• Investigative Magnetic Resonance Imaging
• /
• v.17 no.4
• /
• pp.259-266
• /
• 2013

Purpose : To investigate the blood pharmacokinetics and bio-distribution of DTPA-bis-amide (L3) Gd(III) complexes. Materials and Methods: The pharmacokinetics and bio-distribution of Gd $(L3)(H_2O){\cdot}nH_2O$ were investigated in Sprague-Dawley rats after intravenous administration at a dose of 0.1 mmol Gd/kg. The Gd content in the blood, various tissues, and organs was determined by ICP-AES. Blood pharmacokinetic parameters were calculated using a two-compartment model. Results: The half-lives of ${\alpha}$ phase and ${\beta}$ phase Gd $(L3)(H_2O){\cdot}nH_2O$ were $2.286{\pm}0.11$ min and $146.1{\pm}7.5$ min, respectively. The bio-distribution properties reveal that the complex is mainly excreted by the renal pathway, and possibly excreted by the hepatobiliary route. The concentration ratio of Gd (III) was significantly higher in the liver and spleen than in other organs, and small amounts of Gd (III) ion were detected in the blood or other tissues of rats only after 7 days of intravenous administration. Conclusion: The MRI contrast agent Gd $(L3)(H_2O){\cdot}nH_2O$ provides prolonged blood pool retention in the circulation and then clears rapidly with minimal accumulation of Gd(III) ions. The synthesis of gadolinium complexes with well-balanced lipophilicity and hydrophilicity shows promise for their further development as blood pool MRI contrast agents.

• Bulletin of the Korean Chemical Society
• /
• v.32 no.3
• /
• pp.1022-1026
• /
• 2011

The syntheses of DTPA-bis(amide) conjugates of phosphonated cyclohexane moieties (5a-d) and their Gd(III) complexes of the type $[Gd(L)(H_2O)]{\cdot}nH_2O$ (6a-d; L = 5a-d) are described. All new compounds have been characterized by microanalysis and spectroscopic techniques. High $r_1$ relaxivities of aqueous solutions of 6a-d are observed to be in the range of $10.7-18.3\;mM^{-1}sec^{-1}$, which compare much better than that of $Omniscan^{(R)}$ ($r_1=3.90\;mM^{-1}sec^{-1}$).

• Bulletin of the Korean Chemical Society
• /
• v.27 no.7
• /
• pp.1038-1042
• /
• 2006

A new type of DTPA-bis-amides (L1-L4) and their Gd(III)-complexes of the type $[Gd(L)(H_2O)]{\cdot}nH_2O$ (5: L1; 6: L2; 7: L3; 8: L4) have been prepared and characterized by analytical and spectroscopic techniques. The X-ray crystal structure of 8 has been determined for structural confirmation. The coordination geometry adopts a tricapped trigonal prism geometry with L4 acting as a chelate octadentate and a water molecule in the coordination sphere. Crystals are monoclinic, $P2_1$, a = 14.468(3), b = 19.235(4), c = 13.527(2) $\AA$ $\beta$ = $107.245(3)^{\circ}$, V = 3595.2(11) $\AA^3$, Z = 4, $D_{calc}$ = 1.570. Significant increases in relaxivities are observed with 6 and 7 as compared with that of $Omniscan^{(R)}$, a commercial MR agent: R1 = 12.46 $mM^{-1}\;s^{-1}$, R2 = 8.76 $mM^{-1}\;s^{-1}$ for 6; R1 = 12.77 nm-1 s-1, R2 = 7.60 mM-1 s-1 for 7; R1 = 4.9 $mM^{-1}\;s^{-1}$, R2 = 4.8 $mm^{-1}\;s^{-1}$ for $Omniscan^{(R)}$. In the case of 5, however, both R1 and R2 are found to be lower to show 2.09 $mM^{-1}\;s^{-1}$, and 1.82 $mM^{-1}\;s^{-1}$, respectively.

• Bulletin of the Korean Chemical Society
• /
• v.34 no.10
• /
• pp.2900-2904
• /
• 2013

We present the synthesis and characterization of DTPA-bis(histidylamide) (1a), DTPA-bis(aspartamide) (1b), and their gadolinium complexes of the type $[Gd(L)(H_2O)]$ (2a:L = 1a; 2b:L = 1b). Thermodynamic stabilities and $R_1$ relaxivities of 2a-b compare well with Omniscan$^{(R)}$, a well-known commercial, extracellular (ECF) MRI CA which adopts the DTPA-bis(amide) framework for the chelate: $R_1$ = 5.5 and 5.1 $mM^{-1}$ for 2a and 2b, respectively. Addition of the Cu(II) ion to a solution containing 2b triggers relaxivity enhancement to raise $R_1$ as high as 15.3 $mM^{-1}$, which corresponds to a 300% enhancement. Such an increase levels off at the concentration beyond two equiv. of Cu(II), suggesting the formation of a trimetallic ($Gd/Cu_2$) complex in situ. Such a relaxivity increase is almost negligible with Zn(II) and other endogenous ions such as Na(I), K(I), Mg(II), and Ca(II). In vivo MR images and the signal-to-noise ratio (SNR) obtained with an aqueous mixture of 2b and Cu(II) ion in an 1:2 ratio demonstrate the potentiality of 2 as a copper responsive MRI CA.

• Investigative Magnetic Resonance Imaging
• /
• v.10 no.1
• /
• pp.20-25
• /
• 2006

Purpose : To evaluate the NMR relaxation properties of newly developed high performance paramagnetic complexes. Materials and methods : 4-aminomethylcyclohexane carboxylic acid (0.63g, 4 mmol) was mixed with the suspension solution of DMF (15mL) and DTPA-bis-anhydride (0.71g, 2 mmol) to synthesize the ligand. The ligand was then mixed with Gd2O3 (0.18g, 0.5 mmol) to synthesize Gd-chelate. For the measurement of magnetic relaxivity of paramagnetic compounds, the compounds were diluted to 1mM and then the relaxation times were measured at 1.5T(64 MHz). Inversion-recovery pulse sequence was employed for T1 relaxation measurement and CPMG(Carr-Purcell-Meiboon-Gill) pulse sequence was employed for T2 relaxation measurement. Using MATLAB(Version 7.1) program, T1 magnetic relaxation map, R1 map, T2 magnetic relaxation map and R2 map were developed to represent magnetic relaxation time and magnetic relaxivity as image. Results : Compared to $R1=4.9mM^{-1}sec^{-1}$ and $R2=4.8mM^{-1}sec^{-1}$ of Omniscan (Gadodiamide), which is commercially available paramagnetic MR agent, R1 of SUK090(Gd-C32H74N5O24) was $12.46mM^{-1}sec^{-1}$ and R1 of SUK091(Gd-C34H78N5O24) was $12.77mM^{-1}sec^{-1}$. However, R1 of SUK092(Gd-C30H56N5O17) was decreased to $2.09mM^{-1}sec^{-1}$. In case of R2, SUK090(Gd-C32H74N5O24) was $8.76mM^{-1}sec^{-1}$ and SUK091(Gd-C34H78N5O24) was $7.60mM^{-}1sec^{-1}$ whereas SUK092(Gd-C30H56N5O17) was decreased to $1.82mM^{-1}sec^{-1}$. Conclusion : Among three new paramagnetic complexes, SUK090(Gd-C32H74N5O24) and SUK091(Gd-C34H78N5O24) showed higher T1, T2 magnetic relaxation rates than that of commercially available paramagnetic MR agent and thus expected to have more contrast enhancement effect.