Manganese(III)-transferrin [Mn(III)-Tf] was investigated as a way to accomplish manganese-labeling of murine hepatocytes for MRI contrast. It is postulated that Mn(III)-Tf can exploit the same transferrin-receptor-dependent and -independent metabolic pathways used by hepatocytes to transport the iron analog Fe(III)-Tf. More specifically, it was investigated whether manganese delivered by transferrin could give MRI contrast in hepatocytes. Comparison of the T1 and T2 relaxation times of Mn(III)-Tf and Fe(III)-Tf over the same concentration range showed that the r1 relaxivities of the two metalloproteins are the same in vitro, with little contribution from paramagnetic enhancement. The degree of manganese cell labeling following incubation for 2-7 h in 31.5 microm Mn(III)-Tf was comparable to that of hepatocytes incubated in 500 microm Mn2+ for 1 h. The intrinsic manganese tissue relaxivity between Mn(III)-Tf-labeled and Mn2+-labeled cells was found to be the same, consistent with Mn(III) being released from transferrin and reduced to Mn2+. For both treatment regimens, manganese uptake by hepatocytes appeared to saturate in the first 1-2 h of the incubation period and may explain why the efficiency of hepatocyte cell labeling by the two methods appeared to be comparable in spite of the approximately 16-fold difference in effective manganese concentration. Hepatocytes continuously released manganese, as detected by MRI, and this was the same for both Mn2+- and Mn(III)-Tf-labeled cells. Manganese release may be the result of normal hepatocyte function, much in the same way that hepatocytes excrete manganese into the bile in vivo. This approach exploits a biological process-namely receptor binding, endocytosis and endosomal acidification-to initiate the release of an MRI contrast agent, potentially conferring more specificity to the labeling process. The ubiquitous expression of transferrin receptors by eukaryotic cells should make Mn(III)-Tf particularly useful for manganese labeling of a wide variety of cells both in culture and in vivo.

中文翻译：

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使用锰 (III)-转铁蛋白对鼠肝细胞进行锰细胞标记。

锰 (III)-转铁蛋白 [Mn(III)-Tf] 被研究作为一种用于完成 MRI 对比的鼠肝细胞锰标记的方法。据推测，Mn(III)-Tf 可以利用肝细胞用于运输铁类似物 Fe(III)-Tf 的相同的转铁蛋白受体依赖性和非依赖性代谢途径。更具体地说，研究了转铁蛋白递送的锰是否可以在肝细胞中提供 MRI 对比度。Mn(III)-Tf 和 Fe(III)-Tf 在相同浓度范围内的 T1 和 T2 弛豫时间的比较表明，两种金属蛋白的 r1 弛豫时间在体外是相同的，顺磁增强的贡献很小。在 31.5 microm Mn(III)-Tf 中孵育 2-7 小时后锰细胞标记的程度与在 500 microm Mn2+ 中孵育 1 小时的肝细胞相媲美。发现 Mn(III)-Tf 标记的细胞和 Mn2+ 标记的细胞之间的内在锰组织弛豫是相同的，这与从转铁蛋白中释放并还原为 Mn2+ 的 Mn(III) 一致。对于这两种治疗方案，肝细胞对锰的吸收似乎在潜伏期的前 1-2 小时内饱和，这可以解释为什么尽管存在大约 16 倍的差异，但两种方法的肝细胞标记效率似乎相当有效锰浓度。MRI 检测到，肝细胞不断释放锰，这对于 Mn2+- 和 Mn(III)-Tf 标记的细胞是相同的。锰的释放可能是正常肝细胞功能的结果，与肝细胞在体内将锰排泄到胆汁中的方式非常相似。这种方法利用生物学过程——即受体结合、内吞作用和内体酸化——来启动 MRI 造影剂的释放，可能赋予标记过程更多的特异性。真核细胞对转铁蛋白受体的普遍表达应该使 Mn(III)-Tf 特别适用于培养和体内多种细胞的锰标记。