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使用六氨基乙酰丙酸对卵巢癌进行光动力诊断:一项临床前研究。

Photodynamic diagnosis of ovarian cancer using hexaminolaevulinate: a preclinical study.

作者信息

Lüdicke F, Gabrecht T, Lange N, Wagnières G, Van Den Bergh H, Berclaz L, Major A L

机构信息

Fondation pour Recherches Médicales, University of Geneva, 64 Avenue de la Roseraie, Switzerland.

出版信息

Br J Cancer. 2003 Jun 2;88(11):1780-4. doi: 10.1038/sj.bjc.6600958.

Abstract

The unfailing detection of micrometastases during surgery of patients suffering from ovarian cancer is mandatory for the optimal management of this disease. Thus, the present study aimed at determining the feasibility of detecting micrometastases in an ovarian cancer model using the intraperitoneal administration of the photosensitiser precursor hexaminolaevulinate (HAL). For this purpose, HAL was applied intraperitoneally at different concentrations (4-12 mM) to immunocompetent Fischer 344 rats bearing a syngeneic epithelial ovarian carcinoma. The tumours were visualised laparoscopically using both white and blue light (D-light, Karl Storz, Tuttlingen, Germany), and the number of peritoneal micrometastases detected through HAL-induced photodiagnosis (PD) was compared to standard white light visualisation. Fluorescence spectra were recorded with an optical fibre-based spectrofluorometer and the fluorescence intensities were compared to the protoporphyrin IX (PpIX) fluorescence induced by 5-aminolevulinic acid under similar conditions. The number of metastases detected by the PD blue light mode was higher than when using standard white light abdominal inspection for all applied concentrations. Twice as many cancer lesions were detected by fluorescence than by white light inspection. The hexyl-ester derivative produced higher PpIX fluorescence than its parent substance aminolevulinic acid at the same concentration and application time. Fluorescence contrast between healthy and cancerous tissue was excellent for both compounds. To overcome poor diagnostic efficiency and to detect peritoneal ovarian carcinoma foci in the large surface area of the human peritoneal cavity, HAL fluorescence-based visualisation techniques may acquire importance in future and lead to a more correct staging of early ovarian cancer.

摘要

在卵巢癌患者手术过程中始终如一地检测微转移对于该疾病的最佳管理至关重要。因此,本研究旨在确定在卵巢癌模型中通过腹腔内给予光敏剂前体六氨基乙酰丙酸(HAL)来检测微转移的可行性。为此,将不同浓度(4 - 12 mM)的HAL腹腔内应用于患有同基因上皮性卵巢癌的免疫活性Fischer 344大鼠。使用白光和蓝光(德国图特林根卡尔·史托斯公司的D光)通过腹腔镜观察肿瘤,并将通过HAL诱导的光诊断(PD)检测到的腹膜微转移数量与标准白光观察进行比较。用基于光纤的分光荧光计记录荧光光谱,并将荧光强度与在类似条件下由5 - 氨基乙酰丙酸诱导的原卟啉IX(PpIX)荧光进行比较。对于所有应用浓度,PD蓝光模式检测到的转移灶数量均高于使用标准白光腹部检查时的数量。荧光检测到的癌灶数量是白光检查的两倍。在相同浓度和应用时间下,己酯衍生物产生的PpIX荧光高于其母体物质氨基乙酰丙酸。两种化合物在健康组织和癌组织之间的荧光对比度都非常好。为了克服诊断效率低下的问题并检测人类腹膜腔大表面积中的腹膜卵巢癌病灶,基于HAL荧光的可视化技术未来可能会变得重要,并导致早期卵巢癌的分期更加准确。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c61f/2377128/fa143daab78d/88-6600958f1.jpg

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