1. Getting a lead on Pb 2+ -amide chelators for 203/212 Pb radiopharmaceuticals.
- Author
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Ingham A, Kostelnik TI, McNeil BL, Patrick BO, Choudhary N, Jaraquemada-Peláez MG, and Orvig C
- Subjects
- Coordination Complexes chemical synthesis, Crystallography, X-Ray, Lead Radioisotopes chemistry, Ligands, Molecular Conformation, Radiopharmaceuticals chemical synthesis, Thermodynamics, Amides chemistry, Chelating Agents chemistry, Coordination Complexes chemistry, Lead chemistry, Radiopharmaceuticals chemistry
- Abstract
Amide-based chelators DTPAm, EGTAm and ampam were synthesized to investigate which chelator most ideally coordinates [
nat/203 Pb]Pb2+ ions for potential radiopharmaceutical applications.1 H NMR spectroscopy was used to study each metal-ligand complex in the solution state. The1 H NMR spectrum of [Pb(DTPAm)]2+ revealed minimal isomerization and fluxional behaviour compared to [Pb(EGTAm)]2+ and [Pb(ampam)]2+ , both of which showed fewer spectral changes indicative of less static behaviour. The solid-state coordination properties of each complex were also examined from single crystal structures that were studied by X-ray diffraction (XRD). In the solid-state, octadentate DTPAm coordinated Pb2+ to form an eight-coordinate hemidirected complex; octadentate EGTAm coordinated Pb2+ forming a ten-coordinate holodirected complex with a bidentate NO3 - ion also coordinated to the metal centre; decadentate ampam completely encapsulated the Pb2+ ion to form a ten-coordinate holodirected complex with a C2 axis of symmetry. Potentiometric titrations were carried out to assess the thermodynamic stability of each metal-ligand complex. The pM values obtained for [Pb(DTPAm)]2+ , [Pb(EGTAm)]2+ and [Pb(ampam)]2+ were 9.7, 7.2 and 10.2, respectively. The affinity of each chelator for Pb2+ ions was tested by [203 Pb]Pb2+ radiolabeling studies to evaluate their prospects as chelators for [203/212 -based radiopharmaceuticals. DTPAm radiolabeled [2+ -based radiopharmaceuticals. DTPAm radiolabeled [203 Pb]Pb2+ ions achieving molar activities as high as 3.5 MBq μmol-1 within 15 minutes, at 25 °C, whereas EGTAm and ampam produced lower molar activities of 0.25 MBq μmol-1 within 30 minutes, at 37 °C. EGTAm and ampam were therefore deemed unsuitable for [203/212 Pb]Pb2+ -based radiopharmaceutical applications, while DTPAm warrants further studies.- Published
- 2021
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