Gd Complexes of DO3A-(Biphenyl-2,2′-bisamides) Conjugates as MRI Blood-Pool Contrast Agents

• Published in: ACS medicinal chemistry letters Vol. 3; no. 12; pp. 1003 - 1007
• Main Authors: Jung, Ki-Hye, Kim, Hee-Kyung, Park, Ji-Ae, Nam, Ki Soo, Lee, Gang Ho, Chang, Yongmin, Kim, Tae-Jeong
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 13.12.2012; Amer Chemical Soc
• Subjects: Chemistry, Medicinal; Letter; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Science & Technology; Gd chelates; DO3A; brain tumor; biphenyl; MRI BPCA; ANGIOGRAPHY; THERAPY; MS-325; HUMAN SERUM-ALBUMIN; B22956/1
• ISSN: 1948-5875; 1948-5875
• DOI: 10.1021/ml300223b

We report the synthesis of DO3A derivatives of 2,2′-diaminobiphenyl (1a,b) and their Gd complexes of the type [Gd(1)(H2O)]·xH2O (2a,b) for use as new MRI blood-pool contrast agents (BPCAs) that provide strong and prolonged vascular enhancement. Pharmacokinetic inertness of 2 compares well with that of structurally related Dotarem, a DOTA-based MRI CA currently in use. The R 1 relaxivity in water reaches 7.3 mM–1 s–1, which is approximately twice as high as that of Dotarem (R 1 = 3.9 mM–1 s–1). They show interaction with HSA to give association constants (K a) in the order of two (∼102), revealing the existence of the blood-pool effect. The in vivo MR images of mice obtained with 2 are coherent, showing strong signal enhancement in both heart, abdominal aorta, and small vessels. Furthermore, the brain tumor is vividly enhanced for an extended period of time.