Modelling novel PDT approaches to target peripheral lung cancers (Conference Presentation)

L. Lilge, C. McFadden, K. Ramadan, Zhangcheng Zheng, Fynn Schwiegelshohn, Vaughn Betz, M. Cypel
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Abstract

While the prevalence of central bronchial tumours is declining, that of peripheral lung tumours is increasing. Peripheral lung tumours present either as individual index lesion or as field cancerization, requiring for the former targeting of particular confined volumes of lung tissue versus a therapy for an entire lung or particular lobes thereof. Using FullMonte, a Monte Carlo code; the ability to achieve a tumour selective PDT by transbronchial light source placement was simulated for 525, 665 and 808 nm wavelength. Simulations were executed utilizing in silica models with up to 10 generations of the bronchial tree, tissue photosensitizer concentrations taken from literature or measure in preclinical model systems and tissue optical properties measured with alive ex vivo pig and human lungs perfused with either blood or a transparent low cellular (STEEN) fluid. The measured effective attenuation coefficients [cm-1] at the three wavelengths for ventilated lungs with either blood 1.26±1.07, 1.93±0.534, 1.09±0.93 or STEEN fluid 1.01±0.873, 0.901±0.318, 0.641±0.31 used as perfusate. When modelling the PDT dose distribution in the lung’s the bronchial air ducts up to the eight generations perturb the fluence considerably. In all simulations, a dose sufficient to cause necrosis in 98% of the target volume placement of 3 source fibres albeit with various extent of normal lung tumour damage. Full coverage of an entire lung lobe with only three source fibres placed does not provide for effective coverage of the diffuse disease unless a very high selective uptake of the photosensitizer in malignant tissues can be achieved.
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模拟针对周围性肺癌的新型PDT方法(会议报告)
虽然中枢性支气管肿瘤的患病率在下降,但周围性肺肿瘤的患病率却在上升。周围性肺肿瘤表现为个体指数病变或野区癌变,需要前者靶向特定受限体积的肺组织,而不是针对整个肺或其特定叶的治疗。使用FullMonte,一个蒙特卡罗代码;通过525、665和808 nm波长的经支气管光源放置来实现肿瘤选择性PDT的能力进行了模拟。模拟使用多达10代支气管树的二氧化硅模型,从文献或临床前模型系统中测量的组织光敏剂浓度,以及用血液或透明低细胞(STEEN)液体灌注的活猪和人肺测量的组织光学特性。血(1.26±1.07)、(1.93±0.534)、(1.09±0.93)或STEEN液(1.01±0.873)、(0.901±0.318)、(0.641±0.31)作灌注物时,通气肺在三个波长下的有效衰减系数[cm-1]。在对肺内PDT剂量分布进行建模时,8代支气管气管对剂量分布的影响相当大。在所有的模拟中,一个剂量足以在98%的目标体积内造成3个源纤维的坏死,尽管有不同程度的正常肺肿瘤损伤。仅放置三个源纤维对整个肺叶的完全覆盖并不能有效覆盖弥漫性疾病,除非能在恶性组织中实现非常高的光敏剂选择性吸收。
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