5-aminolevulinic acid induced endogenous porphyrin fluorescence in 9L and C6 brain tumours and in the normal rat brain
5-aminolevulinic acid induced endogenous porphyrin fluorescence in 9L and C6 brain tumours and in the normal rat brain
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DOI：
10.1007/s007010050132
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发表时间：
1998-01-01
影响因子：
2.4
通讯作者：
Wolbers, JG
中科院分区：
文献类型：
--
作者：
Hebeda, KM;Saarnak, AE;Wolbers, JG
光动力疗法的一种新方法是使用内源性卟啉使肿瘤对光敏感。在23只患有颅内9 L或C6肿瘤的大鼠中研究了静脉注射5-氨基乙酰丙酸（ALA，200 mg kg（-1））后内源性卟啉的诱导作用。在0、2、4、6、8和22小时后处死大鼠，用标准荧光显微镜和共聚焦激光扫描显微镜研究脑组织切片中内源性卟啉的荧光分布。在2只皮层冷冻损伤的大鼠中研究了血脑屏障破坏对卟啉产生的作用，并在体外用ALA孵育9 L和C6肿瘤细胞培养物8小时。用荧光分光光度计测量细胞培养物和脑切片中的荧光。从2小时开始在体外肿瘤细胞中检测到卟啉，并且主要从2至8小时在离体肿瘤切片中检测到卟啉，到22小时卟啉荧光几乎消失。在ALA给药后2至6小时，对侧脑显示低荧光水平。在给予ALA后6小时，在冷冻损伤部位测量到低荧光。C6的荧光是不规则的，荧光边缘很差。在两种肿瘤模型中，在肿瘤周围的脑中也检测到荧光，有时在对侧白色物质和脑室室管膜和软脑膜中也检测到荧光。与没有肿瘤的大鼠中没有卟啉荧光相比，在荷瘤大鼠的正常脑中卟啉荧光的轻微增加归因于通过肿瘤中产生的卟啉的大量流动的运输，并且也可能是循环卟啉或ALA从肿瘤血管泄漏。
A new approach in photodynamic therapy is the use of endogenous porphyrins for sensitisation of tumours to light. The induction of endogenous porphyrins after intravenous injection of 5-amino-levulinic acid (ALA, 200 mg kg(-1)) was studied in 23 rats, bearing intracranial 9L or C6 tumours. After 0, 2, 4, 6, 8, and 22 hours the rats were sacrificed and the fluorescence distribution of endogenous porphyrins was studied in brain tissue sections with a standard fluorescence microscope and a confocal laser scanning microscope. The role of blood-brain barrier disruption on porphyrin production was studied in 2 rats with a cryo-lesion of the cortex.Additionally, 9L and C6 tumour cell cultures were incubated with ALA for 8 hours in vitro. Fluorescence was measured with a fluorescence spectrophotometer in cell cultures and in the brain sections. Porphyrins were detected in vitro in the tumour cells from 2 hours onwards and ex vivo in the tumour sections mainly from 2 to 8 hours, by 22 hours porphyrin fluorescence had almost disappeared. The contralateral brain showed low fluorescence levels between 2 and 6 hours after ALA administration. At the site of the cryo-lesions low fluorescence was measured 6 hours after ALA administration.The 9L tumours fluoresced homogeneously, with a sharp demarcation towards normal brain tissue. Fluorescence in the C6 rumours was patchy, with a poorly fluorescing edge. In both tumour models fluorescence was also detected in brain surrounding the tumour and sometimes in contralateral white matter and ventricle ependyma and pia mater. The slight increase of porphyrin fluorescence in the normal brain of tumour bearing rats, compared to the absence of this in rats without a tumour, was attributed to transport by bulk flow of porphyrins made in the tumours, and possibly also of circulating porphyrins or ALA leaking from the tumour vessels.