Comparative study of the radiobiological effects induced on adherent vs suspended cells by BNCT, neutrons and gamma rays treatments

Cansolino, Laura; Clerici, Anna Maria; Zonta, C.; Dionigi, Paolo; Mazzini, Giuliano; Liberto, Riccardo Di; Altieri, S.; Ballarini, F.; Bortolussi, Silva; Carante, Mario Pietro; Ferrari, Matteo; González, Sara Josefina; Postuma, Ian; Protti, Nicoletta; Cruz, Gustavo A. Santa; Ferrari, Cinzia

doi:10.1016/j.apradiso.2015.07.054

Cited by 5 publications

(5 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3 Rat osteosarcoma UMR-106 cell survival curves as a function of the absorbed dose. Experimental values correspond to data published in [ 21 ], and the new measurements carried out in this work …”

Section: Resultssupporting

confidence: 84%

“…Figure 3 depicts the UMR-106 cell survival data along with the fit for the photon reference radiation, the neutron beam-only component (without presence of boron) and the neutron beam with boron. Reported experimental values account for data published in previous studies [ 21 ], and for new experiments carried out in this work. The uncertainty of the dose values in the beam-only curve is dominated by the error of the boron concentration measured, in the order of 1 ppm, close to the sensitivity limit of the measurement technique.…”

Section: Resultsmentioning

confidence: 99%

“…The experimental points were fitted using a modified linear quadratic model, that provided both CBE/RBE factors for osteosarcoma, and the parameters for the iso-effective dose calculation. The assessment of cell survival as a function of the dose has been previously reported [ 21 ]. Neutron irradiations took place in the Thermal Column of the TRIGA reactor, University of Pavia, and photon irradiation (Co-60 source) at the S. Matteo Polyclinic Foundation in Pavia.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Understanding the potentiality of accelerator based-boron neutron capture therapy for osteosarcoma: dosimetry assessment based on the reported clinical experience

et al. 2017

View full text Add to dashboard Cite

BackgroundOsteosarcoma is the most frequent primary malignant bone tumour, and its incidence is higher in children and adolescents, for whom it represents more than 10% of solid cancers. Despite the introduction of adjuvant and neo-adjuvant chemotherapy that markedly increased the success rate in the treatment, aggressive surgery is still needed and a considerable percentage of patients do not survive due to recurrences or early metastases. Boron Neutron Capture Therapy (BNCT), an experimental radiotherapy, was investigated as a treatment that could allow a less aggressive surgery by killing infiltrated tumour cells in the surrounding healthy tissues. BNCT requires an intense neutron beam to ensure irradiation times of the order of 1 h. In Italy, a Radio Frequency Quadrupole (RFQ) proton accelerator has been designed and constructed for BNCT, and a suitable neutron spectrum was tailored by means of Monte Carlo calculations. This paper explores the feasibility of BNCT to treat osteosarcoma using this neutron source based on accelerator.MethodsThe therapeutic efficacy of BNCT was analysed evaluating the dose distribution obtained in a clinical case of femur osteosarcoma. Mixed field dosimetry was assessed with two different formalisms whose parameters were specifically derived from radiobiological experiments involving in vitro UMR-106 osteosarcoma cell survival assays and boron concentration assessments in an animal model of osteosarcoma. A clinical case of skull osteosarcoma treated with BNCT in Japan was re-evaluated from the point of view of dose calculation and used as a reference for comparison.ResultsThe results in the case of femur osteosarcoma show that the RFQ beam would ensure a suitable tumour dose painting in a total irradiation time of less than an hour. Comparing the dosimetry between the analysed case and the treated patient in Japan it turns out that doses obtained in the femur tumour are at least as good as the ones delivered in the skull osteosarcoma. The same is concluded when the comparison is carried out taking into account osteosarcoma irradiations with photon radiation therapy.ConclusionsThe possibility to apply BNCT to osteosarcoma would allow a multimodal treatment consisting in neo-adjuvant chemotherapy, high-LET selective radiation treatment and a more conservative surgery.

show abstract

Section: Resultssupporting

confidence: 84%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Understanding the potentiality of accelerator based-boron neutron capture therapy for osteosarcoma: dosimetry assessment based on the reported clinical experience

et al. 2017

View full text Add to dashboard Cite

show abstract

“…A common feature of our study and others [ 22 , 34 ] is the use of cell suspensions for the irradiation. A study investigating different cell culture models used during the irradiation was led by Cansolino and colleagues [ 35 ]. Here, the SF for cell suspension and adherent cells was determined for rat colon adenocarcinoma cell lines.…”

Section: Discussionmentioning

confidence: 99%

Comparative study of the effects of different radiation qualities on normal human breast cells

et al. 2017

View full text Add to dashboard Cite

BackgroundAs there is a growing number of long-term cancer survivors, the incidence of carcinogenesis as a late effect of radiotherapy is getting more and more into the focus. The risk for the development of secondary malignant neoplasms might be significantly increased due to exposure of healthy tissue outside of the target field to secondary neutrons, in particular in proton therapy. Thus far, the radiobiological effects of these neutrons and a comparison with photons on normal breast cells have not been sufficiently characterised.MethodsMCF10A cells were irradiated with doses of up to 2 Gy with neutrons of different energy spectra and X-rays for comparison. The biological effects of neutrons with a broad energy distribution ( = 5.8 MeV), monoenergetic neutrons (1.2 MeV, 0.56 MeV) and of the mixed field of gamma’s and secondary neutrons ( = 70.5 MeV) produced by 190 MeV protons impinging on a water phantom, were analysed. The clonogenic survival and the DNA repair capacity were determined and values of relative biological effectiveness were compared. Furthermore, the influence of radiation on the sphere formation was observed to examine the radiation response of the potential fraction of stem like cells within the MCF10A cell population.ResultsX-rays and neutrons caused dose-dependent decreases of survival fractions after irradiations with up to 2 Gy. Monoenergetic neutrons with an energy of 0.56 MeV had a higher effectiveness on the survival fraction with respect to neutrons with higher energies and to the mixed gamma - secondary neutron field induced by proton interactions in water. Similar effects were observed for the DNA repair capacity after exposure to ionising radiation (IR). Both experimental endpoints provided comparable values of the relative biological effectiveness. Significant changes in the sphere formation were notable following the various radiation qualities.ConclusionThe present study compared the radiation response of MCF10A cells after IR with neutrons and photons. For the first time it was shown that monoenergetic neutrons with energies around 1 MeV have stronger radiobiological effects on normal human breast cells with respect to X rays, to neutrons with a broad energy distribution ( = 5.8 MeV), and to the mixed gamma - secondary neutron field given by interactions of 190 MeV protons in water. The results of the present study are highly relevant for further investigations of radiation-induced carcinogenesis and are very important in perspective for a better risk assessment after secondary neutron exposure in the field of conventional and proton radiotherapy.Electronic supplementary materialThe online version of this article (10.1186/s13014-017-0895-8) contains supplementary material, which is available to authorized users.

show abstract

“…The in vitro neutron irradiation experimental procedures were modified from reported studies [59, 60]: cells seeded in 96-well plates at a density of 3,000/100 μL/well were cultured for 24 h, and 200 μL of each of the formulations suspended in medium at a final equivalent concentration of 20 μg/mL 10 B. Following 3 h or 16 h incubation, cells were washed three times and 450 μL fresh medium was added to fully fill each well.…”

Section: Methodsmentioning

confidence: 99%

Cyclic-RGDyC functionalized liposomes for dual-targeting of tumor vasculature and cancer cells in glioblastoma: An in vitro boron neutron capture therapy study

et al. 2017

View full text Add to dashboard Cite

The efficacy of boron neutron capture therapy depends on the selective delivery of 10B to the target. Integrins αvβ3 are transmembrane receptors over-expressed in both glioblastoma cells and its neovasculature. In this study, a novel approach to dual-target glioblastoma vasculature and tumor cells was investigated. Liposomes (124 nm) were conjugated with a αvβ3 ligand, cyclic arginine-glycine-aspartic acid-tyrosine-cysteine peptide (c(RGDyC)-LP) (1% molar ratio) through thiol-maleimide coupling. Expression of αvβ3 in glioblastoma cells (U87) and human umbilical vein endothelial cells (HUVEC), representing tumor angiogenesis, was determined using Western Blotting with other cells as references. The results showed that both U87 and HUVEC had stronger expression of αvβ3 than other cell types, and the degree of cellular uptake of c(RGDyC)-LP correlated with the αvβ3-expression levels of the cells. In contrast, control liposomes without c(RGDyC) showed little cellular uptake, regardless of cell type. In an in vitro boron neutron capture therapy study, the c(RGDyC)-LP containing sodium borocaptate generated more rapid and significant lethal effects to both U87 and HUVEC than the control liposomes and drug solution. Interestingly, neutron irradiated U87 and HUVEC showed different types of subsequent cell death. In conclusion, this study has demonstrated the potential of a new dual-targeting strategy using c(RGDyC)-LP to improve boron neutron capture therapy for glioblastoma.

show abstract

Comparative study of the radiobiological effects induced on adherent vs suspended cells by BNCT, neutrons and gamma rays treatments

Cited by 5 publications

References 25 publications

Understanding the potentiality of accelerator based-boron neutron capture therapy for osteosarcoma: dosimetry assessment based on the reported clinical experience

Understanding the potentiality of accelerator based-boron neutron capture therapy for osteosarcoma: dosimetry assessment based on the reported clinical experience

Comparative study of the effects of different radiation qualities on normal human breast cells

Cyclic-RGDyC functionalized liposomes for dual-targeting of tumor vasculature and cancer cells in glioblastoma: An in vitro boron neutron capture therapy study

Contact Info

Product

Resources

About