How do HYNIC-conjugated peptides bind technetium? Insights from LC-MS and stability studies

Hydrazinonicotinamide (HYNIC) is an established bifunctional complexing agent for technetium-99m ((99m)Tc) but the structure of the technetium coordination sphere remains uncertain. To gain further insight into this, we have prepared conjugates of HYNIC and hydrazinobenzoic acid (HYBA) with a model...

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Veröffentlicht in:Dalton transactions : an international journal of inorganic chemistry 2007-01 (43), p.4998-5007
Hauptverfasser: King, Robert C, Surfraz, M Bashir-Uddin, Biagini, Stefano C G, Blower, Philip J, Mather, Stephen J
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Sprache:eng
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Zusammenfassung:Hydrazinonicotinamide (HYNIC) is an established bifunctional complexing agent for technetium-99m ((99m)Tc) but the structure of the technetium coordination sphere remains uncertain. To gain further insight into this, we have prepared conjugates of HYNIC and hydrazinobenzoic acid (HYBA) with a model peptide, and radiolabelled them with (99m)Tc using three well-established co-ligand systems: EDDA, tricine and tricine-nicotinic acid. The labelled peptides were studied by LC-MS and by subjecting them to serum stability and protein binding assays. For each co-ligand system, HYNIC conjugates formed fewer and more stable labelled species than the corresponding HYBA conjugates. LC-MS analysis showed that all conjugates contained one hydrazine moiety bound to Tc, that binding of Tc to HYNIC-peptide and co-ligand occurs with displacement of 5H(+) indicating a Tc formal oxidation state of +5, and that the Tc has no oxo- or halide ligands. LC-MS also shows that complexes formed with the HYNIC conjugate contain fewer coordinating co-ligand molecules than the HYBA conjugate indicating that HYNIC is able to more effectively satisfy the coordination requirement of technetium, perhaps by binding in chelating mode.
ISSN:1477-9226
1477-9234
DOI:10.1039/b705111e