Fluorescence image-guided brain tumour resection with adjuvant metronomic photodynamic therapy: pre-clinical model and technology development
Fluorescence image-guided brain tumour resection with adjuvant metronomic photodynamic therapy: pre-clinical model and technology development
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DOI：
10.1039/b414829k
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发表时间：
2005-01-01
影响因子：
3.1
通讯作者：
Wilson, BC
中科院分区：
文献类型：
--
作者：
Bogaards, A;Varma, A;Wilson, BC
荧光引导切除（FGR）和光动力治疗（PDT）先前分别进行了研究，其目的分别是增加脑肿瘤切除的范围和选择性地破坏切除后的残余肿瘤。无论是临床前还是临床，这两种技术都显示出提高生存率的趋势。我们假设结合这些技术将进一步延缓肿瘤的再生长。为了证明技术的可行性，我们在这里评估荧光成像和PDT治疗技术在一个特定的颅内肿瘤模型。该模型是将肿瘤细胞注射到正常兔脑内生长的VX2癌。使用操作显微镜进行白光成像，使用定制的同轴激发和检测荧光成像系统进行FGR。PDT治疗光采用脑内植入发光二极管（LED）。用于FGR和PDT的荧光光敏剂均为ala诱导的PpIX。对于PDT， ALA （100 mg kg(-1)）和弱光剂量（15和30 J）在较长时间内给予，我们称之为节拍PDT （mPDT）。18只荷瘤兔平均分为3组：对照组（未切除）；FGR;FGR其次是mPDT。全脑组织学切片（H&E染色）显示原发性和复发性肿瘤。革兰氏染色未见细菌学感染。TUNEL染色证实mpdt诱导肿瘤细胞选择性死亡。结果表明，综合治理在技术上是可行的，该模型是评价综合治理效果的候选模型。需要进一步优化mPDT治疗参数（药物/光剂量率）以提高生存率。
Fluorescence-guided resection (FGR) and photodynamic therapy (PDT) have previously been investigated separately with the objectives, respectively, of increasing the extent of brain tumour resection and of selectively destroying residual tumour post-resection. Both techniques have demonstrated trends towards improved survival, pre-clinically and clinically. We hypothesize that combining these techniques will further delay tumour re-growth. In order to demonstrate technical feasibility, we here evaluate fluorescence imaging and PDT treatment techniques in a specific intracranial tumour model. The model was the VX2 carcinoma grown by injection of tumour cells into the normal rabbit brain. An operating microscope was used for white light imaging and a custom-built fluorescence imaging system with co-axial excitation and detection was used for FGR. PDT treatment light was applied by intracranially-implanted light emitting diodes (LED). The fluorescent photosensitizer used for both FGR and PDT was ALA-induced PpIX. For PDT, ALA (100 mg kg(-1)) and low light doses (15 and 30 J) were administered over extended periods, which we refer to as metronomic PDT (mPDT). Eighteen tumour bearing rabbits were divided equally into three groups: controls (no resection); FGR; and FGR followed by mPDT. Histological whole brain sections (H&E stain) showed primary and recurrent tumours. No bacteriological infections were found by Gram staining. Selective tumour cell death through mPDT-induced apoptosis was demonstrated by TUNEL stain. These results demonstrate that the combined treatment is technically feasible and this model is a candidate to evaluate it. Further optimization of mPDT treatment parameters (drug/light dose rates) is required to improve survival.