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 (64)Cu(II) complex of the scFv conjugated to another commonly used macrocycle, DOTA. The scFvanti-LIBS-MeCOSar conjugate was radiolabeled with (64)Cu(II) 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-(64)CuMeCOSar in the injured vessel was significantly higher than the noninjured vessel. Positron emission tomography (PET) was used to show accumulation of scFvanti-LIBS-(64)CuMeCOSar with high and specific uptake in the injured vessel. ScFvanti-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.
authors.affiliation: Vascular Biotechnology Laboratory, Baker IDI , Melbourne, Australia.
authors.forename: Karen
authors.initials: K
authors.lastname: Alt
authors.forename: Brett M
authors.initials: BM
authors.lastname: Paterson
authors.forename: Katie
authors.initials: K
authors.lastname: Ardipradja
authors.forename: Christine
authors.initials: C
authors.lastname: Schieber
authors.forename: Gojko
authors.initials: G
authors.lastname: Buncic
authors.forename: Bock
authors.initials: B
authors.lastname: Lim
authors.forename: Stan S
authors.initials: SS
authors.lastname: Poniger
authors.forename: Bjoern
authors.initials: B
authors.lastname: Jakoby
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Wang
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: O'Keefe
authors.forename: Henri J
authors.initials: HJ
authors.lastname: Tochon-Danguy
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Scott
authors.forename: Uwe
authors.initials: U
authors.lastname: Ackermann
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Peter
authors.forename: Paul S
authors.initials: PS
authors.lastname: Donnelly
authors.forename: Christoph E
authors.initials: CE
authors.lastname: Hagemeyer
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002339:Carotid Arteries / Q000503:physiopathology; D002614:Chelating Agents / Q000737:chemistry*; D003300:Copper / Q000737:chemistry; D003301:Copper Radioisotopes / Q000737:chemistry; D003952:Diagnostic Imaging; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D007249:Inflammation; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008807:Mice, Inbred BALB C; D015539:Platelet Activation; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D057127:Single-Chain Antibodies / Q000737:chemistry*; D013927:Thrombosis / Q000175:diagnosis; D055114:X-Ray Microtomography
chemical_list: D002614:Chelating Agents; D003301:Copper Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; D008024:Ligands; D019275:Radiopharmaceuticals; D057127:Single-Chain Antibodies; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D003300:Copper