Synthesis of trifunctional somatostatin based derivatives for improved cellular and subcellular uptake

It is now well established that the biological effects of Auger-emitting radionuclides are critically dependent on their subcellular location. Therefore, for their use in molecular imaging and targeted radionuclide therapy, attempts should be made to increase the nuclear specificity of the carriers. In the present paper the synthesis of novel trifunctional somatostatin derivatives containing a nuclear localization motif is described. These derivatives of DOTA⁰, Tyr³]-octreotide (DOTATOC, DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) were obtained in high yields using Fmoc peptide synthesis in solid and in solution phase.