CLINICAL RADIATION AND DRUG PROTECTION WITH WR-2721

WR-2721是一种保护正常组织的磷酸化氨基硫醇化合物 在实验动物中选择性地(与肿瘤相比)。人类 毒理学研究即将完成。WR-2721可能对人类有用1) 减少放射治疗和烷化剂的不良反应 各种正常组织，2)允许更高剂量的放射治疗和某些 不增加标准剂量毒性的化疗药物 3)减少放射治疗疗程提供的总时间 减少患者成本和不便。 尽管缺乏对WR-2721的具体检测，但有两个有希望的方法 正在制定定量方法；a)免疫定量 单抗，b)高电化学法检测 高效液相色谱。这些信息可以提供给 最大限度地提高WR-2721在正常组织和 肿瘤，以优化输液次数和间隔从预处理 WR-2721和烷化剂治疗或放射治疗。 环磷酰胺前用WR-2721预处理的剂量修饰因子， 氮芥末、顺铂和各种不同的分馏表 放射治疗将在人类受试者身上确定。减少不良反应 WR-2721的预处理效果将在多个方面进行研究 解剖位置。 WR-2721给药降低血钙和矛盾 甲状旁腺激素水平。这种效应的临床应用将是 探索过了。由于WR-2721似乎能增加静脉血氧含量， 这种观察的机制及其对保护的影响将是 调查过了。

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.