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

本提案的目标是进一步临床前开发独特的双光子激活光动力疗法（TPPDT）三位一体，包括无毒卟啉光敏剂，肿瘤靶向组和成像功能，为目前生存率低且治疗选择少的复发性和难治性头颈部深部皮肤表面肿瘤提供无创图像引导治疗。SensoPath Technologies将详细了解该过程的剂量学，包括靶向肿瘤表面受体的相互作用，800- 840nm范围内的脉冲近红外（NIR）激光的递送，最佳浓度的药物递送方法，以及氧水平在肿瘤血液供应中的作用。在图像引导TPPDT中，肿瘤的照射由其整个肿瘤3D体积的数字化图像控制，将定义和合并光学肿瘤边缘，以确保整个肿瘤得到治疗。在组织幻象和异种移植SCID小鼠模型中计划的图像定义肿瘤治疗将为有效治疗伴侣犬深部自发性头颈部肿瘤提供必要的信息，作为一种门诊低成本的人类临床治疗模型，恢复迅速，疤痕少，无pdt后光敏性。

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.