Pre-targeting amyloid-β with antibodies for potential molecular imaging of Alzheimer's disease†
Katherine A.
Morgan, 
a
Michael
de Veer,
b
Cormac A. A.
Kelderman,
d
Jonathan M.
White,
a
Brett M.
Paterson
bd
and
Paul S.
Donnelly
*a
a
Michael
de Veer,
b
Cormac A. A.
Kelderman,
d
Jonathan M.
White,
a
Brett M.
Paterson
bd
and
Paul S.
Donnelly
*a
Abstract
With the aim of developing the concept of pretargeted click chemistry for the diagnosis of Alzheimer's disease two antibodies specific for amyloid-β were modified to incorporate trans-cyclooctene functional groups. Two bis(thiosemicarbazone) compounds with pendant 1,2,4,5-tetrazine functional groups were prepared and radiolabelled with positron emitting copper-64. The new copper-64 complexes rapidly react with the trans-cyclooctene functionalized antibodies in a bioorthogonal click reaction and cross the blood–brain barrier in mice.
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