Wang Xingyu, Gronchi Fabrizio, Bensimon Michael, Mercier Thomas, Decosterd Laurent Arthur, Wagnières Georges, Debefve Elodie, Ris Hans-Beat, Letovanec Igor, Peters Solange, Perentes Jean Yannis
Departement of Thoracic Surgery, Centre Hospitalier Universitaire Vaudois, Lausanne, VD, Switzerland.
Department of Anesthesiology, Centre Hospitalier Universitaire Vaudois, Lausanne, VD, Switzerland.
Lasers Surg Med. 2015 Dec;47(10):807-16. doi: 10.1002/lsm.22422. Epub 2015 Sep 28.
Low-dose, Visudyne®-mediated photodynamic therapy (photo-induction) was shown to selectively enhance tumor vessel transport causing increased uptake of systemically administered chemotherapy in various tumor types grown on rodent lungs. The present experiments explore the efficacy of photo-induced vessel modulation combined to intravenous (IV) liposomal cisplatin (Lipoplatin®) on rodent lung tumors and the feasibility/toxicity of this approach in porcine chest cavities.
Three groups of Fischer rats underwent orthotopic sarcoma (n = 14), mesothelioma (n = 14), or adenocarcinoma (n = 12) implantation on the left lung. Half of the animals of each group had photo-induction (0.0625 mg/kg Visudyne®, 10 J/cm(2) ) followed by IV administration of Lipoplatin® (5 mg/kg) and the other half received Lipoplatin® without photo-induction. Then, two groups of minipigs underwent intrapleural thoracoscopic (VATS) photo-induction (0.0625 mg/kg Visudyne®; 30 J/cm(2) hilum; 10 J/cm(2) apex/diaphragm) with in situ light dosimetry in combination with IV Lipoplatin® administration (5 mg/kg). Protocol I (n = 6) received Lipoplatin® immediately after light delivery and Protocol II (n = 9) 90 minutes before light delivery. Three additional animals received Lipoplatin® and VATS pleural biopsies but no photo-induction (controls). Lipoplatin® concentrations were analyzed in blood and tissues before and at regular intervals after photo-induction using inductively coupled plasma mass spectrometry.
Photo-induction selectively increased Lipoplatin® uptake in all orthotopic tumors. It significantly increased the ratio of tumor to lung Lipoplatin® concentration in sarcoma (P = 0.0008) and adenocarcinoma (P = 0.01) but not in mesothelioma, compared to IV drug application alone. In minipigs, intrapleural photo-induction combined to systemic Lipoplatin® was well tolerated with no toxicity at 7 days for both treatment protocols. The pleural Lipoplatin® concentrations were not significantly different at 10 and 30 J/cm(2) locations but they were significantly higher in protocol I compared to II (2.37 ± 0.7 vs. 1.37 ± 0.7 ng/mg, P < 0.001).
Visudyne®-mediated photo-induction selectively enhances the uptake of IV administered Lipoplatin® in rodent lung tumors. Intrapleural VATS photo-induction with identical treatment conditions combined to IV Lipoplatin chemotherapy is feasible and well tolerated in a porcine model. Lasers Surg. Med. 47:807-816, 2015. © 2015 Wiley Periodicals, Inc.
低剂量的维速达尔介导的光动力疗法（光诱导）已被证明可选择性增强肿瘤血管运输，使全身给药的化疗药物在啮齿动物肺部生长的各种肿瘤类型中的摄取增加。本实验探讨光诱导血管调节联合静脉注射（IV）脂质体顺铂（乐铂）对啮齿动物肺部肿瘤的疗效以及该方法在猪胸腔中的可行性/毒性。
三组Fischer大鼠在左肺植入原位肉瘤（n = 14）、间皮瘤（n = 14）或腺癌（n = 12）。每组动物的一半进行光诱导（0.0625 mg/kg维速达尔，10 J/cm²），随后静脉注射乐铂（5 mg/kg），另一半只接受乐铂而不进行光诱导。然后，两组小型猪接受胸腔镜下（VATS）胸膜内光诱导（0.0625 mg/kg维速达尔；肺门处30 J/cm²；肺尖/膈肌处10 J/cm²）并进行原位光剂量测定，同时静脉注射乐铂（5 mg/kg）。方案I（n = 6）在光照后立即给予乐铂，方案II（n = 9）在光照前90分钟给予乐铂。另外三只动物接受乐铂和VATS胸膜活检但不进行光诱导（对照组）。使用电感耦合等离子体质谱法在光诱导前及光诱导后的定期时间点分析血液和组织中的乐铂浓度。
光诱导选择性增加了所有原位肿瘤中乐铂的摄取。与单独静脉给药相比，它显著增加了肉瘤（P = 0.0008）和腺癌（P = 0.01）中肿瘤与肺乐铂浓度的比值，但在间皮瘤中未增加。在小型猪中，胸膜内光诱导联合全身乐铂给药耐受性良好，两种治疗方案在7天时均无毒性。在10和30 J/cm²部位的胸膜乐铂浓度无显著差异，但方案I中的浓度显著高于方案II（2.37±0.7对1.37±0.7 ng/mg，P < 0.001）。
维速达尔介导的光诱导选择性增强了静脉注射的乐铂在啮齿动物肺部肿瘤中的摄取。在相同治疗条件下，胸膜内VATS光诱导联合静脉乐铂化疗在猪模型中是可行的且耐受性良好。《激光外科与医学》47:807 - 816，2015年。© 2015威利期刊公司
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