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A Triazacyclononane‐Based Bifunctional Phosphinate Ligand for the Preparation of Multimeric 68 Ga Tracers for Positron Emission Tomography
Author(s) -
Notni Johannes,
Hermann Petr,
Havlíčková Jana,
Kotek Jan,
Kubíček Vojtěch,
Plutnar Jan,
Loktionova Natalia,
Riss Patrick Johannes,
Rösch Frank,
Lukeš Ivan
Publication year - 2010
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200903281
Subject(s) - chemistry , protonation , ligand (biochemistry) , bifunctional , chelation , dota , chemical stability , crystallography , tris , nuclear chemistry , inorganic chemistry , organic chemistry , ion , biochemistry , receptor , catalysis
For application in positron emission tomography (PET), PrP9 , a N , N ′, N′′ ‐trisubstituted triazacyclononane with methyl(2‐carboxyethyl)phosphinic acid pendant arms, was developed as 68 Ga 3+ complexing agent. The synthesis is short and inexpensive. Ga III and Fe III complexes of PrP9 were characterized by single‐crystal X‐ray diffraction. Stepwise protonation constants and thermodynamic stabilities of metal complexes were determined by potentiometry. The Ga III complex possesses a high thermodynamic stability (log K [GaL] =26.24) and a high degree of kinetic inertness. 68 Ga labeling of PrP9 is possible at ambient temperature and in a wide pH range, also at pH values as low as 1. This means that for the first time, the neat eluate of a TiO 2 ‐based 68 Ge/ 68 Ga generator (typically consisting of 0.1 M HCl) can be directly used for labeling purposes. The rate of 68 Ga activity incorporation at pH 3.3 and 20 °C is higher than for the established chelators DOTA and NOTA. Tris‐amides of PrP9 with amino acid esters were synthesized to act as models for multimeric peptide conjugates. These conjugates exhibit radiolabeling properties similar to those of unsubstituted PrP9 .