title: A Comparison of Dose Metrics to Predict Local Tumor Control for Photofrin-mediated Photodynamic Therapy.
abstract: This preclinical study examines light fluence, photodynamic therapy (PDT) dose and "apparent reacted singlet oxygen," [1O2]rx, to predict local control rate (LCR) for Photofrin-mediated PDT of radiation-induced fibrosarcoma (RIF) tumors. Mice bearing RIF tumors were treated with in-air fluences (50-250 J cm-2) and in-air fluence rates (50-150 mW cm-2) at Photofrin dosages of 5 and 15 mg kg-1and a drug-light interval of 24 h using a 630-nm, 1-cm-diameter collimated laser. A macroscopic model was used to calculate [1O2]rxand PDT dose based on in vivo explicit dosimetry of the drug concentration, light fluence and tissue optical properties. PDT dose and [1O2]rxwere defined as a temporal integral of drug concentration and fluence rate, and singlet oxygen concentration consumed divided by the singlet oxygen lifetime, respectively. LCR was stratified for different dose metrics for 74 mice (66 + 8 control). Complete tumor control at 14 days was observed for [1O2]rx≥ 1.1 mm or PDT dose ≥1200 μm J cm-2but cannot be predicted with fluence alone. LCR increases with increasing [1O2]rxand PDT dose but is not well correlated with fluence. Comparing dosimetric quantities, [1O2]rxoutperformed both PDT dose and fluence in predicting tumor response and correlating with LCR.
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA.|Department of Laser Medicine, Chinese PLA General Hospital, Beijing, China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Qiu
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA.|Department of Physics and Astronomy, University of Pennsylvania, Philadelphia, PA.
authors.forename: Michele M
authors.initials: MM
authors.lastname: Kim
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA.
authors.forename: Rozhin
authors.initials: R
authors.lastname: Penjweini
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA.
authors.forename: Jarod C
authors.initials: JC
authors.lastname: Finlay
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA.
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Busch
authors.affiliation: Department of Biostatistics, University of Pennsylvania, Philadelphia, PA.
authors.forename: Tianhao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Biostatistics, University of Pennsylvania, Philadelphia, PA.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Guo
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Cengel
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA.
authors.forename: Charles B
authors.initials: CB
authors.lastname: Simone
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA.
authors.forename: Eli
authors.initials: E
authors.lastname: Glatstein
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Zhu
mesh_terms: D000818:Animals; D017323:Dihematoporphyrin Ether / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D008809:Mice, Inbred C3H; D009381:Neoplasms, Radiation-Induced / Q000188:drug therapy* / Q000378:metabolism; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D026082:Singlet Oxygen / Q000378:metabolism
chemical_list: D017319:Photosensitizing Agents; D026082:Singlet Oxygen; D017323:Dihematoporphyrin Ether