Intrauterine 5-aminolevulinic acid induces selective endometrial fluorescence in the rhesus and cynomolgus monkey.
OBJECTIVE
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 (i.v.) 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 i.v. (n = 11) route. Spectrophoto-fluorometric 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 dosages 24-50-fold greater than that required to induce endometrial 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-aminolevulinic acid causes a transient increase in the serum aspartate aminotransferase level. No other evidence of acute or delayed systemic toxicity was observed.
Yang
J Z
JZ
Department of Obstetrics and Gynecology, Queen's University, Kingston, Ontario, Canada.
Van Vugt
D A
DA
Roy
B N
BN
Kennedy
J C
JC
Foster
W G
WG
Reid
R L
RL
D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002584:Cervix Uteri; D004717:Endometrium / Q000166:cytology / Q000187:drug effects / Q000473:pathology*; D005260:Female; D007267:Injections; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008856:Microscopy, Fluorescence; D010052:Ovariectomy; D013997:Time Factors; D014599:Uterus
D015415:Biomarkers; D000622:Aminolevulinic Acid; D001219:Aspartate Aminotransferases