Vallabhajosula S R, Harwig J F, Wolf W
Eur J Nucl Med. 1982;7(10):462-8. doi: 10.1007/BF00253083.
When injected at tracer levels into the blood, radiogallium as 67Ga-citrate binds to, and it transported to the site of the tumor by, transferrin. The process by which transferrin-bound Ga is converted to tumor-bound Ga is not fully understood, but may involve the differential physiology of neoplasms compared with normal tissues. Based on the slight acidity known to be exhibited by the extracellular fluid of many animal and human tumors, we have studied the effect of pH on stability and dissociation of the Ga-transferrin complex and on the uptake of Ga by tumor cells in vitro and animal tumors in vivo. When plasma from rabbits injection 67Ga-citrate was dialyzed at pH 6.5-7.5, dissociation of Ga from transferrin showed an inverse pH-dependence. A similar inverse dependence on pH was observed for the uptake of Ga by L1210 leukemia cells and Ehrlich ascites cells incubated with Ga-transferrin complex. Tumor uptake of Ga in rats bearing Walker-256 carcinosarcoma or Murphystum lymphosarcoma whose tumor pH had been further lowered by administration of glucose showed a statistically significant increase over control rats receiving no glucose. These results demonstrate that the stability of the Ga-transferrin complex is pH-dependent and suggest that dissociation of this complex due to decreased pH at the tumor site may be one factor involved in tumor localization and binding of Ga.
当以示踪剂水平注入血液时，放射性镓以67Ga-柠檬酸盐的形式与转铁蛋白结合，并通过转铁蛋白被转运至肿瘤部位。转铁蛋白结合的镓转化为肿瘤结合的镓的过程尚未完全明了，但可能涉及肿瘤与正常组织不同的生理学特性。基于许多动物和人类肿瘤细胞外液呈现的轻微酸性，我们研究了pH对镓-转铁蛋白复合物稳定性和解离以及对体外肿瘤细胞和体内动物肿瘤摄取镓的影响。当对注射了67Ga-柠檬酸盐的兔子的血浆在pH 6.5 - 7.5进行透析时，镓从转铁蛋白的解离呈现出与pH呈反比关系。在用镓-转铁蛋白复合物孵育的L1210白血病细胞和艾氏腹水癌细胞摄取镓的过程中也观察到了类似的对pH的反比关系。在接种了Walker-256癌肉瘤或Murphystum淋巴肉瘤的大鼠中，通过给予葡萄糖使肿瘤pH进一步降低，这些大鼠的肿瘤对镓的摄取与未接受葡萄糖的对照大鼠相比有统计学上的显著增加。这些结果表明，镓-转铁蛋白复合物的稳定性依赖于pH，并提示由于肿瘤部位pH降低导致该复合物的解离可能是参与镓在肿瘤部位定位和结合的一个因素。
