Multifunctional Photosensitizers for Image-guided PDT of Brain Tumors

用于脑肿瘤图像引导 PDT 的多功能光敏剂

• 批准号: 8053603
• 负责人: Ravindra K. Pandey
• 金额: $ 6.45万
• 依托单位: ROSWELL PARK CANCER INSTITUTE CORP
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2013-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8053603
• 关键词: Adjuvant Therapy; Animals; Avidity; Binding; Biodistribution; Biological; Biology; Brain; Brain Neoplasms; Cancer Patient; Cells; Characteristics; Charge; Clinical; Clinical Data; Clinical Trials; Complement; Complex; Data; Detection; Development; Diagnostic Neoplasm Staging; Drug Kinetics; Excision; Failure; Fluorescence; Fluorescent Dyes; Fluorochrome; Generations; Glioma; Goals; HPPH; Half-Life; Image; In Vitro; Individual; Integrin Binding; Integrins; Intervention; Invaded; Investigation; Label; Laboratory Study; Lesion; Ligands; Light; Link; Local Therapy; Location; Magnetic Resonance Imaging; Malignant Glioma; Malignant Neoplasms; Mammary Neoplasms; Measures; Modality; Modeling; Molecular; Molecular Target; Mus; Neoplasm Metastasis; Normal tissue morphology; Operative Surgical Procedures; Optics; Patients; Peptides; Photochemotherapy; Photosensitizing Agents; Phototoxicity; Play; Porfimer Sodium; Porphyrins; Positron-Emission Tomography; Primary Brain Neoplasms; Process; Production; Property; RGD (sequence); Radiation therapy; Radioisotopes; Radiopharmaceuticals; Recurrence; Research; Role; Singlet Oxygen; Site; Skin; Specificity; Staging; Survival Rate; Therapeutic; Tissues; Toxic effect; Tracer; Treatment Efficacy; Validation; Work; absorption; advanced disease; analog; base; brain tissue; cancer therapy; chemotherapy; chromophore; conventional therapy; cyanine dye; design; flexibility; fluorophore; image guided therapy; image visualization; imaging modality; improved; in vivo; irradiation; lipophilicity; malignant breast neoplasm; melanoma; mouse model; neoplastic cell; neovasculature; novel; novel strategies; optical fiber; optical imaging; outcome forecast; palliation; porphyrin a; pre-clinical; quantum; receptor; response; standard care; treatment site; treatment strategy; tumor; tumor specificity; uptake

Photodynamic therapy (PDT) is an effective local therapy based on a tumor localizing photosensitizer (PS) activated by light directed at the treatment site. Current photosensitizers demonstrate some tumor selectivity, and light can be delivered almost anywhere in the body by thin, flexible optical fibers. However, for small, bulky, or buried lesions, it may be difficult to detect the malignancies and/or to properly place the optical fibers to illuminate the full extent of the tumor. We hypothesize development of a new approach to guided therapy utilizing highly selective optical and PET imaging, allowing tumor visualization, image-guided placement of the optical fibers, and subsequent photodynamic destruction of the lesions. Our project involves synthesis, characterization and pre-clinical validation of novel conjugates of tumor- avid PS carrying unique, near infrared (NIR) fluorescent dyes and the long half-life PET agent 124I. Preliminary work shows these conjugates provide very high in vivo tumor selectivity, while maintaining. We will determine if the conjugate selectivity can be further enhanced by linking tumor- or neovasculature-selective molecular targeting ligands such as an v3 integrin binding peptide. In addition, our approach can be extended to multi- modality interventions: The conjugate can deliver therapeutic radioisotopes, and PDT can super-additively potentiate radiotherapy. The aims of this project are as follow: Aim 1: To prepare and characterize multi-functional conjugates containing a tumor-avidlong -wavelength photosensitizer linked to novel NIR cyanine dyes with the option of a 124I-label and a RGD peptide moiety that binds to tumor and neovasulature associated with integrin (v3). Aim 2: To characterize the different conjugates in vitro. Aim 3: To examine in animals the imaging and therapeutic potential of the conjugates and determine any added benefits of integrin targeted conjugates for imaging and therapy. This ¿see and treat¿ approach targets cancers with an agent that can be detected by light and radioimaging, and then activated at a different wavelength to destroy the tumors. It is important to detect cancer at early stage as it plays critical role in cancer patient management since detection of stage 1 cancer is associated with a >90% 5 year survival rate. Our approach of designing ¿Multimodality Agents¿ for the detection and treatment of cancer could play a major role in cancer therapy. The initial biological data obtained from the proposed compounds in mice model are quite promising in imaging tumors and tumor metastases without any significant toxicity. Therefore, this research warrants further investigation.

光动力治疗（PDT）是一种基于肿瘤定位光敏剂的有效局部治疗方法