Synthesis of nonionic gadolinium chelates useful as contrast agents for magnetic resonance imaging: 1,4,7-tris(carboxymethyl)-10-substituted-1,4,7,10-tetraazacyclododecanes and their corresponding gadolinium chelates

Dischino, Douglas D.; Delaney, Edward J.; Emswiler, John; Gaughan, G. T.; Prasad, J. Siva; Srivastava, S. K.; Tweedle, Michael F.

doi:10.1021/ic00006a020

Cited by 152 publications

(72 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The Eu 3+ and Tb 3+ complexes of the N-benzyl substituted ligand DO3ABn have X-ray structures with a nine-coordinated ion bound to seven donor atoms of the ligand, an oxygen of one innersphere water and another oxygen from a bridging carboxylate of a neighboring complex, resulting in the formation of tetrameric aggregates. The coordination geometry of the Ln 3+ ion is a capped SA (θ = 40 • ), and both the (λλλλ) and (δδδδ) isomers are present in each tetrameric unit (racemate) [330,331]. The hydration numbers of Ln(DO3A) (Ln = Eu, Gd, Tb) (q = 1.8-1.9) and Gd(DO3MA) (q = 1.4), as obtained by luminescence lifetime and relaxivity measurements [326,332], correspond to a hydration equilibrium in solutions, as shown by UV-vis spectrometry [333].…”

Section: Do3a and Derivativesmentioning

confidence: 99%

Structure, Dynamics, and Computational Studies of Lanthanide‐Based Contrast Agents

Peters

Djanashvili

Geraldes

et al. 2013

The Chemistry of Contrast Agents in Medical Magnetic Resonance Imaging

View full text Add to dashboard Cite

Section: Do3a and Derivativesmentioning

confidence: 99%

Structure, Dynamics, and Computational Studies of Lanthanide‐Based Contrast Agents

Peters

Djanashvili

Geraldes

et al. 2013

The Chemistry of Contrast Agents in Medical Magnetic Resonance Imaging

View full text Add to dashboard Cite

“…DO3P was synthesized as follows (Scheme 1). A 500-mL roundbottom flask was loaded with N-formylcyclen (1-formyl-1,4,7,10-tetraazacyclododecane) (5.00 g) and triethyl phosphite (15.00 g, 20% excess) and the flask was immersed in an ice bath [41]. Paraformaldehyde (2.47 g, 10% excess) was added in small portions over a period of 30 min.…”

Section: Reagents and Instrumentationmentioning

confidence: 99%

“…DO3P was synthesized by reacting the monoprotected cyclen derivative 1-formylcyclen [41] with 3 equiv of paraformaldehyde and triethyl phosphite as described for DO2P [31]. Acid hydrolysis of the phosphonate bis(ethyl ester) in hydrochloric acid cleaved both the phosphonate ester groups and the N-formyl protection.…”

Section: Synthesismentioning

confidence: 99%

In vivo behavior of copper-64-labeled methanephosphonate tetraaza macrocyclic ligands

et al. 2003

View full text Add to dashboard Cite

Copper-64 ( T(1/2)=12.7 h; beta(+): 0.653 MeV, 17.4%; beta(-): 0.578 MeV, 39%) is produced in a biomedical cyclotron and has applications in both imaging and therapy. Macrocyclic chelators are widely used as bifunctional chelators to bind copper radionuclides to antibodies and peptides owing to their relatively high kinetic stability. In this paper, we evaluated three tetraaza macrocyclic ligands with two, three, and four pendant methanephosphonate functional groups. DO2P [1,4,7,10-tetraazacyclododecane-1,7-di(methanephosphonic acid)], DO3P [1,4,7,10-tetraazacyclododecane-1,4,7-tri(methanephosphonic acid)], and DOTP [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra(methanephosphonic acid)] were all radiolabeled with (64)Cu in high radiochemical yields. Copper-64-labeled DO2P and DOTP were highly stable in rat serum out to 24 h, while (64)Cu-DO3P remained 73% intact, with the remainder possibly forming a (64)Cu(.)2DO3P dimer by 24 h. The biodistribution experiments were performed in normal Sprague-Dawley rats. Of the three complexes, (64)Cu-DO2P demonstrated the most optimal clearance through the blood and liver. Copper-64-DO3P and (64)Cu-DOTP exhibited higher liver uptake and longer retention of liver activity, possibly because of the large negative charge of the complexes under physiological conditions. All three (64)Cu-labeled complexes showed high accumulation in bone, likely due to the binding of the methanephosphonate groups to hydroxyapatite. These results suggest that this series of methanephosphonate macrocyclic ligands may be useful as potential bone-imaging agents. The thermodynamic stability constants of the Cu(II) complexes with these three ligands were determined, and were found to be significantly higher than those of their acetate analogues. The Cu(II)-DO2P complex exhibited the highest stability constant among divalent transition metal ion DO2P complexes. Metabolism studies of (64)Cu-DO2P in rat liver suggest that the DO2P ligand may be used as a bifunctional chelator for copper radionuclides in radiodiagnostic or radiotherapeutic studies.

show abstract

“…There are many procedures differing in reaction condition and solvents used. Reaction with chloroacetic acid was carried out in alkaline aqueous solution (KOH, pH around 9) at 60 • C [199]. Better yield (70%) was achieved at a pH around 10 and room temperature [200].…”

Section: Derivatives With Acetate Pendant Armsmentioning

confidence: 99%

Synthesis and Characterization of Ligands and their Gadolinium(III) Complexes

Kotek¹,

Kubíček²,

Hermann³

et al. 2013

The Chemistry of Contrast Agents in Medical Magnetic Resonance Imaging

View full text Add to dashboard Cite

Synthesis of nonionic gadolinium chelates useful as contrast agents for magnetic resonance imaging: 1,4,7-tris(carboxymethyl)-10-substituted-1,4,7,10-tetraazacyclododecanes and their corresponding gadolinium chelates

Cited by 152 publications

References 1 publication

Structure, Dynamics, and Computational Studies of Lanthanide‐Based Contrast Agents

Structure, Dynamics, and Computational Studies of Lanthanide‐Based Contrast Agents

In vivo behavior of copper-64-labeled methanephosphonate tetraaza macrocyclic ligands

Synthesis and Characterization of Ligands and their Gadolinium(III) Complexes

Contact Info

Product

Resources

About