Preclinical study in cats of the pro-photosensitizer 5-aminolevulinic acid

To determine whether feline cells were able to convert 5-aminolevulinic acid (ALA) to protoporphyrin IX (PpIX) in vivo and in vitro, whether i.v. administration of ALA to healthy cats resulted in adverse effects, and whether PpIX accumulated in a squamous cell carcinoma (SCC) of a cat. 4 healthy adu...

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Published inAmerican journal of veterinary research Vol. 60; no. 11; p. 1364
Main Authors Lucroy, M D, Edwards, B F, Peavy, G M, Krasieva, T B, Griffey, S M, Stiles, J B, Madewell, B R
Format Journal Article
LanguageEnglish
Published United States 01.11.1999
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Abstract To determine whether feline cells were able to convert 5-aminolevulinic acid (ALA) to protoporphyrin IX (PpIX) in vivo and in vitro, whether i.v. administration of ALA to healthy cats resulted in adverse effects, and whether PpIX accumulated in a squamous cell carcinoma (SCC) of a cat. 4 healthy adult cats and 1 adult cat with a cutaneous SCC. In vitro production of PpIX was determined by incubating Crandell feline kidney cells with ALA. Effects of ALA administration and in vivo production of PpIX were determined by administering ALA (100, 200, or 400 mg/kg of body weight) to healthy cats and collecting skin biopsy specimens for up to 24 hours after drug administration. Blood samples were collected for CBC and serum biochemical analyses, and necropsies were performed. Accumulation of PpIX in a SCC was determined by treating a cat with a facial SCC with ALA and collecting specimens of the tumor and adjacent grossly normal skin. Incubation of ALA with feline cells resulted in time- and dose-dependent cytoplasmic accumulation of PpIX in vitro. After i.v. ALA administration, PpIX was detected in all tissues examined, with the highest fluorescence intensity in epithelia and in squamous cell carcinoma. The tumor-to-skin fluorescence intensity ratio was 5. All cats developed hepatotoxicoses. Results from this limited number of cats suggest that ALA may be a useful photosensitizer in cats, but that doses > 100 mg/kg, i.v., may not be safe.
AbstractList To determine whether feline cells were able to convert 5-aminolevulinic acid (ALA) to protoporphyrin IX (PpIX) in vivo and in vitro, whether i.v. administration of ALA to healthy cats resulted in adverse effects, and whether PpIX accumulated in a squamous cell carcinoma (SCC) of a cat. 4 healthy adult cats and 1 adult cat with a cutaneous SCC. In vitro production of PpIX was determined by incubating Crandell feline kidney cells with ALA. Effects of ALA administration and in vivo production of PpIX were determined by administering ALA (100, 200, or 400 mg/kg of body weight) to healthy cats and collecting skin biopsy specimens for up to 24 hours after drug administration. Blood samples were collected for CBC and serum biochemical analyses, and necropsies were performed. Accumulation of PpIX in a SCC was determined by treating a cat with a facial SCC with ALA and collecting specimens of the tumor and adjacent grossly normal skin. Incubation of ALA with feline cells resulted in time- and dose-dependent cytoplasmic accumulation of PpIX in vitro. After i.v. ALA administration, PpIX was detected in all tissues examined, with the highest fluorescence intensity in epithelia and in squamous cell carcinoma. The tumor-to-skin fluorescence intensity ratio was 5. All cats developed hepatotoxicoses. Results from this limited number of cats suggest that ALA may be a useful photosensitizer in cats, but that doses > 100 mg/kg, i.v., may not be safe.
Author Lucroy, M D
Griffey, S M
Stiles, J B
Edwards, B F
Peavy, G M
Madewell, B R
Krasieva, T B
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Snippet To determine whether feline cells were able to convert 5-aminolevulinic acid (ALA) to protoporphyrin IX (PpIX) in vivo and in vitro, whether i.v....
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StartPage 1364
SubjectTerms Aminolevulinic Acid - pharmacokinetics
Aminolevulinic Acid - therapeutic use
Aminolevulinic Acid - toxicity
Animals
Biotransformation
Carcinoma, Squamous Cell - drug therapy
Carcinoma, Squamous Cell - metabolism
Carcinoma, Squamous Cell - pathology
Carcinoma, Squamous Cell - veterinary
Cat Diseases - drug therapy
Cat Diseases - pathology
Cats
Cell Line
Female
Kidney
Male
Orchiectomy
Ovariectomy
Photosensitizing Agents - pharmacokinetics
Photosensitizing Agents - therapeutic use
Photosensitizing Agents - toxicity
Protoporphyrins - pharmacokinetics
Skin - drug effects
Skin - metabolism
Skin Neoplasms - drug therapy
Skin Neoplasms - metabolism
Skin Neoplasms - pathology
Skin Neoplasms - veterinary
Title Preclinical study in cats of the pro-photosensitizer 5-aminolevulinic acid
URI https://www.ncbi.nlm.nih.gov/pubmed/10566810
Volume 60
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