Versatile new bis(thiosemicarbazone) bifunctional chelators: Synthesis, conjugation to bombesin(7-14)-NH2, and copper-64 radiolabeling

Brett Paterson, John A. Karas, Denis B. Scanlon, Jonathan M. White, Paul Stephen Donnelly

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New bifunctional derivatives of diacetyl-bis(4-methylthiosemicarbazone) (H2atsm) have been prepared by a selective transamination reaction of a new dissymmetric bis(thiosemicarbazone) precursor H2L1. The new derivatives contain an aliphatic carboxylic acid (H2L2 and H2L3), t-butyl carbamate (H2L 4), or ammonium ion (H2L5) functional group. The new ligands and copper(II) complexes have been characterized by NMR spectroscopy, mass spectrometry, and microanalysis. The complex CuII(L 4) was structurally characterized by X-ray crystallography and shows the metal center to be in an N2S2 distorted square planar coordination geometry. Electrochemical measurements show that the copper(II) complexes undergo a reversible reduction attributable to a Cu(II)/Cu(I) process. The ligands and the copper(II) complexes featuring a carboxylic acid functional group have been conjugated to the tumor targeting peptide bombesin(7-14)- NH2. The bifunctional peptide conjugates were radiolabeled with copper-64 in the interest of developing new positron emission tomography (PET) imaging agents. The conjugates were radiolabeled with copper- 64 rapidly in high radiochemical purity (> 95%) at room temperature under mild conditions and were stable in a cysteine and histidine challenge study.

Original languageEnglish
Pages (from-to)1884-1893
Number of pages10
JournalInorganic Chemistry
Issue number4
Publication statusPublished - 15 Feb 2010
Externally publishedYes

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