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

被引：42

作者：

Alt, Karen ^{[1
,2
]}

Paterson, Brett M. ^{[3
,4
]}

Ardipradja, Katie ^{[1
,2
,5
,6
,7
]}

Schieber, Christine ^{[3
,4
]}

Buncic, Gojko ^{[3
,4
]}

Lim, Bock ^{[1
,2
]}

Poniger, Stan S. ^{[5
,6
]}

Jakoby, Bjoern ^{[8
,9
]}

Wang, Xiaowei ^{[2
]}

O'Keefe, Graeme J. ^{[5
,6
,7
]}

Tochon-Dansuy, Henri J. ^{[5
,6
]}

Scott, Andrew M. ^{[5
,6
,7
,10
]}

Ackermann, Uwe ^{[5
,6
,7
,10
]}

Peter, Karlheinz ^{[2
,11
]}

Donnelly, Paul S. ^{[3
,4
]}

Hagemeyer, Christoph E. ^{[1
,12
]}

机构：

[1] Baker IDI, Vasc Biotechnol Lab, Melbourne, Vic, Australia

[2] Baker IDI, Atherothrombosis & Vasc Lab, Melbourne, Vic, Australia

[3] Univ Melbourne, Sch Chem, Melbourne, Vic, Australia

[4] Univ Melbourne, Mol Sci & Biotechnol Inst Bio21, Melbourne, Vic, Australia

[5] Austin Hlth, Dept Nucl Med, Melbourne, Vic, Australia

[6] Austin Hlth, Ctr PET, Melbourne, Vic, Australia

[7] Univ Melbourne, Dept Med Dent & Hlth Sci, Melbourne, Vic, Australia

[8] Siemens Healthcare, Erlangen, Germany

[9] Univ Surrey, Guildford GU2 5XH, Surrey, England

[10] Austin Hlth, Ludwig Inst Canc Res, Melbourne, Vic, Australia

[11] Monash Univ, Cent Clin Sch, Melbourne, Vic 3004, Australia

[12] RMIT Univ, Sch Appl Sci, Melbourne, Vic, Australia

来源：

MOLECULAR PHARMACEUTICS | 2014年 / 11卷 / 08期

基金：

英国医学研究理事会; 澳大利亚研究理事会; 澳大利亚国家健康与医学研究理事会;

关键词：

platelets; integrin GPIIb/IIIa; single-chain antibody; positron emission tomography; Cu-64; chelator; MONOCLONAL-ANTIBODIES; LIGAND; RADIOPHARMACEUTICALS; INFLAMMATION; GPIIB/IIIA; NEUROBLASTOMA; DISEASE; CANCER;

D O I：

10.1021/mp500209a

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Imaging of activated platelets using an activation specific anti-GPIIb/IIIa integrin single-chain antibody (scFv(anti-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 Cu-64(II) complex of the scFv conjugated to another commonly used macrocycle, DOTA. The scFv(anti-LIBs)-MeCOSar conjugate was radio-labeled with Cu-64(II) rapidly under mild conditions and with higher specific activity than scFv(anti-LIBs)-DOTA. The utility of scFv(anti-LIBs)-MeCOSar as a diagnostic agent was assessed in vivo in a mouse model of acute thrombosis. The uptake of scFv(anti-LIBs)-(64)CuMeCOSar in the injured vessel was significantly higher than the noninjured vessel. Positron emission tomography (PET) was used to show accumulation of scFv(anti-LIBs)-(64)CuMeCOSar with high and specific uptake in the injured vessel. scFv(anti-LIBs)-(64)CuMeCOSar 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.

引用

页码：2855 / 2863

页数：9

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