Hautmann Hubert, Pichler Josef P, Stepp Herbert, Baumgartner Reinhold, Gamarra Fernando, Huber Rudolf M
Medizinische Klinik I, Klinikum rechts der Isar, Technische Universität, Munich, Germany.
Respir Res. 2007 Apr 19;8(1):33. doi: 10.1186/1465-9921-8-33.
In the diagnosis of early-stage lung cancer photosensitizer-enhanced fluorescence bronchoscopy with inhaled 5-aminolevolinic acid (5-ALA) increases sensitivity when compared to white-light bronchoscopy. This investigation was to evaluate the in vivo tissue pharmacokinetics of inhaled 5-ALA within the bronchial mucosa in order to define the time optimum for its application prior to bronchoscopy.
Patients with known or suspected bronchial carcinoma were randomized to receive 200 mg 5-ALA via inhalation 1, 2, 3, 4 or 6 hours before flexible fluorescence bronchoscopy was performed. Macroscopically suspicious areas as well as areas with visually detected porphyrin fluorescence and normal control sites were measured spectroscopically. Biopsies for histopathology were obtained from suspicious areas as well as from adjacent normal areas.
Fluorescence bronchoscopy performed in 19 patients reveals a sensitivity for malignant and premalignant changes (moderate dysplasia) which is almost twice as high as that of white-light bronchoscopy, whereas specificity is reduced. This is due to false-positive inflammatory lesions which also frequently show increased porphyrin fluorescence. Malignant and premalignant alterations produced fluorescence values that are up to 5 times higher than those of normal tissue. According to the pharmacokinetics of porphyrin fluorescence measured by spectroscopy, the optimum time range for 5-ALA application is 80-270 min prior to fluorescence bronchoscopy, with an optimum at 160 min.
According to our results we propose inhalation of 5-ALA 160 min prior to fluorescence bronchoscopy, suggesting that this time difference provides the best tumor/normal tissue fluorescence ratio.
在早期肺癌的诊断中,与白光支气管镜检查相比,吸入5-氨基酮戊酸(5-ALA)的光敏剂增强荧光支气管镜检查可提高敏感性。本研究旨在评估吸入5-ALA在支气管黏膜内的体内组织药代动力学,以确定支气管镜检查前其应用的最佳时间。
已知或疑似支气管癌的患者被随机分组,在进行柔性荧光支气管镜检查前1、2、3、4或6小时通过吸入接受200mg 5-ALA。对宏观上可疑的区域以及视觉上检测到卟啉荧光的区域和正常对照部位进行光谱测量。从可疑区域以及相邻的正常区域获取用于组织病理学检查的活检样本。
对19例患者进行的荧光支气管镜检查显示,其对恶性和癌前病变(中度发育异常)的敏感性几乎是白光支气管镜检查的两倍,而特异性降低。这是由于假阳性炎症病变也经常显示卟啉荧光增加。恶性和癌前改变产生的荧光值比正常组织高5倍。根据光谱测量的卟啉荧光药代动力学,5-ALA应用的最佳时间范围是荧光支气管镜检查前80-270分钟,最佳时间为160分钟。
根据我们的结果,我们建议在荧光支气管镜检查前160分钟吸入5-ALA,表明这个时间差可提供最佳的肿瘤/正常组织荧光比值。