Oral versus intravenous administration of 5-aminolaevulinic acid for photodynamic therapy.
Oral versus intravenous administration of 5-aminolaevulinic acid for photodynamic therapy.
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DOI：
10.1038/bjc.1993.284
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发表时间：
1993-07
影响因子：
8.8
通讯作者：
Bown, S G
中科院分区：
文献类型：
--
作者：
Loh, C S;MacRobert, A J;Bedwell, J;Regula, J;Krasner, N;Bown, S G
内源性合成的原卟啉IX（PpIX）后，管理的5-氨基乙酰丙酸（ALA）是一种有效的光敏剂的光动力疗法（PDT）。静脉内给药后，PpIX主要在中空内脏的粘膜中蓄积，在光照下，粘膜消融导致粘膜下层和肌层相对保留。与传统的外源性光敏剂如血卟啉衍生物和酞菁相比，口服ALA是有效的。口服ALA也更简单、安全、便宜，更容易被患者接受。我们研究了卟啉敏化动力学曲线在胃，结肠和膀胱正常大鼠肠内和胃肠外给予ALA冷冻组织切片显微荧光光度研究。静脉和口服给药后，所有三个器官中的粘液细胞均表现出比基础平滑肌更高的荧光水平。在使用的最高剂量（200 mg kg-1 i.v.，400 mg kg-1口服），且剂量较低时稍早。两种给药途径的时间动力学相似，但需要较高的口服剂量才能达到相同的PpIX组织浓度。在胃粘膜中实现了最高水平的荧光，并且在结肠和膀胱粘膜中降低了水平。每种给药途径在每个器官中实现了相似程度的粘膜选择性，但需要超过40 mg kg-1的口服剂量才能实现可测量的PpIX致敏作用。在一项初步临床研究中，2例不能手术的直肠腺癌患者口服30 mg kg-1 ALA，1例乙状结肠癌患者口服60 mg kg-1 ALA。在随后的24小时内对正常和肿瘤区域进行连续活检。这些标本的荧光显微镜显示最大积累的PpIX 4至6小时后，管理的30毫克kg-1 ALA。有更大的PpIX积累在肿瘤比相邻的正常粘膜中的两名患者。在接受60 mg kg-1 ALA的患者中，PpIX在肿瘤中的优先蓄积更大。
Endogenously synthesised protoporphyrin IX (PpIX) following the administration of 5-amino-laevulinic acid (ALA) is an effective photosensitiser for photodynamic therapy (PDT). Following intravenous administration, PpIX accumulates predominantly in mucosa of hollow viscera and on light exposure, mucosal ablation results with relative sparing of the submucosa and muscularis layers. Oral administration is effective with ALA in contrast to conventional exogenous photosensitisers such as haematoporphyrin derivative and phthalocyanines. Oral administration of ALA is also simpler, safer, cheaper and more acceptable to patients. We studied the porphyrin sensitisation kinetics profile in the stomach, colon and bladder in normal rats following enterally and parenterally administered ALA using microscopic fluorescence photometric studies of frozen tissue sections. Mucosal cells in all three organs exhibit higher fluorescence levels as compared with underlying smooth muscle following both intravenous and oral administration. Peak concentration were seen 4 h after sensitisation at the highest doses used (200 mg kg-1 i.v., 400 mg kg-1 oral), and slightly earlier with lower doses. The temporal kinetics of both routes of administration were similar although a higher oral dose was required to achieve the same tissue concentration of PpIX. The highest level of fluorescence was achieved in the gastric mucosa and in decreasing levels, colonic and bladder mucosa. A similar degree of mucosal selectivity was achieved in each organ with each route of administration but an oral dose in excess of 40 mg kg-1 was required to achieve measurable PpIX sensitisation. In a pilot clinical study, two patients with inoperable rectal adenocarcinomas were given 30 mg kg-1 and one patient with sigmoid colon carcinoma was given 60 mg kg-1 ALA orally. Serial biopsies of normal and tumour areas were taken over the subsequent 24 h. Fluorescence microscopy of these specimens showed maximum accumulation of PpIX 4 to 6 h after administration of 30 mg kg-1 ALA. There was greater PpIX accumulation in tumour than adjacent normal mucosa in two patients. Preferential PpIX accumulation in tumour was greater in the patient receiving 60 mg kg-1 ALA.