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

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.