Manganese Complex of Ethylenediaminetetraacetic Acid (EDTA)-Benzothiazole Aniline (BTA) Conjugate as a Potential Liver-Targeting MRI Contrast Agent

• Published in: Journal of medicinal chemistry Vol. 60; no. 7; pp. 2993 - 3001
• Main Authors: Islam, Md. Kamrul, Kim, Soyeon, Kim, Hee-Kyung, Park, Subin, Lee, Gang-Ho, Kang, Hyo Jeung, Jung, Jae-Chang, Park, Joon-Suk, Kim, Tae-Jeong, Chan, Yongmin
• Format: Journal Article
• Language: English
• Published: WASHINGTON Amer Chemical Soc 13.04.2017
• Subjects: Aniline Compounds - chemistry; Aniline Compounds - pharmacokinetics; Animals; Benzothiazoles - chemistry; Benzothiazoles - pharmacokinetics; Cell Line, Tumor; Chelating Agents - chemistry; Chelating Agents - pharmacokinetics; Chemistry, Medicinal; Contrast Media - chemistry; Contrast Media - pharmacokinetics; Coordination Complexes - analogs & derivatives; Coordination Complexes - pharmacokinetics; Edetic Acid - chemistry; Hepatocytes - pathology; Humans; Life Sciences & Biomedicine; Liver - cytology; Liver - diagnostic imaging; Liver - pathology; Liver Neoplasms - diagnostic imaging; Liver Neoplasms - pathology; Magnetic Resonance Imaging - methods; Male; Manganese - chemistry; Manganese - pharmacokinetics; Mice, Inbred BALB C; Mice, Nude; Pharmacology & Pharmacy; Science & Technology; CHELATE; GADOLINIUM; ENHANCEMENT; NEPHROGENIC SYSTEMIC FIBROSIS
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/acs.jmedchem.6b01799

A novel manganese(II) complex based on an ethylenediaminetetraacetic acid (EDTA) coordination cage bearing a benzothiazole aniline (BTA) moiety (Mn-EDTA-BTA) was designed and synthesized for use as a liver-specific MRI contrast agent with high chelation stability. In addition to forming a hydrophilic, stable complex with Mn2+, this new Mn chelate was rapidly taken up by liver hepatocytes and excreted by the kidneys and biliary system. The kinetic inertness and R-1 relaxivity of the complex were much higher than those of mangafodipir trisodium (MnDPDP), a clinically approved liver-specific MRI contrast agent. The diagnostic utility of this new Mn complex in MRI was, demonstrated by high-sensitivity tumor detection in an animal model of liver cancer.