A Single-Pot Template Reaction Towards a Manganese-Based T1 Contrast Agent

被引:44
作者
Anbu, Sellamuthu [1 ,2 ]
Hoffmann, Sabrina H. L. [3 ]
Carniato, Fabio [4 ]
Kenning, Lawrence [5 ]
Price, Thomas W. [6 ]
Prior, Timothy J. [2 ]
Botta, Mauro [4 ]
Martins, Andre F. [3 ,7 ]
Stasiuk, Graeme J. [6 ]
机构
[1] Univ Hull, Dept Biomed Sci, Cottingham Rd, Kingston Upon Hull HU6 7RX, N Humberside, England
[2] Univ Hull, Dept Chem, Cottingham Rd, Kingston Upon Hull HU6 7RX, N Humberside, England
[3] Eberhard Karls Univ Tubingen, Werner Siemens Imaging Ctr, Dept Preclin Imaging & Radiopharm, Rontgenweg 13-1, D-72076 Tubingen, Germany
[4] Univ Piemonte Orientale, Dipartimento Sci & Innovaz Tecnol, Viale Teresa Michel 11, I-15121 Alessandria, Italy
[5] Hull Royal Infirm Hosp NHS Trust, MRI Ctr, Anlaby Rd, Kingston Upon Hull HU3 2JZ, N Humberside, England
[6] Kings Coll London, Dept Imaging Chem & Biol, Sch Biomed Engn & Imaging Sci, St Thomas Hosp, Fourth Floor Lambeth Wing, London SE1 7EH, England
[7] Univ Tubingen, Cluster Excellence iFIT EXC 2180 Image Guided & F, Tubingen, Germany
基金
英国工程与自然科学研究理事会;
关键词
bishydrated MnCA; blood pool agents; in  vivo MRI; Mn-based contrast agents; template synthesis; NEPHROGENIC SYSTEMIC FIBROSIS; HUMAN SERUM-ALBUMIN; MN2+ COMPLEXES; WATER EXCHANGE; GADOLINIUM DEPOSITION; MAGNETIC-PROPERTIES; MN(II) CHELATE; MRI; RELAXIVITY; STABILITY;
D O I
10.1002/anie.202100885
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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 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=4.2x10(3) 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.
引用
收藏
页码:10736 / 10744
页数:9
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