title: Phase I clinical trial of the use of zinc phthalocyanine tetrasulfonate as a photosensitizer for photodynamic therapy in dogs.
abstract: OBJECTIVE
  To determine the threshold for acute toxicosis of parenterally administered zinc phthalocyanine tetrasulfonate (ZnPcS(4)), a candidate second-generation photosensitizer, in mice and evaluate the compound's safety in a phase I clinical trial of ZnPcS(4)-based photodynamic therapy (PDT) in pet dogs with naturally occurring tumors.
  
  
  METHODS
  Male Swiss-Webster mice and client-owned dogs with naturally occurring neoplasms.
  
  
  METHODS
  For the study of acute toxicosis, mice were given graded doses of ZnPcS(4). To determine safety, a rapid-titration phase I clinical trial of ZnPcS(4)-based PDT in tumor-bearing dogs was conducted.
  
  
  RESULTS
  In mice, administration of >or= 100 mg of ZnPcS(4)/kg resulted in renal tubular necrosis 24 hours after IP injection. In tumor-bearing dogs, ZnPcS(4) doses <or= 4 mg/kg induced no signs of toxicosis and resulted in partial to complete tumor responses in 10 of 12 dogs 4 weeks after PDT. Tumor remission was observed with ZnPcS(4) doses as low as 0.25 mg/kg.
  
  
  CONCLUSIONS
  A conservative starting dose of ZnPcS(4) was arrived at on the basis of mouse toxicosis findings. Zinc phthalocyanine tetrasulfonate-based PDT was tolerated well by all dogs and warrants further study. The identification of the maximum tolerated dose through traditional phase I clinical trials may be unnecessary for evaluating novel PDT protocols.
authors.affiliation: Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Antonella
authors.initials: A
authors.lastname: Borgatti-Jeffreys
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Hooser
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Miller
authors.forename: Michael D
authors.initials: MD
authors.lastname: Lucroy
mesh_terms: D000818:Animals; D004283:Dog Diseases / Q000628:therapy*; D004285:Dogs; D005260:Female; D007211:Indoles / Q000627:therapeutic use* / Q000633:toxicity*; D007673:Kidney Cortex Necrosis / Q000139:chemically induced; D008297:Male; D051379:Mice; D009369:Neoplasms / Q000628:therapy / Q000662:veterinary*; D009942:Organometallic Compounds / Q000627:therapeutic use* / Q000633:toxicity*; D010778:Photochemotherapy / Q000379:methods / Q000662:veterinary*; D017319:Photosensitizing Agents / Q000627:therapeutic use* / Q000633:toxicity*; D018675:Toxicity Tests
chemical_list: D007211:Indoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; C052735:zinc tetrasulfophthalocyanine