female; D005453:Fluorescence; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal / Q000379:methods; D009368:Neoplasm Transplantation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012984:Software; D019265:Spectroscopy, Near-Infrared / Q000379:methods; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D000939:Epitopes; D018719:Erb-b2 Receptor Tyrosine Kinases