title: Comparing desferrioxamine and light fractionation enhancement of ALA-PpIX photodynamic therapy in skin cancer.
abstract: Aminolevulinic acid (ALA)-based photodynamic therapy (PDT) provides selective uptake and conversion of ALA into protoporphyrin IX (PpIX) in actinic keratosis and squamous cell carcinoma, yet large response variations in effect are common between individuals. The aim of this study was to compare pre-treatment strategies that increase the therapeutic effect, including fractionated light delivery during PDT (fPDT) and use of iron chelator desferrioxamine (DFO), separately and combined.
  
  
  
  Optical measurements of fluorescence were used to quantify PpIX produced, and the total amount of PpIX photobleached as an implicit measure of the photodynamic dose. In addition, measurements of white light reflectance were used to quantify changes in vascular physiology throughout the PDT treatment.
  
  
  
  fPDT produced both a replenishment of PpIX and vascular re-oxygenation during a 2 h dark interval between the first and second PDT light fractions. The absolute photodynamic dose was increased 57% by fPDT, DFO and their combination, as compared with PDT group (from 0.7 to 1.1). Despite that light fractionation increased oedema and scab formation during the week after treatment, no significant difference in long-term survival has been observed between treatment groups. However, outcomes stratified on the basis of measured photodynamic dose showed a significant difference in long-term survival.
  
  
  
  The assessment of implicit photodynamic dose was a more significant predictor of efficacy for ALA-PDT skin cancer treatments than prescription of an enhanced treatment strategy, likely because of high individual variation in response between subjects.
authors: Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA.|CAPES Foundation, Ministry of Education of Brazil, Brasilia 70040-020, Brazil.
authors: Ana Luiza Ribeiro
authors: AL
authors: de Souza
authors: Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA.
authors: Kayla
authors: K
authors: Marra
authors: Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA.
authors: Jason
authors: J
authors: Gunn
authors: Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA.|Department of Surgery, Geisel School of Medicine, Dartmouth College, Lebanon, NH 03756, USA.
authors: Kimberley S
authors: KS
authors: Samkoe
authors: Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA.
authors: Stephen Chad
authors: SC
authors: Kanick
authors: Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA.
authors: Scott C
authors: SC
authors: Davis
authors: Department of Surgery, Geisel School of Medicine, Dartmouth College, Lebanon, NH 03756, USA.
authors: M Shane
authors: MS
authors: Chapman
authors: Department of Biomedical Engineering, Cleveland Clinic, Cleveland, OH 44195, USA.
authors: Edward V
authors: EV
authors: Maytin
authors: Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors: Tayyaba
authors: T
authors: Hasan
authors: Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA.|Department of Surgery, Geisel School of Medicine, Dartmouth College, Lebanon, NH 03756, USA.
authors: Brian W
authors: BW
authors: Pogue
mesh_terms: D000622:Aminolevulinic Acid / Q000627:therapeutic use*; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D003676:Deferoxamine / Q000494:pharmacology / Q000627:therapeutic use*; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006418:Heme / Q000096:biosynthesis; D006801:Humans; D054023:Lasers, Semiconductor; D008029:Lighting / Q000295:instrumentation / Q000379:methods; D051379:Mice; D008819:Mice, Nude; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011524:Protoporphyrins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011897:Random Allocation; D017262:Siderophores / Q000494:pharmacology / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D017319:Photosensitizing Agents; D011524:Protoporphyrins; D017262:Siderophores; D006418:Heme; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX; D003676:Deferoxamine