INTRAUTERINE 5-AMINOLEVULINIC ACID INDUCES SELECTIVE ENDOMETRIAL FLUORESCENCE IN THE RHESUS AND CYNOMOLGUS MONKEY

OBJECTIVES: To evaluate the selectivity of endometrial photosensitizat ion after intrauterine 5-aminolevulinic acid administration in nonhuma n primates, and to assess acute and chronic systemic toxicity after in travenous (IV) delivery of 5-aminolevulinic acid. METHODS: Ovariectomi zed cynomolgus monkeys (n = 19) aged 6-18 years and ovariectomized rhe usus monkeys (n = 3) aged 9-14 years were used in these studies. 5-ami nolevulinic acid at various doses was administered by a transfundal (n = 8), transcervical (n = 3), or IV (n = 11) route. Spectrophotoflurom etric readings and fluorescence microscopy were used to assess 5-amino levulinic acid-induced photosensitization of uterine tissues; respirat ion, heart rate, blood biochemistry, and behavior were used to evaluat e potential acute and delayed systemic toxicity. RESULTS: Endometrial fluorescence was achieved in all animals after administration of 5-ami nolevulinic acid. Characteristic spectrophotofluorescence peaks of pro toporphyrin IX (PpIX) in the endometrium but not myometrium confirmed selective endometrial PpIX production from 5-aminolevulinic acid. A tr ansient (less than 1 week) increase in serum aspartate aminotransferas e was observed after systemic instillation of 5-aminolevulinic acid in dosages 24-50-fold greater than that required to induce endometrial p hotosensitization after intrauterine injection. CONCLUSIONS: The endom etrium but not myometrium in nonhuman primates is capable of convertin g 5-aminolevulinic acid into protoporphyrin IX. At large doses, system ic 5-aminolevulinic acid causes a transient increase in the serum aspa rtate aminotransferase level. No other evidence of acute or delayed sy stemic toxicity was observed.