Single-Chain antibody conjugated to a cage amine chelator and labeled with positron-emitting copper-64 for diagnostic imaging of activated platelets

K Alt; BM Paterson; K Ardipradja; C Schieber; G Buncic; B Lim; SS Poniger; B Jakoby; X Wang; GJ Okeefe; HJ Tochon-Danguy; AM Scott; U Ackermann; K Peter; PS Donnelly; CE Hagemeyer

Journal article

Single-Chain antibody conjugated to a cage amine chelator and labeled with positron-emitting copper-64 for diagnostic imaging of activated platelets

K Alt, BM Paterson, K Ardipradja, C Schieber, G Buncic, B Lim, SS Poniger, B Jakoby, X Wang, GJ Okeefe, HJ Tochon-Danguy, AM Scott, U Ackermann, K Peter, PS Donnelly, CE Hagemeyer

Molecular Pharmaceutics | Published : 2014

DOI: 10.1021/mp500209a

Abstract

Imaging of activated platelets using an activation specific anti-GPIIb/IIIa integrin single-chain antibody (scFvanti-LIBS) conjugated to a positron emitting copper-64 complex of a cage amine sarcophagine chelator (MeCOSar) is reported. This tracer was compared in vitro to a 64CuII complex of the scFv conjugated to another commonly used macrocycle, DOTA. The scFvanti-LIBS-MeCOSar conjugate was radiolabeled with 64CuII rapidly under mild conditions and with higher specific activity than scFvanti-LIBS-DOTA. The utility of scFvanti-LIBS-MeCOSar as a diagnostic agent was assessed in vivo in a mouse model of acute thrombosis. The uptake of scFvanti-LIBS- 64CuMeCOSar in the injured vessel was signi..

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University of Melbourne Researchers

Xiaowei Wang Author

Andrew Scott Author

Uwe Ackermann Author

Karlheinz Peter Author

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Grants

Awarded by National Health and Medical Research Council (NHMRC)

Awarded by German Research Foundation

Awarded by National Heart Foundation

Awarded by Australian Research Council Future Fellowship

Awarded by NHMRC Career Development Fellowship

Awarded by Australian Research Council

Funding Acknowledgements

This work was funded by the National Health and Medical Research Council (NHMRC), Grants 1029249, 1017670, and 1011418 as well as the Australian Research Council (P.S.D.). K.Al. is supported by the German Research Foundation (Al 1521/1-1). K.Ar. is supported by the NHMRC and the National Heart Foundation (586740). K.P. is supported by an Australian Research Council Future Fellowship (FT0992210). C.E.H. is supported by a NHMRC Career Development Fellowship (472668). This research was undertaken using equipment provided by Monash Biomedical Imaging, Monash University as part of the Victorian Biomedical Imaging Capability (Victorian Government). The work was also supported in part by the Victorian Government's Operational Infrastructure Support Program, Victoria's Science Agenda Strategic Project Fund and the PET Solid Target Laboratory, an ANSTO-Austin-LICR Cyclotron Partnership.