title: Synthesis, characterization and biological evaluation of a (67)Ga-labeled (η(6)-Tyr)Ru(η(5)-Cp) peptide complex with the HAV motif.
abstract: Heterobimetallic complexes with the evolutionary, well-preserved, histidyl-alanyl-valinyl (HAV) sequence for cadherin targeting, an organometallic Ru core with anticancer activity and a radioactive moiety for imaging may hold potential as theranostic agents for cancer. Visible-light irradiation of the HAVAY-NH2 pentapeptide in the presence of [(η(5)-Cp)Ru(η(6)-naphthalene)](+) resulted in the formation of a full sandwich type complex, (η(6)-Tyr-RuCp)-HAVAY-NH2 in aqueous solution, where the metal ion is connected to the Tyr (Y) unit of the peptide. Conjugation of this complex to 2,2'-(7-(1-carboxy-4-((4-isothiocyanatobenzyl)amino)-4-oxobutyl)-1,4,7-triazonane-1,4-diyl)diacetic acid (NODA-GA) and subsequent metalation of the resulting product with stable ((nat)Ga) and radioactive ((67)Ga) isotope yielded (nat)Ga/(67)Ga-NODA-GA-[(η(6)-Tyr-RuCp)-HAVAY-NH2]. The non-radioactive compounds were characterized by NMR spectroscopy and Mass Spectrometry. The cellular uptake and cytotoxicity of the radioactive and non-radioactive complexes, respectively, were evaluated in various human cancer cell lines characterized by different levels of N- or E-cadherins expression. Results from these studies indicate moderate cellular uptake of the radioactive complexes. However, the inhibition of the cell proliferation was not relevant.
authors.affiliation: Department of Inorganic and Analytical Chemistry, University of Debrecen, H-4010 Debrecen, P.O.Box 21, Hungary.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Bihari
authors.affiliation: Centro de Ciências e Tecnologias Nucleares (C(2)TN), Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10 (km 139,7), 2695-066 Bobadela LRS, Portugal.
authors.forename: Filipe
authors.initials: F
authors.lastname: Vultos
authors.affiliation: Centro de Ciências e Tecnologias Nucleares (C(2)TN), Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10 (km 139,7), 2695-066 Bobadela LRS, Portugal.
authors.forename: Célia
authors.initials: C
authors.lastname: Fernandes
authors.affiliation: Centro de Ciências e Tecnologias Nucleares (C(2)TN), Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10 (km 139,7), 2695-066 Bobadela LRS, Portugal.
authors.forename: Lurdes
authors.initials: L
authors.lastname: Gano
authors.affiliation: Centro de Ciências e Tecnologias Nucleares (C(2)TN), Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10 (km 139,7), 2695-066 Bobadela LRS, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Santos
authors.affiliation: Centro de Ciências e Tecnologias Nucleares (C(2)TN), Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10 (km 139,7), 2695-066 Bobadela LRS, Portugal.
authors.forename: João D G
authors.initials: JD
authors.lastname: Correia
authors.affiliation: Department of Inorganic and Analytical Chemistry, University of Debrecen, H-4010 Debrecen, P.O.Box 21, Hungary. Electronic address: buglyo@science.unideb.hu.
authors.forename: Péter
authors.initials: P
authors.lastname: Buglyó
mesh_terms: D020816:Amino Acid Motifs; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000494:pharmacology; D005710:Gallium Radioisotopes / Q000737:chemistry; D015870:Gene Expression; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D006801:Humans; D009281:Naphthalenes / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry*; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D012428:Ruthenium / Q000737:chemistry*; D000068936:Theranostic Nanomedicine / Q000379:methods
chemical_list: D015703:Antigens, CD; D000970:Antineoplastic Agents; C513384:CDH1 protein, human; C050361:CDH2 protein, human; D015820:Cadherins; D056831:Coordination Complexes; D005710:Gallium Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; D009281:Naphthalenes; D009842:Oligopeptides; D009942:Organometallic Compounds; D012428:Ruthenium
keywords: Cadherin; Full sandwich ruthenium complex; Gallium complex; HAV sequence; Oligopeptide conjugate; Radiolabeling