Two structurally constrained chelators based on a fused bicyclic scaffold, [(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 68Ga radiolabeling under truly physiological conditions (pH 7.4).
PIDAZTA: Structurally Constrained Chelators for Efficient Formation of Stable Gallium‐68 Complexes at Physiological pH
Giovenzana, Giovanni Battista
;Negri, Roberto;Tóth, Imre;
2019-01-01
Abstract
Two structurally constrained chelators based on a fused bicyclic scaffold, [(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 68Ga radiolabeling under truly physiological conditions (pH 7.4).I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
