Bis(thiosemicarbazones) as bifunctional chelators for the room temperature 64-copper labeling of peptides

Abstract

A range of new carboxylate functionalised bis(thiosemicarbazone) ligands and their Cu(II) complexes have been prepared, fully characterised and radiolabeled in high yield with both (64)Cu and (99m)Tc. Conjugation to a bombesin derivative was achieved using standard solid phase synthetic methodologies and the (64)Cu-labeled conjugate was shown to have good tumour uptake in mice with xenografted PC-3 tumours.

Recent advances in chelator design and labelling methodology for 68Ga radiopharmaceuticals

“…Pascu and co‐workers have further developed chelators based on the ATSM type thiosemicarbazone structure, which has previously been used for 64 Cu peptide labelling . The backbone of the ligand is modified to add aromatic groups so the ligand can be used as a multimodal PET/optical agent with gallium‐68 and other functional groups to increase aqueous solubility.…”

Copper-64 radiolabelling of the C2A domain of synaptotagmin I using a functionalised bis(thiosemicarbazone): A pre- and post-labelling comparison

“…Others and ourselves have previously reported bifunctional bis(thiosemicarbazones) for conjugation to peptides, leading to metalloconjugates with specific tumour uptake [16][17][18]. We reasoned that C2A modified with a single, site-specifically attached bis(thiosemicarbazone) chelator may achieve high yield, rapid copper radiolabelling at room temperature.…”

“…The hydrazinic proligand H 2 ATSE/A [16] was coupled to 3-maleimidopropionic acid to afford H 2 ATSE/AMal (Scheme 1) using a previously reported method [17]. Copper complexation to afford 64 Cu-or CuATSE/AMal was performed with 64 Cu(OAc) 2 or Cu(OAc) 2 using standard procedures [16,17].…”

VPAC1 Targeted 64 Cu-TP3805 kit preparation and its evaluation

“…N 2 S 2 type diaminedithiol ligands form a stable, neutral and planar complex with Cu 2+ ions and permits radiolabeling at physiological pH [19]. Previously we accomplished 64 Cu chelation was accomplished by synthesizing protected diaminedithiol (N 2 S 2 )-VPAC1 analog (TP3805) [20] and successfully evaluated VPAC-1 receptors specific imaging in xenograft animal tumor model and transgenic mice for breast and prostate cancer [21–24].…”