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

JOURNAL OF CONTROLLED RELEASE

卷:280

Article

Alberti, Diego¹  Deagostino, Annamaria²  Toppino, Antonio²  Protti, Nicoletta^3,4  Bortolussi, Silva^3,4  Altieri, Saverio^3,4  Aime, Silvio^1,5  Crich, Simonetta Geninatti¹ 

[1] Univ Torino, Dept Mol Biotechnol & Hlth Sci, Via Nizza 52, I-10126 Turin, Italy

[2] Univ Torino, Dept Chem, Via Pietro Giuria 7, I-10125 Turin, Italy

[3] Univ Pavia, Dept Phys, Via Agostino Bassi 6, I-27100 Pavia, Italy

[4] Univ Pavia, Natl Inst Nucl Phys INFN, Via Agostino Bassi 6, I-27100 Pavia, Italy

[5] Sede Secondaria MBC, IBB CNR, Via Nizza 52, I-10126 Turin, Italy

关键词: Mesothelioma;    Boron Neutron Capture Therapy;    Magnetic Resonance Imaging (MRI);    Low Density Lipoproteins;   

DOI  :  10.1016/j.jconrel.2018.04.043

来源: Elsevier

【 摘 要 】

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 mu g/g), significantly higher than in the surrounding tissue (3.5 mu g/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.

【 授权许可】

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