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光敏剂氨基乙酰丙酸和氨基乙酰丙酸己酯在鸡胚绒毛尿囊膜中包埋的口腔面部肿瘤中的药代动力学。

Pharmacokinetics of the photosensitizers aminolevulinic acid and aminolevulinic acid hexylester in oro-facial tumors embedded in the chorioallantois membrane of a hen's egg.

作者信息

Hoppenheit Christian, Hüttenberger Dirk, Foth Hans-Jochen, Spitzer Wolfgang J, Reichert Torsten E, Müller-Richter Urs D A

机构信息

Department of Maxillofacial Surgery, University of Saarland, Germany.

出版信息

Cancer Biother Radiopharm. 2006 Dec;21(6):569-78. doi: 10.1089/cbr.2006.21.569.

Abstract

BACKGROUND

Oral squamous-cell carcinoma is a frequent form of cancer in the head and neck region. The survival rate is poor. Therapy success is highly dependent on the stage of cancer development at which diagnosis is made. The disease is mostly diagnosed at a late stage. Photodynamic diagnosis is a new tool for screening examinations. This technique calls for reliable photosensitizers, such as aminolevulinic acid (ALA) and aminolevulinic acid hexylester (h-ALA). ALA and h-ALA are the source material for the synthesis of protoporphyrin IX in tumor cells. Protoporphyrin IX has a high detection rate for tumor tissue within a reasonable period of time.

METHODS

Tumor specimens were harvested from oral carcinomas and basaliomas of the face. The vital cells of the specimens and the human tumor cell line (CLS- 354) were cultured in a 90% RPMI and 10% fetal bovine serum medium. A constant number of 50,000 cells from each specimen and the cell line were transferred to an in vivo model on the hen's egg model. The grown specimens were tested for tumor fluorescence with ALA and h-ALA. The intensity of tumor fluorescence during the following 24 hours was measured spectroscopically as the degree of concentration of protoporphyrin IX within the cells.

RESULTS

All tumors showed higher protoporphyrin IX enrichment and fluorescence, compared to healthy tissue. Using h-ALA, the peak concentration of protoporphyrin IX was achieved 20%-25% more quickly with 3- or 6-mM solutions than with ALA. The highest contrast between tumorous and healthy tissue achieved owing to fluorescence was 1:11 using h-ALA, compared to 1:5 using ALA with the peak concentrations of protoporphyrin IX.

CONCLUSIONS

Using h-ALA, the peak concentration of protoporphyrin IX, compared to ALA, is achieved 20% percent more quickly and with twice as much contrast between tumorous and healthy tissue (1:11 compared and 1:5, respectively). This facilitates a faster, better discrimination between tumorous and healthy tissue.

摘要

背景

口腔鳞状细胞癌是头颈部常见的癌症形式。其生存率较低。治疗成功高度依赖于诊断时癌症发展的阶段。该疾病大多在晚期被诊断出来。光动力诊断是一种用于筛查检查的新工具。这项技术需要可靠的光敏剂,如氨基乙酰丙酸(ALA)和氨基乙酰丙酸己酯(h - ALA)。ALA和h - ALA是肿瘤细胞中合成原卟啉IX的原料。原卟啉IX在合理时间内对肿瘤组织具有较高的检测率。

方法

从口腔癌和面部基底细胞癌中获取肿瘤标本。将标本的活细胞和人肿瘤细胞系(CLS - 354)在90% RPMI和10%胎牛血清培养基中培养。从每个标本和细胞系中取固定数量的50000个细胞转移到鸡胚模型的体内模型中。用ALA和h - ALA对生长的标本进行肿瘤荧光检测。在接下来的24小时内,通过光谱测量肿瘤荧光强度,作为细胞内原卟啉IX的浓度程度。

结果

与健康组织相比,所有肿瘤均显示出更高的原卟啉IX富集和荧光。使用h - ALA,3 mM或6 mM溶液比使用ALA更快20% - 25%达到原卟啉IX的峰值浓度。由于荧光,肿瘤组织与健康组织之间达到的最高对比度,使用h - ALA时为1:11,而使用ALA达到原卟啉IX峰值浓度时为1:5。

结论

与ALA相比,使用h - ALA能更快20%达到原卟啉IX的峰值浓度,且肿瘤组织与健康组织之间的对比度是ALA的两倍(分别为1:11和1:5)。这有助于更快、更好地区分肿瘤组织和健康组织。

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