An innovative therapeutic approach for malignant mesothelioma treatment based on the use of Gd/boron multimodal probes for MRI guided BNCT

Diego Alberti, Annamaria Deagostino, Antonio Toppino, Nicoletta Protti, Silva Bortolussi, Saverio Altieri, Silvio Aime, Simonetta Geninatti Crich

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

The aim of this study is to develop an innovative imaging guided approach based on Boron Neutron Capture Therapy, for the treatment of mesothelioma, assisted by the quantification of the in vivo boron distribution by MRI. The herein reported results demonstrate that overexpressed Low Density Lipoproteins receptors can be successfully exploited to deliver to mesothelioma cells a therapeutic dose of boron (26 μg/g), significantly higher than in the surrounding tissue (3.5 μg/g). Boron and Gd cells uptake was assessed by ICP-MS and MRI on two mesothelioma (ZL34, AE17) and two healthy (MRC-5 and NMuMg) cell lines. An in vivo model was prepared by subcutaneous injection of ZL34 cells in Nu/Nu mice. After irradiation with thermal neutrons, tumor growth was evaluated for 40 days by MRI. Tumor masses of boron treated mice showed a drastic reduction of about 80–85%. The obtained results appear very promising providing patients affected by this rare disease with an improved therapeutic option, exploiting LDL transporters.

Original languageEnglish
Pages (from-to)31-38
Number of pages8
JournalJournal of Controlled Release
Volume280
DOIs
Publication statusPublished - Jun 28 2018
Externally publishedYes

Keywords

  • Boron Neutron Capture Therapy
  • Low Density Lipoproteins
  • Magnetic Resonance Imaging (MRI)
  • Mesothelioma

ASJC Scopus subject areas

  • Pharmaceutical Science

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