title: Photodynamic therapy of intracranial tissues: a preclinical comparative study of four different photosensitizers.
abstract: OBJECTIVE
  The effectiveness of four different photosensitizers for intracranial photodynamic therapy (PDT) of normal brain tissues and an intracranial tumor was investigated in rabbits, using the photodynamic threshold model.
  
  
  CONCLUSIONS
  PDT is currently being investigated as an adjuvant treatment to surgical resection and/or radio chemotherapy of intracranial neoplasms. While possible neurotoxic side effects of the treatment have been noted, only limited preclinical data quantifying the response of intracranial normal and tumor tissues following PDT are available.
  
  
  METHODS
  The photodynamic threshold dose values for the four photosensitizers, Photofrin, 5-aminolevulinic acid (ALA)-induced Protoporphyrin IX (PpIX), Tin Ethyl Etiopurpurin (SnET2), and chloroaluminum phthalocyanine (AlClPc), were determined using measured light fluence distributions, photosensitizer concentration in tissue, and histologically-determined extent of necrosis following PDT. These measurements were made in normal rabbit brain and in an intracranially-implanted carcinoma (VX2).
  
  
  RESULTS
  For Photofrin, AlClPc, and SnET2 (in an emulsion delivery vehicle) normal grey and white matter were very sensitive to PDT, showing a significantly lower threshold dose value than VX2-tumor. For ALA-induced PpIX and SnET2 (in liposome) very little or no white matter damage was observed. Additionally, ALA-PpIX showed significantly lower concentration in white matter than in cortex and tumor. Normal brain structures lacking a blood-brain barrier showed high uptake of all photosensitizers and, hence, are at risk of collateral damage during PDT.
  
  
  CONCLUSIONS
  For clinical PDT of most adult intracranial neoplasms ALA-induced PpIX appears to be promising, and SnET2 (liposomal) has potential for selective tumor destruction with relative sparing of white matter. Other normal brain structures and, for the other photosensitizers, also white matter are at risk of collateral damage, if exposed to light during PDT.
authors.affiliation: Department of Medical Biophysics, University of Toronto, Ontario, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Lilge
authors.forename: B C
authors.initials: BC
authors.lastname: Wilson
mesh_terms: D000818:Animals; D001128:Argon; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017323:Dihematoporphyrin Ether / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005069:Evaluation Studies as Topic; D006414:Hematoporphyrin Photoradiation; D007211:Indoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D053685:Laser Therapy; D008297:Male; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011166:Porphyrins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D011524:Protoporphyrins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D011817:Rabbits
chemical_list: D007211:Indoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D011166:Porphyrins; D011524:Protoporphyrins; C044797:chloroaluminum phthalocyanine; C063166:tin etiopurpurin; D001128:Argon; D017323:Dihematoporphyrin Ether; C028025:protoporphyrin IX