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

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.