title: A theranostic approach based on the use of a dual boron/Gd agent to improve the efficacy of Boron Neutron Capture Therapy in the lung cancer treatment.
abstract: This study aims at developing an innovative theranostic approach for lung tumor and metastases treatment, based on Boron Neutron Capture Therapy (BNCT). It relies on to the use of low density lipoproteins (LDL) as carriers able to maximize the selective uptake of boron atoms in tumor cells and, at the same time, to quantify the in vivo boron distribution by magnetic resonance imaging (MRI). Tumor cells uptake was initially assessed by ICP-MS and MRI on four types of tumor (TUBO, B16-F10, MCF-7, A549) and one healthy (N-MUG) cell lines. Lung metastases were generated by intravenous injection of a Her2+ breast cancer cell line (i.e. TUBO) in BALB/c mice and transgenic EML4-ALK mice were used as primary tumor model. After neutron irradiation, tumor growth was followed for 30-40 days by MRI. Tumor masses of boron treated mice increased markedly slowly than the control group. From the clinical editor: In this article, the authors described an improvement to existing boron neutron capture therapy. The dual MRI/BNCT agent, carried by LDLs, was able to maximize the selective uptake of boron in tumor cells, and, at the same time, quantify boron distribution in tumor and in other tissues using MRI. Subsequent in vitro and in vivo experiments showed tumor cell killing after neutron irradiation.
authors.affiliation: Department of Molecular Biotechnology and Health Sciences; University of Torino, Torino, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Alberti
authors.affiliation: Department of Nuclear and Theoretical Physics, University of Pavia, Pavia, Italy; Nuclear Physics National Institute (INFN), section of Pavia, Pavia, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Protti
authors.affiliation: Department of Chemistry, University of Torino, Torino, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Toppino
authors.affiliation: Department of Chemistry, University of Torino, Torino, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Deagostino
authors.affiliation: Department of Molecular Biotechnology and Health Sciences; University of Torino, Torino, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Lanzardo
authors.affiliation: Department of Nuclear and Theoretical Physics, University of Pavia, Pavia, Italy; Nuclear Physics National Institute (INFN), section of Pavia, Pavia, Italy.
authors.forename: Silva
authors.initials: S
authors.lastname: Bortolussi
authors.affiliation: Department of Nuclear and Theoretical Physics, University of Pavia, Pavia, Italy; Nuclear Physics National Institute (INFN), section of Pavia, Pavia, Italy.
authors.forename: Saverio
authors.initials: S
authors.lastname: Altieri
authors.affiliation: Department of Molecular Biotechnology and Health Sciences; University of Torino, Torino, Italy; Center for Experimental Research and Medical Studies (CERMS), Città della Salute e della Scienza, Torino, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Voena
authors.affiliation: Department of Molecular Biotechnology and Health Sciences; University of Torino, Torino, Italy; Center for Experimental Research and Medical Studies (CERMS), Città della Salute e della Scienza, Torino, Italy; Department of Pathology, Children's Hospital Harvard Medical School, Boston, MA, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Chiarle
authors.affiliation: Department of Molecular Biotechnology and Health Sciences; University of Torino, Torino, Italy. Electronic address: simonetta.geninatti@unito.it.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Geninatti Crich
authors.affiliation: Department of Molecular Biotechnology and Health Sciences; University of Torino, Torino, Italy.
authors.forename: Silvio
authors.initials: S
authors.lastname: Aime
mesh_terms: D000818:Animals; D001895:Boron / Q000494:pharmacology*; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D005260:Female; D005682:Gadolinium / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D008325:Mammary Neoplasms, Experimental / Q000473:pathology / Q000532:radiotherapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis
chemical_list: D005682:Gadolinium; D001895:Boron
keywords: Boron Neutron Capture Therapy (BNCT); Carboranes; Low density lipoproteins (LDL); MRI; Theranostic agents