瑞典林雪平大学开发出一种新药，不但能够防止化疗产生的毒副作用，还能在一定程度上强化肿瘤的治疗效果。一个国际药物评估组织正在对该药的临床效果进行验证，新药有望在1到2年内上市。相关研究发表在《转化肿瘤学》杂志上。
化疗也称化学疗法，是利用对细胞有毒的药物杀死肿瘤细胞、抑制其生长和繁殖并促进其分化的一种治疗方法，是目前治疗肿瘤及某些自身免疫性疾病的主要手段之一。但这种方法在杀伤肿瘤细胞的同时，也会将正常细胞和免疫细胞一同杀灭，因此，患者普遍有明显的恶心呕吐等副作用。
新研究从一种被称为锰福地吡（mangafodipir）的药物开始，这种药物通常作为核磁共振检查的造影剂。一次偶然的机会，研究人员发现锰福地吡能够在癌症治疗中保护健康细胞。
论文第一作者、瑞典林雪平大学教授罗夫·安德森称，他们发现锰福地吡会影响氧自由基的形成，而这是导致化疗副作用的一大主要原因。
于是，研究人员用患癌小鼠进行实验，在对小鼠进行化疗的同时配合使用锰福地吡。结果发现，化疗药物在抑制肿瘤的同时并未对白细胞造成损伤，由白细胞构成的免疫屏障依旧在发挥作用。而唯一的问题是，锰福地吡的使用导致了锰在小鼠体内的大量释放，大剂量的锰同样有毒，可能导致脑损伤等其他副作用。
为了避免锰可能带来的危害，研究人员用钙对锰福地吡中的锰进行了部分替换，生成了一种名为钙锰福地吡（calmangafodipir）的化合物。
实验证实，新生成的这种化合物不但能够更加有效地保护健康细胞、抑制癌细胞，还更加稳定和安全。
目前，一组结肠癌患者正在接受临床试验，以确定这种新药的疗效和安全性，相关研究有望在年内获得结果。
Superior therapeutic index of calmangafodipir in comparison to mangafodipir as a chemotherapy adjunct
Karlsson JO, Kurz T, Flechsig S, Näsström J, Andersson RG
Mangafodipir is a magnetic resonance imaging contrast agent with manganese superoxide dismutase (MnSOD) mimetic activity. The MnSOD mimetic activity protects healthy cells against oxidative stress-induced detrimental effects, e.g., myelosuppressive effects of chemotherapy drugs. The contrast property depends on in vivo dissociation of Mn(2+) from mangafodipir-about 80% dissociates after injection. The SOD mimetic activity, however, depends on the intact Mn complex. Complexed Mn(2+) is readily excreted in the urine, whereas dissociated Mn(2+) is excreted slowly via the biliary route. Mn is an essential but also a potentially neurotoxic metal. For more frequent therapeutic use, neurotoxicity due to Mn accumulation in the brain may represent a serious problem. Replacement of 4/5 of Mn(2+) in mangafodipir with Ca(2+) (resulting in calmangafodipir) stabilizes it from releasing Mn(2+) after administration, which roughly doubles renal excretion of Mn. A considerable part of Mn(2+) release from mangafodipir is governed by the presence of a limited amount of plasma zinc (Zn(2+)). Zn(2+) has roughly 10(3) and 10(9) times higher affinity than Mn(2+) and Ca(2+), respectively, for fodipir. Replacement of 80% of Mn(2+) with Ca(2+) is enough for binding a considerable amount of the readily available plasma Zn(2+), resulting in considerably less Mn(2+) release and retention in the brain and other organs. At equivalent Mn(2+) doses, calmangafodipir was significantly more efficacious than mangafodipir to protect BALB/c mice against myelosuppressive effects of the chemotherapy drug oxaliplatin. Calmangafodipir did not interfere negatively with the antitumor activity of oxaliplatin in CT26 tumor-bearing syngenic BALB/c mice, contrary calmangafodipir increased the antitumor activity.
