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Journal of the Society for Gynecologic Investigation, Vol. 3, No. 3, 152-157 (1996)
DOI: 10.1177/107155769600300309

Intrauterine 5-Aminolevulinic Acid Induces Selective Endometrial Fluorescence in the Rhesus and Cynomolgus Monkey

Jack Z. Yang, MD, PhD

Dean A. Van Vugt, PhD

Brenda N. Roy, BScH

James C. Kennedy, MD, PhD

Warren G. Foster, PhD

Department of Obsterics and Gynecology, the Department of Physiology, the Department of Oncology and Pathology, Queen's University, Kingston, Ontario, Canada, and the Reproductive Toxicology Section, Health Protection Branch, Health Canada, Ottawa, Ontario, Canada

Robert L. Reid, MD

Department of Obsterics and Gynecology, the Department of Physiology, the Department of Oncology and Pathology, Queen's University, Kingston, Ontario, Canada, and the Reproductive Toxicology Section, Health Protection Branch, Health Canada, Ottawa, Ontario, Canada; Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Queen's University, Kingston, Ontario, Canada K7L 3N6

Objectives: To evaluate the selectivity of endometrial photosensitization after intrauterine 5-aminolevulinic acid administration in nonhuman primates, and to assess acute and chronic systemic toxicity after intravenous (IV) delivery of 5-aminolevulinic acid.

Methods: Ovariectomized cynomolgus monkeys (n = 19) aged 6-18 years and ovariectomized rheusus monkeys (n = 3) aged 9-14 years were used in these studies. 5-aminolevulinic acid at various doses was administered by a transfundal (n = 8), transcervical (n = 3), or IV (n = 11) route. Spectrophotofluorometric readings and fluorescence microscopy were used to assess 5-aminolevulinic acid-induced photosensitization of uterine tissues; respiration, heart rate, blood biochemistry, and behavior were used to evaluate potential acute and delayed systemic toxicity.

Results: Endometrial fluorescence was achieved in all animals after administration of 5-aminolevulinic acid. Characteristic spectrophotofluorescence peaks of protoporphyrin IX (PpIX) in the endometrium but not myometrium confirmed selective endometrial PpIX production from 5-aminolevulinic acid. A transient (less than 1 week) increase in serum aspartate aminotransferase was observed after systemic instillation of 5-aminolevulinic acid in dosage 24-50-fold greater than that required to induce endometrical photosensitization after intrauterine injection.

Conclusions: The endometrium but not myometrium in nonhuman primates is capable of converting 5-aminolevulinic acid into protoporphyrin IX. At large doses, systemic 5-aminolevulnic acid causes a transient increase in the serum aspartate aminotransferase level. No other evidence of acute or delayed systemic toxicity was observed.

Key Words: 5-Aminolevulinic acid • photosensitization • endometrium • rhesus and cynomolgus monkey


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