CORE--PHOTOSENSITIZER EVALUATION

描述：(申请人的描述)这个项目的一个重点是了解使酞菁(Pc)Pc4和其他一些PC作为PDT有效光敏剂(PS)的结构决定因素。为了实现这一目标，该计划继续将重点放在开发新的Pc化合物上。人们希望其中一些化合物对PDT具有更好的抗肿瘤性能。光敏剂评估核心的目的是在项目1中合成的PC上建立基本的体外和体内数据。为此，核心提供标准化分析中产生的信息。每一种新合成的Pc都与Pc4平行进行评估，化合物的光动力效能在标准化测试系统中被评为“劣”、“等”或“优”Pc4。然后，结果被传达给项目调查人员。之所以选择与Pc4相关的新合成化合物的排名，是因为a)这是最先合成的6个化合物中的先导化合物，b)其他项目对该化合物有丰富的经验和数据，c)国家癌症研究所药物决策网络已经完成了Pc4的临床前药代动力学、有效性和毒理学研究，并已推荐用于临床试验。该核心还生成关于选定的有前景的PS的更详细的信息。为此，由该核心和项目1-5的调查人员作出决定。为了确保治疗的一致性，并考虑到成本效益，该核心还将与项目2和项目5合作，对Pc4(和其他PC)PDT反应进行活体评估。保留了正在进行的工作中概述的核心的六项职能，并对它们进行了微调。此外，还增加了两个额外的功能。核心的功能是：1.测定新合成的PS在正辛酸和生理盐水之间的分配。2.对PS进行初步的体外评价。3.确定PS的初始光动力反应。4.测定PS在体内血浆、肿瘤等组织中的分布。5.测定PS的全身毒性和皮肤光敏反应。6.详细研究所选PS的PDT效应。7.观察精选多糖硫酸酯对人肿瘤裸鼠移植瘤的治疗作用。8.参与项目2和项目5中评估Pc 4(和其他PC)的体内效应的研究。

DESCRIPTION: (Applicant's Description) One emphasis of this program project is to understand the structural determinants which make phthalocyanine (Pc) Pc 4 and a few other PCs as effective photosensitizers (PS) for PDT. To achieve this goal, this program continues to have an emphasis on developing new Pc compounds. It is hoped that some of these may have better antitumor properties for PDT. The purpose of the Photosensitizer Evaluation Core is to establish basic in vitro and in vivo data on the PCs synthesized in Project 1. For this purpose, the core provides information generated in standardized analyses. Each newly synthesized Pc is assessed in parallel with Pc 4, and the photodynamic efficacy of the compound is rated in the standardized test system as 'inferior,' 'equal,' or 'superior' Pc 4. The results are then communicated to the program investigators. The choice for ranking of newly synthesized compounds in relation to Pc 4 is made because a) this was the lead compound among the first 6 synthesized, b) other projects have considerable experience and data with this compound, and c) preclinical pharmacokinetics, efficacy and toxicology of Pc 4 have been completed by the Drug Decision Network of the National Cancer Institute and it has been recommended for clinical testing. This core also generates more detailed infomation on selected promising PS. For this, the decision is made by this core and the investigators of Projects 1-5. To ensure uniformity of the treatment and in consideration of cost effectiveness, this core, in collaboration with Project 2, and 5, will also conduct in vivo evaluation of the Pc 4 (and other PCs) PDT response. The six functions of the core outlined in the ongoing work are retained and they have been fine tuned. In addition, two additional functions are added. The functions of the core are: 1. To determine the partioning of newly synthesized PS between n-octonal vs. saline. 2. To conduct initial in vitro evaluation of PS 3. To define initial PDT responses of PS. 4. To determine distribution of PS in plasma, tumor and other tissues in vivo. 5. To determine systemic toxicity and cutaneous photosensitivity responses of PS. 6. To study detailed PDT effects of selected PS. 7. To determine the efficacy of selected PS in human tumor xenografts in nude mice. 8. To participate in studies assessing in vivo effects of Pc 4 (and other Pcs) in Projects 2, and 5.