title: Synthesis, characterization and radiolabeling of polymeric nano-micelles as a platform for tumor delivering.
abstract: The use of nanoparticles for diagnostic approaches leads to higher accumulation in the targeting tissue promoting a better signal-to-noise ratio and consequently, early tumor detection through scintigraphic techniques. Such approaches have inherent advantages, including the possibility of association with a variety of gamma-emitting radionuclides available, among them, Tecnethium-99m (99mTc).99mTc is readily conjugated with nanoparticles using chelating agents, such as diethylenetriaminepentaacetic acid (DTPA). Leveraging this approach, we synthesized polymeric micelles (PM) consisting of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-mPEG2000) functionalized with DTPA for radiolabeling with99mTc. Micelles made up of DSPE-mPEG2000and DSPE-PEG2000-DTPA had a mean diameter of  ∼10nm, as measured by DLS and SAXS techniques, and a zeta potential of -2.7±1.1mV. Radiolabeled micelles exhibited high radiochemical yields and stability. In vivo assays indicated long blood circulation time (456.3min). High uptake in liver, spleen and kidneys was observed in the biodistribution and imaging studies on healthy and tumor-bearing mice. In addition, a high tumor-to-muscle ratio was detected, which increased over time, showing accumulation of the PM in the tumor region. These findings indicate that this system is a promising platform for simultaneous delivery of therapeutic agents and diagnostic probes.
authors.affiliation: Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Caroline Mari Ramos
authors.initials: CMR
authors.lastname: Oda
authors.affiliation: Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Renata Salgado
authors.initials: RS
authors.lastname: Fernandes
authors.affiliation: Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Sávia Caldeira
authors.initials: SC
authors.lastname: de Araújo Lopes
authors.affiliation: Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Mônica Cristina
authors.initials: MC
authors.lastname: de Oliveira
authors.affiliation: Department of Clinical and Toxicological Analyses, Faculty of Pharmacy, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Valbert Nascimento
authors.initials: VN
authors.lastname: Cardoso
authors.affiliation: Department of Biochemistry and Imunology, Biological Science Institute, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Daniel Moreira
authors.initials: DM
authors.lastname: Santos
authors.affiliation: Department of Biochemistry and Imunology, Biological Science Institute, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Adriano Monteiro
authors.initials: AM
authors.lastname: de Castro Pimenta
authors.affiliation: Department of Physics, Exact Sciences Institute, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Angelo
authors.initials: A
authors.lastname: Malachias
authors.affiliation: Department of Physics, Exact Sciences Institute, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Rogério
authors.initials: R
authors.lastname: Paniago
authors.affiliation: Department of Drug Discovery and Pharmaceutical Sciences, Medical University of South Carolina, United States.
authors.forename: Danyelle M
authors.initials: DM
authors.lastname: Townsend
authors.affiliation: Department of Nuclear Medicine, University of Southern California, Los Angeles, CA, United States.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Colletti
authors.affiliation: Department of Nuclear Medicine, Imaging and Clinical Pathology, Santa Maria della Misericordia Hospital, Rovigo, Italy. Electronic address: domenico.rubello@libero.it.
authors.forename: Domenico
authors.initials: D
authors.lastname: Rubello
authors.affiliation: Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Ricardo José
authors.initials: RJ
authors.lastname: Alves
authors.affiliation: Department of Clinical and Toxicological Analyses, Faculty of Pharmacy, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors.forename: André Luís Branco
authors.initials: ALB
authors.lastname: de Barros
authors.affiliation: Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, Minas Gerais, Brazil. Electronic address: elaineleite@ufmg.br.
authors.forename: Elaine Amaral
authors.initials: EA
authors.lastname: Leite
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D011868:Radioisotopes / Q000737:chemistry*; D014018:Tissue Distribution / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; D008823:Micelles; D011108:Polymers; D011868:Radioisotopes; D011092:Polyethylene Glycols; C000595210:polyethylene glycol 2000
keywords: Characterization; Platform for tumor delivering; Polymeric micelles; Radiolabeling; Synthesis