CORE--PHOTOSENSITIZER EVALUATION

点击翻译按钮获取中文摘要

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.