title: 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.
abstract: Direct attachment of unprotected DOTA (1,4,7,10-tetraazacyclododecane-N',N",N"',N""-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.
authors.affiliation: Novartis Pharma AG, Basle, Switzerland. rainer.albert@pharma.novartis.com
authors.forename: R
authors.initials: R
authors.lastname: Albert
authors.forename: P
authors.initials: P
authors.lastname: Smith-Jones
authors.forename: B
authors.initials: B
authors.lastname: Stolz
authors.forename: C
authors.initials: C
authors.lastname: Simeon
authors.forename: H
authors.initials: H
authors.lastname: Knecht
authors.forename: C
authors.initials: C
authors.lastname: Bruns
authors.forename: J
authors.initials: J
authors.lastname: Pless
mesh_terms: D004337:Drug Carriers; D006573:Heterocyclic Compounds, 1-Ring / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D007202:Indicators and Reagents; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D015282:Octreotide / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D017481:Receptors, Somatostatin / Q000378:metabolism*; D015021:Yttrium Radioisotopes / Q000493:pharmacokinetics
chemical_list: D004337:Drug Carriers; D006573:Heterocyclic Compounds, 1-Ring; D007202:Indicators and Reagents; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin; D015021:Yttrium Radioisotopes; C116641:octreotide, DOTA-Phe(1)-; D015282:Octreotide; C106246:Edotreotide