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Toward 68Ga and 64Cu Positron Emission Tomography Probes: Is H2dedpa-N,N′-pram the Missing Link for dedpa Conjugation?
dc.contributor.author | Blas, Andrés de | |
dc.contributor.author | Rodríguez-Blas, Teresa | |
dc.contributor.author | Pena Bonhome, Celia | |
dc.contributor.author | Fiaccabrino, Desiree | |
dc.contributor.author | Rama, Tamara | |
dc.contributor.author | Fernández-Pavón, Daniel | |
dc.contributor.author | Southcott, Lily | |
dc.contributor.author | Zhang, Zhengxing | |
dc.contributor.author | Lin, Kuo-Shyan | |
dc.contributor.author | Patrick, Brian | |
dc.contributor.author | Schaffer, Paul | |
dc.contributor.author | Orvig, Chris | |
dc.contributor.author | Jaraquemada-Peláez, María de Guadalupe | |
dc.date.accessioned | 2024-09-02T17:23:09Z | |
dc.date.available | 2024-09-02T17:23:09Z | |
dc.date.issued | 2023 | |
dc.identifier.citation | Pena-Bonhome, C., Fiaccabrino, D., Rama, T., Fernández-Pavón, D., Southcott, L., Zhang, Z., Lin, K.-S., de Blas, A., Patrick, B. O., Schaffer, P., Orvig, C., Jaraquemada-Peláez, M. d. G., & Rodríguez-Blas, T. (2023). Toward 68Ga and 64Cu Positron Emission Tomography Probes: Is H2dedpa-N,N′-pram the Missing Link for dedpa Conjugation? Inorganic Chemistry, 62(50), 20593-20607. https://doi.org/10.1021/ACS.INORGCHEM.2C04123 | es_ES |
dc.identifier.uri | http://hdl.handle.net/2183/38809 | |
dc.description.abstract | [Abstract] H2dedpa-N,N′-pram (H2L1), a new chelator derived from the hexadentate ligand 1,2-bis[[(6-carboxypyridin-2-yl)methyl]amino]ethane (H2dedpa), which incorporates 3-propylamine chains anchored to the secondary amines of the ethylenediamine core of the latter, has emerged as a very promising scaffold for preparing 68Ga- and 64Cu-based positron emission tomography probes. This new platform is cost-effective and easy to prepare, and the two pendant primary amines make it versatile for the preparation of bifunctional chelators by conjugation and/or click chemistry. Reported herein, we have also included the related H2dedpa-N,N′-prpta (H2L2) platform as a simple structural model for its conjugated systems. X-ray crystallography confirmed that the N4O2 coordination sphere provided by the dedpa2– core is maintained at both Ga(III) and Cu(II). The complex formation equilibria were deeply investigated by a thorough multitechnique approach with potentiometric, NMR spectrometric, and UV–vis spectrophotometric titrations, revealing effective chelation. The thermodynamic stability of the Ga(III) complexes at physiological relevant conditions is slightly higher than that of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), the common and clinically approved chelator used in the clinic [pGa = 19.5 (dedpa-N,N′-pram) and 20.8 (dedpa-N,N′-prpta) versus 18.5 (DOTA) at identical conditions], and significantly higher for the Cu(II) complexes [pCu = 21.96 (dedpa-N,N′-pram) and 22.8 (dedpa-N,N′-prpta) versus 16.2 (DOTA)], which are even more stable than that of the parent ligand dedpa2– (pCu = 18.5) and that of 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) (pCu = 18.5). This high stability found for Cu(II) complexes is related to the conversion of the secondary amines of the ethylenediamine core of dedpa2– into tertiary amines, whereby the architecture of the new H2L1 chelator is doubly optimal in the case of this metal ion: high accessibility of the primary amine groups and their incorporation via the secondary amines, which contributes to a significant increase in the stability of the metal complex. Quantitative labeling of both chelators with both radionuclides ([68Ga]Ga3+ and [64Cu]Cu2+) was observed within 15 min at room temperature with concentrations as low as 10–5 M. Furthermore, serum stability studies confirmed a high radiochemical in vitro stability of all systems and therefore confirmed H2L1 as a promising and versatile chelator for further radiopharmaceutical in vivo studies. | es_ES |
dc.description.sponsorship | We thank NSERC for PGS-D and UBC for Four Year Fellowships (to L.S.), the NSERC CREATE IsoSiM training program at TRIUMF (to L.S.), as well as NSERC Discovery Grants (to C.O. and P.S.). TRIUMF receives additional funding via a contribution agreement with the National Research Council of Canada. M.d.G.J.-P. gratefully acknowledges the technical assistance of T. R. Masvikeni. C.P.-B., T.R., A.d.B., and T.R.-B. are grateful to the Spanish Ministry of Science and Innovation (CTQ2016-74862-P) and Xunta de Galicia (ED431B 2022/40) for financial support. C.P.-B. also thanks Xunta de Galicia for a Ph.D. fellowship. We also appreciate the help of Dr. A. Llamas (Unidade de Raios X RIAIDT at University of Santiago de Compostela, Spain) for useful crystallographic discussions. Funding for open access charge provided by Universidade da Coruña/CISUG. | es_ES |
dc.description.sponsorship | Xunta de Galicia; ED431B 2022/40 | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | ACS Publications | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/CTQ2016-74862-P/ES/IMAGEN MOLECULAR MULTIMODAL: DISEÑO DE SONDAS BIMODALES PARA LA TECNICA HIBRIDA PET-IRM | es_ES |
dc.relation.uri | https://doi.org/10.1021/ACS.INORGCHEM.2C04123 | es_ES |
dc.rights | CC-BY 4.0 | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | Amines | es_ES |
dc.subject | Ions | es_ES |
dc.subject | Ligands | es_ES |
dc.subject | Mechanisms of action | es_ES |
dc.subject | Metals | es_ES |
dc.title | Toward 68Ga and 64Cu Positron Emission Tomography Probes: Is H2dedpa-N,N′-pram the Missing Link for dedpa Conjugation? | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.access | info:eu-repo/semantics/openAccess | es_ES |
UDC.journalTitle | Inorganic Chemistry | es_ES |
UDC.volume | 62 | es_ES |
UDC.issue | 50 | es_ES |
UDC.startPage | 20593 | es_ES |
UDC.endPage | 20607 | es_ES |
dc.identifier.doi | 10.1021/ACS.INORGCHEM.2C04123 |
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