OTHER FUNCTIONS TOPIC 255, PHASE II, "TARGETED TWO-PHOTON PHOTODYNAMIC THERAPY T

这项建议的目标是进一步开发独特的双光子激活光动力学疗法(TPPDT)三联体，该三联体包含无毒的卟啉光敏剂、肿瘤靶向组和成像功能，为目前存活率低且治疗方案少的皮肤表面以下复发和难治性头颈部肿瘤提供无创图像引导治疗。SensoPath技术公司将对这一过程的剂量学有详细的了解，包括靶向肿瘤表面受体的相互作用、800-840 nm范围内脉冲近红外(NIR)激光的传递、具有最佳浓度的药物传递方法，以及氧气水平在肿瘤S血液供应中的作用。图像引导的TPPDT，其中肿瘤的照射由其在整个肿瘤的3D体积中的数字化图像控制，将定义并合并光学肿瘤边缘，以确保整个肿瘤得到治疗。计划在组织模体和异种移植SCID小鼠模型中进行的图像定义肿瘤治疗将提供有效治疗伴犬自发性头部和颈部深部肿瘤所需的信息，作为一种用于人类临床治疗的门诊低成本模型，具有恢复快、疤痕少和PDT后无光敏性。

The objectives of this proposal are to further preclinical development of unique two-photon-activated photodynamic therapy (TPPDT) triads that incorporate a nontoxic porphyrin photosensitizer, a tumor targeting group, and an imaging functionality, providing for noninvasive image-guided treatment of recurrent and refractory head and neck tumors deep below the skin surface that currently have low survival rates and few treatment options. SensoPath Technologies will develop a detailed understanding of the dosimetry of the process, involving the interplay of targeting the receptor on the tumor surface, the delivery of pulsed near infrared (NIR) laser light in the range 800-840 nm, the method of drug delivery with optimized concentration, and the role of oxygen level in the tumor¿s blood supply. Image-guided TPPDT, in which the irradiation of the tumor is controlled by its digitized image throughout the 3D volume of the tumor, will define and incorporate optical tumor margins to ensure that the entire tumor is treated. Planned image-defined tumor treatment in tissue phantoms and xenograft SCID mouse models will provide the information necessary to effectively treat deep spontaneous head and neck tumors in companion canines as an out-patient low-cost model for human clinical treatment with rapid recovery, little scarring and no post-PDT light sensitivity.