Department of Neurosurgery, University Hospital of Münster, Münster, Germany.
Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Neurosurgery. 2019 Oct 1;85(4):E739-E746. doi: 10.1093/neuros/nyz129.
Five-aminolevulinic acid (5-ALA) is well established for fluorescence-guided resections of malignant gliomas by eliciting the accumulation of fluorescent protoporphyrin IX (PpIX) in tumors. Because of the assumed time point of peak fluorescence, 5-ALA is recommended to be administered 3 h before surgery. However, the actual time dependency of tumor fluorescence has not yet been evaluated in humans and may have important implications.
To investigate the time dependency of PpIX by measuring fluorescence intensities in tumors at various time points during surgery.
Patients received 5-ALA (20 mg/kg b.w.) 3 to 4 h before surgery. Fluorescence intensities (FI) and estimated tumor PpIX concentrations (CPPIX) were measured in the tumors over time with a hyperspectral camera. CPPIX was assessed using hyperspectral imaging and by evaluating fluorescence phantoms with known CPPIX.
A total of 201 samples from 68 patients were included in this study. On average, maximum values of calculated FI and CPPIX were observed between 7 and 8 h after 5-ALA administration. FI and CPPIX both reliably distinguished central strong and marginal weak fluorescence, and grade III compared to grade IV gliomas. Interestingly, marginal (weak) fluorescence was observed to peak later than strong fluorescence (8-9 vs 7-8 h).
In human in Situ brain tumor tissue, we determined fluorescence after 5-ALA administration to be maximal later than previously thought. In consequence, 5-ALA should be administered 4 to 5 h before surgery, with timing adjusted to internal logistical circumstances and factors related to approaching the tumor.
5-氨基酮戊酸（5-ALA）通过在肿瘤中诱发光敏剂原卟啉 IX（PpIX）的积累，已被广泛应用于恶性脑胶质瘤的荧光引导切除。由于假定的荧光峰值时间，建议在手术前 3 小时给予 5-ALA。然而，肿瘤荧光的实际时间依赖性尚未在人体中得到评估，这可能具有重要意义。
通过在手术过程中的不同时间点测量肿瘤中的荧光强度，来研究 PpIX 的时间依赖性。
患者在手术前 3 至 4 小时接受 5-ALA（20mg/kg b.w.）治疗。使用高光谱相机随时间测量肿瘤中的荧光强度（FI）和估计的肿瘤 PpIX 浓度（CPPIX）。通过高光谱成像评估 CPPIX，并通过评估具有已知 CPPIX 的荧光体模来评估 CPPIX。
本研究共纳入了 68 名患者的 201 个样本。平均而言，在给予 5-ALA 后 7 至 8 小时观察到计算出的 FI 和 CPPIX 的最大值。FI 和 CPPIX 都能可靠地区分中央强荧光和边缘弱荧光，以及 3 级与 4 级胶质瘤。有趣的是，边缘（弱）荧光的峰值比强荧光晚（8-9 小时比 7-8 小时）。
在人类原位脑肿瘤组织中，我们确定了 5-ALA 给药后的荧光强度比之前认为的要晚。因此，5-ALA 应在手术前 4 至 5 小时给予，具体时间应根据内部后勤情况和接近肿瘤的相关因素进行调整。
