title: Pc 4 photodynamic therapy of U87-derived human glioma in the nude rat.
abstract: OBJECTIVE
  As a potential therapy for malignant glioma, we tested the phthalocyanine photosensitizer Pc 4 for: (1) rapid clearance from the vasculature, (2) specificity for glioma, and (3) tumoricidal photosensitizing capability.
  
  
  METHODS
  Parenchymal injection of U87 cells into athymic rat brains (N = 100) was followed after 12 days by tail vein injection of 0.5 mg/kg Pc 4. After 1 day, the tumor was illuminated with either 5 (N = 11) or 30 (N = 16) J/cm(2) red light at 672 nm. Sacrifice was 1 day later. The brains from these 27 animals underwent H&E (necrosis) and TUNEL assay (apoptosis) histology. Pc 4 concentration of explanted brains and tumors (N = 16), and all blood samples (N = 52) were determined by HPLC-MS 1 day post Pc 4 administration.
  
  
  RESULTS
  Tumor-specific apoptosis was almost uniformly seen; however, necrosis was found mostly in the high-light-dose group. Pc 4 concentration in bulk tumor averaged 3.8 times greater than in normal brain.
  
  
  CONCLUSIONS
  These results warrant expanding this pre-clinical study to seek effective baseline Pc 4 drug- and light-doses and infusion-to-photoirradiation timing that would be necessary for a Pc 4-mediated PDT clinical trial for glioma patients.
authors.affiliation: Department of Surgery, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: George
authors.forename: Yusra
authors.initials: Y
authors.lastname: Ahmad
authors.forename: Davood
authors.initials: D
authors.lastname: Varghai
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Li
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Berlin
authors.forename: David
authors.initials: D
authors.lastname: Jackowe
authors.forename: Marc
authors.initials: M
authors.lastname: Jungermann
authors.forename: Michael S
authors.initials: MS
authors.lastname: Wolfe
authors.forename: Lothar
authors.initials: L
authors.lastname: Lilge
authors.forename: Ali
authors.initials: A
authors.lastname: Totonchi
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Morris
authors.forename: Allyn
authors.initials: A
authors.lastname: Peterson
authors.forename: W David
authors.initials: WD
authors.lastname: Lust
authors.forename: Malcolm E
authors.initials: ME
authors.lastname: Kenney
authors.forename: Charles L
authors.initials: CL
authors.lastname: Hoppel
authors.forename: Jiayang
authors.initials: J
authors.lastname: Sun
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Oleinick
authors.forename: David
authors.initials: D
authors.lastname: Dean
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007275:Injections, Intravenous; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats; D011923:Rats, Nude
chemical_list: D007211:Indoles; D017319:Photosensitizing Agents; C107448:phthalocyanine Pc 4