Evaluation of chelating agents based on pyridine-azacrown compounds H₄PATA, PATAM, and H₄PATPA for ⁶⁸Ga and ¹⁷⁷Lu

In this article, we present the synthesis and characterization of three macrocyclic chelators, H₄PATA, PATAM, and H₄PATPA, based on a pyridine-azacrown compound. Their complexation with ⁶⁸Ga and ¹⁷⁷Lu has been thoroughly investigated using MALDI TOF MS, ¹H NMR spectroscopy, radiolabeling studies, and experiments in vitro with fetal bovine serum and a 1000-fold molar excess of H₄EDTA. Our studies have shown that the chelators H₄PATA and H₄PATPA form complexes at room temperature with both radionuclides (RCY > 80 % and > 90 % for complexes with H₄PATA and H₄PATPA after 30 min, respectively). The chelator PATAM requires high temperature (95 °C) for complexation. In vitro stability assays in fetal bovine serum as well as H₄EDTA-challenge revealed that transchelation occurs for all complexes with ⁶⁸Ga. However, complexes of the ligands H₄PATA and PATAM with ¹⁷⁷Lu were found stable. Thus, taking into account the radiolabeling at room temperature and in vitro stability of the complex [¹⁷⁷Lu]Lu·PATA, our investigations revealed the chelator H₄PATA is a candidate for radiopharmaceutical use with ¹⁷⁷Lu.