title: Molecular targeting radiotherapy with cyclo-RGDFK(C) peptides conjugated to 177Lu-labeled gold nanoparticles in tumor-bearing mice.
abstract: Peptides based on the cyclic Arg-Gly-Asp (RGD) sequence have been designed to antagonize the function of alpha(v)beta(3) integrin, thereby inhibiting angiogenesis. The conjugation of RGD peptides to radiolabeled gold nanoparticles (AuNP) produces biocompatible and stable multimeric systems with target-specific molecular recognition. The aim of this research was to evaluate the therapeutic response of 177Lu-AuNP-RGD in athymic mice bearing alpha(v)beta(3)-integrin-positive C6 gliomas and compare it with that of 177Lu-AuNP or 177Lu-RGD. The radiation absorbed dose, metabolic activity (SUV, [18F]fluor-deoxy-glucose-microPET/CT), histological characteristics and VEGF gene expression (by real-time polymerase chain reaction) in tumor tissues following treatment with 177Lu-AuNP-RGD, 177Lu-AuNP or 177Lu-RGD were assessed. Of the radiopharmaceuticals evaluated, 1177Lu-AuNP-RGD delivered the highest tumor radiation absorbed dose (63.8 +/- 7.9 Gy). These results correlated with the observed therapeutic response, in which 177Lu-AuNP-RGD significantly (p < 0.05) induced less tumor progression, less tumor metabolic activity, fewer intratumoral vessels and less VEGF gene expression than the other radiopharmaceuticals, a consequence of high tumor retention and a combination of molecular targeting therapy (multimeric RGD system) and radiotherapy (177Lu). There was a low uptake in non-target organs and no induction of renal toxicity. 177Lu-labeled gold nanoparticles conjugated to cyclo-RGDfK(C) demonstrate properties suitable for use as an agent for molecular targeting radiotherapy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Vilchis-Juárez
authors.forename: Guillermina
authors.initials: G
authors.lastname: Ferro-Flores
authors.forename: Clara
authors.initials: C
authors.lastname: Santos-Cuevas
authors.forename: Enrique
authors.initials: E
authors.lastname: Morales-Avila
authors.forename: Blanca
authors.initials: B
authors.lastname: Ocampo-García
authors.forename: Lorenza
authors.initials: L
authors.lastname: Díaz-Nieto
authors.forename: Myrna
authors.initials: M
authors.lastname: Luna-Gutiérrez
authors.forename: Nallely
authors.initials: N
authors.lastname: Jiménez-Mancilla
authors.forename: Martha
authors.initials: M
authors.lastname: Pedraza-López
authors.forename: Leobardo
authors.initials: L
authors.lastname: Gómez-Oliván
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D002478:Cells, Cultured; D059248:Chemoradiotherapy / Q000379:methods*; D006046:Gold / Q000627:therapeutic use*; D008187:Lutetium / Q000737:chemistry / Q000627:therapeutic use*; D008297:Male; D053768:Metal Nanoparticles / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D058990:Molecular Targeted Therapy / Q000379:methods*; D058726:Nanoconjugates / Q000627:therapeutic use*; D009369:Neoplasms / Q000532:radiotherapy*; D009389:Neovascularization, Pathologic; D010456:Peptides, Cyclic / Q000737:chemistry / Q000627:therapeutic use*; D011868:Radioisotopes / Q000737:chemistry / Q000627:therapeutic use*; D051381:Rats; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D058726:Nanoconjugates; D010456:Peptides, Cyclic; D011868:Radioisotopes; D008187:Lutetium; D006046:Gold