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New tris(hydroxypyridinone) bifunctional chelators containing isothiocyanate groups provide a versatile platform for rapid one-step labeling and PET imaging with 68Ga3+

Research output: Contribution to journalArticlepeer-review

Michelle T Ma, Carleen Cullinane, Cinzia Imberti, Julia Baguña Torres, Samantha Y A Terry, Peter Roselt, Rodney J Hicks, Philip J Blower

Original languageEnglish
Pages (from-to)309–318
JournalBioconjugate Chemistry
Early online date2 Sep 2015
Accepted/In press18 Aug 2015
E-pub ahead of print2 Sep 2015
Published17 Feb 2016


  • New Tris(hydroxypyridinone) Bifunctional_MA_Accepted 18Aug2015_GOLD VoR

    New_Tris_hydroxypyridinone_Bifunctional_MA_Online_18Aug2015_GOLD_VoR.pdf, 1.27 MB, application/pdf

    Uploaded date:10 Aug 2016

    Version:Final published version

    Licence:CC BY

    This is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.

King's Authors


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 treatment with generator-produced (68)Ga(3+) 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 (68)Ga(3+)-labeled THP peptide conjugates retain affinity for the αvβ3 integrin receptor, clear within 1-2 h from circulation, and undergo receptor-mediated tumor uptake in vivo. We conclude that bifunctional THP chelators can be used for simple, efficient labeling of (68)Ga biomolecules under mild conditions suitable for peptides and proteins.

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