A single pot template reaction towards a manganese based T1 contrast agent

Sellamuthu Anbu; Sabrina  Hoffmann; Fabio  Carniato; Lawrence  Kenning; Thomas Price; Timothy J. Prior; Mauro Botta; Andre F.  Martins; Graeme Stasiuk

doi:10.1002/anie.202100885

A single pot template reaction towards a manganese based T1 contrast agent

Sellamuthu Anbu, Sabrina Hoffmann, Fabio Carniato, Lawrence Kenning, Thomas Price, Timothy J. Prior, Mauro Botta, Andre F. Martins, Graeme Stasiuk

Imaging Chemistry & Biology

Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Röntgenweg 13/1, 72076 Tübingen, Germany.
Dipartimento di Scienze e InnovazioneTecnologica, Università del Piemonte Orientale ‘A. Avogadro’, Alessandria, Viale Teresa Michel 11, 15121, Italy.
MRI centre, Hull Royal Infirmary Hospital NHS Trust, Anlaby Road, Hull, HU3 2JZ, UK.
Cluster of Excellence iFIT (EXC 2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tuebingen, Germany.
University of Hull
University of Lisbon

Research output: Contribution to journal › Article › peer-review

42 Citations (Scopus)

Abstract

Manganese-based contrast agents (MnCAs) have emerged as suitable alternatives to gadolinium-based contrast agents (GdCAs). However, due to their kinetic lability and laborious synthetic procedures, only a few MnCAs have found clinical MRI application. In this work, we have employed a highly innovative single-pot template synthetic strategy to develop a MnCA, MnL ^Me, and studied the most important physicochemical properties in vitro. MnL ^Me displays optimized r ₁ relaxivities at both medium (20 and 64 MHz) and high magnetic fields (300 and 400 MHz) and an enhanced r ₁ ^b=21.1 mM ⁻¹ s ⁻¹ (20 MHz, 298 K, pH 7.4) upon binding to BSA (K _a=4.2×10 ³ M ⁻¹). In vivo studies show that MnL ^Me is cleared intact into the bladder through renal excretion and has a prolonged blood half-life compared to the commercial GdCA Magnevist. MnL ^Me shows great promise as a novel MRI contrast agent.

Original language	English
Pages (from-to)	10736-10744
Number of pages	9
Journal	ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume	60
Issue number	19
DOIs	https://doi.org/10.1002/anie.202100885
Publication status	Published - 3 May 2021

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@article{b11ed58030504476b13f3f3ae3d54102,

title = "A single pot template reaction towards a manganese based T1 contrast agent",

abstract = "Manganese-based contrast agents (MnCAs) have emerged as suitable alternatives to gadolinium-based contrast agents (GdCAs). However, due to their kinetic lability and laborious synthetic procedures, only a few MnCAs have found clinical MRI application. In this work, we have employed a highly innovative single-pot template synthetic strategy to develop a MnCA, MnL Me, and studied the most important physicochemical properties in vitro. MnL Me displays optimized r 1 relaxivities at both medium (20 and 64 MHz) and high magnetic fields (300 and 400 MHz) and an enhanced r 1 b=21.1 mM −1 s −1 (20 MHz, 298 K, pH 7.4) upon binding to BSA (K a=4.2×10 3 M −1). In vivo studies show that MnL Me is cleared intact into the bladder through renal excretion and has a prolonged blood half-life compared to the commercial GdCA Magnevist. MnL Me shows great promise as a novel MRI contrast agent. ",

author = "Sellamuthu Anbu and Sabrina Hoffmann and Fabio Carniato and Lawrence Kenning and Thomas Price and Prior, {Timothy J.} and Mauro Botta and Martins, {Andre F.} and Graeme Stasiuk",

note = "Funding Information: S.A. gratefully acknowledges the Departments of Chemistry and Biomedical Sciences, the University of Hull, for providing laboratory space and instruments access to carrying out this work. The work has also been partially supported by the RSC Research Fund grant (RF19‐7464). G.J.S. would like to thank the MRC for funding (MR/T002573/1). A.F.M. gratefully acknowledges the funding and support by the Swiss Werner Siemens Foundation and the Faculty of Medicine at the University of Tuebingen (Nachwuchsgruppen‐Programm). The work was also funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy—EXC 2180‐390900677. M.B. and F.C. are grateful to Universit{\`a} del Piemonte Orientale for financial support (FARC 2019). We thank also Dr. Christoph Trautwein and Georgy Berezhnoy for assistance performing H NMR and relaxometric studies at the Bruker Spectrometer 14.1 T. 1 Funding Information: S.A. gratefully acknowledges the Departments of Chemistry and Biomedical Sciences, the University of Hull, for providing laboratory space and instruments access to carrying out this work. The work has also been partially supported by the RSC Research Fund grant (RF19-7464). G.J.S. would like to thank the MRC for funding (MR/T002573/1). A.F.M. gratefully acknowledges the funding and support by the Swiss Werner Siemens Foundation and the Faculty of Medicine at the University of Tuebingen (Nachwuchsgruppen-Programm). The work was also funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy?EXC 2180-390900677. M.B. and F.C. are grateful to Universit? del Piemonte Orientale for financial support (FARC 2019). We thank also Dr. Christoph Trautwein and Georgy Berezhnoy for assistance performing 1H NMR and relaxometric studies at the Bruker Spectrometer 14.1 T. Publisher Copyright: {\textcopyright} 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = may,

day = "3",

doi = "10.1002/anie.202100885",

language = "English",

volume = "60",

pages = "10736--10744",

journal = "ANGEWANDTE CHEMIE-INTERNATIONAL EDITION",

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T1 - A single pot template reaction towards a manganese based T1 contrast agent

AU - Anbu, Sellamuthu

AU - Hoffmann, Sabrina

AU - Carniato, Fabio

AU - Kenning, Lawrence

AU - Price, Thomas

AU - Prior, Timothy J.

AU - Botta, Mauro

AU - Martins, Andre F.

AU - Stasiuk, Graeme

N1 - Funding Information: S.A. gratefully acknowledges the Departments of Chemistry and Biomedical Sciences, the University of Hull, for providing laboratory space and instruments access to carrying out this work. The work has also been partially supported by the RSC Research Fund grant (RF19‐7464). G.J.S. would like to thank the MRC for funding (MR/T002573/1). A.F.M. gratefully acknowledges the funding and support by the Swiss Werner Siemens Foundation and the Faculty of Medicine at the University of Tuebingen (Nachwuchsgruppen‐Programm). The work was also funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy—EXC 2180‐390900677. M.B. and F.C. are grateful to Università del Piemonte Orientale for financial support (FARC 2019). We thank also Dr. Christoph Trautwein and Georgy Berezhnoy for assistance performing H NMR and relaxometric studies at the Bruker Spectrometer 14.1 T. 1 Funding Information: S.A. gratefully acknowledges the Departments of Chemistry and Biomedical Sciences, the University of Hull, for providing laboratory space and instruments access to carrying out this work. The work has also been partially supported by the RSC Research Fund grant (RF19-7464). G.J.S. would like to thank the MRC for funding (MR/T002573/1). A.F.M. gratefully acknowledges the funding and support by the Swiss Werner Siemens Foundation and the Faculty of Medicine at the University of Tuebingen (Nachwuchsgruppen-Programm). The work was also funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy?EXC 2180-390900677. M.B. and F.C. are grateful to Universit? del Piemonte Orientale for financial support (FARC 2019). We thank also Dr. Christoph Trautwein and Georgy Berezhnoy for assistance performing 1H NMR and relaxometric studies at the Bruker Spectrometer 14.1 T. Publisher Copyright: © 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/5/3

Y1 - 2021/5/3

N2 - Manganese-based contrast agents (MnCAs) have emerged as suitable alternatives to gadolinium-based contrast agents (GdCAs). However, due to their kinetic lability and laborious synthetic procedures, only a few MnCAs have found clinical MRI application. In this work, we have employed a highly innovative single-pot template synthetic strategy to develop a MnCA, MnL Me, and studied the most important physicochemical properties in vitro. MnL Me displays optimized r 1 relaxivities at both medium (20 and 64 MHz) and high magnetic fields (300 and 400 MHz) and an enhanced r 1 b=21.1 mM −1 s −1 (20 MHz, 298 K, pH 7.4) upon binding to BSA (K a=4.2×10 3 M −1). In vivo studies show that MnL Me is cleared intact into the bladder through renal excretion and has a prolonged blood half-life compared to the commercial GdCA Magnevist. MnL Me shows great promise as a novel MRI contrast agent.

AB - Manganese-based contrast agents (MnCAs) have emerged as suitable alternatives to gadolinium-based contrast agents (GdCAs). However, due to their kinetic lability and laborious synthetic procedures, only a few MnCAs have found clinical MRI application. In this work, we have employed a highly innovative single-pot template synthetic strategy to develop a MnCA, MnL Me, and studied the most important physicochemical properties in vitro. MnL Me displays optimized r 1 relaxivities at both medium (20 and 64 MHz) and high magnetic fields (300 and 400 MHz) and an enhanced r 1 b=21.1 mM −1 s −1 (20 MHz, 298 K, pH 7.4) upon binding to BSA (K a=4.2×10 3 M −1). In vivo studies show that MnL Me is cleared intact into the bladder through renal excretion and has a prolonged blood half-life compared to the commercial GdCA Magnevist. MnL Me shows great promise as a novel MRI contrast agent.

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U2 - 10.1002/anie.202100885

DO - 10.1002/anie.202100885

M3 - Article

SN - 1433-7851

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JO - ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

JF - ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

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ER -

A single pot template reaction towards a manganese based T1 contrast agent

Abstract

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