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

其他功能主题 255，第二阶段，“靶向双光子光动力治疗 T

• 批准号: 8564239
• 负责人: CHARLES SPANGLER
• 金额: $ 149.99万
• 依托单位: SENSOPATH TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-28 至 2014-09-27
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8564239
• 关键词: Canis familiaris; Cells; Cicatrix; Clinical Treatment; Companions; Coupled; Development; Drug Delivery Systems; Ensure; Epidermal Growth Factor Receptor; Family Felidae; Future; Gel; Head and Neck Neoplasms; Head and Neck Squamous Cell Carcinoma; Human; Image; Imaging Phantoms; Implant; Lasers; Light; Lung; Lung Neoplasms; Methods; Modeling; Optics; Outpatients; Oxygen; Patients; Phase; Photochemotherapy; Photophobia; Photosensitizing Agents; Physiologic pulse; Porphyrins; Process; Recovery; Recurrence; Refractory; Role; SCID Mice; Skin; Surface; Survival Rate; System; Technology; Testing; Tissues; Triad Acrylic Resin; Tumor Volume; Xenograft procedure; charge coupled device camera; cost; dosimetry; fluorescence imaging; irradiation; mouse model; neoplastic cell; pre-clinical; prototype; receptor; tissue phantom; tumor; tumor vascular supply; two-photon

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.

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技术将对该过程的剂量学有详细的理解，涉及将受体靶向肿瘤表面上的相互作用，在800-840 nm范围内的脉冲接近红外（NIR）激光的传递，药物递送的方法与优化浓度的方法，以及牛根水平的作用，在Tumygen水平上的作用。图像引导的TPPDT，其中肿瘤的辐照在整个肿瘤的3D体积中受其数字化图像的控制，将定义并掺入光学肿瘤边缘，以确保对整个肿瘤进行处理。计划的图像定义的肿瘤治疗在组织幻像和异种移植物SCID小鼠模型中将提供有效治疗伴侣犬类中深层赞助的头颈部肿瘤作为一种门诊低成本模型，以快速恢复，几乎没有疤痕，没有PDT后光灵敏度。