title: Gd complexes of macrocyclic diethylenetriaminepentaacetic acid (DTPA) biphenyl-2,2'-bisamides as strong blood-pool magnetic resonance imaging contrast agents.
abstract: We report the synthesis of macrocyclic DTPA conjugates of 2,2'-diaminobiphenyl and their Gd complexes of the type [Gd(L)(H(2)O)]·xH(2)O (2a,b; L = 1a,b) for use as new MRI blood-pool contrast agents (MRI BPCAs). Pharmacokinetic inertness of 2 compares well with those of analogous Gd-DTPA MRI CAs currently in use. The present system also shows very high stability in human serum. The R(1) relaxivity reaches 10.9 mM(-1) s(-1), which is approximately 3 times as high as that of structurally related Gd-DOTA (R(1) = 3.7 mM(-1) s(-1)). The R(1) relaxivity in HSA goes up to 37.2 mM(-1) s(-1), which is almost twice as high as that of MS-325, a leading BPCA, demonstrating a strong blood pool effect. The in vivo MR images of mice obtained with 2b are coherent, showing strong signal enhancement in heart, abdominal aorta, and small vessels. Even the brain tumor is vividly enhanced for an extended period of time. The structural uniqueness of 2 is that it is neutral in charge and thus makes no resort to electrostatic interaction, supposedly one of the essential factors for the blood-pool effect.
authors.affiliation: Department of Applied Chemistry, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Ki-Hye
authors.initials: KH
authors.lastname: Jung
authors.forename: Hee-Kyung
authors.initials: HK
authors.lastname: Kim
authors.forename: Gang Ho
authors.initials: GH
authors.lastname: Lee
authors.forename: Duk-Sik
authors.initials: DS
authors.lastname: Kang
authors.forename: Ji-Ae
authors.initials: JA
authors.lastname: Park
authors.forename: Kyeong Min
authors.initials: KM
authors.lastname: Kim
authors.forename: Yongmin
authors.initials: Y
authors.lastname: Chang
authors.forename: Tae-Jeong
authors.initials: TJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000175:diagnosis; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000138:chemical synthesis*; D056831:Coordination Complexes / Q000138:chemical synthesis*; D004355:Drug Stability; D019786:Gadolinium DTPA / Q000737:chemistry*; D005910:Glioma / Q000175:diagnosis; D006801:Humans; D007700:Kinetics; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D051379:Mice; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D012709:Serum Albumin / Q000737:chemistry
chemical_list: D003287:Contrast Media; D056831:Coordination Complexes; D012709:Serum Albumin; D004369:Pentetic Acid; D019786:Gadolinium DTPA