Two structurally constrained chelators based on a fused bicyclic scaffold, 4-amino-4-methylperhydro-pyrido[1,2-a][1,4]diazepin-N,N',N'-triacetic acids [(4R*,10aS*)-PIDAZTA (L1) and (4R*,10aR*)-PIDAZTA (L2)], were designed for the preparation of GaIII -based radiopharmaceuticals. The stereochemistry of the ligand scaffold has a deep impact on the properties of the complexes, with unexpected [Ga(L2)OH] species being superior in terms of both thermodynamic stability and inertness. This peculiar behavior was rationalized on the basis of molecular modeling and appears to be related to a better fit in size of GaIII into the cavity of L2. Fast and efficient formation of the GaIII chelates at room temperature was observed at pH values between 7 and 8, which enables 68 Ga radiolabeling under truly physiological conditions (pH 7.4).

PIDAZTA: Structurally Constrained Chelators for the Efficient Formation of Stable Gallium-68 Complexes at Physiological pH / E. Farkas, A. Vágner, R. Negri, L. Lattuada, I. Tóth, V. Colombo, D. Esteban-Gómez, C. Platas-Iglesias, J. Notni, Z. Baranyai, G.B. Giovenzana. - In: CHEMISTRY-A EUROPEAN JOURNAL. - ISSN 0947-6539. - 25:45(2019 May 31), pp. 10698-10709.

PIDAZTA: Structurally Constrained Chelators for the Efficient Formation of Stable Gallium-68 Complexes at Physiological pH

V. Colombo;
2019

Abstract

Two structurally constrained chelators based on a fused bicyclic scaffold, 4-amino-4-methylperhydro-pyrido[1,2-a][1,4]diazepin-N,N',N'-triacetic acids [(4R*,10aS*)-PIDAZTA (L1) and (4R*,10aR*)-PIDAZTA (L2)], were designed for the preparation of GaIII -based radiopharmaceuticals. The stereochemistry of the ligand scaffold has a deep impact on the properties of the complexes, with unexpected [Ga(L2)OH] species being superior in terms of both thermodynamic stability and inertness. This peculiar behavior was rationalized on the basis of molecular modeling and appears to be related to a better fit in size of GaIII into the cavity of L2. Fast and efficient formation of the GaIII chelates at room temperature was observed at pH values between 7 and 8, which enables 68 Ga radiolabeling under truly physiological conditions (pH 7.4).
chelates; gallium; kinetics; radiochemistry; thermodynamics
Settore CHIM/03 - Chimica Generale e Inorganica
31-mag-2019
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/658451
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