Hydroxypyridinone Chelators: From Iron Scavenging to Radiopharmaceuticals for PET Imaging with Gallium-68

Ruslan Cusnir; Cinzia Imberti; Robert C Hider; Philip J Blower; Michelle T Ma

doi:10.3390/ijms18010116

Hydroxypyridinone Chelators: From Iron Scavenging to Radiopharmaceuticals for PET Imaging with Gallium-68

Ruslan Cusnir, Cinzia Imberti, Robert C Hider, Philip J Blower, Michelle T Ma

Research output: Contribution to journal › Article › peer-review

49 Citations (Scopus)

348 Downloads (Pure)

Abstract

Derivatives of 3,4-hydroxypyridinones have been extensively studied for in vivo Fe(3+) 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 Fe(3+) 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, (68)Ga(3+), which is clinically used for molecular imaging in positron emission tomography (PET). THP-peptide bioconjugates rapidly and quantitatively complex (68)Ga(3+) at ambient temperature, neutral pH and micromolar concentrations of ligand, making them amenable to kit-based radiosynthesis of (68)Ga PET radiopharmaceuticals. (68)Ga-labelled THP-peptides accumulate at target tissue in vivo, and are excreted largely via a renal pathway, providing high quality PET images.

Original language	English
Article number	116
Journal	International Journal of Molecular Sciences
Volume	18
Issue number	1
DOIs	https://doi.org/10.3390/ijms18010116
Publication status	Published - 8 Jan 2017

Access to Document

10.3390/ijms18010116Licence: CC BY

Hydroxypyridinone Chelators_CUSNIR_Published8January2017_GOLD VoR (CC-BY)Final published version, 4.91 MBLicence: CC BY

Cite this

@article{6324e9e569bf4f6b9d897796bd38d4e0,

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 Fe(3+) 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 Fe(3+) 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, (68)Ga(3+), which is clinically used for molecular imaging in positron emission tomography (PET). THP-peptide bioconjugates rapidly and quantitatively complex (68)Ga(3+) at ambient temperature, neutral pH and micromolar concentrations of ligand, making them amenable to kit-based radiosynthesis of (68)Ga PET radiopharmaceuticals. (68)Ga-labelled THP-peptides accumulate at target tissue in vivo, and are excreted largely via a renal pathway, providing high quality PET images.",

author = "Ruslan Cusnir and Cinzia Imberti and Hider, {Robert C} and Blower, {Philip J} and Ma, {Michelle T}",

year = "2017",

month = jan,

day = "8",

doi = "10.3390/ijms18010116",

language = "English",

volume = "18",

journal = "International Journal of Molecular Sciences",

issn = "1661-6596",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "1",

}

TY - JOUR

T1 - Hydroxypyridinone Chelators: From Iron Scavenging to Radiopharmaceuticals for PET Imaging with Gallium-68

AU - Cusnir, Ruslan

AU - Imberti, Cinzia

AU - Hider, Robert C

AU - Blower, Philip J

AU - Ma, Michelle T

PY - 2017/1/8

Y1 - 2017/1/8

N2 - Derivatives of 3,4-hydroxypyridinones have been extensively studied for in vivo Fe(3+) 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 Fe(3+) 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, (68)Ga(3+), which is clinically used for molecular imaging in positron emission tomography (PET). THP-peptide bioconjugates rapidly and quantitatively complex (68)Ga(3+) at ambient temperature, neutral pH and micromolar concentrations of ligand, making them amenable to kit-based radiosynthesis of (68)Ga PET radiopharmaceuticals. (68)Ga-labelled THP-peptides accumulate at target tissue in vivo, and are excreted largely via a renal pathway, providing high quality PET images.

AB - Derivatives of 3,4-hydroxypyridinones have been extensively studied for in vivo Fe(3+) 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 Fe(3+) 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, (68)Ga(3+), which is clinically used for molecular imaging in positron emission tomography (PET). THP-peptide bioconjugates rapidly and quantitatively complex (68)Ga(3+) at ambient temperature, neutral pH and micromolar concentrations of ligand, making them amenable to kit-based radiosynthesis of (68)Ga PET radiopharmaceuticals. (68)Ga-labelled THP-peptides accumulate at target tissue in vivo, and are excreted largely via a renal pathway, providing high quality PET images.

U2 - 10.3390/ijms18010116

DO - 10.3390/ijms18010116

M3 - Article

C2 - 28075350

SN - 1661-6596

VL - 18

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

IS - 1

M1 - 116

ER -

Hydroxypyridinone Chelators: From Iron Scavenging to Radiopharmaceuticals for PET Imaging with Gallium-68

Abstract

Access to Document

Fingerprint

Cite this