Radiochemical and biological characteristics of 99mTc-UBI 29-41 for imaging of bacterial infections
Radiochemical and biological characteristics of 99mTc-UBI 29-41 for imaging of bacterial infections
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DOI：
10.1016/s0969-8051(02)00292-5
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发表时间：
2002-05-01
影响因子：
3.1
通讯作者：
Nibbering, PH
中科院分区：
文献类型：
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作者：
Welling, MM;Mongera, S;Nibbering, PH
来源于ubiquicidine的Tc-99 m-UBI 29-41标记的肽，在实验动物中靶向细菌和真菌感染，但不靶向无菌炎症过程。本文报道了这种放射性试剂的放射化学和生物学特征以及UBI 29-41的氨基酸序列对感染成像的重要性。Tc-99 m-UBI 29-41和这种肽的放射性标记的乱序形式，即Tc-99 m-Sc-UBI 29-41的放射化学分析，显示两种肽都被快速标记，（10分钟内）和有效，几乎没有胶体形成（小于总放射性的5%）和极少量的游离高锝酸盐在含有放射性标记肽的制剂中，此外，与细菌的肽的协会可以与过量的未标记的肽竞争，这种协会被证明是温度依赖性的。基于此体外数据，我们得出结论，用Tc-99 m标记的肽，通过这种直接的方法是快速，有效的，和safe.Scintigraphy表明，放射性迅速从循环中删除（半衰期UBI 29-41和Sc-UBI 29-41分别为16和21分钟），主要是通过肾清除。对小鼠血液的分析表明，静脉注射的Tc-99 m-肽中只有一小部分与血细胞相关。尽管两种放射性标记的肽在感染部位迅速积累，但Tc-99 m-UBI 29-41的值高于Tc-99 m-Se-UBI 29 -41（P < 0.05）。此外，在注射Tc-99 m-UBI 29 - 41之前，将过量的未标记的UBI 29 -41注射到葡萄球菌感染的小鼠中，而不是Sc-UBI 29-41，显著地（P < 0.05）减少了该放射性药物在感染部位的积累。此外，与含有放射性标记的UBI 29 - 41的未纯化制剂相比，我们观察到使用无载体放射性标记的UBI 29 - 41的小鼠感染部位的Tc-99 m-U131 29- 41的量显著（P < 0.01）更高。该体内数据表明Tc-99 m-UBI 29-41的氨基酸序列有助于其在感染部位的积累。(C)2002年爱思唯尔科技有限公司All rights reserved.
A technetium-99m-labeled peptide derived from ubiquicidine, further referred to as Tc-99m-UBI 29-41, targets bacterial and fungal infections, but not sterile inflammatory processes, in experimental animals. This paper reports on the radiochemical and biological features of this radioactive agent and the importance of the amino acid sequence of UBI 29-41 for imaging of infections.Radiochemical analyses of Tc-99m-UBI 29-41 and a radiolabeled scrambled version of this peptide, i.e. Tc-99m-Sc-UBI 29-41, revealed that both peptides were labeled rapidly (within 10 min) and effectively with little colloid formation (less than 5% of the total radioactivity) and very little free pertechnetate (or radioactive intermediates) in the preparations containing radiolabeled peptide. Furthermore, association of the peptides with bacteria could be competed with excess unlabeled peptide and this association proved to be temperature-dependent. Based on this in vitro data we concluded that labeling of peptides with Tc-99m by this direct method is rapid, efficient, and safe.Scintigraphy demonstrated that radioactivity is rapidly removed from the circulation (half-lifes of UBI 29-41 and Sc-UBI 29-41 were 16 and 21 min, respectively) mainly by renal clearance. Analysis of murine blood revealed that only a small proportion of the intravenously injected Tc-99m-peptides is associated with blood cells. Although both radiolabeled peptides accumulated rapidly at sites of infection, the values for Tc-99m-UBI 29-41 were higher (P < 0.05) than for Tc-99m-Se-UBI 29-41. Moreover, injection of excess unlabeled UBI 29-41, but not Sc-UBI 29-41, into Staphylococcus a tire its-infected mice prior to injection of Tc-99m-UBI 29-41 significantly (P < 0.05) reduced the accumulation of this radiopharmaceutical at the site of infection. In addition, we observed significantly (P < 0.01) higher amounts of Tc-99m-U131 29-41 at the site of infection in mice using a carrier-free radiolabeled UBI 29-41 as compared with unpurified preparations containing radiolabeled UBI 29-41. This in vivo data indicates that the amino acid sequence of Tc-99m-UBI 29-41 contributes to its accumulation at the site of infection. (C) 2002 Elsevier Science Inc. All rights reserved.