Single-Chain Antibody Conjugated to a Cage Amine Chelator and Labeled with Positron-Emitting Copper-64 for Diagnostic Imaging of Activated Platelets

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 scF...

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Bibliographic Details
Published in:Molecular pharmaceutics 2014-08, Vol.11 (8), p.2855-2863
Main Authors: Alt, Karen, Paterson, Brett M, Ardipradja, Katie, Schieber, Christine, Buncic, Gojko, Lim, Bock, Poniger, Stan S, Jakoby, Bjoern, Wang, Xiaowei, O’Keefe, Graeme J, Tochon-Danguy, Henri J, Scott, Andrew M, Ackermann, Uwe, Peter, Karlheinz, Donnelly, Paul S, Hagemeyer, Christoph E
Format: Article
Language:English
Subjects:
Animals
Blood Platelets - drug effects
Blood Platelets - metabolism
Carotid Arteries - physiopathology
Chelating Agents - chemistry
Copper - chemistry
Copper Radioisotopes - chemistry
Diagnostic Imaging
Disease Models, Animal
Flow Cytometry
Heterocyclic Compounds, 1-Ring - chemistry
Inflammation
Ligands
Magnetic Resonance Spectroscopy
Mice
Mice, Inbred BALB C
Platelet Activation
Positron-Emission Tomography
Radiopharmaceuticals
Single-Chain Antibodies - chemistry
Thrombosis - diagnosis
X-Ray Microtomography
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Summary: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.
ISSN:1543-8384
1543-8392
DOI:10.1021/mp500209a