Infrared spectroscopic study of the model metal-ligand-antibody systems: What information on the structure and stability of systems can be obtained?
- 作者：Marie Reková ; Pavel Mat臎jka ; pavel.matejka@vscht.cz ; V臎ra Jediná ; ková ; -K艡í ; 啪ová
- 关键词：Yttrium ; Lutetium ; FTIR spectroscopy ; Immunoconjugate ; Partial least squares regression
- 刊名：Vibrational Spectroscopy
- 出版年：2012
- 期刊代码：113_09242031
- 类别：ms
- 出版时间：July, 2012
- 卷：61
- 期：Complete
- 页码：78-84
- 文件大小：616 K
摘要
In this study we investigated the possibility of using infrared spectroscopy for the characterization of the ligand (diethylenetriaminepentaacetic acid, DTPA) in various aqueous media (water and different buffers), the antibody (immunoglobulin G, IgG), the metal-ligand complexes (Y-DTPA and Lu-DTPA) and the metal-ligand-antibody conjugates (Y-DTPA-IgG and Lu-DTPA-IgG). The aim was to describe behaviour of individual components, and to find spectral markers of complexes and/or conjugates formation. The reason of the choice of Lu and Y was the potential use of their radionuclides to form radiopharmaceutical species for nuclear medicine. We performed kinetic measurements to describe the stability/instability of individual systems. Multivariate data analysis allowed finding out spectral regions related to different chemical processes. Hydrolysis effect of the diethylenetriaminepentaacetic acid dianhydride (cDTPAA) in water was confirmed in unbuffered aqueous solution. Nevertheless, the study of cDTPAA in various buffered media showed evident suppression of hydrolysis. Thus, appropriate buffers were selected as media for complexation reactions with Y and Lu. Characteristic marker bands of complexation were identified. Human IgG in phosphate buffer and its interaction with the metal-ligand complexes were studied. Observation of new bands, band shifts and intensity changes revealed formation of the metal-ligand-IgG conjugates together with a somewhat changed secondary structure of IgG. We demonstrated the possibility of vibrational spectroscopic monitoring of the preparation steps of the metal-ligand-antibody conjugates as potential radiopharmaceutical products.