Phase I clinical trial of the use of zinc phthalocyanine tetrasulfonate as a photosensitizer for photodynamic therapy in dogs.

Full 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.

ANIMALS:
Male Swiss-Webster mice and client-owned dogs with naturally occurring neoplasms.

PROCEDURES:
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 AND CLINICAL RELEVANCE:
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.

Learn Faster Today Improve your study skills

Author information

Author/s: Borgatti-Jeffreys, Antonella (A); Hooser, Stephen B (SB); Miller, Margaret A (MA); Lucroy, Michael D (MD);

Affiliation: Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA.

Journal and publication information

Publication Type: Clinical Trial, Phase I; Journal Article

Journal: American journal of veterinary research (Am J Vet Res), published in United States. (Language: eng)

Reference: 2007-Apr; vol 68 (issue 4) : pp 399-404

Dates: Created 2007/04/02; Completed 2007/07/27;

PMID: 17397295, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article (including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
Dog Diseases - therapy
Dogs
Female
Indoles - therapeutic use; toxicity
Kidney Cortex Necrosis - chemically induced
Male

Male
Mice
Neoplasms - therapy; veterinary
Organometallic Compounds - therapeutic use; toxicity
Photochemotherapy - methods; veterinary
Photosensitizing Agents - therapeutic use; toxicity
Toxicity Tests

Associated Chemicals: Indoles (0) ; Organometallic Compounds (0) ; Photosensitizing Agents (0) ; zinc tetrasulfophthalocyanine (61586-86-5)

These are the highest related articles currently in the database:

See 100+ related articles.