title: Real-time monitoring of hemodynamic changes in tumor vessels during photoimmunotherapy using optical coherence tomography.
abstract: Photoimmunotherapy (PIT) is a cell-specific cancer therapy based on an armed antibody conjugate that induces rapid and highly selective cancer cell necrosis after exposure to near-infrared (NIR) light. The PIT treatment also induces the superenhanced permeability and retention effect, which allows high concentrations of nanoparticles to accumulate in the tumor bed. In our pilot studies, optical coherence tomography (OCT) reveals dramatic hemodynamic changes during PIT. We developed and applied speckle variance analysis, Doppler flow measurement, bulk motion removal, and automatic region of interest selection to quantify vessel diameter and blood velocity within tumors in vivo. OCT imaging reveals that blood velocity in peripheral tumor vessels quickly drops below the detection limit while the vessel lumen remains open (4 vessels from 3 animals). On the other hand, control tumor vessels (receive NIR illumination but no PIT drug) do not show the sustained blood velocity drop (5 vessels from 3 animals). Ultraslow blood velocity could result in a long drug circulation time in tumor. Increase of the blood pool volume within the central tumor (shown in histology) may be the leading cause of the periphery blood velocity drop and could also increase the drug pool volume in tumor vessels.
authors.affiliation: University of Maryland, Fischell Department of Bioengineering, 2218 Jeong H. Kim Engineering Building, College Park, Maryland 20742, United States.
authors.forename: Chia-Pin
authors.initials: CP
authors.lastname: Liang
authors.affiliation: National Institute of Health, National Cancer Institute, Molecular Imaging Program, Bldg 10, Room B3B47, Bethesda, Maryland 20892-1088, United States.
authors.forename: Takahito
authors.initials: T
authors.lastname: Nakajima
authors.affiliation: National Institute of Health, National Cancer Institute, Molecular Imaging Program, Bldg 10, Room B3B47, Bethesda, Maryland 20892-1088, United States.
authors.forename: Rira
authors.initials: R
authors.lastname: Watanabe
authors.affiliation: National Institute of Health, National Cancer Institute, Molecular Imaging Program, Bldg 10, Room B3B47, Bethesda, Maryland 20892-1088, United States.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Sato
authors.affiliation: National Institute of Health, National Cancer Institute, Molecular Imaging Program, Bldg 10, Room B3B47, Bethesda, Maryland 20892-1088, United States.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Choyke
authors.affiliation: University of Maryland, Fischell Department of Bioengineering, 2218 Jeong H. Kim Engineering Building, College Park, Maryland 20742, United States.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: National Institute of Health, National Cancer Institute, Molecular Imaging Program, Bldg 10, Room B3B47, Bethesda, Maryland 20892-1088, United States.
authors.forename: Hisataka
authors.initials: H
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D005260:Female; D006439:Hemodynamics / Q000502:physiology*; D007167:Immunotherapy; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D019047:Phantoms, Imaging; D010789:Phototherapy; D041623:Tomography, Optical Coherence / Q000379:methods*; D059016:Tumor Microenvironment