Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf

Novel 64Cu-labeled bombesins capable of GRP receptor-targeted tumor imaging

Ruffani, A.; Stephan, H.; Bergmann, R.; Pietzsch, J.; Steinbach, J.; Graham, B.; Spiccia, L.

A new macrocyclic ligand, 2-[4,7-bis(2-pyridylmethyl)-1,4,7-triazacyclononan-1-yl]acetic acid (1), binds copper strongly and the resulting radiocopper(II)-ligand complex exhibits high in vivo stability. The pendant carboxylic group enables this derivative to be conjugated to the N-terminal amino acid residues of peptides. Exploiting this, two stabilized bombesin derivatives have been coupled to 1 and radiolabeled with the positron emitter copper-64.
In vitro binding characteristics of the [64Cu]CuII-labeled bombesin conjugates in gastrinreleasing peptide receptor (GRPR) overexpressing prostate cancer (PC-3) cells have been evaluated. Biodistribution studies performed in Wistar rats indicate a specific uptake in the GRPR-rich pancreas and rapid renal elimination. Small animal PET imaging studies confirmed a high extent of tumor accumulation in NMRI nu/nu mice bearing the human prostate tumor PC-3. Incorporation of one additional glutamic acid residue within the spacer between bombesin and the radiolabeled complex leads to a higher tumor-to-muscle uptake ratio.

Keywords: TACN; bombesin; copper-64; prostate cancer; small animal positron emission tomography

  • Poster
    International Symposium on Technetium and other Radiometals in Chemistry and Medicine, 08.-11.09.2010, Bressanone, Italy
  • Abstract in refereed journal
    Nuclear Medicine and Biology 37(2010)6, 692-693
    DOI: 10.1016/j.nucmedbio.2010.04.093
  • Contribution to external collection
    U. Mazzi, W. C. Eckelman, W. A. Volkert: Technetium and Other Radiometals in Chemistry and Medicine, Padova: SGEditoriali Padova, 2010, 217-220

Publ.-Id: 14305