Sajisevi Mirabelle, Rigual Nestor R, Bellnier David A, Seshadri Mukund
Department of Head and Neck Surgery, Roswell Park Cancer Institute, Elm and Carlton streets, Buffalo, NY, USA.
Department of Head and Neck Surgery, Roswell Park Cancer Institute, Elm and Carlton streets, Buffalo, NY, USA ; Department of Cell Stress Biology (Photodynamic Therapy Center), Roswell Park Cancer Institute, Elm and Carlton streets, Buffalo, NY, USA.
J Oral Maxillofac Surg Med Pathol. 2015 Mar;27(2):159-165. doi: 10.1016/j.ajoms.2013.12.003.
Photodynamic therapy (PDT) is a clinically approved minimally invasive treatment for cancer. In this preclinical study, using an imaging-guided approach, we examined the potential utility of PDT in the management of bulky squamous cell carcinomas (SCCs).
To mimic bulky oropharyngeal cancers seen in the clinical setting, intramuscular SCCs were established in six-to-eight week old female C3H mice. Animals were injected with the photosensitizer, 2-[hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH; 0.4 μmol/kg, i.v.) and tumors were illuminated 24 hours post injection with 665 nm light. PDT as a single treatment modality was administered by surface illumination or by interstitial placement of fibers (iPDT). Magnetic resonance imaging was used to guide treatment and assess tumor response to PDT along with correlative histopathologic assessment.
Interstitial HPPH-PDT resulted in a marked change on T2 maps 24 hours post treatment compared to untreated controls or transcutaneous illumination. Corresponding apparent diffusion coefficient maps also showed hyperintense areas in tumors following iPDT suggestive of effective photodynamic cell kill. Histologic sections (H&E) confirmed presence of extensive tumor necrosis following iPDT.
These results highlight the potential utility of PDT in the treatment of bulky oropharyngeal cancers. The findings of our study also demonstrate the utility of MRI as a non-invasive tool for mapping of early tissue response to PDT.
光动力疗法(PDT)是一种临床认可的癌症微创治疗方法。在这项临床前研究中,我们采用成像引导方法,研究了PDT在治疗巨大鳞状细胞癌(SCC)中的潜在效用。
为模拟临床所见的巨大口咽癌,在6至8周龄雌性C3H小鼠中建立肌肉内SCC模型。给动物注射光敏剂2-[己氧基乙基]-2-去乙烯基焦脱镁叶绿酸-a(HPPH;0.4 μmol/kg,静脉注射),并在注射后24小时用665 nm光照射肿瘤。PDT作为单一治疗方式,通过表面照射或纤维间质置入(iPDT)给药。使用磁共振成像引导治疗并评估肿瘤对PDT的反应,同时进行相关的组织病理学评估。
与未治疗的对照组或经皮照射相比,间质HPPH-PDT治疗后24小时T2图上出现明显变化。相应的表观扩散系数图也显示iPDT后肿瘤内有高信号区,提示有效的光动力细胞杀伤。组织学切片(苏木精-伊红染色)证实iPDT后存在广泛的肿瘤坏死。
这些结果突出了PDT在治疗巨大口咽癌中的潜在效用。我们研究的结果还证明了MRI作为一种非侵入性工具在绘制早期组织对PDT反应方面的效用。