Functionalised copper-64 complexes as precursors of potential PET imaging agents for neurodegenerative disorders Journal Article


Authors: Holland, J. P.; Jones, M. W.; Bonnitcha, P. D.; Lewis, J. S.; Dilworth, J. R.
Article Title: Functionalised copper-64 complexes as precursors of potential PET imaging agents for neurodegenerative disorders
Abstract: A range of unsymmetrical bis(thiosemicarbazonato)zinc(ii) and copper(ii) complexes functionalised with structural features of the neuroactive agents dopamine and tropinone have been synthesised. The new ligands and complexes have been characterised by using mass spectrometry, elemental analysis, NMR, infrared and electronic absorption spectroscopy techniques. Transmetallation reactions of the zinc(ii) analogues with <sup>64</sup>Cu(OAc)<sub>2</sub> in aqueous solution were found to be a rapid and efficient method for preparing <sup>64</sup>Cu-radiolabelled complexes for potential use as in vivo tracers in positron emission tomography (PET). Oxygen-dependent cellular association assays in EMT6 murine carcinoma cells revealed that despite conjugation of the tropinone group and reduced lipophilicity, the bis(thiosemicarbazonato) copper(ii) complex retains hypoxia-selectively in vitro. The results demonstrate that recognised neuroactive pharmacophores can be conjugated to the bis(thiosemicarbazonato)copper(ii) core as potential precursors of <sup>64</sup>Cu-radiopharmaceuticals for imaging of neurodegenerative disorders. © 2009 The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.
Keywords: controlled study; unclassified drug; nonhuman; positron emission tomography; mass spectrometry; animal cell; mouse; complex formation; oxygen; animal experiment; drug structure; hypoxia; isotope labeling; polymerization; radiopharmaceutical agent; chemical structure; precursor; aqueous solution; nuclear magnetic resonance; dopamine; copper 64; carcinoma cell; diacetyl 2 (4 n allyl 3 thiosemicarbazonato] 3 (4 n amino 3 thiosemicarbazonato)zinc; diacetyl 2 (4 n allyl 3 thiosemicarbazonato] 3 (4 n tropimine 3 thiosemicarbazonato)copper; diacetyl 2 (4 n allyl 3 thiosemicarbazonato] 3 (4 n tropimine 3 thiosemicarbazonato)zinc; diacetyl 2 (4 n ethyl 3 thiosemicarbazonato] 3 (4 n amino 3 thiosemicarbazonato)zinc; diacetyl 2 (4 n ethyl 3 thiosemicarbazonato] 3 (4 n tropimine 3 thiosemicarbazonato)copper; diacetyl 2 (4 n ethyl 3 thiosemicarbazonato] 3 (4 n tropimine 3 thiosemicarbazonato)zinc; diacetyl 2 [4 n(3,4 dimethoxyphenethyl) 3 thiosemicarbazido] 3 (4 n ethyl 3 thiosemicarbazide); diacetyl 2 [4 n(3,4 dimethoxyphenethyl) 3 thiosemicarbazonato] 3 (4 n ethyl 3 thiosemicarbazonato)copper; diacetyl 2 [4 n(3,4 dimethoxyphenethyl) 3 thiosemicarbazonato] 3 (4 n ethyl 3 thiosemicarbazonato)zinc; absorption spectroscopy; chemical reaction; degenerative disease; drug conjugation; infrared spectroscopy; lipophilicity; metallation; synthesis
Journal Title: New Journal of Chemistry
Volume: 33
Issue: 9
ISSN: 1144-0546
Publisher: Royal Society of Chemistry  
Date Published: 2009-01-01
Start Page: 1845
End Page: 1852
Language: English
DOI: 10.1039/b902895a
PROVIDER: scopus
DOI/URL:
Notes: --- - "Export Date: 30 November 2010" - "CODEN: NJCHE" - "Source: Scopus"
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MSK Authors
  1. Jason Philip Holland
    30 Holland
  2. Jason S Lewis
    245 Lewis