转铁蛋白受体缺失或富集的转染细胞和肿瘤中镓-67的摄取情况。

Luttropp C A, Jackson J A, Jones B J, Sohn M H, Lynch R E, Morton K A

Imaging Service, VA Medical Center, Portland, Oregon 97207, USA.

J Nucl Med. 1998 Aug;39(8):1405-11.

UNLABELLED

Gallium-67 has been a controversial tumor-imaging agent in nuclear medicine for decades. This controversy centers on why tumors are variable in gallium-avidity, whether 67Ga uptake is a transferrin-independent or dependent process, and whether tumors and normal tissues differ in mechanism of uptake. If the factors that control uptake of 67Ga were understood better, then efforts to improve oncologic imaging with 67Ga by increasing the tumor activity, or by decreasing the background, may be warranted.

METHODS

Conventional systems for evaluating the mechanism and control of 67Ga uptake have significant limitations. We have endeavored to circumvent these by developing a pair of transfected cell lines. One cell line has no transferrin receptor. In the other, the human transferrin receptor has been restored by transfection and is over-expressed constitutively, without the necessity to manipulate factors such as cell growth or iron content. The uptake of 67Ga, both as a citrate salt and as a gallium-transferrin complex, was examined in these pairs of cells in vitro. The effect of calcium and of soluble (ionic) iron concentration on 67Ga uptake also was determined. Tumors were grown as explants of these cells in nude mice and comparisons of uptake of 67Ga by these tumors in vivo were made.

RESULTS

The in vivo uptake of 67Ga is significantly increased in tumors in which the transferrin receptor is overexpressed, compared to those without a functional transferrin receptor. However, a notable amount of accumulation of 67Ga also occurs, both in vitro and in vivo, by a transferrin-independent route. In vitro experiments demonstrate that the uptake of 67Ga by the transferrin-independent route can be enhanced further to levels that equal or exceed those achieved by the transferrin-dependent route by increasing the content of calcium or iron salts in the incubation medium.

CONCLUSION

Significant transferrin-independent uptake of 67Ga occurs both in vitro and in vivo. This uptake can be stimulated further in vitro, suggesting that in vivo enhancement might also be possible to enhance the utility of the radiometal for tumor imaging.

未标记

几十年来，镓 - 67在核医学中一直是一种存在争议的肿瘤显像剂。这场争议集中在肿瘤对镓的摄取为何存在差异、67Ga摄取是转铁蛋白非依赖性还是依赖性过程，以及肿瘤和正常组织在摄取机制上是否不同。如果能更好地理解控制67Ga摄取的因素，那么通过提高肿瘤活性或降低背景来改善67Ga肿瘤显像的努力可能是有必要的。

方法

评估67Ga摄取机制和控制的传统系统存在显著局限性。我们通过开发一对转染细胞系来努力规避这些问题。一种细胞系没有转铁蛋白受体。另一种细胞系通过转染恢复了人转铁蛋白受体并组成性过表达，无需操纵细胞生长或铁含量等因素。在体外研究了这对细胞对柠檬酸镓盐和镓 - 转铁蛋白复合物中67Ga的摄取。还确定了钙和可溶性（离子）铁浓度对67Ga摄取的影响。将这些细胞的外植体在裸鼠体内培养成肿瘤，并对这些肿瘤在体内对67Ga的摄取进行比较。

结果

与没有功能性转铁蛋白受体的肿瘤相比，转铁蛋白受体过表达的肿瘤中67Ga的体内摄取显著增加。然而，在体外和体内，67Ga也通过转铁蛋白非依赖性途径发生显著积累。体外实验表明，通过增加孵育培养基中钙盐或铁盐的含量，67Ga通过转铁蛋白非依赖性途径的摄取可以进一步提高到等于或超过转铁蛋白依赖性途径所达到的水平。