CLINICAL RADIATION AND DRUG PROTECTION WITH WR-2721

WR-2721是一种具有保护正常组织作用的磷酸化氨基硫醇化合物 选择性地（与肿瘤相比）在实验动物中。 人类 毒理学检测即将完成 WR-2721可用于人类1） 减少放射治疗和烷化剂对 各种正常组织，2）允许更高剂量的放射治疗和某些 不增加标准剂量的毒性的化学治疗剂 3）减少放射治疗疗程的总时间， 减少患者成本和不便。 尽管缺乏WR-2721的特异性测定，但两种有希望的方法， 定量方法，正在开发; a）免疫定量， 单克隆抗体，和B）电化学检测， 高效液相色谱法 这些可以提供信息， 最大化WR-2721在正常组织与 肿瘤，以优化预处理的输注时间和间隔， WR-2721和用烷化剂或放射疗法治疗。 环磷酰胺前WR-2721预处理的剂量修饰因子， 氮芥，顺铂和各种分馏时间表， 将在人类受试者中确定放射治疗。 减少不利影响 WR-2721预处理的影响将在多个 解剖部位 WR-2721给药可降低血清钙， 甲状旁腺激素水平 这种效果的临床实用性将是 探讨了 由于WR-2721似乎增加静脉血氧含量， 这种观察的机制及其对保护的影响将是 研究了

WR-2721 is phosphorylated aminothiol compound which protects normal tissues selectively (as compared to tumor) in experimental animals. Human toxicology is nearing completion. WR-2721 may be useful in humans to 1) decrease the adverse effects of radiotherapy and alkylating agents on various normal tissues, 2) allow higher doses of radiotherapy and certain chemotherapeutic agents without increasing the toxicity of standard doses of each , 3) decrease the overall time of radiotherapy courses providing lesser patient costs and inconvenience. Although specific assays for WR-2721 are lacking, two promising quantitative methods, are being developed; a) immunoquantitation with monoclonal antibodies, and b) electrochemical detection with high performance liquid chromatography. These may provide information to maximize the difference in WR-2721 concentration in normal tissues vs. tumor, to optimize infusion times and intervals from pretreatment with WR-2721 and treatment with alkylating agents or radiotherapy. Dose modifying factors with WR-2721 pretreatment before cyclophosphamide, nitrogen mustard, cis-platinum and various fractionation schedules of radiotherapy will be determined in human subjects. Reduction in adverse effects by pretreatment with WR-2721 will be investigated in multiple anatomic sites. WR-2721 administration decreases serum calcium and paradoxically parathormone levels. The clinical usefulness of this effect will be explored. Since WR-2721 appears to increase venous blood oxygen content, the mechanisms of this observation and its influence on protection will be investigated.