TUMOR PHOTOTHERAPY--NEW PHOTODYNAMIC SENSITIZERS

在继续这一合作的过程中需要检验的假设 项目是光疗适用于高度湿疹的治疗。 色素肿瘤，如皮肤恶性黑色素瘤(CMM)。这 假设将通过以下方式进行评估：(A)确定以下限制 光动力疗法(PDT)治疗色素性肿瘤，(B)确定 光动力疗法可应用于经高度漂白后的黑色素瘤。 峰值功率光，以及(C)确定光热的有用性 对此类肿瘤的治疗(PTT)。这一假设将通过以下方式进行检验 合成一系列近红外光吸收光敏剂 光动力疗法和羟色胺疗法的化合物及其有效性分析。化合物 要合成的将是具有金属中心的具有 各种轴向和周向取代基，将提供溶解性和 肿瘤保留修饰。 光物理测量将解决有关自然界的问题， 低位电子态和Will的寿命和失活模式 协助确定化合物的作用能力 PDT和HT模式。药代动力学研究将解决药物的分布 小鼠体内对光动力疗法和羟色胺的潜在增敏剂(B16恶性 黑色素瘤)；而光疗测试将确定 各种增敏剂，并允许为临床设计方案 评估。

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.