title: Gd-complexes of 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-1,4,7,10-tetraacetic acid (DOTA) conjugates of tranexamates as a new class of blood-pool magnetic resonance imaging contrast agents.
abstract: Gd-complexes of the type [Gd(L)(H(2)O)]·xH(2)O (5a-c), where L is DOTA conjugates of tranexamic acid (4a) and tranexamic esters (4b,c), have been prepared as a new class of MRI blood-pool contrast agents (BPCAs). Thermodynamic stability (K(GdL)) and pharmacokinetic inertness of 5 compare well with or better than those of analogous MRI contrasting agents (CAs) such as Gd-DOTA and Gd-DTPA-BMA. Their R(1)-relaxivities are significantly higher than those of any of the clinically used MRI CAs. T(1)-weighted MR images of mice administered by 5c demonstrate high blood-pool effect with simultaneous contrast enhancement in liver. The structural uniqueness of 5c lies in the fact that it adopts macrocyclic DOTA instead of acyclic DTPA. In addition, 5c is nonionic and makes no resort to aromatic substituent(s) in the chelate backbone for the blood-pool enhancement. The nature of hepatobiliary uptake demonstrated by 5c may be explained in terms of lipophilicity of tranexamate in the chelate (4c). The cell cytotoxicity test shows no toxicity found with 5, suggesting their use as a practical MRI BPCAs.
authors.affiliation: Department of Applied Chemistry, Kyungpook National University, Buk-gu, Daegu, Republic of Korea.
authors.forename: Sungwook
authors.initials: S
authors.lastname: Gu
authors.forename: Hee-Kyung
authors.initials: HK
authors.lastname: Kim
authors.forename: Gang Ho
authors.initials: GH
authors.lastname: Lee
authors.forename: Bong-Seok
authors.initials: BS
authors.lastname: Kang
authors.forename: Yongmin
authors.initials: Y
authors.lastname: Chang
authors.forename: Tae-Jeong
authors.initials: TJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D001769:Blood; D002460:Cell Line; D003287:Contrast Media / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D004952:Esters; D005682:Gadolinium; D006573:Heterocyclic Compounds, 1-Ring / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D008099:Liver / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009928:Organ Specificity; D013329:Structure-Activity Relationship; D014148:Tranexamic Acid / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D003287:Contrast Media; D056831:Coordination Complexes; D004952:Esters; D006573:Heterocyclic Compounds, 1-Ring; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D014148:Tranexamic Acid; D005682:Gadolinium