Poster (Scientific congresses and symposiums)
Strategies of regioselective radiolabeling of Nanofitin binder for imaging
Goux, Marine; Dammicco, Sylvestre; Becker, Guillaume et al.
2015BioForum 2015
 

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Keywords :
Nanofitin; Labelling; FBEM
Abstract :
[en] Recently, new strategies emerged in the field of monoclonal antibodies radiolabeling for PET imaging with the use of positron emitter such as fluorine-18, zirconium-89 or gallium-68. Despite their important role in the therapeutic world, antibodies have many disadvantages related to their structure. Moreover, conjugation of chelating agent often occurs on lysines, which is non-regioselective and leads to a heterogeneous mixture of products. In addition, the slow clearance of antibodies can be a problem to obtain a good contrast when they are used in imaging. To address these different limitations, we developed a chemistry-free chelating system consisting of a highly phosphorylatable peptide tag fused genetically to a Nanofitin. A specific phosphorylation step, with the alpha subunit of the casein kinase II, generates a nanocluster of 4 phosphates that can interact strongly with metal ion like zirconium or gallium. This strategy has already demonstrated its powerfulness for the stable and specific anchoring of protein on zirconium phosphonate-based microarray [1]. Considering this tag has been created to specifically anchoring protein on zirconium phosphonate-based microarray, we are currently working on a sequence derived from calcium-binding proteins to chelate specifically lanthanides[2]. As described by Pardoux et al.[3], our strategy is to functionalize this sequence with a phosphate nanocluster able to chelate zirconium or gallium. Our first results shown that a mono-phosphorylatable tag phosphorylated in vitro is able to chelate terbium(III) with a lower affinity than the wild type. Considering that terbium(III) is bigger than gallium(III) or zirconium(IV), we can suppose that the cage obtained is too small but suitable for other ions. In order to validate our hypothesis, we have planned to radiolabel those tags and determine their affinity for gallium(III). In order to validate the use of Nanofitin as a potent alternative tool for in vivo imaging, we have made biokinetic studies in mice with PET and MRI imaging. In these studies, we have radiolabelled with fluorine-18 a Nanofitin and we are currently making use of its specific binding to a cell-surface receptor to target a very precise cell population by using an animal model. Once the phosphorylatable tag optimized for regioselective radiolabelling and the Nanofitin targeting validated in an animal model, the next steps will be to combine these two approaches: we will fuse genetically the tag to the specific Nanofitin, radiolabel it with gallium-68 and perform the biokinetic study of this new radiopharmaceutical product. [1] M. Cinier, M. Petit, F. Pecorari, D. R. Talham, B. Bujoli, and C. Tellier, “Engineering of a phosphorylatable tag for specific protein binding on zirconium phosphonate based microarrays.,” J. Biol. Inorg. Chem., vol. 17, no. 3, pp. 399–407, Mar. 2012. [2] L. J. Martin, “Development of Lanthanide-Binding Tags (LBTs) as powerful and versatile peptides for use in studies of proteins and protein interactions,” 2008. [3] R. Pardoux, S. Sauge-merle, D. Lemaire, P. Delangle, L. Guilloreau, J. Adriano, and C. Berthomieu, “Modulating Uranium Binding Affinity in Engineered Calmodulin EF-Hand Peptides : Effect of Phosphorylation,” PLoS One, vol. 7, no. 8, 2012.
Research center :
GIGA CRC (Cyclotron Research Center) In vivo Imaging-Aging & Memory - ULiège
Disciplines :
Biotechnology
Author, co-author :
Goux, Marine ;  Université de Liège - ULiège > Doct. sc. bioméd. & pharma. (Bologne)
Other collaborator :
Dammicco, Sylvestre ;  Université de Liège > Département de chimie (sciences) > Laboratoire de chimie organique de synthèse
Becker, Guillaume ;  Université de Liège > Centre de recherches du cyclotron
Bahri, Mohamed Ali  ;  Université de Liège > Centre de recherches du cyclotron
Plenevaux, Alain  ;  Université de Liège > Centre de recherches du cyclotron
Luxen, André ;  Université de Liège > Département de chimie (sciences) > Laboratoire de chimie organique de synthèse
Language :
English
Title :
Strategies of regioselective radiolabeling of Nanofitin binder for imaging
Publication date :
May 2015
Event name :
BioForum 2015
Event place :
Liège, Belgium
Event date :
le 13 mai 2015
Audience :
International
Funders :
Région Pays de la Loire
Available on ORBi :
since 23 June 2015

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