TUMOR PHOTOTHERAPY--NEW PHOTODYNAMIC SENSITIZERS

肿瘤光疗--新型光动力增敏剂

• 批准号: 2092102
• 负责人: MICHAEL A RODGERS
• 金额: $ 17.74万
• 依托单位: BOWLING GREEN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-09-01 至 1998-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2092102
• 关键词: analog; chemical association; chemical structure; chemical synthesis; combination cancer therapy; disease /disorder model; infrared radiation; laboratory mouse; laser therapy; low density lipoprotein; melanins; melanoma; neoplasm /cancer pharmacology; neoplasm /cancer photoradiation therapy; neoplasm /cancer thermotherapy; nonhuman therapy evaluation; pharmacokinetics; photobiology; photosensitizing agents; phthalocyanin; radiation dosage; tissue /cell culture

The hypothesis to be tested in the continuation of this collaborative project is that phototherapy is applicable to the treatment of highly pigmented tumors such as cutaneous malignant melanoma (CMM). This hypothesis is to be evaluated by (a) establishing the limits of photodynamic therapy (PDT) in pigmented tumors, (b)establishing whether PDT can be applied to melanotic tumors that have been prebleached by high- peak-power light, and (c) establishing the usefulness of photothermal therapy (PTT) to such tumors. The hypothesis will be tested by synthesizing a series of near-IR-light absorbing photosensitizing compounds for PDT and for HT and assaying their effectiveness. Compounds to be synthesized will be metallo-centered naphthalocyanines having various axial and peripheral substituents that will provide solubility and tumor retention modifications. Photophysical measurements will address questions about the nature, lifetime, and deactivation modes of low-lying electronic states and will assist in characterizing the capabilities of the compounds to act in the PDT and HT modes. Pharmacokinetic studies will address the distribution of potential sensitizers for PDT and HT within murine systems (B16 malignant melanoma); and phototherapeutic tests will determine the effectiveness of the various sensitizers and allow the design of protocols for clinical evaluation.

在继续这项合作中要检验的假设 项目是，光疗是适用于治疗高度 色素性肿瘤，如皮肤恶性黑色素瘤（CMM）。这 假设将通过（a）确定 色素性肿瘤中的光动力疗法（PDT），（B）确定是否 PDT可以应用于已经被高浓度的光化学漂白剂预漂白的黑色素瘤， 峰值功率光，（c）建立光热的有用性 PTT疗法（PTT）治疗此类肿瘤。该假设将通过以下方式进行检验： 合成了一系列近红外光吸收光敏剂， 用于PDT和HT的化合物并测定它们的有效性。化合物 将合成的是金属中心的萘酞菁， 各种轴向和外周取代基，其将提供溶解性， 肿瘤保留修饰。 光物理测量将解决有关自然的问题， 寿命和低电子态的失活模式， 有助于表征化合物在细胞中起作用的能力。 PDT和HT模式。药代动力学研究将讨论 小鼠系统内PDT和HT的潜在致敏剂（B16恶性 黑色素瘤）;和光疗测试将确定的有效性， 各种致敏剂，并允许设计用于临床的方案 评价