TY - JOUR
T1 - Polymerizable Gd(iii) building blocks for the synthesis of high relaxivity macromolecular MRI contrast agents
AU - Berki, Thomas R.
AU - Martinelli, Jonathan
AU - Tei, Lorenzo
AU - Willcock, Helen
AU - Butler, Stephen J.
N1 - Publisher Copyright:
© The Royal Society of Chemistry 2021.
PY - 2021/3/21
Y1 - 2021/3/21
N2 - A new synthetic strategy for the preparation of macromolecular MRI contrast agents (CAs) is reported. Four gadolinium(iii) complexes bearing either one or two polymerizable methacrylamide groups were synthesized, serving as monomers or crosslinkers for the preparation of water-soluble, polymeric CAs using Reversible Addition-Fragmentation Chain Transfer (RAFT) polymerization. Using this approach, macromolecular CAs were synthesized with different architectures, including linear, hyperbranched polymers and gels. The relaxivities of the polymeric CAs were determined by NMR relaxometry, revealing an up to 5-fold increase in relaxivity (60 MHz, 310 K) for the linear polymers compared with the clinically used CA, Gd-DOTA. Moreover, hyperbranched polymers obtained from Gd(iii) crosslinkers, displayed even higher relaxivities up to 22.8 mM−1s−1, approximately 8 times higher than that of Gd-DOTA (60 MHz, 310 K). A detailed NMRD study revealed that the enhanced relaxivities of the hyperbranched polymers were obtained by limiting the local motion of the crosslinked Gd(iii) chelate. The versatility of RAFT polymerization of Gd(iii) monomers and crosslinkers opens the doors to more advanced polymeric CAs capable of multimodal, bioresponsive or targeting properties.
AB - A new synthetic strategy for the preparation of macromolecular MRI contrast agents (CAs) is reported. Four gadolinium(iii) complexes bearing either one or two polymerizable methacrylamide groups were synthesized, serving as monomers or crosslinkers for the preparation of water-soluble, polymeric CAs using Reversible Addition-Fragmentation Chain Transfer (RAFT) polymerization. Using this approach, macromolecular CAs were synthesized with different architectures, including linear, hyperbranched polymers and gels. The relaxivities of the polymeric CAs were determined by NMR relaxometry, revealing an up to 5-fold increase in relaxivity (60 MHz, 310 K) for the linear polymers compared with the clinically used CA, Gd-DOTA. Moreover, hyperbranched polymers obtained from Gd(iii) crosslinkers, displayed even higher relaxivities up to 22.8 mM−1s−1, approximately 8 times higher than that of Gd-DOTA (60 MHz, 310 K). A detailed NMRD study revealed that the enhanced relaxivities of the hyperbranched polymers were obtained by limiting the local motion of the crosslinked Gd(iii) chelate. The versatility of RAFT polymerization of Gd(iii) monomers and crosslinkers opens the doors to more advanced polymeric CAs capable of multimodal, bioresponsive or targeting properties.
UR - http://www.scopus.com/inward/record.url?scp=85103295869&partnerID=8YFLogxK
U2 - 10.1039/d0sc04750c
DO - 10.1039/d0sc04750c
M3 - Article
SN - 2041-6520
VL - 12
SP - 3999
EP - 4013
JO - Chemical Science
JF - Chemical Science
IS - 11
ER -