title: Photofrin uptake in the tumor and normal tissues of patients receiving intraperitoneal photodynamic therapy.
abstract: OBJECTIVE
  A phase II trial of Photofrin-mediated i.p. photodynamic therapy shown in a previous report limited efficacy and significant acute, but not chronic, toxicity. A secondary aim of this trial and the subject of this report is to determine Photofrin uptake in tumor and normal tissues.
  
  
  METHODS
  Patients received Photofrin, 2.5 mg/kg, i.v., 48 hours before debulking surgery. Photofrin uptake was measured by spectroflurometric analysis of drug extracted from tumor and normal tissues removed at surgery. Differences in drug uptake among these tissues were statistically considered using mixed-effects models.
  
  
  RESULTS
  Photofrin concentration was measured in 301 samples collected from 58 of 100 patients enrolled on the trial. In normal tissues, drug uptake significantly (P<0.0001) differed as a function of seven different tissue types. In the toxicity-limiting tissue of intestine, the model-based mean (SE) Photofrin level was 2.70 ng/mg (0.32 ng/mg) and 3.42 ng/mg (0.24 ng/mg) in full-thickness large and small intestine, respectively. In tumors, drug uptake significantly (P=0.0015) differed as a function of patient cohort: model-based mean Photofrin level was 3.32 to 5.31 ng/mg among patients with ovarian, gastric, or small bowel cancer; 2.09 to 2.45 ng/mg among patients with sarcoma and appendiceal or colon cancer; and 0.93 ng/mg in patients with pseudomyxoma. Ovarian, gastric, and small bowel cancers showed significantly higher Photofrin uptake than full-thickness large and/or small intestine. However, the ratio of mean drug level in tumor versus intestine was modest (<or=2.31).
  
  
  CONCLUSIONS
  Some selectivity is found in Photofrin uptake between tumor and normal tissues of the peritoneal cavity, but absolute differences in drug uptake relative to toxicity-limiting normal tissues (intestine) are small. This narrow differential in drug selectivity likely contributes to a narrow window in therapeutic application, which has been previously reported.
authors.affiliation: Department of Radiation Oncology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6072, USA.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hahn
authors.forename: Mary E
authors.initials: ME
authors.lastname: Putt
authors.forename: James
authors.initials: J
authors.lastname: Metz
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Shin
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Rickter
authors.forename: Chandrakala
authors.initials: C
authors.lastname: Menon
authors.forename: Debbie
authors.initials: D
authors.lastname: Smith
authors.forename: Eli
authors.initials: E
authors.lastname: Glatstein
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Fraker
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Busch
mesh_terms: D001706:Biopsy; D015331:Cohort Studies; D017323:Dihematoporphyrin Ether / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy; D006801:Humans; D007274:Injections, Intraperitoneal; D008954:Models, Biological; D009928:Organ Specificity; D010051:Ovarian Neoplasms / Q000188:drug therapy; D010778:Photochemotherapy / Q000379:methods*; D012509:Sarcoma / Q000188:drug therapy; D014018:Tissue Distribution
chemical_list: D017323:Dihematoporphyrin Ether