Synthesis of High Relaxivity Gadolinium AAZTA Tetramers as Building Blocks for Bioconjugation

Bioconjugate Chemistry
Martina TripepiS Aime

Abstract

Molecular imaging requires the specific accumulation of contrast agents at the target. To exploit the superb resolution of MRI for applications in molecular imaging, gadolinium chelates, as the MRI contrast agents (CA), have to be conjugated to a specific vector able to recognize the epitope of interest. Several Gd(III)-chelates can be chemically linked to the same binding vector in order to deliver multiple copies of the CA (multimers) in a single targeting event thus increasing the sensitivity of the molecular probe. Herein three novel bifunctional agents, carrying one functional group for the bioconjugation to targeting vectors and four Gd(III)-AAZTA chelate functions for MRI contrast enhancement (AAZTA = 6-amino-6-methylperhydro-1,4-diazepinetetraacetic acid), are reported. The relaxivity in the tetrameric derivatives is 16.4 ± 0.2 mMGd-1 s-1 at 21.5 MHz and 25 °C, being 2.4-fold higher than that of parent, monomeric Gd(III)-AAZTA. These compounds can be used as versatile building blocks to insert preformed, high relaxivity, and high density Gd-centers to biological targeting vectors. As an example, we describe the use of these bifunctional Gd(III)-chelates to label a fibrin-targeting peptide.

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Citations

Sep 27, 2018·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·Amerigo PagotoEnzo Terreno
Feb 16, 2019·Journal of Peptide Science : an Official Publication of the European Peptide Society·Carlo DiaferiaAntonella Accardo
Mar 4, 2020·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Mani SalarianJenny J Yang
Oct 2, 2020·Organic & Biomolecular Chemistry·Jonathan MartinelliKristina Djanashvili
Jun 12, 2021·Chemistry : a European Journal·Loredana LeoneLorenzo Tei

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