Synthesis and characterization of pH-sensitive, biotinylated MRI contrast agents and their conjugates with avidin
Samo za registrovane korisnike
2013
Autori
Vibhute, Sandip M.Engelmann, Joern
Verbić, Tatjana
Maier, Martin E.
Logothetis, Nikos K.
Angelovski, Goran
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
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 r(1) and r(2) 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.
Izvor:
Organic and Biomolecular Chemistry, 2013, 11, 8, 1294-1305Izdavač:
- Royal Soc Chemistry, Cambridge
Finansiranje / projekti:
- German Ministry for Education and Research (BMBF) [FKZ: 01EZ0813]
- Max-Planck Society
- German Research Foundation (DFG) [AN 716/2-1]
Napomena:
- Supplementary material: http://cherry.chem.bg.ac.rs/handle/123456789/3532
DOI: 10.1039/c2ob26555a
ISSN: 1477-0520
PubMed: 23223612
WoS: 000314368200005
Scopus: 2-s2.0-84875841582
Kolekcije
Institucija/grupa
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Vibhute, Sandip M. AU - Engelmann, Joern AU - Verbić, Tatjana AU - Maier, Martin E. AU - Logothetis, Nikos K. AU - Angelovski, Goran PY - 2013 UR - https://cherry.chem.bg.ac.rs/handle/123456789/1595 AB - 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 r(1) and r(2) 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. PB - Royal Soc Chemistry, Cambridge T2 - Organic and Biomolecular Chemistry T1 - Synthesis and characterization of pH-sensitive, biotinylated MRI contrast agents and their conjugates with avidin VL - 11 IS - 8 SP - 1294 EP - 1305 DO - 10.1039/c2ob26555a ER -
@article{ author = "Vibhute, Sandip M. and Engelmann, Joern and Verbić, Tatjana and Maier, Martin E. and Logothetis, Nikos K. and Angelovski, Goran", year = "2013", 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 r(1) and r(2) 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.", publisher = "Royal Soc Chemistry, Cambridge", journal = "Organic and Biomolecular Chemistry", title = "Synthesis and characterization of pH-sensitive, biotinylated MRI contrast agents and their conjugates with avidin", volume = "11", number = "8", pages = "1294-1305", doi = "10.1039/c2ob26555a" }
Vibhute, S. M., Engelmann, J., Verbić, T., Maier, M. E., Logothetis, N. K.,& Angelovski, G.. (2013). Synthesis and characterization of pH-sensitive, biotinylated MRI contrast agents and their conjugates with avidin. in Organic and Biomolecular Chemistry Royal Soc Chemistry, Cambridge., 11(8), 1294-1305. https://doi.org/10.1039/c2ob26555a
Vibhute SM, Engelmann J, Verbić T, Maier ME, Logothetis NK, Angelovski G. Synthesis and characterization of pH-sensitive, biotinylated MRI contrast agents and their conjugates with avidin. in Organic and Biomolecular Chemistry. 2013;11(8):1294-1305. doi:10.1039/c2ob26555a .
Vibhute, Sandip M., Engelmann, Joern, Verbić, Tatjana, Maier, Martin E., Logothetis, Nikos K., Angelovski, Goran, "Synthesis and characterization of pH-sensitive, biotinylated MRI contrast agents and their conjugates with avidin" in Organic and Biomolecular Chemistry, 11, no. 8 (2013):1294-1305, https://doi.org/10.1039/c2ob26555a . .