The Influence of the Combination of Carboxylate and Phosphinate Pendant Arms in 1,4,7-Triazacyclononane-Based Chelators on Their 68Ga Labelling Properties

Molecules

Gปor Máté²  Jakub Šimeპk³  Miroslav Pniok¹  István Kertész²  Johannes Notni³  Hans-Jürgen Wester³  László Galuska²  Petr Hermann¹ 

[1] Department of Inorganic Chemistry, Charles University in Prague, Hlavova 2030, 12840 Prague 2, Czech Republic; E-Mail:;Department of Nuclear Medicine, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, H-4032 Debrecen, Hungary; E-Mails:;Lehrstuhl für Pharmazeutische Radiochemie, Technische Universität München, Walther-Meissner-Strasse 3, D-85748 Garching, Germany; E-Mails:

关键词: positron emission tomography;    metal complexes;    macrocyclic ligands;    radiopharmaceuticals;    tacn derivative;    phosphinate complexes;    gallium complexes;    radiolabelling;    PET tracer development;    molecular imaging;   

DOI  :  10.3390/molecules200713112

来源: mdpi

【 摘 要 】

In order to compare the coordination properties of 1,4,7-triazacyclononane (tacn) derivatives bearing varying numbers of phosphinic/carboxylic acid pendant groups towards ⁶⁸Ga, 1,4,7-triazacyclononane-7-acetic-1,4-bis(methylenephosphinic) acid (NOPA) and 1,4,7-triazacyclononane-4,7-diacetic-1-[methylene(2-carboxyethyl)phosphinic] acid (NO2AP) were synthesized using Mannich reactions with trivalent or pentavalent forms of H-phosphinic acids as phosphorus components. Stepwise protonation constants logK_1–3 12.06, 3.90 and 1.95, and stability constants with Ga^III and Cu^II, logK_GaL 24.01 and logK_CuL 16.66, were potentiometrically determined for NOPA. Both ligands were labelled with ⁶⁸Ga and compared with NOTA (tacn-N,N′,N″-triacetic acid) and NOPO, a TRAP-type [tacn-N,N′,N″-tris(methylenephosphinic acid)] chelator. At pH 3, NOPO and NOPA showed higher labelling efficiency (binding with lower ligand excess) at both room temperature and 95 °C, compared to NO2AP and NOTA. Labelling efficiency at pH = 0–3 correlated with a number of phosphinic acid pendants: NOPO >> NOPA > NO2AP >> NOTA; however, it was more apparent at 95 °C than at room temperature. By contrast, NOTA was found to be labelled more efficiently at pH > 4 compared to the ligands with phosphinic acids. Overall, replacement of a single phosphinate donor with a carboxylate does not challenge ⁶⁸Ga labelling of TRAP-type chelators. However, the presence of carboxylates facilitates labelling at neutral or weakly acidic pH.

【 授权许可】

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