title: In vivo fluorescence lifetime imaging for monitoring the efficacy of the cancer treatment.
abstract: OBJECTIVE
  Advances in tumor biology created a foundation for targeted therapy aimed at inactivation of specific molecular mechanisms responsible for cell malignancy. In this paper, we used in vivo fluorescence lifetime imaging with HER2-targeted fluorescent probes as an alternative imaging method to investigate the efficacy of targeted therapy with 17-DMAG (an HSP90 inhibitor) on tumors with high expression of HER2 receptors.
  
  
  METHODS
  HER2-specific Affibody, conjugated to Alexafluor 750, was injected into nude mice bearing HER2-positive tumor xenograft. The fluorescence lifetime was measured before treatment and monitored after the probe injections at 12 hours after the last treatment dose, when the response to the 17-DMAG therapy was the most pronounced as well as a week after the last treatment when the tumors grew back almost to their pretreatment size.
  
  
  RESULTS
  Imaging results showed significant difference between the fluorescence lifetimes at the tumor and the contralateral site (∼0.13 ns) in the control group (before treatment) and 7 days after the last treatment when the tumors grew back to their pretreatment dimensions. However, at the time frame that the treatment had its maximum effect (12 hours after the last treatment), the difference between the fluorescence lifetime at the tumor and contralateral site decreased to 0.03 ns.
  
  
  CONCLUSIONS
  The results showed a good correlation between fluorescence lifetime and the efficacy of the treatment. These findings show that in vivo fluorescence lifetime imaging can be used as a promising molecular imaging tool for monitoring the treatment outcome in preclinical models and potentially in patients.
authors.affiliation: Authors' Affiliations: NIH/National Institute of Child Health and Human Development, Bethesda;
authors.forename: Yasaman
authors.initials: Y
authors.lastname: Ardeshirpour
authors.affiliation: Authors' Affiliations: NIH/National Institute of Child Health and Human Development, Bethesda;
authors.forename: Victor
authors.initials: V
authors.lastname: Chernomordik
authors.affiliation: Authors' Affiliations: NIH/National Institute of Child Health and Human Development, Bethesda; Division of Physics, Office of Science and Engineering Laboratories, CDRH, FDA, Silver Spring;
authors.forename: Moinuddin
authors.initials: M
authors.lastname: Hassan
authors.affiliation: NIH/National Cancer Institute, Rockville, Maryland; and UT MD Anderson Cancer Center, Houston, Texas.
authors.forename: Rafal
authors.initials: R
authors.lastname: Zielinski
authors.affiliation: NIH/National Cancer Institute, Rockville, Maryland; and.
authors.forename: Jacek
authors.initials: J
authors.lastname: Capala
authors.affiliation: Authors' Affiliations: NIH/National Institute of Child Health and Human Development, Bethesda; amir@helix.nih.gov.
authors.forename: Amir
authors.initials: A
authors.lastname: Gandjbakhche
mesh_terms: D000818:Animals; D016227:Benzoquinones / Q000008:administration & dosage / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D005453:Fluorescence; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D064593:Heterografts; D006801:Humans; D007259:Infrared Rays; D047029:Lactams, Macrocyclic / Q000008:administration & dosage / Q000378:metabolism; D051379:Mice; D057054:Molecular Imaging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000378:metabolism; D013997:Time Factors
chemical_list: D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; C533351:affibody (ZHER2-342)2; C448659:17-(dimethylaminoethylamino)-17-demethoxygeldanamycin