Synthesis and study of a new complexone-N,N?,N?-tris-(dihydroxyphosphorylmethyl)-1,4,7-triazacyclononane

Кабачник, М. И.; Medved, T. Ya.; Polikarpov, Yu. M.; Shcherbakov, B. K.; Bel'skii, F. I.; Matrosov, E. I.; Пасечник, М. П.

doi:10.1007/bf00947831

Cited by 8 publications

(9 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The triazamacrocyclic ligands NOTA, NOTP, and NOTPME were synthesized and characterized by nuclear magnetic resonance (NMR) spectroscopy as described elsewhere (11,15,16). Solutions of the Ga 3ϩ chelates for NMR analysis were obtained by mixing stoichiometric amounts of Ga(NO 3 ) 3 and each of the ligands in D 2 O (at 20-mM concentrations) and adjusting the pH to 7 with diluted DCl and NaOD.…”

Section: Materials Reagents and General Methodsmentioning

confidence: 99%

Characterisation of 67Ga3+ complexes of triaza macrocyclic ligands: biodistribution and clearance studies

Prata

Santos

Geraldes

et al. 1999

Nuclear Medicine and Biology

View full text Add to dashboard Cite

ABSTRACT. The67 Ga 3؉ complexes of three triazamacrocycles, 1,4,7-triazacyclononane-N,N,N؆-triacetic acid (NOTA), its phosphonate analog 1,4,7-triazacyclononane-N,N,N؆-tris(methylenephosphonic) acid (NOTP), and the monoethyl ester of NOTP, 1,4,7-triazacyclononane-N,N,N؆-tris (methylenephosphonatemonoethylester) (NOTPME) were studied for possible use as radiopharmaceuticals. Biodistribution studies and gamma imaging were performed in Wistar rats. The present results demonstrated that all the macrocyclic complexes studied display renal clearance and are almost completely eliminated within 24 h. We have thus demonstrated a charge-clearance relationship for a series of stable and well characterized complexes. The high stability and rapid renal excretion properties displayed by the NOTA and NOTPME chelates support their possible application as imaging agents for kidney structural and functional studies. NUCL MED BIOL 26;6:707-710, 1999.

show abstract

Section: Materials Reagents and General Methodsmentioning

confidence: 99%

Characterisation of 67Ga3+ complexes of triaza macrocyclic ligands: biodistribution and clearance studies

Prata

Santos

Geraldes

et al. 1999

Nuclear Medicine and Biology

View full text Add to dashboard Cite

show abstract

“…The first synthesis of DOTP was reported in 1984 [13,14]. Since then, DOTP and its monoesters have been extensively studied for their potential applications as MRI contrast agents and clinical uses as NMR shift and relaxation reagents [1,15,16,17,18,19,20,21,22,23,24,25] because of the structural similarity to their DOTA [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra(acetic acid)] analogues.…”

Section: Introductionmentioning

confidence: 99%

“…A number of derivatives of tetraazacyclododecanes with pendant methanephosphonate functional groups have been synthesized and their thermodynamic stability, dissociation kinetics, metal selectivity, and coordination behavior with divalent and trivalent transition metal ions and lanthanide ions have been examined [31,32,33] [13,14]. By electronic absorption spectrophotometry and electron paramagnetic resonance (EPR) spectroscopy, the solution structure of the Cu(II)-DOTP complex was recently determined to be a square-pyramidal geometry with four ring-nitrogen atoms defining the equatorial plane, while the axial position is probably occupied by an oxygen from one methanephosphonate side-arm [34].…”

Section: Introductionmentioning

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

“…The stability constants in aqueous solution (at 298 K) of copper(II) complexes with polyaza ligands have been determined by several authors: NOTA, logK ML ϭ 21.63 (1  NaClO 4 ); [21] DOTA, logK ML ϭ 22.25 [0.1  (CH 3 ) 4 NNO 3 ], [22][23][24] 22.72 (0.1  KCl); [25] NOTP, logK ML ϭ 21.3 (1  KNO 3 ); [26] DOTP, logK ML ϭ25.4 (1  KNO 3 ). [27] The presence of protonated species in aqueous solution (MH n L, n is typically 1 or 2), along with the more stable nonprotonated form (ML), has been detected for some Cu II macrocyclic chelates.…”

Section: Introductionmentioning

confidence: 99%

Study of Copper(II) Polyazamacrocyclic Complexes by Electronic Absorption Spectrophotometry and EPR Spectroscopy

Geraldes

Marques

Castro

et al. 2000

Eur. J. Inorg. Chem.

View full text Add to dashboard Cite

Synthesis and study of a new complexone-N,N?,N?-tris-(dihydroxyphosphorylmethyl)-1,4,7-triazacyclononane

Cited by 8 publications

References 8 publications

Characterisation of 67Ga3+ complexes of triaza macrocyclic ligands: biodistribution and clearance studies

Characterisation of 67Ga3+ complexes of triaza macrocyclic ligands: biodistribution and clearance studies

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

Study of Copper(II) Polyazamacrocyclic Complexes by Electronic Absorption Spectrophotometry and EPR Spectroscopy

Contact Info

Product

Resources

About