Photodynamic therapy induced esophageal stricture--an animal model: from mouse to pig.
BACKGROUND
A major limitation of photodynamic therapy (PDT) for Barrett's esophagus is the development of esophageal stricture. We developed an animal model of PDT-induced esophageal stricture to elucidate the mechanism of stricture development. Our studies began in a mouse but, due to its limitations, we advanced to a porcine model.


METHODS
In the mouse model, 62 mice were injected with Photofrin (2-10 mg/kg) 48 h prior to photoactivation. Light energy (20-400 Joules/cm (J)) was delivered with a laser probe as a single dose, or fractionated doses (20-150 J). Animals were sacrificed when showing signs of distress or 6 to 18 weeks post-illumination. Esophagus was removed, with gross and microscopic examination performed on frozen specimens. To develop a pig model, six pigs were injected with Photofrin (2 mg/kg) 48 h prior to photoactivation. Light energy (400 J) was delivered via an endoscope using a laser probe as a single dose or repeated at 48 h. Animals were sacrificed if they could not eat soft food or lost more than 10% of their original weight according to the University of Pittsburgh Institutional Animal Care and Use Committee.


RESULTS
Exposure of mice to doses of 400 J x 1, 125 J x 3, or 150 J x 3 fractions resulted in severe lung damage and death in 90% of the mice without any evidence of esophageal stricture. Lower energy levels caused minor lung damage and no change in the endothelial layer or a stricture. In pigs, exposure of 400 J as one or two fractions resulted in weight loss of 10% within 3 weeks. Endoscopy, upper GI, contrast swallow, and pathological and histological examination showed evidence of esophageal stricture at the exposed area.


CONCLUSIONS
In the mouse model, pulmonary toxicity is the limiting factor following esophageal PDT exposure. In the pig model we induced esophageal stricture following PDT. This is the first animal model created to study esophageal strictures resulting from PDT.
Perry
Yaron
Y
Department of Surgery, Section of Thoracic Surgery, University of Pittsburgh Medical Center Health System, Pittsburgh, Pennsylvania, USA.
Epperly
Michael W
MW
Fernando
Hiran C
HC
Klein
Ed
E
Finkelstein
Sid
S
Greenberger
Joel S
JS
Luketich
James D
JD
D000622:Aminolevulinic Acid / Q000494:pharmacology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D004940:Esophageal Stenosis / Q000209:etiology* / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D010778:Photochemotherapy / Q000009:adverse effects*; D013552:Swine
D000622:Aminolevulinic Acid