应用血清蛋白结合置换法研究^(99m)Tc-MAG3 的药代动力学改变。

Pharmacokinetic alteration of (99m)Tc-MAG3 using serum protein binding displacement method.

机构信息

School of Health Sciences, College of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa 920-0942, Japan.

出版信息

Nucl Med Biol. 2013 Apr;40(3):366-70. doi: 10.1016/j.nucmedbio.2012.12.002. Epub 2013 Jan 9.

DOI:10.1016/j.nucmedbio.2012.12.002

PMID:23312701

Abstract

INTRODUCTION

When a radiopharmaceutical is simultaneously administered with a medicine that has high affinity for the same plasma protein, the radiopharmaceutical is released at higher concentrations in blood, leading to enhanced transfer into target tissues. This is known as the serum protein binding displacement method. In this study, we investigated the pharmacokinetic alteration of technetium-99m-labeled mercaptoacetylglycylglycylglycine ((99m)Tc-MAG3) using the serum protein binding displacement method.

METHODS

Rat and human serum protein binding rates of (99m)Tc-MAG3 were measured by ultrafiltration with or without displacers of human serum albumin (HSA) binding sites I and II (200μM and 400μM loading). Male Wistar rats were injected with (99m)Tc-MAG3 (740kBq/0.3mL saline) via the tail vein, and biodistribution was assessed at 2, 5, 10 and 15min. Dynamic whole-body images were obtained for (99m)Tc-MAG3 (11.1MBq/0.3mL saline)-injected rats, with or without HSA displacers.

RESULTS

(99m)Tc-MAG3 strongly bound to HSA (87.37%±2.13%). Using HSA site I displacers, the free fraction of (99m)Tc-MAG3 increased significantly (1.20 to 1.47 times) when compared with controls. For biodistribution and imaging, rapid blood clearance was observed with bucolome (BCL) loading, which is an HSA site I displacer. With BCL loading, peak times for rat renograms were respectively shifted from 240s to 110s, and from 170s to 120s.

CONCLUSIONS

We found that (99m)Tc-MAG3 bound to the HSA binding site I. It was confirmed that pharmacokinetic distribution of (99m)Tc-MAG3 is altered by presence of BCL, which leads to increases in the free fraction of (99m)Tc-MAG3, and BCL produced rapid blood clearance and fast peak times on rat renograms. The serum protein binding displacement method using (99m)Tc-MAG3 and BCL, a safe displacer for humans, may be applicable to clinical study and lead to better diagnostic images with shorter waiting times and lower radiation doses for patients.

摘要

简介

当放射性药物与对同一血浆蛋白具有高亲和力的药物同时给药时，放射性药物会以更高的浓度在血液中释放，从而导致更多地转移到靶组织中。这被称为血清蛋白结合置换法。在这项研究中，我们使用血清蛋白结合置换法研究了锝-99m 标记的巯基乙酰基甘氨酰甘氨酰甘氨酸（Tc-99m-MAG3）的药代动力学变化。

方法

通过超滤法测量大鼠和人血清蛋白结合率Tc-99m-MAG3，有无人血清白蛋白（HSA）结合部位 I 和 II（200μM 和 400μM 加载）的置换剂。雄性 Wistar 大鼠通过尾静脉注射 Tc-99m-MAG3（740kBq/0.3mL 生理盐水），并在 2、5、10 和 15 分钟时评估生物分布。对 Tc-99m-MAG3（11.1MBq/0.3mL 生理盐水）注射大鼠进行动态全身成像，有无 HSA 置换剂。

结果

Tc-99m-MAG3 与 HSA 强烈结合（87.37%±2.13%）。使用 HSA 部位 I 置换剂时，与对照组相比，Tc-99m-MAG3 的游离分数显著增加（1.20 至 1.47 倍）。对于生物分布和成像，使用 HSA 部位 I 置换剂布考洛姆（BCL）时，观察到快速清除血液。用 BCL 负载时，大鼠肾图的峰值时间分别从 240s 变为 110s，从 170s 变为 120s。

结论

我们发现 Tc-99m-MAG3 与 HSA 结合部位 I 结合。证实 BCL 的存在改变了 Tc-99m-MAG3 的药代动力学分布，导致 Tc-99m-MAG3 的游离分数增加，BCL 产生快速清除血液和大鼠肾图上的快速峰值时间。使用 Tc-99m-MAG3 和 BCL（一种对人体安全的置换剂）的血清蛋白结合置换法可能适用于临床研究，并为患者带来更好的诊断图像，等待时间更短，辐射剂量更低。