Issue 33, 2021

Getting a lead on Pb2+-amide chelators for 203/212Pb radiopharmaceuticals

Abstract

Amide-based chelators DTPAm, EGTAm and ampam were synthesized to investigate which chelator most ideally coordinates [nat/203Pb]Pb2+ ions for potential radiopharmaceutical applications. 1H NMR spectroscopy was used to study each metal–ligand complex in the solution state. The 1H 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 [203Pb]Pb2+ radiolabeling studies to evaluate their prospects as chelators for [203/212Pb]Pb2+-based radiopharmaceuticals. DTPAm radiolabeled [203Pb]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 [203/212Pb]Pb2+-based radiopharmaceutical applications, while DTPAm warrants further studies.

Graphical abstract: Getting a lead on Pb2+-amide chelators for 203/212Pb radiopharmaceuticals

Supplementary files

Article information

Article type
Paper
Submitted
20 Mot 2021
Accepted
20 Upu 2021
First published
22 Upu 2021

Dalton Trans., 2021,50, 11579-11595

Getting a lead on Pb2+-amide chelators for 203/212Pb radiopharmaceuticals

A. Ingham, T. I. Kostelnik, B. L. McNeil, B. O. Patrick, N. Choudhary, M. D. G. Jaraquemada-Peláez and C. Orvig, Dalton Trans., 2021, 50, 11579 DOI: 10.1039/D1DT01653A

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