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

该提案的目的是进一步临床前开发独特的双光子激活光动力学疗法（TPPDT）三联体，其包含无毒卟啉光敏剂，肿瘤靶向基团和成像功能，为皮肤表面以下深处的复发性和难治性头颈部肿瘤提供非侵入性图像引导治疗，目前生存率低，治疗选择少。SensoPath Technologies将详细了解该过程的剂量测定，包括靶向肿瘤表面受体的相互作用，在800-840 nm范围内输送脉冲近红外（NIR）激光，优化浓度的药物输送方法，以及氧气水平在肿瘤血液供应中的作用。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，将定义并结合光学肿瘤边缘，以确保整个肿瘤得到治疗。在组织模型和异种移植物SCID小鼠模型中计划的图像定义的肿瘤治疗将提供有效治疗伴侣犬中的深部自发性头颈部肿瘤所需的信息，作为用于人类临床治疗的门诊低成本模型，具有快速恢复、疤痕少和PDT后无光敏感性。

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.