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脑肿瘤中 5-氨基酮戊酸给药后原卟啉 IX 的实时体内动力学及其与胶质母细胞瘤的比较分析。

Real-time in vivo kinetics of protoporphyrin IX after administration of 5-aminolevulinic acid in meningiomas and comparative analyses with glioblastomas.

机构信息

Department of Neurosurgery, University Hospital Münster, Münster, Germany.

Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.

出版信息

Acta Neurochir (Wien). 2020 Sep;162(9):2197-2202. doi: 10.1007/s00701-020-04353-2. Epub 2020 May 2.

DOI:10.1007/s00701-020-04353-2
PMID:32361907
Abstract

BACKGROUND

The usefulness of 5-aminolevulinic acid (5-ALA)-mediated fluorescence-guided surgery (FGS) in meningiomas is intensely discussed. However, data about kinetics of 5-ALA and protoporphyrin (Pp) IX in meningiomas are lacking.

METHODS

As the first study so far, we performed longitudinal intraoperative real-time ex situ measurements of fluorescence intensity and PpIX concentrations during FGS of ten benign and two atypical meningiomas. Kinetics were subsequently compared with data from 229 glioblastomas.

RESULTS

Spectroscopy revealed fluorescence (median 2945.65 a.u.) and PpIX accumulation (median 18.31 μg/ml) in all 43 analyzed samples. Fluorescence intensity (2961.50 a.u. vs 118.41 a.u.; p < .001) and PpIX concentrations (18.72 μg/ml vs .98 μg/ml; p < .001) were higher in samples with (N = 30) than without (N = 2) visible intraoperative tumor fluorescence. ROC curve analyses revealed a PpIX cut-off concentration of 3.85 μg/ml (AUC = .992, p = .005) and a quantitative fluorescence cut-off intensity of 286.73 a.u. (AUC = .983, p = .006) for intraoperative visible tumor fluorescence. Neither fluorescence intensity (p = .356) nor PpIX (p = .631) differed between atypical and benign meningiomas. Fluorescence and PpIX peaked 7-8 h following administration of 5-ALA. Meningiomas displayed a higher fluorescence intensity (p = .012) and PpIX concentration (p = .005) than glioblastomas 5-6 h after administration of 5-ALA. Although fluorescence was basically maintained, PpIX appeared to be cleared faster in meningiomas than in glioblastomas.

CONCLUSIONS

Kinetics of PpIX and fluorescence intensity differ between meningiomas and glioblastomas in the early phase after 5-ALA administration. Modification of the timing of drug administration might impact visibility of intraoperative fluorescence and helpfulness of FGS and should be investigated in future analyses.

摘要

背景

5-氨基酮戊酸(5-ALA)介导的荧光引导手术(FGS)在脑膜瘤中的应用价值存在争议。然而,脑膜瘤中 5-ALA 和原卟啉(Pp)IX 的动力学数据尚不清楚。

方法

作为目前为止的第一项研究,我们对 10 例良性和 2 例非典型脑膜瘤的 FGS 进行了术中实时离体荧光强度和 PpIX 浓度的纵向测量。随后将动力学与 229 例胶质母细胞瘤的数据进行了比较。

结果

光谱分析显示,在 43 个分析样本中均有荧光(中位数 2945.65 a.u.)和 PpIX 积累(中位数 18.31μg/ml)。与术中无可见肿瘤荧光的样本(N=30)相比,有可见肿瘤荧光的样本(N=2)的荧光强度(2961.50 a.u. vs 118.41 a.u.;p<0.001)和 PpIX 浓度(18.72μg/ml vs.98μg/ml;p<0.001)更高。ROC 曲线分析显示,术中可见肿瘤荧光的 PpIX 截断浓度为 3.85μg/ml(AUC=0.992,p=0.005),定量荧光截断强度为 286.73 a.u.(AUC=0.983,p=0.006)。无论在非典型脑膜瘤还是良性脑膜瘤中,荧光强度(p=0.356)和 PpIX(p=0.631)均无差异。5-ALA 给药后 7-8 小时达到荧光和 PpIX 的峰值。与胶质母细胞瘤相比,5-ALA 给药后 5-6 小时,脑膜瘤的荧光强度(p=0.012)和 PpIX 浓度(p=0.005)更高。尽管荧光基本保持不变,但 PpIX 在脑膜瘤中的清除速度似乎比在胶质母细胞瘤中更快。

结论

5-ALA 给药后早期,脑膜瘤和胶质母细胞瘤之间的 PpIX 和荧光强度动力学存在差异。药物给药时间的调整可能会影响术中荧光的可见性和 FGS 的有效性,应在未来的分析中进行研究。

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