Cyclization of RGD peptide sequences via the macrocyclic chelator DOTA for integrin imaging.

Two bicyclic compounds containing Arg-Gly-Asp (RGD) motifs (RGDf and RGD) were synthesized by cyclizing the peptide sequence across the macrocyclic ring of DOTA via two non-adjacent carboxylate pendent arms. The Lu(3+) or Cu(2+) complexes of these compounds, c(DOTA-RGDf) and c(DOTA-RGD), showed a metal dependent affinity towards integrin α(v)β(3)in vitro and the (177)Lu(3+) or (64)Cu(2+) labelled derivatives showed specific tumour uptake in MCF7 and U87MG tumour bearing mice.