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


METHODS
4 healthy adult cats and 1 adult cat with a cutaneous SCC.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Lucroy
M D
MD
Center for Companion Animal Health, School of Veterinary Medicine, University of California, Davis 95616, USA.
Edwards
B F
BF
Peavy
G M
GM
Krasieva
T B
TB
Griffey
S M
SM
Stiles
J B
JB
Madewell
B R
BR
D000622:Aminolevulinic Acid / Q000493:pharmacokinetics* / Q000627:therapeutic use / Q000633:toxicity*; D000818:Animals; D001711:Biotransformation; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D002371:Cat Diseases / Q000188:drug therapy* / Q000473:pathology; D002415:Cats; D002460:Cell Line; D005260:Female; D007668:Kidney; D008297:Male; D009919:Orchiectomy; D010052:Ovariectomy; D017319:Photosensitizing Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use / Q000633:toxicity*; D011524:Protoporphyrins / Q000493:pharmacokinetics; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012878:Skin Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*
D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX