title: Hydroxypyridinone Chelators: From Iron Scavenging to Radiopharmaceuticals for PET Imaging with Gallium-68.
abstract: Derivatives of 3,4-hydroxypyridinones have been extensively studied for in vivo Fe3+sequestration. Deferiprone, a 1,2-dimethyl-3,4-hydroxypyridinone, is now routinely used for clinical treatment of iron overload disease. Hexadentate tris(3,4-hydroxypyridinone) ligands (THP) complex Fe3+at very low iron concentrations, and their high affinities for oxophilic trivalent metal ions have led to their development for new applications as bifunctional chelators for the positron emitting radiometal,68Ga3+, which is clinically used for molecular imaging in positron emission tomography (PET). THP-peptide bioconjugates rapidly and quantitatively complex68Ga3+at ambient temperature, neutral pH and micromolar concentrations of ligand, making them amenable to kit-based radiosynthesis of68Ga PET radiopharmaceuticals.68Ga-labelled THP-peptides accumulate at target tissue in vivo, and are excreted largely via a renal pathway, providing high quality PET images.
authors.affiliation: Division of Imaging Sciences and Biomedical Engineering, King's College London, Fourth Floor Lambeth Wing, St. Thomas' Hospital, London SE1 7EH, UK. ruslan.cusnir@kcl.ac.uk.
authors.forename: Ruslan
authors.initials: R
authors.lastname: Cusnir
authors.affiliation: Division of Imaging Sciences and Biomedical Engineering, King's College London, Fourth Floor Lambeth Wing, St. Thomas' Hospital, London SE1 7EH, UK. cinzia.imberti@kcl.ac.uk.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Imberti
authors.affiliation: Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK. robert.hider@kcl.ac.uk.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Hider
authors.affiliation: Division of Imaging Sciences and Biomedical Engineering, King's College London, Fourth Floor Lambeth Wing, St. Thomas' Hospital, London SE1 7EH, UK. philip.blower@kcl.ac.uk.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Blower
authors.affiliation: Division of Imaging Sciences and Biomedical Engineering, King's College London, Fourth Floor Lambeth Wing, St. Thomas' Hospital, London SE1 7EH, UK. michelle.ma@kcl.ac.uk.
authors.forename: Michelle T
authors.initials: MT
authors.lastname: Ma
mesh_terms: D000818:Animals; D002614:Chelating Agents / Q000494:pharmacology*; D005710:Gallium Radioisotopes / Q000737:chemistry*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011728:Pyridones / Q000737:chemistry / Q000494:pharmacology*; D019275:Radiopharmaceuticals / Q000494:pharmacology*
chemical_list: D002614:Chelating Agents; D005710:Gallium Radioisotopes; D011728:Pyridones; D019275:Radiopharmaceuticals; D007501:Iron
keywords: bifunctional chelators; deferiprone; gallium; hydroxypyridinone; iron overload; molecular imaging; positron emission tomography