title: Synthesis of Gd and (68)Ga complexes in conjugation with a conformationally optimized RGD sequence as potential MRI and PET tumor-imaging probes.
abstract: We report the synthesis of novel chelates of Gd and (68)Ga with DPTA, DOTA, HP-DOA3, as well as with AAZTA, a novel chelating agent developed by our research group. These chelating agents were appropriately conjugated, prior to metal complexation, with DB58, an RGD peptidomimetic, conformationally constrained on an azabicycloalkane scaffold and endowed with high affinity for integrin α(ν)β(3) . Because α(ν)β(3) is involved in neo-angiogenesis in solid tumors and is also directly expressed in cancer cells (e.g. glioblastomas, melanomas) and ovarian, breast, and prostate cancers, these constructs could prove useful as molecular imaging probes in cancer diagnosis by MRI or PET techniques. Molecular modeling, integrin binding assays, and relaxivity assessments allowed the selection of compounds suitable for multiple expression on dendrimeric or nanoparticulate structures. These results also led us to an exploratory investigation of (68)Ga complexation for the promising (68)Ga-PET technique; the AAZTA complex 15((68)Ga) exhibited uptake in a xenograft model of glioblastoma, suggesting potentially useful developments with new probes with improved affinity.
authors.affiliation: Consiglio Nazionale delle Ricerche, Istituto di Scienze e Tecnologie Molecolari, Via Fantoli 16/15, 20138, Milano, Italy. leonardo.manzoni@istm.cnr.it
authors.forename: Leonardo
authors.initials: L
authors.lastname: Manzoni
authors.forename: Laura
authors.initials: L
authors.lastname: Belvisi
authors.forename: Daniela
authors.initials: D
authors.lastname: Arosio
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Bartolomeo
authors.forename: Aldo
authors.initials: A
authors.lastname: Bianchi
authors.forename: Chiara
authors.initials: C
authors.lastname: Brioschi
authors.forename: Federica
authors.initials: F
authors.lastname: Buonsanti
authors.forename: Claudia
authors.initials: C
authors.lastname: Cabella
authors.forename: Cesare
authors.initials: C
authors.lastname: Casagrande
authors.forename: Monica
authors.initials: M
authors.lastname: Civera
authors.forename: Marilenia
authors.initials: M
authors.lastname: De Matteo
authors.forename: Lorenza
authors.initials: L
authors.lastname: Fugazza
authors.forename: Luciano
authors.initials: L
authors.lastname: Lattuada
authors.forename: Federico
authors.initials: F
authors.lastname: Maisano
authors.forename: Luigi
authors.initials: L
authors.lastname: Miragoli
authors.forename: Cristina
authors.initials: C
authors.lastname: Neira
authors.forename: Michael
authors.initials: M
authors.lastname: Pilkington-Miksa
authors.forename: Carlo
authors.initials: C
authors.lastname: Scolastico
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry; D005682:Gadolinium / Q000737:chemistry; D005710:Gallium Radioisotopes / Q000737:chemistry; D005909:Glioblastoma / Q000000981:diagnostic imaging; D006801:Humans; D008279:Magnetic Resonance Imaging; D051379:Mice; D008819:Mice, Nude; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism; D049268:Positron-Emission Tomography; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry; D014183:Transplantation, Heterologous
chemical_list: D056831:Coordination Complexes; D005710:Gallium Radioisotopes; D009842:Oligopeptides; D019275:Radiopharmaceuticals; C047981:arginyl-glycyl-aspartic acid; D005682:Gadolinium