Evaluation of ALA-induced PpIX as a photosensitizer for PDT in cats

Michael D. Lucroy, Benjamin F. Edwards, George M. Peavy, Tatiana B. Krasieva, Stephen M Griffey, Bruce R. Madewell

Research output: Contribution to journalArticle

Abstract

Given exogenously, ALA defeats intrinsic regulatory feedback mechanisms allowing intracellular accumulation of protoporphyrin IX (PpIx), a highly efficient photosensitizer. In vivo, PpIX synthesis in neoplastic mammary tissues averages 20-fold higher than in normal mammary tissues. PpIX is retained intracellularly, unlike perivascular localization of other photosensitizers, and it is then cleared quickly from the body. In vitro, ALA induced PpIx production in our laboratory in 6 cell lines tested, including an established feline kidney cell line and dermal fibroblasts from primary skin biopsy explant, resulting in photosensitization. Fluorescent microscopy confirmed PpIX production in skin adnexae following ALA administration in a normal cat. To evaluate toxicity, three cats were treated with a single i.v. dose of ALA (either 100, 200, or 400 mg/kg) and followed for 7 days. Cats receiving 100 or 200 mg/kg ALA i.v. had elevated liver enzymes and bilirubin within 24 hours. Histopathology revealed hydropic changes in the liver and renal fibrosis. The cat receiving 400 mg/kg ALA intravenously had cutaneous flush, bradycardia and apnea associated with ALA administration; within 24 hours the cat was lethargic, anorectic and icteric. ALT, AST and bilirubin concentrations had increased significantly. At necropsy the liver had a prominent lobular pattern; histopathology revealed severe periportal hepatitis and splenic necrosis. Systemically administered ALA induces PpIX production, but toxicity may preclude its clinical application in the cat. PpIX levels seem to be more time dependent than dose dependent at these three ALA doses and they are well beyond the saturation point for adequate PpIX conversion. The literature is scant regarding toxicity associated with parenteral administration of ALA.

Original languageEnglish (US)
Pages (from-to)445-449
Number of pages5
JournalProceedings of SPIE - The International Society for Optical Engineering
Volume3245
DOIs
StatePublished - 1997

Fingerprint

Photosensitizer
Photosensitizing Agents
Photosensitizers
cats
Toxicity
Liver
Dose
Bilirubin
Skin
evaluation
Evaluation
Cells
liver
toxicity
Tissue
Fibrosis
Appetite Depressants
Necrosis
Fibroblasts
Biopsy

Keywords

  • Aminolevulinic acid
  • Cat
  • Photodynamic therapy
  • Protoporphyrin IX
  • Toxicity

ASJC Scopus subject areas

  • Electrical and Electronic Engineering
  • Condensed Matter Physics

Cite this

Evaluation of ALA-induced PpIX as a photosensitizer for PDT in cats. / Lucroy, Michael D.; Edwards, Benjamin F.; Peavy, George M.; Krasieva, Tatiana B.; Griffey, Stephen M; Madewell, Bruce R.

In: Proceedings of SPIE - The International Society for Optical Engineering, Vol. 3245, 1997, p. 445-449.

Research output: Contribution to journalArticle

Lucroy, Michael D. ; Edwards, Benjamin F. ; Peavy, George M. ; Krasieva, Tatiana B. ; Griffey, Stephen M ; Madewell, Bruce R. / Evaluation of ALA-induced PpIX as a photosensitizer for PDT in cats. In: Proceedings of SPIE - The International Society for Optical Engineering. 1997 ; Vol. 3245. pp. 445-449.
@article{19d87e740c8b46ad8a6df9f4eb8f1633,
title = "Evaluation of ALA-induced PpIX as a photosensitizer for PDT in cats",
abstract = "Given exogenously, ALA defeats intrinsic regulatory feedback mechanisms allowing intracellular accumulation of protoporphyrin IX (PpIx), a highly efficient photosensitizer. In vivo, PpIX synthesis in neoplastic mammary tissues averages 20-fold higher than in normal mammary tissues. PpIX is retained intracellularly, unlike perivascular localization of other photosensitizers, and it is then cleared quickly from the body. In vitro, ALA induced PpIx production in our laboratory in 6 cell lines tested, including an established feline kidney cell line and dermal fibroblasts from primary skin biopsy explant, resulting in photosensitization. Fluorescent microscopy confirmed PpIX production in skin adnexae following ALA administration in a normal cat. To evaluate toxicity, three cats were treated with a single i.v. dose of ALA (either 100, 200, or 400 mg/kg) and followed for 7 days. Cats receiving 100 or 200 mg/kg ALA i.v. had elevated liver enzymes and bilirubin within 24 hours. Histopathology revealed hydropic changes in the liver and renal fibrosis. The cat receiving 400 mg/kg ALA intravenously had cutaneous flush, bradycardia and apnea associated with ALA administration; within 24 hours the cat was lethargic, anorectic and icteric. ALT, AST and bilirubin concentrations had increased significantly. At necropsy the liver had a prominent lobular pattern; histopathology revealed severe periportal hepatitis and splenic necrosis. Systemically administered ALA induces PpIX production, but toxicity may preclude its clinical application in the cat. PpIX levels seem to be more time dependent than dose dependent at these three ALA doses and they are well beyond the saturation point for adequate PpIX conversion. The literature is scant regarding toxicity associated with parenteral administration of ALA.",
keywords = "Aminolevulinic acid, Cat, Photodynamic therapy, Protoporphyrin IX, Toxicity",
author = "Lucroy, {Michael D.} and Edwards, {Benjamin F.} and Peavy, {George M.} and Krasieva, {Tatiana B.} and Griffey, {Stephen M} and Madewell, {Bruce R.}",
year = "1997",
doi = "10.1117/12.312318",
language = "English (US)",
volume = "3245",
pages = "445--449",
journal = "Proceedings of SPIE - The International Society for Optical Engineering",
issn = "0277-786X",
publisher = "SPIE",

}

TY - JOUR

T1 - Evaluation of ALA-induced PpIX as a photosensitizer for PDT in cats

AU - Lucroy, Michael D.

AU - Edwards, Benjamin F.

AU - Peavy, George M.

AU - Krasieva, Tatiana B.

AU - Griffey, Stephen M

AU - Madewell, Bruce R.

PY - 1997

Y1 - 1997

N2 - Given exogenously, ALA defeats intrinsic regulatory feedback mechanisms allowing intracellular accumulation of protoporphyrin IX (PpIx), a highly efficient photosensitizer. In vivo, PpIX synthesis in neoplastic mammary tissues averages 20-fold higher than in normal mammary tissues. PpIX is retained intracellularly, unlike perivascular localization of other photosensitizers, and it is then cleared quickly from the body. In vitro, ALA induced PpIx production in our laboratory in 6 cell lines tested, including an established feline kidney cell line and dermal fibroblasts from primary skin biopsy explant, resulting in photosensitization. Fluorescent microscopy confirmed PpIX production in skin adnexae following ALA administration in a normal cat. To evaluate toxicity, three cats were treated with a single i.v. dose of ALA (either 100, 200, or 400 mg/kg) and followed for 7 days. Cats receiving 100 or 200 mg/kg ALA i.v. had elevated liver enzymes and bilirubin within 24 hours. Histopathology revealed hydropic changes in the liver and renal fibrosis. The cat receiving 400 mg/kg ALA intravenously had cutaneous flush, bradycardia and apnea associated with ALA administration; within 24 hours the cat was lethargic, anorectic and icteric. ALT, AST and bilirubin concentrations had increased significantly. At necropsy the liver had a prominent lobular pattern; histopathology revealed severe periportal hepatitis and splenic necrosis. Systemically administered ALA induces PpIX production, but toxicity may preclude its clinical application in the cat. PpIX levels seem to be more time dependent than dose dependent at these three ALA doses and they are well beyond the saturation point for adequate PpIX conversion. The literature is scant regarding toxicity associated with parenteral administration of ALA.

AB - Given exogenously, ALA defeats intrinsic regulatory feedback mechanisms allowing intracellular accumulation of protoporphyrin IX (PpIx), a highly efficient photosensitizer. In vivo, PpIX synthesis in neoplastic mammary tissues averages 20-fold higher than in normal mammary tissues. PpIX is retained intracellularly, unlike perivascular localization of other photosensitizers, and it is then cleared quickly from the body. In vitro, ALA induced PpIx production in our laboratory in 6 cell lines tested, including an established feline kidney cell line and dermal fibroblasts from primary skin biopsy explant, resulting in photosensitization. Fluorescent microscopy confirmed PpIX production in skin adnexae following ALA administration in a normal cat. To evaluate toxicity, three cats were treated with a single i.v. dose of ALA (either 100, 200, or 400 mg/kg) and followed for 7 days. Cats receiving 100 or 200 mg/kg ALA i.v. had elevated liver enzymes and bilirubin within 24 hours. Histopathology revealed hydropic changes in the liver and renal fibrosis. The cat receiving 400 mg/kg ALA intravenously had cutaneous flush, bradycardia and apnea associated with ALA administration; within 24 hours the cat was lethargic, anorectic and icteric. ALT, AST and bilirubin concentrations had increased significantly. At necropsy the liver had a prominent lobular pattern; histopathology revealed severe periportal hepatitis and splenic necrosis. Systemically administered ALA induces PpIX production, but toxicity may preclude its clinical application in the cat. PpIX levels seem to be more time dependent than dose dependent at these three ALA doses and they are well beyond the saturation point for adequate PpIX conversion. The literature is scant regarding toxicity associated with parenteral administration of ALA.

KW - Aminolevulinic acid

KW - Cat

KW - Photodynamic therapy

KW - Protoporphyrin IX

KW - Toxicity

UR - http://www.scopus.com/inward/record.url?scp=0031289740&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031289740&partnerID=8YFLogxK

U2 - 10.1117/12.312318

DO - 10.1117/12.312318

M3 - Article

AN - SCOPUS:0031289740

VL - 3245

SP - 445

EP - 449

JO - Proceedings of SPIE - The International Society for Optical Engineering

JF - Proceedings of SPIE - The International Society for Optical Engineering

SN - 0277-786X

ER -