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使用局部用药5-氨基酮戊酸和苯并卟啉衍生物单酸环进行光动力疗法时对宫颈上皮内瘤变的荧光检测。

Fluorescence detection of cervical intraepithelial neoplasia for photodynamic therapy with the topical agents 5-aminolevulinic acid and benzoporphyrin-derivative monoacid ring.

作者信息

Keefe K A, Chahine E B, DiSaia P J, Krasieva T B, Lin F, Berns M W, Tadir Y

机构信息

Department of Obstetrics and Gynecology, University of California Irvine Medical Center, USA.

出版信息

Am J Obstet Gynecol. 2001 May;184(6):1164-9. doi: 10.1067/mob.2001.113123.

Abstract

OBJECTIVE

The aim of this study was to determine whether 2 photosensitizers, benzoporphyrin-derivative monoacid ring and 5-aminolevulinic acid, are selectively absorbed by dysplastic cervical cells after topical administration.

STUDY DESIGN

This phase I clinical trial involved 18 women with biopsy-proven cervical intraepithelial neoplasia at the Beckman Laser Institute, Irvine, Calif. Colposcopically directed cervical biopsy specimens obtained after 1.5, 3, or 6 hours of exposure to a randomly assigned photosensitizer were evaluated for selective drug absorption with hematoxylin and eosin staining and fluorescence microscopy.

RESULTS

After exposure to 5-aminolevulinic acid, cervical tissue showed maximal fluorescence in dysplastic cells relative to normal cells, with negligible stromal fluorescence. According to our detection methods benzoporphyrin-derivative monoacid ring demonstrated nonselective, diffusion-driven uptake, with fluorescence appearing in the superficial cells, followed by nonselective drug absorption in the remaining cells and stroma of the epithelium.

CONCLUSION

Our data demonstrated selective absorption of 5-aminolevulinic acid by dysplastic cervical cells. This agent therefore represents a promising photosensitizing prodrug for the treatment of cervical intraepithelial neoplasia with photodynamic therapy.

摘要

目的

本研究旨在确定两种光敏剂,即苯并卟啉衍生物单酸环和5-氨基酮戊酸,局部给药后是否能被发育异常的宫颈细胞选择性吸收。

研究设计

这项I期临床试验纳入了18名女性,她们均在加利福尼亚州欧文市的贝克曼激光研究所经活检证实患有宫颈上皮内瘤变。在随机分配的光敏剂暴露1.5、3或6小时后,通过阴道镜引导获取宫颈活检标本,并用苏木精和伊红染色以及荧光显微镜对其进行选择性药物吸收评估。

结果

暴露于5-氨基酮戊酸后,宫颈组织中发育异常细胞相对于正常细胞显示出最大荧光,基质荧光可忽略不计。根据我们的检测方法,苯并卟啉衍生物单酸环表现出非选择性的、由扩散驱动的摄取,荧光出现在表层细胞中,随后上皮的其余细胞和基质出现非选择性药物吸收。

结论

我们的数据表明发育异常的宫颈细胞对5-氨基酮戊酸有选择性吸收。因此,该药物代表了一种有前景的光敏前体药物,可用于光动力疗法治疗宫颈上皮内瘤变。

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