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

Edit Farkas, Adrienn Vágner, Roberto Negri, Luciano Lattuada, Imre Tóth, Valentina Colombo, David Esteban-Gómez, Carlos Platas-Iglesias, Johannes Notni, Zsolt Baranyai, Giovanni B. Giovenzana

Research output: Contribution to journalArticle

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 68Ga radiolabeling under truly physiological conditions (pH 7.4).

Original languageEnglish
Pages (from-to)10698-10709
Number of pages12
JournalChemistry - A European Journal
Volume25
Issue number45
DOIs
Publication statusPublished - Jan 1 2019

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Keywords

  • chelates
  • gallium
  • kinetics
  • radiochemistry
  • thermodynamics

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

Cite this

Farkas, E., Vágner, A., Negri, R., Lattuada, L., Tóth, I., Colombo, V., Esteban-Gómez, D., Platas-Iglesias, C., Notni, J., Baranyai, Z., & Giovenzana, G. B. (2019). PIDAZTA: Structurally Constrained Chelators for the Efficient Formation of Stable Gallium-68 Complexes at Physiological pH. Chemistry - A European Journal, 25(45), 10698-10709. https://doi.org/10.1002/chem.201901512