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Nanoparticles for Radiation Therapy Enhancement: the Key Parameters.

Retif P, Pinel S, Toussaint M, Frochot C, Chouikrat R, Bastogne T, Barberi-Heyob M - Theranostics (2015)

Bottom Line: It does not establish an exhaustive list of the works in this field but rather propose constructive criticisms pointing out critical factors that could improve the nano-radiation therapy.Whereas most reviews show the chemists and/or biologists points of view, the present analysis is also seen through the prism of the medical physicist.We observed a lack of standardization in preclinical studies that could partially explain the low number of translation to clinical applications for this innovative therapeutic strategy.

View Article: PubMed Central - PubMed

Affiliation: 1. CHR Metz-Thionville, Hôpital de Mercy, Service de radiothérapie, 1 allée du Château, Ars-Laquenexy, 57530, France; ; 2. Université de Lorraine, CRAN, UMR 7039, Campus Sciences, BP 70239, Vandœuvre-lès-Nancy Cedex, 54506, France; ; 3. CNRS, CRAN, UMR 7039, Vandœuvre-lès-Nancy Cedex, 54506, France;

ABSTRACT
This review focuses on the radiosensitization strategies that use high-Z nanoparticles. It does not establish an exhaustive list of the works in this field but rather propose constructive criticisms pointing out critical factors that could improve the nano-radiation therapy. Whereas most reviews show the chemists and/or biologists points of view, the present analysis is also seen through the prism of the medical physicist. In particular, we described and evaluated the influence of X-rays energy spectra using a numerical analysis. We observed a lack of standardization in preclinical studies that could partially explain the low number of translation to clinical applications for this innovative therapeutic strategy. Pointing out the critical parameters of high-Z nanoparticles radiosensitization, this review is expected to contribute to a larger preclinical and clinical development.

No MeSH data available.


Plot of the calculated DMF values from publications versus beam energy. For energies up to 200 kV, we identified 21 publications dealing with in vitro, 2 in vivo and 2 with both in vitro and in vivo experiments during the period 2008-2014. In the range from 200 kV to 1 MV, 3 in vitro publications were studied. Upon in vitro experiments, the DMF varies from 0.1 to 1.2. Lower values (which are representative of a high radiosensitization) were observed for lower energies. Concerning high-energy beams, 13 publications were analyzed for in vitro, 1 for in vivo experiments and 1 for both; 1 used a 4 MV beam, 13 a 6 MV, 1 a 10 MV and 1 a 15 MV. Upon in vitro experiments, the DMF varies from 0.7 to 0.8 for passive GNP, 0.5 for PEG-coated GNP and 0.6 for a Photofrin® and quantum dots combination.
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Figure 3: Plot of the calculated DMF values from publications versus beam energy. For energies up to 200 kV, we identified 21 publications dealing with in vitro, 2 in vivo and 2 with both in vitro and in vivo experiments during the period 2008-2014. In the range from 200 kV to 1 MV, 3 in vitro publications were studied. Upon in vitro experiments, the DMF varies from 0.1 to 1.2. Lower values (which are representative of a high radiosensitization) were observed for lower energies. Concerning high-energy beams, 13 publications were analyzed for in vitro, 1 for in vivo experiments and 1 for both; 1 used a 4 MV beam, 13 a 6 MV, 1 a 10 MV and 1 a 15 MV. Upon in vitro experiments, the DMF varies from 0.7 to 0.8 for passive GNP, 0.5 for PEG-coated GNP and 0.6 for a Photofrin® and quantum dots combination.

Mentions: A plot of the calculated DMF values versus beam energy is illustrated on figure 3. Due to the multitude of irradiations settings and environments between experiments, the inter-study comparison of the DMF should be considered with care. Moreover, in some studies, the energy is not the only parameter that varied. Therefore, in order to analyze the source energy parameter only, we have decided to focus on the analysis of papers where the energy was the only variable (Fig. 3). Rahman et al.49 reported high dose enhancement (DMF ≤ 0.1) at 80 and 150 kV in the same study. Survival curves were obtained using a colorimetric method. It seems that in the presence of NPs, curves do not follow the LQ model anymore (α → 0 when the concentration increases). The authors concluded that their results gave an indication of some energy dependence because the source was the only parameter that was changed. Brun et al.40 assessed the effect of 6 combinations energy/filtration. They could not clearly observe an energy dependence but did not directly measure the cell survival. Their conclusions were based on a plot of the dose enhancement factor versus the effective X-ray energy but the enhancement factor was linked to the loss of supercoiled DNA. In another study, Brun et al. 50 evaluated the enhancement of X-ray-induced degradations of human centrin 2 proteins (Hscen2). Centrins are small acidic proteins, highly conserved in eukaryotes, from algae and yeast to humans. They demonstrated that X-ray-induced degradations could not lead to explicit energy dependence. However, one could regret that non-standard biological assays were used in these studies. Recently, Rahman et al. 51 observed the influence of the energy of synchrotron-based mono-energetic photon beams (from 30 to 100 keV) and found out that the optimal energy was 40 keV. However, no correlation was made between the source energy and the in-vitro radiosensitization by NPs.


Nanoparticles for Radiation Therapy Enhancement: the Key Parameters.

Retif P, Pinel S, Toussaint M, Frochot C, Chouikrat R, Bastogne T, Barberi-Heyob M - Theranostics (2015)

Plot of the calculated DMF values from publications versus beam energy. For energies up to 200 kV, we identified 21 publications dealing with in vitro, 2 in vivo and 2 with both in vitro and in vivo experiments during the period 2008-2014. In the range from 200 kV to 1 MV, 3 in vitro publications were studied. Upon in vitro experiments, the DMF varies from 0.1 to 1.2. Lower values (which are representative of a high radiosensitization) were observed for lower energies. Concerning high-energy beams, 13 publications were analyzed for in vitro, 1 for in vivo experiments and 1 for both; 1 used a 4 MV beam, 13 a 6 MV, 1 a 10 MV and 1 a 15 MV. Upon in vitro experiments, the DMF varies from 0.7 to 0.8 for passive GNP, 0.5 for PEG-coated GNP and 0.6 for a Photofrin® and quantum dots combination.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4493540&req=5

Figure 3: Plot of the calculated DMF values from publications versus beam energy. For energies up to 200 kV, we identified 21 publications dealing with in vitro, 2 in vivo and 2 with both in vitro and in vivo experiments during the period 2008-2014. In the range from 200 kV to 1 MV, 3 in vitro publications were studied. Upon in vitro experiments, the DMF varies from 0.1 to 1.2. Lower values (which are representative of a high radiosensitization) were observed for lower energies. Concerning high-energy beams, 13 publications were analyzed for in vitro, 1 for in vivo experiments and 1 for both; 1 used a 4 MV beam, 13 a 6 MV, 1 a 10 MV and 1 a 15 MV. Upon in vitro experiments, the DMF varies from 0.7 to 0.8 for passive GNP, 0.5 for PEG-coated GNP and 0.6 for a Photofrin® and quantum dots combination.
Mentions: A plot of the calculated DMF values versus beam energy is illustrated on figure 3. Due to the multitude of irradiations settings and environments between experiments, the inter-study comparison of the DMF should be considered with care. Moreover, in some studies, the energy is not the only parameter that varied. Therefore, in order to analyze the source energy parameter only, we have decided to focus on the analysis of papers where the energy was the only variable (Fig. 3). Rahman et al.49 reported high dose enhancement (DMF ≤ 0.1) at 80 and 150 kV in the same study. Survival curves were obtained using a colorimetric method. It seems that in the presence of NPs, curves do not follow the LQ model anymore (α → 0 when the concentration increases). The authors concluded that their results gave an indication of some energy dependence because the source was the only parameter that was changed. Brun et al.40 assessed the effect of 6 combinations energy/filtration. They could not clearly observe an energy dependence but did not directly measure the cell survival. Their conclusions were based on a plot of the dose enhancement factor versus the effective X-ray energy but the enhancement factor was linked to the loss of supercoiled DNA. In another study, Brun et al. 50 evaluated the enhancement of X-ray-induced degradations of human centrin 2 proteins (Hscen2). Centrins are small acidic proteins, highly conserved in eukaryotes, from algae and yeast to humans. They demonstrated that X-ray-induced degradations could not lead to explicit energy dependence. However, one could regret that non-standard biological assays were used in these studies. Recently, Rahman et al. 51 observed the influence of the energy of synchrotron-based mono-energetic photon beams (from 30 to 100 keV) and found out that the optimal energy was 40 keV. However, no correlation was made between the source energy and the in-vitro radiosensitization by NPs.

Bottom Line: It does not establish an exhaustive list of the works in this field but rather propose constructive criticisms pointing out critical factors that could improve the nano-radiation therapy.Whereas most reviews show the chemists and/or biologists points of view, the present analysis is also seen through the prism of the medical physicist.We observed a lack of standardization in preclinical studies that could partially explain the low number of translation to clinical applications for this innovative therapeutic strategy.

View Article: PubMed Central - PubMed

Affiliation: 1. CHR Metz-Thionville, Hôpital de Mercy, Service de radiothérapie, 1 allée du Château, Ars-Laquenexy, 57530, France; ; 2. Université de Lorraine, CRAN, UMR 7039, Campus Sciences, BP 70239, Vandœuvre-lès-Nancy Cedex, 54506, France; ; 3. CNRS, CRAN, UMR 7039, Vandœuvre-lès-Nancy Cedex, 54506, France;

ABSTRACT
This review focuses on the radiosensitization strategies that use high-Z nanoparticles. It does not establish an exhaustive list of the works in this field but rather propose constructive criticisms pointing out critical factors that could improve the nano-radiation therapy. Whereas most reviews show the chemists and/or biologists points of view, the present analysis is also seen through the prism of the medical physicist. In particular, we described and evaluated the influence of X-rays energy spectra using a numerical analysis. We observed a lack of standardization in preclinical studies that could partially explain the low number of translation to clinical applications for this innovative therapeutic strategy. Pointing out the critical parameters of high-Z nanoparticles radiosensitization, this review is expected to contribute to a larger preclinical and clinical development.

No MeSH data available.