Journal article
New Tris(hydroxypyridinone) Bifunctional Chelators Containing Isothiocyanate Groups Provide a Versatile Platform for Rapid One-Step Labeling and PET Imaging with 68Ga3
MT Ma, C Cullinane, C Imberti, J Baguna Torres, SYA Terry, P Roselt, RJ Hicks, PJ Blower
Bioconjugate Chemistry | Published : 2016
Abstract
Two new bifunctional tris(hydroxypyridinone) (THP) chelators designed specifically for rapid labeling with 68Ga 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 68Ga3+ 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 68Ga3+-labeled THP peptide conjugat..
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Awarded by Medical Research Council
Funding Acknowledgements
M.T.M. acknowledges the support of the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA grant agreement number 299009, and the Royal Society of Chemistry through a Researcher Mobility Fellowship. S.Y.A.T. was supported by a grant from Leukaemia and Lymphoma Research. J.B.-T. was supported by a grant from the Alzheimer's Society. We thank Wayne Noonan, Kerry Ardley, and Rachael Walker for expert technical support. We thank David C. Muller (Genetic Epidemiology Group, International Agency for Research on Cancer) for his statistical advice and support. This research was supported by the Centre of Excellence in Medical Engineering funded by the Wellcome Trust and EPSRC (WT088641/Z/09/Z), the KCL and UCL Comprehensive Cancer Imaging Centre funded by CRUK and EPSRC in association with the MRC and DoH (England), and by the NIHR Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the DoH.