Journal article
Enhancing PET Signal at Target Tissue in Vivo: Dendritic and Multimeric Tris(hydroxypyridinone) Conjugates for Molecular Imaging of αvβ3 Integrin Expression with Gallium-68
C Imberti, SYA Terry, C Cullinane, F Clarke, GH Cornish, NK Ramakrishnan, P Roselt, AP Cope, RJ Hicks, PJ Blower, MT Ma
Bioconjugate Chemistry | AMER CHEMICAL SOC | Published : 2017
Abstract
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 coordinate up to three Ga3+ ions. This derivative has been conjugated to a trimeric peptide (RGD3) containing three peptide groups that target the αvβ3 integrin receptor. The resulting dendritic compound, HP9-RGD3, can be radiolabeled in 97% radiochemical yield at a 3-fold higher specific activity than its ho..
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Awarded by Guy's and St Thomas' NHS Foundation Trust
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. C.I. acknowledges the NIHR Biomedical Research Centre for a PhD studentship. G.H.C., F.C and A.P.C. acknowledge the support of Arthritis Research UK under grant number 20525. We thank Wayne Noonan, Kerry Ardley, and Rachael Walker for expert technical support. We thank Cristina Sanchez-Blanco for collecting the arthritogenic serum from KRN+ x NOD offspring. This research was supported by the Centre of Excellence in Medical Engineering Centre 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.