Direct synthesis of [DOTA-DPhe1]-octreotide and [DOTA-DPhe1, Tyr3]-octreotide (SMT487): Two conjugates for systemic delivery of radiotherapeutical nuclides to somatostatin receptor positive tumors in man

Direct attachment of unprotected DOTA (1,4,7,10-tetraazacyclododecane-N′,N″,N ,Nʹʹʹʹ-tetraacetic acid) to partially suitably protected octreotide or [Tyr3]-octreotide leads after deprotection to [DOTA-DPhe1]-octreotide (III) and [DOTA-DPhe1, Tyr3]-octreotide (IV). These DOTA-containing somatostatin analogs, when labeled with a radiotherapeutic nuclide, are useful as antitumor agents. The partially protected peptides are accessible via solid phase peptide synthesis (SPPS) followed by selective cleavage under mild acidic conditions from the resin.