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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.


(A) Illustration of a clinical scenario where a volume (blue) has to be irradiated while a part of an organ (green) has to be protected. (B) A simple anterior beam is irradiating the blue volume. (C) The beam energy is maximum in the irradiation field and is reduced out of the field. (D) Given that the interaction probability is higher for low-energy photons, the radiosensitization in presence of NPs should be higher out of the irradiation field. In this case, the green volume that has to be protected would be in the most radiosenzitized area.
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Figure 6: (A) Illustration of a clinical scenario where a volume (blue) has to be irradiated while a part of an organ (green) has to be protected. (B) A simple anterior beam is irradiating the blue volume. (C) The beam energy is maximum in the irradiation field and is reduced out of the field. (D) Given that the interaction probability is higher for low-energy photons, the radiosensitization in presence of NPs should be higher out of the irradiation field. In this case, the green volume that has to be protected would be in the most radiosenzitized area.

Mentions: As organs at risks may be at the vicinity of the tumor and given that there is some evidence of an energy dependence of the radiosensitization by NPs, this observation has to be taken into consideration when prescribing NPs (Fig. 6). Therefore, it is of utmost importance that radiosensitizing NPs concentrate in the tumor and not in the healthy organs at its vicinity. That is why it has been suggested that GNP-based radiosensitizers should have targeting moieties (e.g. glucose, antibodies) to improve NP uptake by tumor cells. For example, Chattopadhyay et al. demonstrated that trastuzumab-conjugated GNPs were well-internalized into HER-2 overexpressing SK-BR-3 breast cancer, while non-targeted NPs had little or no internalization in these cells, and trastuzumab-conjugated GNP have led to 5 times more DNA double strand breaks than the non-targeted GNP. It should also be noticed that the energy spectrum of radiation therapy beams always depends on the clinical setting (depth, field size, in-field localization of NPs, etc.). Scarboro et al. calculated 6 MV energy spectra variations with treatment parameters 62. They showed that when the depth along the central axis increased, the low-energy contribution of the spectrum increased and the high-energy part decreased. For instance, for a 10 cm x 10 cm field, at a depth of 10.0 cm the flux of particles which carry an energy of 100 keV is two times more important than at a depth of 1.6 cm. Therefore, the radiosensitizing effect of NPs may be slightly more important for deep tumors. They also noticed that off axis spectra contained dramatically more low energy components that central axis ones.


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)

(A) Illustration of a clinical scenario where a volume (blue) has to be irradiated while a part of an organ (green) has to be protected. (B) A simple anterior beam is irradiating the blue volume. (C) The beam energy is maximum in the irradiation field and is reduced out of the field. (D) Given that the interaction probability is higher for low-energy photons, the radiosensitization in presence of NPs should be higher out of the irradiation field. In this case, the green volume that has to be protected would be in the most radiosenzitized area.
© Copyright Policy
Related In: Results  -  Collection

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Figure 6: (A) Illustration of a clinical scenario where a volume (blue) has to be irradiated while a part of an organ (green) has to be protected. (B) A simple anterior beam is irradiating the blue volume. (C) The beam energy is maximum in the irradiation field and is reduced out of the field. (D) Given that the interaction probability is higher for low-energy photons, the radiosensitization in presence of NPs should be higher out of the irradiation field. In this case, the green volume that has to be protected would be in the most radiosenzitized area.
Mentions: As organs at risks may be at the vicinity of the tumor and given that there is some evidence of an energy dependence of the radiosensitization by NPs, this observation has to be taken into consideration when prescribing NPs (Fig. 6). Therefore, it is of utmost importance that radiosensitizing NPs concentrate in the tumor and not in the healthy organs at its vicinity. That is why it has been suggested that GNP-based radiosensitizers should have targeting moieties (e.g. glucose, antibodies) to improve NP uptake by tumor cells. For example, Chattopadhyay et al. demonstrated that trastuzumab-conjugated GNPs were well-internalized into HER-2 overexpressing SK-BR-3 breast cancer, while non-targeted NPs had little or no internalization in these cells, and trastuzumab-conjugated GNP have led to 5 times more DNA double strand breaks than the non-targeted GNP. It should also be noticed that the energy spectrum of radiation therapy beams always depends on the clinical setting (depth, field size, in-field localization of NPs, etc.). Scarboro et al. calculated 6 MV energy spectra variations with treatment parameters 62. They showed that when the depth along the central axis increased, the low-energy contribution of the spectrum increased and the high-energy part decreased. For instance, for a 10 cm x 10 cm field, at a depth of 10.0 cm the flux of particles which carry an energy of 100 keV is two times more important than at a depth of 1.6 cm. Therefore, the radiosensitizing effect of NPs may be slightly more important for deep tumors. They also noticed that off axis spectra contained dramatically more low energy components that central axis ones.

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.