Kinetics, localization, and mechanism of 5-aminolevulinic acid-induced porphyrin accumulation in normal and Barrett's-like rat esophagus.
OBJECTIVE
Photodynamic therapy may selectively destroy Barrett's epithelium in the esophagus. To optimize photosensitizer administration, the kinetics of 5-aminolevulinic acid (ALA)-induced porphyrin accumulation in the normal and Barrett's-like esophagus were studied in the rat.


METHODS
Animals received 200 mg/kg ALA intravenously (n = 21) or orally (n = 21). Six rats served as controls. At t = 1, 2, 3, 4, 6, 12, and 24 hr, porphyrin concentration in the esophagus was measured by using chemical extraction, and porphyrin localization was determined by laser scanning microscopy (LSM). In addition, in 20 animals, porphobilinogen deaminase, ferrochelatase, and iron concentration were determined. In a second group (n = 24), an esophagojejunostomy was performed to induce a Barrett's-like esophagus. After 18 weeks, animals received ALA, and LSM was performed at t = 1, 2, 3, 4, 6, 8, and 12 hr.


RESULTS
Porphyrin accumulation in normal mucosa was 3.5-fold higher than in muscularis, with a maximum at 3 hr after ALA administration. With LSM, strong homogeneous fluorescence of the squamous epithelium was shown, with minor fluorescence of submucosa and muscularis. In Barrett's-like epithelium, fluorescence was heterogeneous but was also restricted to epithelial cells. There was no difference in fluorescence intensity between Barrett's-like and adjacent squamous epithelium. Porphobilinogen deaminase activity was higher and iron concentration was lower in the mucosa than in the muscularis (P < 0.001).


CONCLUSIONS
ALA-induced porphyrin accumulation selectively occurs in esophageal mucosa, whether normal or Barrett's-like, compared with the muscularis, with a maximum at 3 hr after ALA administration. Selectivity may be caused by a different activity of heme-synthetic enzymes or relative iron deficiency in the mucosa.
Department of Surgery, Erasmus University Medical Faculty, Rotterdam, The Netherlands. vandenboogert@heel.fgg.eur.nl
J
J
van den Boogert
A B
AB
Houtsmuller
F W
FW
de Rooij
R W
RW
de Bruin
P D
PD
Siersema
R
R
van Hillegersberg
D000284:Administration, Oral; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D001471:Barrett Esophagus / Q000188:drug therapy*; D004195:Disease Models, Animal; D004947:Esophagus / Q000187:drug effects / Q000473:pathology; D005453:Fluorescence; D007275:Injections, Intravenous; D008297:Male; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011166:Porphyrins / Q000032:analysis*; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D017319:Photosensitizing Agents; D011166:Porphyrins; D000622:Aminolevulinic Acid