Endometrial ablation by means of photodynamic therapy with photofrin II.
OBJECTIVE
Photodynamic therapy is a technique in which tissue is irradiated with light after the use of a photosensitizing drug that produces singlet oxygen, which has a cytotoxic effect. The feasibility of using photodynamic therapy with photofrin II for endometrial ablation was studied.


METHODS
Fifty-eight rabbits were studied. Preferential uptake of photofrin II by endometrial tissue, compared with the myometrium, was established by drug extraction and fluorescence microscopy after administration of photofrin II intravenously. Dosimetry for endometrial ablation was established by administering photofrin II in 1, 2, 5, and 10 mg/kg doses and laser light (630 nm) at radiant exposures of 100 and 200 J/cm2. Histologic examination was performed at 24 hours, 5 days, and 10 days after treatment. There were two control groups. One group received laser light but no photofrin II, and the other received photofrin II without laser light.


RESULTS
The concentration of photofrin II was three times higher in the endometrium than in the myometrium at doses of 1 and 2 mg/kg. Fluorescence microscopy of frozen sections of endometrium and myometrium showed a predominantly perivascular fluorescence from photofrin II. A dose of 1 and 2 mg/kg and a flow of 100 J/cm2 was adequate for endometrial ablation in rabbits. At 24 hours after treatment there was extensive hemorrhage and evidence of cell death in the entire endometrium and mild hemorrhage in 10% to 50% of the inner circular layer of the myometrium. At 5 days after treatment necrosis of the entire endometrium and the inner half of the myometrium was seen, but the outer half of the myometrium and the serosa were normal. There were no cases of uterine perforation. Similar results were seen at 10 days after treatment, except for the additional presence of inflammatory cells. Neither control group (drug without light, light without drug) showed any injury to the endometrium at 24 hours.


CONCLUSIONS
We conclude that endometrial ablation can be effectively achieved in rabbits by means of photodynamic therapy with photofrin II without significant complications.
Bhatta
N
N
Vincent Gynecology Service, Wellman Laboratories of Photomedicine, Massachusetts General Hospital, Boston 02114.
Anderson
R R
RR
Flotte
T
T
Schiff
I
I
Hasan
T
T
Nishioka
N S
NS
D000818:Animals; D017323:Dihematoporphyrin Ether / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D008856:Microscopy, Fluorescence; D010778:Photochemotherapy; D011817:Rabbits
D017323:Dihematoporphyrin Ether