Wang Yabo, Wang Xingyu, Le Bitoux Marie-Aude, Wagnieres Georges, Vandenbergh Hubert, Gonzalez Michel, Ris Hans-Beat, Perentes Jean Y, Krueger Thorsten
Department of Thoracic and Vascular Surgery, Centre Hospitalier Universitaire Vaudois, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland.
Lasers Surg Med. 2015 Apr;47(4):323-30. doi: 10.1002/lsm.22329. Epub 2015 Jan 12.
The pre-conditioning of tumor vessels by low-dose photodynamic therapy (L-PDT) was shown to enhance the distribution of chemotherapy in different tumor types. However, how light dose affects drug distribution and tumor response is unknown. Here we determined the effect of L-PDT fluence on vascular transport in human mesothelioma xenografts. The best L-PDT conditions regarding drug transport were then combined with Lipoplatin(®) to determine tumor response.
Nude mice bearing dorsal skinfold chambers were implanted with H-Meso1 cells. Tumors were treated by Visudyne(®) -mediated photodynamic therapy with 100 mW/cm(2) fluence rate and a variable fluence (5, 10, 30, and 50 J/cm(2) ). FITC-Dextran (FITC-D) distribution was assessed in real time in tumor and normal tissues. Tumor response was then determined with best L-PDT conditions combined to Lipoplatin(®) and compared to controls in luciferase expressing H-Meso1 tumors by size and whole body bioluminescence assessment (n = 7/group).
Tumor uptake of FITC-D following L-PDT was significantly enhanced by 10-fold in the 10 J/cm(2) but not in the 5, 30, and 50 J/cm(2) groups compared to controls. Normal surrounding tissue uptake of FITC-D following L-PDT was significantly enhanced in the 30 J/cm(2) and 50 J/cm(2) groups compared to controls. Altogether, the FITC-D tumor to normal tissue ratio was significantly higher in the 10 J/cm(2) group compared others. Tumor growth was significantly delayed in animals treated by 10 J/cm2-L-PDT combined to Lipoplatin(®) compared to controls.
Fluence of L-PDT is critical for the optimal distribution and effect of subsequently administered chemotherapy. These findings have an importance for the clinical translation of the vascular L-PDT concept in the clinics.
低剂量光动力疗法（L-PDT）对肿瘤血管的预处理已被证明可增强化疗药物在不同肿瘤类型中的分布。然而，光剂量如何影响药物分布和肿瘤反应尚不清楚。在此，我们确定了L-PDT光通量对人恶性间皮瘤异种移植瘤血管运输的影响。然后将关于药物运输的最佳L-PDT条件与乐铂（®）联合使用，以确定肿瘤反应。
将携带背部皮褶小室的裸鼠植入H-Meso1细胞。用维速达尔（®）介导的光动力疗法对肿瘤进行治疗，光通量率为100 mW/cm²，光通量可变（5、10、30和50 J/cm²）。实时评估肿瘤组织和正常组织中异硫氰酸荧光素-葡聚糖（FITC-D）的分布。然后将最佳L-PDT条件与乐铂（®）联合使用来确定肿瘤反应，并通过大小和全身生物发光评估，与表达荧光素酶的H-Meso1肿瘤中的对照组进行比较（每组n = 7）。
与对照组相比，L-PDT后10 J/cm²组肿瘤对FITC-D的摄取显著增强了10倍，而5、30和50 J/cm²组未增强。与对照组相比，L-PDT后30 J/cm²和50 J/cm²组正常周围组织对FITC-D的摄取显著增强。总体而言，10 J/cm²组的FITC-D肿瘤与正常组织比率显著高于其他组。与对照组相比，接受10 J/cm²-L-PDT联合乐铂（®）治疗的动物肿瘤生长显著延迟。
L-PDT的光通量对于后续化疗药物的最佳分布和效果至关重要。这些发现对于血管L-PDT概念在临床中的临床转化具有重要意义。
