Synthesis and evaluation of a 99mTc-BAT-phenylbenzothiazole conjugate as a potential in vivo tracer for visualization of amyloid β

We have conjugated S,S′-bis-trityl-N-BOC-N′-acetic acid-1,2-ethylenedicysteamine, a protected bis-amino-bis-thiol (BAT) tetraligand, with 2-(4′-aminophenyl)-1,3-benzothiazole, a derivative of thioflavin-T with known affinity for amyloid. The conjugate was efficiently labelled with 99mTc by heating of the protected precursor in diluted hydrochloric acid followed by neutralization and heating in the presence of 99mTc-tartrate. It was demonstrated that the 99mTc-BAT-phenylbenzothiazole conjugate binds in vitro to amyloid β present in postmortem brain slices of Alzheimer’s patients. Despite its high lipophilicity and neutral character, the radiolabelled conjugate did not cross the blood–brain barrier to a sufficient degree and therefore is not useful for detection of Alzheimer’s disease. Further evaluation of this 99mTc-labelled tracer agent could elucidate its potential usefulness to visualize amyloid plaques in peripheral amyloidosis.

Graphical abstractA protected bis-amino-bis-thiol (BAT) tetraligand was conjugated with 2-(4′-aminophenyl)-1,3-benzothiazole, a derivative of thioflavin-T with known affinity for amyloid. The conjugate was efficiently labelled with 99mTc and biologically evaluated.Figure optionsDownload full-size imageDownload as PowerPoint slide