title: Distribution of photosensitizers in bladder cancer spheroids: implications for intravesical instillation of photosensitizers for photodynamic therapy of bladder cancer.
abstract: OBJECTIVE
  Uniform intratumor distribution of sufficient photosensitizer is one of the important aspects of photodynamic therapy for solid tumors.
  
  
  METHODS
  Multicellular spheroids derived from a human transitional cell carcinoma cell line (MGHU3) were used as a surrogate system of tiny solid tumors to study intratumor distribution of photosensitizers. Photosensitizers included Photofrin, hypocrellins (HBEA-R1/R2, HBBA-R2), aluminum phthalocyanine chloride (AlPC), benzoporphyrin derivative monoacid ring A (BPD-MA), protoporphyrin-IX (PpIX), and liposomal formulations of HBBA-R2 and BPD-MA. Spheroids were incubated with various doses of the above drugs for 1-4 hours, and were examined by confocal microscopy.
  
  
  RESULTS
  Histology showed all cells were healthy in spheroids less than 400 microm in diameter. Scanning electron microscopy showed tight cell-to-cell interdigitation in spheroids. HBEA-R1/R2 distributed more uniformly in spheroids than other drugs. Free hypocrellins and BPD-MA penetrated spheroids centripetally deeper than AlPC, Photofrin, and PpIX. Liposomal HBBA-R2 and BPD-MA penetrated less than their free formulations.
  
  
  CONCLUSIONS
  The spheroids mimic solid tumors prior to neovascularization. Based on drug distribution in spheroids, hypocrellins and BPD-MA appear superior to Photofrin, AlPC and PpIX for intravesical administration for bladder cancer phototherapy.
authors.affiliation: Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Zhengwen
authors.initials: Z
authors.lastname: Xiao
authors.forename: Christian B
authors.initials: CB
authors.lastname: Hansen
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Allen
authors.forename: Gerald G
authors.initials: GG
authors.lastname: Miller
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Moore
mesh_terms: D000283:Administration, Intravesical; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018874:Spheroids, Cellular / Q000187:drug effects / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D017319:Photosensitizing Agents