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

doi:10.1021/mp500209a

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

Research output: Contribution to journal › Article › Research › peer-review

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 language	English
Pages (from-to)	2855-2863
Number of pages	9
Journal	Molecular Pharmaceutics
Volume	11
Issue number	8
DOIs	https://doi.org/10.1021/mp500209a
Publication status	Published - 2014
Externally published	Yes

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Alt, K. M., Paterson, B. M., Ardipradja, K., Schieber, C., Buncic, G., Lim, B., Poniger, S., Jakoby, B., Wang, X., O'Keefe, G. J., Tochon-Danguy, H., Scott, A. M., Ackermann, U., Peter, K., Donnelly, P. S., & Hagemeyer, C. E. (2014). Single-Chain antibody conjugated to a cage amine chelator and labeled with positron-emitting copper-64 for diagnostic imaging of activated platelets. Molecular Pharmaceutics, 11(8), 2855-2863. https://doi.org/10.1021/mp500209a

Alt, Karen Maria ; Paterson, Brett M ; Ardipradja, Katie ; Schieber, Christine ; Buncic, Gojko ; Lim, Bock ; Poniger, Stan ; Jakoby, Bjoern ; Wang, Xiaowei ; O'Keefe, Graeme J ; Tochon-Danguy, Henri ; Scott, Andrew Mark ; Ackermann, Uwe ; Peter, Karlheinz ; Donnelly, Paul Stephen ; Hagemeyer, Christoph Eugen. / Single-Chain antibody conjugated to a cage amine chelator and labeled with positron-emitting copper-64 for diagnostic imaging of activated platelets. In: Molecular Pharmaceutics. 2014 ; Vol. 11, No. 8. pp. 2855-2863.

@article{03fead9eee7b44259db4567b47fdf8b5,

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

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.",

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

year = "2014",

doi = "10.1021/mp500209a",

language = "English",

volume = "11",

pages = "2855--2863",

journal = "Molecular Pharmaceutics",

issn = "1543-8384",

publisher = "American Chemical Society",

number = "8",

}

Alt, KM , Paterson, BM, Ardipradja, K, Schieber, C, Buncic, G, Lim, B, Poniger, S, Jakoby, B, Wang, X, O'Keefe, GJ, Tochon-Danguy, H, Scott, AM, Ackermann, U, Peter, K, Donnelly, PS & Hagemeyer, CE 2014, 'Single-Chain antibody conjugated to a cage amine chelator and labeled with positron-emitting copper-64 for diagnostic imaging of activated platelets', Molecular Pharmaceutics, vol. 11, no. 8, pp. 2855-2863. https://doi.org/10.1021/mp500209a

Single-Chain antibody conjugated to a cage amine chelator and labeled with positron-emitting copper-64 for diagnostic imaging of activated platelets. / Alt, Karen Maria ; Paterson, Brett M; Ardipradja, Katie; Schieber, Christine; Buncic, Gojko; Lim, Bock; Poniger, Stan; Jakoby, Bjoern; Wang, Xiaowei; O'Keefe, Graeme J; Tochon-Danguy, Henri; Scott, Andrew Mark; Ackermann, Uwe; Peter, Karlheinz; Donnelly, Paul Stephen; Hagemeyer, Christoph Eugen.

In: Molecular Pharmaceutics, Vol. 11, No. 8, 2014, p. 2855-2863.

Research output: Contribution to journal › Article › Research › peer-review

TY - JOUR

T1 - Single-Chain antibody conjugated to a cage amine chelator and labeled with positron-emitting copper-64 for diagnostic imaging of activated platelets

AU - Alt, Karen Maria

AU - Paterson, Brett M

AU - Ardipradja, Katie

AU - Schieber, Christine

AU - Buncic, Gojko

AU - Lim, Bock

AU - Poniger, Stan

AU - Jakoby, Bjoern

AU - Wang, Xiaowei

AU - O'Keefe, Graeme J

AU - Tochon-Danguy, Henri

AU - Scott, Andrew Mark

AU - Ackermann, Uwe

AU - Peter, Karlheinz

AU - Donnelly, Paul Stephen

AU - Hagemeyer, Christoph Eugen

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

UR - http://pubs.acs.org/doi/abs/10.1021/mp500209a

U2 - 10.1021/mp500209a

DO - 10.1021/mp500209a

M3 - Article

VL - 11

SP - 2855

EP - 2863

JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

SN - 1543-8384

IS - 8

ER -