A rigidified AAZTA-like ligand as efficient chelator for 68Ga radiopharmaceuticals

Adrienn Vágner, Calogero D'Alessandria, Giuseppe Gambino, Markus Schwaiger, Silvio Aime, Alessandro Maiocchi, Imre Tóth, Z. Baranyai, Lorenzo Tei

Research output: Contribution to journalArticle

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Abstract

The new cyclohexane-fused CyAAZTA ligand was synthesized to increase the structural rigidity of the heptadentate chelator AAZTA with the aim of improving the overall stability of its GaIII complex. The stability constant of Ga(CyAAZTA), determined both by pH-potentiometry (logKGaL=21.39) and by 71Ga NMR (logKGaL=21.92), was found similar to that of GaAAZTA (logKGaL=22.18). The kinetic inertness of Ga(CyAAZTA) was investigated by following its transmetallation and ligand exchange reactions with Cu2+ and human serum transferrin, respectively. The formation of a hydroxido-complex near pH 7 decreases the half-life (t1/2) of the dissociation reactions for Ga(CyAAZTA) compared to Ga(AAZTA) (8.5 h vs 21 h, pH 7.4). However, at pH < 7 the t1/2 of Ga(CyAAZTA) is much longer (234 h at pH 6). Finally, CyAAZTA was successfully radiolabelled with 68Ga in acetate buffer at pH 3.8, in 15 minutes at room temperature at [CyAAZTA]=10 μM, with a labelling yield higher than 80 %. A 1 μM solution of CyAAZTA was successfully labelled (L.Y.: 97.4 %) in 5 minutes at 90 °C. Stability tests in human serum and in the presence of 50 mM DTPA showed no significant decomposition of 68GaCyAAZTA over 90 minutes.

Original languageEnglish
Pages (from-to)163-171
Number of pages9
JournalChemistrySelect
Volume1
Issue number2
DOIs
Publication statusPublished - Jan 1 2016

Fingerprint

Radiopharmaceuticals
Chelating Agents
Ligands
Pentetic Acid
Transferrin
Rigidity
Labeling
Buffers
Acetates
Nuclear magnetic resonance
Decomposition
Kinetics
Temperature

Keywords

  • Chelating ligands
  • Gallium
  • Kinetics
  • Ligand Synthesis
  • Radiolabelling
  • Thermodynamics

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Vágner, A., D'Alessandria, C., Gambino, G., Schwaiger, M., Aime, S., Maiocchi, A., ... Tei, L. (2016). A rigidified AAZTA-like ligand as efficient chelator for 68Ga radiopharmaceuticals. ChemistrySelect, 1(2), 163-171. https://doi.org/10.1002/slct.201500051

A rigidified AAZTA-like ligand as efficient chelator for 68Ga radiopharmaceuticals. / Vágner, Adrienn; D'Alessandria, Calogero; Gambino, Giuseppe; Schwaiger, Markus; Aime, Silvio; Maiocchi, Alessandro; Tóth, Imre; Baranyai, Z.; Tei, Lorenzo.

In: ChemistrySelect, Vol. 1, No. 2, 01.01.2016, p. 163-171.

Research output: Contribution to journalArticle

Vágner, A, D'Alessandria, C, Gambino, G, Schwaiger, M, Aime, S, Maiocchi, A, Tóth, I, Baranyai, Z & Tei, L 2016, 'A rigidified AAZTA-like ligand as efficient chelator for 68Ga radiopharmaceuticals', ChemistrySelect, vol. 1, no. 2, pp. 163-171. https://doi.org/10.1002/slct.201500051
Vágner A, D'Alessandria C, Gambino G, Schwaiger M, Aime S, Maiocchi A et al. A rigidified AAZTA-like ligand as efficient chelator for 68Ga radiopharmaceuticals. ChemistrySelect. 2016 Jan 1;1(2):163-171. https://doi.org/10.1002/slct.201500051
Vágner, Adrienn ; D'Alessandria, Calogero ; Gambino, Giuseppe ; Schwaiger, Markus ; Aime, Silvio ; Maiocchi, Alessandro ; Tóth, Imre ; Baranyai, Z. ; Tei, Lorenzo. / A rigidified AAZTA-like ligand as efficient chelator for 68Ga radiopharmaceuticals. In: ChemistrySelect. 2016 ; Vol. 1, No. 2. pp. 163-171.
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abstract = "The new cyclohexane-fused CyAAZTA ligand was synthesized to increase the structural rigidity of the heptadentate chelator AAZTA with the aim of improving the overall stability of its GaIII complex. The stability constant of Ga(CyAAZTA)−, determined both by pH-potentiometry (logKGaL=21.39) and by 71Ga NMR (logKGaL=21.92), was found similar to that of GaAAZTA (logKGaL=22.18). The kinetic inertness of Ga(CyAAZTA)− was investigated by following its transmetallation and ligand exchange reactions with Cu2+ and human serum transferrin, respectively. The formation of a hydroxido-complex near pH 7 decreases the half-life (t1/2) of the dissociation reactions for Ga(CyAAZTA)− compared to Ga(AAZTA)− (8.5 h vs 21 h, pH 7.4). However, at pH < 7 the t1/2 of Ga(CyAAZTA)− is much longer (234 h at pH 6). Finally, CyAAZTA was successfully radiolabelled with 68Ga in acetate buffer at pH 3.8, in 15 minutes at room temperature at [CyAAZTA]=10 μM, with a labelling yield higher than 80 {\%}. A 1 μM solution of CyAAZTA was successfully labelled (L.Y.: 97.4 {\%}) in 5 minutes at 90 °C. Stability tests in human serum and in the presence of 50 mM DTPA showed no significant decomposition of 68GaCyAAZTA over 90 minutes.",
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AU - Schwaiger, Markus

AU - Aime, Silvio

AU - Maiocchi, Alessandro

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N2 - The new cyclohexane-fused CyAAZTA ligand was synthesized to increase the structural rigidity of the heptadentate chelator AAZTA with the aim of improving the overall stability of its GaIII complex. The stability constant of Ga(CyAAZTA)−, determined both by pH-potentiometry (logKGaL=21.39) and by 71Ga NMR (logKGaL=21.92), was found similar to that of GaAAZTA (logKGaL=22.18). The kinetic inertness of Ga(CyAAZTA)− was investigated by following its transmetallation and ligand exchange reactions with Cu2+ and human serum transferrin, respectively. The formation of a hydroxido-complex near pH 7 decreases the half-life (t1/2) of the dissociation reactions for Ga(CyAAZTA)− compared to Ga(AAZTA)− (8.5 h vs 21 h, pH 7.4). However, at pH < 7 the t1/2 of Ga(CyAAZTA)− is much longer (234 h at pH 6). Finally, CyAAZTA was successfully radiolabelled with 68Ga in acetate buffer at pH 3.8, in 15 minutes at room temperature at [CyAAZTA]=10 μM, with a labelling yield higher than 80 %. A 1 μM solution of CyAAZTA was successfully labelled (L.Y.: 97.4 %) in 5 minutes at 90 °C. Stability tests in human serum and in the presence of 50 mM DTPA showed no significant decomposition of 68GaCyAAZTA over 90 minutes.

AB - The new cyclohexane-fused CyAAZTA ligand was synthesized to increase the structural rigidity of the heptadentate chelator AAZTA with the aim of improving the overall stability of its GaIII complex. The stability constant of Ga(CyAAZTA)−, determined both by pH-potentiometry (logKGaL=21.39) and by 71Ga NMR (logKGaL=21.92), was found similar to that of GaAAZTA (logKGaL=22.18). The kinetic inertness of Ga(CyAAZTA)− was investigated by following its transmetallation and ligand exchange reactions with Cu2+ and human serum transferrin, respectively. The formation of a hydroxido-complex near pH 7 decreases the half-life (t1/2) of the dissociation reactions for Ga(CyAAZTA)− compared to Ga(AAZTA)− (8.5 h vs 21 h, pH 7.4). However, at pH < 7 the t1/2 of Ga(CyAAZTA)− is much longer (234 h at pH 6). Finally, CyAAZTA was successfully radiolabelled with 68Ga in acetate buffer at pH 3.8, in 15 minutes at room temperature at [CyAAZTA]=10 μM, with a labelling yield higher than 80 %. A 1 μM solution of CyAAZTA was successfully labelled (L.Y.: 97.4 %) in 5 minutes at 90 °C. Stability tests in human serum and in the presence of 50 mM DTPA showed no significant decomposition of 68GaCyAAZTA over 90 minutes.

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