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

Karen Maria Alt, Brett M Paterson, Katie Ardipradja, Christine Schieber, Gojko Buncic, Bock Lim, Stan Poniger, Bjoern Jakoby, Xiaowei Wang, Graeme J O'Keefe, Henri Tochon-Danguy, Andrew Mark Scott, Uwe Ackermann, Karlheinz Peter, Paul Stephen Donnelly, Christoph Eugen Hagemeyer

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28 Citations (Scopus)

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 significantly higher than the noninjured vessel. Positron emission tomography (PET) was used to show accumulation of scFvanti-LIBS-64CuMeCOSar with high and specific uptake in the injured vessel. ScFvanti-LIBS- 64CuMeCOSar is an excellent tool for highly sensitive in vivo detection of activated platelets in PET and has the potential to be used for early diagnosis of acute thrombotic events.
Original languageEnglish
Pages (from-to)2855-2863
Number of pages9
JournalMolecular Pharmaceutics
Volume11
Issue number8
DOIs
Publication statusPublished - 2014
Externally publishedYes

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