@article {D1DT01653A,
	title = {Getting a lead on Pb2+-amide chelators for 203/212Pb radiopharmaceuticals},
	journal = {Dalton Trans.},
	volume = {50},
	year = {2021},
	month = {08/2021},
	pages = {11579-11595},
	publisher = {The Royal Society of Chemistry},
	abstract = {<p>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\&ndash;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\&minus; 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\&ndash;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\&minus;1 within 15 minutes{,} at 25 \&deg;C{,} whereas EGTAm and ampam produced lower molar activities of 0.25 MBq μmol\&minus;1 within 30 minutes{,} at 37 \&deg;C. EGTAm and ampam were therefore deemed unsuitable for [203/212Pb]Pb2+-based radiopharmaceutical applications{,} while DTPAm warrants further studies.</p>},
	doi = {10.1039/D1DT01653A},
	url = {http://dx.doi.org/10.1039/D1DT01653A},
	author = {Ingham, Aidan and Kostelnik, Thomas I. and McNeil, Brooke L. and Patrick, Brian O. and Choudhary, Neha and Jaraquemada-Pelaez, Maria de Guadalupe and Orvig, Chris}
}
