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.

Cationic gadolinium chelate for magnetic resonance imaging of cartilaginous defects

“…The kinetic inertness of Gd-DOTA-Am4, Gd-DTPA and Gd-DOTA was assessed via a transmetallation assay using equimolar concentrations of the Gd complexes and ZnCl 2 , in fetal bovine serum. Consistent with previous reports (17)(18)(19)(20), the relaxation ratio R1(t)/R1(0) rapidly increased for samples containing Gd-DTPA, indicative of transmetallation ( Fig. 3A) (21,22).…”

“…Consistent with previous reports (17–20), the relaxation ratio R1(t)/R1(0) rapidly increased for samples containing Gd-DTPA, indicative of transmetallation (Figure 3A). (21, 22) It should be noted that components of fetal bovine serum (e.g.…”

Thermodynamic stability and kinetic inertness of a Gd–DTPA bisamide complex grafted onto gold nanoparticles

“…This indicated that the bisamide complex DTDTPA:Gd showed more extensive transmetallation than the parent compound. This behavior was consistent with what was already determined in GdDTPA bisamide series . The reason for this lies in the substitution of two carboxylate groups by two amide groups in the first coordination sphere of Gd 3+ .…”

Recent Advances in Gadolinium Based Contrast Agents for Bioimaging Applications

“…In a similar approach, Gd-complexes consisting of DOTA conjugates of tranexamic acid and tranexamic esters were prepared as a new class of MRI-BPCAs. The r 1 -relaxivity was significantly higher than those of any of the clinically used MRI CAs [ 161 ]. Table 3 briefly summarizes r 1 , particle size, biotoxicity, specific properties and modality of Gd-CAs.…”