Issue 8, 2013

Synthesis and characterization of pH-sensitive, biotinylated MRI contrast agents and their conjugates with avidin

Abstract

Responsive or smart contrast agents (SCAs) provide new opportunities in magnetic resonance imaging (MRI) to examine a number of physiological and pathological events. However, their application in vivo remains challenging. Therefore, much research is focused on the optimization of their properties, to enable their use in additional imaging modalities, pre-targeted delivery, or to increase the local concentration of the agent. The key feature in the SCA synthetic modification is the retention of their physicochemical properties related to the specific MR response. Here, we report the preparation and characterization of pH sensitive SCAs appended with a phosphonate pendant arm and either an aliphatic (GdL1) or aromatic linker (GdL2). The longitudinal relaxivity of GdL1 and GdL2 increases by 146% and 31%, respectively, while the pH decreases from 9 to 5. These two SCAs were converted to the biotinylated systems GdL3 and GdL4 and their interaction with avidin was investigated. The binding affinity with avidin was assessed with a fluorescence displacement assay and with MRI phantom experiments in a 3T MRI scanner. The fluorometric assay and MRI E-titrations revealed a 3 : 1 binding mode of GdL3–4 to avidin with the binding affinity as high as that of the parent avidin–biotin complex. The high binding affinity was confirmed with MRI by a competitive assay. The avidin–GdL3–4 complexes thus obtained exhibit changes in both r1 and r2 that are pH dependent. The results reveal a new pathway for the modification and improvement of SCAs to make them more suitable for in vivo application.

Graphical abstract: Synthesis and characterization of pH-sensitive, biotinylated MRI contrast agents and their conjugates with avidin

Supplementary files

Article information

Article type
Paper
Submitted
06 Aug 2012
Accepted
15 Nov 2012
First published
16 Nov 2012

Org. Biomol. Chem., 2013,11, 1294-1305

Synthesis and characterization of pH-sensitive, biotinylated MRI contrast agents and their conjugates with avidin

S. M. Vibhute, J. Engelmann, T. Verbić, M. E. Maier, N. K. Logothetis and G. Angelovski, Org. Biomol. Chem., 2013, 11, 1294 DOI: 10.1039/C2OB26555A

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements