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Octadentate Picolinic Acid-Based Bispidine Ligand for Radiometal Ions

TitleOctadentate Picolinic Acid-Based Bispidine Ligand for Radiometal Ions
Publication TypeJournal Article
Year of Publication2017
AuthorsComba, P, Jermilova, U, Orvig, C, Patrick, BO, Ramogida, CF, Rueck, K, Schneider, C, Starke, M
JournalChem. Eur. J.
Date PublishedNOV 13

The synthesis of the octadentate bispidine ligand bearing two picolinic acid pendant arms (H(2)bispa(2)), and its coordination chemistry with radionuclides relevant for nuclear medicine, namely indium(III) (In-111), lutetium(III) (Lu-177), and lanthanum(III) (as surrogate for Ac-225), are reported. The non-radioactive metal complexes of the N6O2-type bispa ligand were characterized by H-1 and (CNMR)-C-13 spectroscopy, elemental analysis, mass spectrometry and single-crystal X-ray analysis. Experimental structural data, computational analysis, complex stabilities determined by potentiometric titration, and ``radiostabilities{''} determined by competition studies in the presence of human serum reveal complex stabilities of H(2)bispa(2) comparable to those of the macrocyclic ``gold standard{''} DOTA. After an incubation time of 1day, 86 and 87% of {[}Lu-177(bispa(2))](+) and {[}Lu-177(DOTA)](-), respectively, remain intact. Importantly, unlike DOTA, H(2)bispa(2) is radiolabeled quantitatively with In-111(III) and Ac-225(III) under ambient conditions, which is an essential aspect when working with heat-sensitive antibodies as targeting vectors. In the case of In-111(III), room temperature radiolabeling of H(2)bispa(2) yields molar activities as high as 70 MBq nmol(-1) within 10 minutes. These are promising results for radiopharmaceutical applications of H(2)bispa(2).