Plasma protein binding of 99mTc-labeled hydrazino nicotinamide derivatized polypeptides and peptides
Plasma protein binding of 99mTc-labeled hydrazino nicotinamide derivatized polypeptides and peptides
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DOI：
10.1016/s0969-8051(00)00200-6
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发表时间：
2001-02-01
影响因子：
3.1
通讯作者：
Saji, H
中科院分区：
文献类型：
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作者：
Ono, M;Arano, Y;Saji, H
6-肼基吡啶-3-羧酸 (HYNIC) 与两个三甘氨酸分子作为共配体，是制备各种分子量的 Tc-99m 标记的多肽和肽时最具吸引力的试剂之一。事实上，Tc-99m-HYNIC 缀合的 IgG 显示出与 In-111 DTPA 缀合的 IgG 相似的放射性生物分布。然而，最近的研究表明，当 Tc-99m 标记程序扩展到低分子量肽时，血浆蛋白结合显着。在本研究中，将使用 Tricine 的 Tc-99m-HYNIC 缀合 IgG、Fab 和 RC160 的药代动力学与其放射性碘对应物进行比较，以评估这种 Tc-99m 标记方法。在小鼠中，与 I-125 标记的对应物相比，[Tc-99m](HYNIC-IgG)(tricine)(2) 和 [Tc-99m](HYNIC-Fab)(tricine)(2) 在组织中显示出持续的放射性定位。 [Tc-99m](HYNIC-IgG)(tricine)(2) 从血液中消除的速度与 I-125 标记的 IgG 相似，而 [Tc-99m](HYNIC Fab)(tricine)(2) 的放射性清除速度明显慢于 I-125 标记的 Fab。在尺寸排阻 HPLC 分析中，在小鼠血浆中孵育 [Tc-99m](HYNIC-IgG)(tricine)(2) 后，放射色谱图几乎没有观察到变化。然而，[Tc-99m](HYNIC-Fab)(tricine)(2) 和 [Tc-99m](HYNIC-RC160)(tricine)(2) 证明血浆中较高分子量组分的放射性显着增加。当 [Tc-99m](HYNIC-RC160)(tricine)(2) 用烟酸 (NIC) 稳定生成 [Tc-99m](HYNIC-RC160)(tricine)(NIC) 时，较高分子量物质的形成减少。 [(TC)-T-99m](HYNIC-RC160)(tricine)(NIC) 还表现出比 [Tc-99m](HyNIC-RC160)(tricine)(2) 更快地从血液中清除放射性。这些发现表明，Tc-99m-HYNIC 标记的（多）肽中的一种三羟甲基甘氨酸配位体将被血浆蛋白取代，以产生表现出缓慢的血液清除率的更高分子量的物质。此外，亲本肽的分子大小在其中一种三羟甲基甘氨酸配体与血浆蛋白的交换反应的进展中发挥重要作用。 (C) 2001 Elsevier Science Inc. 保留所有权利。
6-Hydrazinopyridine-3-carboxylic acid (HYNIC) constitutes one of the most attractive reagents to prepare Tc-99m-labeled polypeptides and peptides of various molecular weights in combination with two tricine molecules as coligands. Indeed, Tc-99m-HYNIC-conjugated IgG showed biodistribution of radioactivity similar to that of In-111 DTPA-conjugated IgG. However, recent studies indicated significant plasma protein binding when the Tc-99m labeling procedure was expanded to low molecular weight peptides. In this study, pharmacokinetics of Tc-99m-HYNIC-conjugated IgG, Fab and RC160 using tricine were compared with their radioiodinated counterparts to evaluate this Tc-99m-labeling method. In mice, [Tc-99m](HYNIC-IgG)(tricine)(2) and [Tc-99m](HYNIC-Fab)(tricine)(2) showed persistent localization of radioactivity in tissues when compared with their I-125-labeled counterparts. [Tc-99m](HYNIC-IgG)(tricine)(2) eliminated from the blood at a rate similar to that of I-125-labeled IgG, while [Tc-99m](HYNIC Fab)(tricine)(2) showed significantly slower clearance of the radioactivity than I-125-labeled Fab. On size-exclusion HPLC analyses, little changes were observed in radiochromatograms after incubation of [Tc-99m](HYNIC-IgG)(tricine)(2) in murine plasma. However, [Tc-99m](HYNIC-Fab)(tricine)(2) and [Tc-99m](HYNIC-RC160)(tricine)(2) demonstrated significant increases in the radioactivity in higher molecular weight fractions in plasma. Formation of higher molecular weight species was reduced when [Tc-99m](HYNIC-RC160)(tricine)(2) was stabilized with nicotinic acid (NIC) to generate [Tc-99m](HYNIC-RC160)(tricine)(NIC). [(TC)-T-99m](HYNIC-RC160)(tricine)(NIC) also demonstrated significantly faster clearance of the radioactivity from the blood than [Tc-99m](HyNIC-RC160)(tricine)(2). These findings suggested that one of the tricine coligands in Tc-99m-HYNIC-labeled (poly)peptides would he replaced with plasma proteins to generate higher molecular weight species that exhibit slow blood clearance. In addition, the molecular sizes of parental peptides played an important role in the progression of the exchange reaction of one of the tricine coligands with plasma proteins. (C) 2001 Elsevier Science Inc. All rights reserved.