New Tris(hydroxypyridinone) Bifunctional Chelators Containing Isothiocyanate Groups Provide a Versatile Platform for Rapid One- Step Labeling and PET Imaging with Ga
نویسندگان
چکیده
Two new bifunctional tris(hydroxypyridinone) (THP) chelators designed specifically for rapid labeling with Ga have been synthesized, each with pendant isothiocyanate groups and three 1,6-dimethyl-3-hydroxypyridin-4-one groups. Both compounds have been conjugated with the primary amine group of a cyclic integrin targeting peptide, RGD. Each conjugate can be radiolabeled and formulated by treatment with generator-produced Ga in over 95% radiochemical yield under ambient conditions in less than 5 min, with specific activities of 60−80 MBq nmol−1. Competitive binding assays and in vivo biodistribution in mice bearing U87MG tumors demonstrate that the new Ga-labeled THP peptide conjugates retain affinity for the αvβ3 integrin receptor, clear within 1−2 h from circulation, and undergo receptormediated tumor uptake in vivo. We conclude that bifunctional THP chelators can be used for simple, efficient labeling of Ga biomolecules under mild conditions suitable for peptides and proteins.
منابع مشابه
New Tris(hydroxypyridinone) Bifunctional Chelators Containing Isothiocyanate Groups Provide a Versatile Platform for Rapid One-Step Labeling and PET Imaging with 68Ga3+
Two new bifunctional tris(hydroxypyridinone) (THP) chelators designed specifically for rapid labeling with (68)Ga have been synthesized, each with pendant isothiocyanate groups and three 1,6-dimethyl-3-hydroxypyridin-4-one groups. Both compounds have been conjugated with the primary amine group of a cyclic integrin targeting peptide, RGD. Each conjugate can be radiolabeled and formulated by tre...
متن کاملEnhancing PET Signal at Target Tissue in Vivo: Dendritic and Multimeric Tris(hydroxypyridinone) Conjugates for Molecular Imaging of αvβ3 Integrin Expression with Gallium-68
Tris(hydroxypyridinone) chelators conjugated to peptides can rapidly complex the positron-emitting isotope gallium-68 (68Ga) under mild conditions, and the resulting radiotracers can delineate peptide receptor expression at sites of diseased tissue in vivo. We have synthesized a dendritic bifunctional chelator containing nine 1,6-dimethyl-3-hydroxypyridin-4-one groups (SCN-HP9) that can coordin...
متن کاملRapid kit-based 68Ga-labelling and PET imaging with THP-Tyr3-octreotate: a preliminary comparison with DOTA-Tyr3-octreotate
BACKGROUND Ge/(68)Ga generators provide an inexpensive source of a PET isotope to hospitals without cyclotron facilities. The development of new (68)Ga-based molecular imaging agents and subsequent clinical translation would be greatly facilitated by simplification of radiochemical syntheses. We report the properties of a tris(hydroxypyridinone) conjugate of the SSTR2-targeted peptide, Tyr(3)-o...
متن کاملHydroxypyridinone Chelators: From Iron Scavenging to Radiopharmaceuticals for PET Imaging with Gallium-68
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 th...
متن کاملComparison of macrocyclic and acyclic chelators for gallium-68 radiolabelling.
Gallium-68 (68Ga) is a positron-emitting isotope used for clinical PET imaging of peptide receptor expression. 68Ga radiopharmaceuticals used in molecular PET imaging consist of disease-targeting biomolecules tethered to chelators that complex 68Ga3+. Ideally, the chelator will rapidly, quantitatively and stably coordinate 68Ga3+ at room temperature, near neutral pH and low chelator concentrati...
متن کامل