Sellamuthu Anbu1,2, Sabrina H L Hoffmann3, Fabio Carniato4, Lawrence Kenning5, Thomas W Price6, Timothy J Prior2, Mauro Botta4, Andre F Martins3,7, Graeme J Stasiuk6. 1. Department of Biomedical Sciences, University of Hull, Cottingham Road, Hull, HU6 7RX, UK. 2. Department of Chemistry, University of Hull, Cottingham Road, Hull, HU6 7RX, UK. 3. Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Röntgenweg 13/1, 72076, Tübingen, Germany. 4. Dipartimento di Scienze e InnovazioneTecnologica, Università del Piemonte Orientale "A. Avogadro", Viale Teresa Michel 11, 15121, Alessandria, Italy. 5. MRI centre, Hull Royal Infirmary Hospital NHS Trust, Anlaby Road, Hull, HU3 2JZ, UK. 6. Department of Imaging Chemistry and Biology, School of Biomedical Engineering and Imaging Sciences, King's College London, Fourth Floor Lambeth Wing, St Thomas' Hospital, London, SE1 7EH, UK. 7. Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies", University of Tuebingen, Germany.
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, MnLMe , and studied the most important physicochemical properties in vitro. MnLMe displays optimized r1 relaxivities at both medium (20 and 64 MHz) and high magnetic fields (300 and 400 MHz) and an enhanced r1 b =21.1 mM-1 s-1 (20 MHz, 298 K, pH 7.4) upon binding to BSA (Ka =4.2×103 M-1 ). In vivo studies show that MnLMe is cleared intact into the bladder through renal excretion and has a prolonged blood half-life compared to the commercial GdCA Magnevist. MnLMe shows great promise as a novel MRI contrast agent.
Manganese-n class="Chemical">basedcontrast 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, MnLMe , and studied the most important physicochemical properties in vitro. MnLMe displays optimized r1 relaxivities at both medium (20 and 64 MHz) and high magnetic fields (300 and 400 MHz) and an enhanced r1 b =21.1 mM-1 s-1 (20 MHz, 298 K, pH 7.4) upon binding to BSA (Ka =4.2×103 M-1 ). In vivo studies show that MnLMe is cleared intact into the bladder through renal excretion and has a prolonged blood half-life compared to the commercial GdCAMagnevist. MnLMe shows great promise as a novel MRI contrast agent.
Authors: Rocío Uzal-Varela; Francisco Pérez-Fernández; Laura Valencia; Aurora Rodríguez-Rodríguez; Carlos Platas-Iglesias; Peter Caravan; David Esteban-Gómez Journal: Inorg Chem Date: 2022-08-22 Impact factor: 5.436