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A novel approach for 99mTc labelling of peptides organometallic Tc(III) complexes for conjugation of bombesin derivatives

Künstler, J.-U.; Veerendra, B.; Sieckman, G. L.; Smith, C. J.; Pietzsch, H.-J.
Among peptides for tumour targeting bombesin (BBS), binding to gastrin releasing peptide receptors (GRPR) and overexpressed by e.g. prostate and breast carcinomas has a great potential. Thus, various labelled bombesins were described in the literature showing a varying pharmacokinetic behaviour depending on the labelling approach, the spacer between the radiometal moiety and the N-terminus as well as modifications in the peptide sequence.
In this study, the bioactive minimal sequence BBS(7-14) was labelled by the Tc-“4+1” mixed-ligand system, where Tc(III) is coordinated by a monodentate isocyanide bearing the peptide and the tetradentate tripodal chelator tris(2-mercaptoethyl)-amine (NS3).
BBS(7-14) was N-terminally modified with Gly-Gly-Gly, β-Ala and Ser-Ser-Ser as spacer groups and functionalized with 4-isocyanomethyl benzoic acid or 4-isocyanobutyric acid. 99mTc labelling was performed in a two-step ligand exchange procedure starting from 99mTc-EDTA/mannitol. The Re analogues were used as references for chemical characterization and in receptor-binding studies. Complex bearing β-Ala-BBN(7-14) exhibited a GRPR-affinity in the subnanomolar range and high uptake in human prostate (PC-3) cancer cells, whereas pancreatic uptake in biodistribution studies using normal mice was low.
Keywords: Technetium, '4+1' Mixed-ligand Complexes, Organometallic, Bombesin, Peptide Labelling
  • Poster
    7th International Symposium on Technetium in Chemistry and Nuclear Medicine, 06.-09.09.2006, Bressanone, Italy
  • Contribution to external collection
    U. Mazzi: Technetium, Rhenium and Other Metals in Chemistry and Nuclear Medicine, Padova: SGE Editoriali, 2006, 88-89884-04-5, 317-318

Permalink: https://www.hzdr.de/publications/Publ-8984
Publ.-Id: 8984