Limits...
Introduction to radiobiology of targeted radionuclide therapy.

Pouget JP, Lozza C, Deshayes E, Boudousq V, Navarro-Teulon I - Front Med (Lausanne) (2015)

Bottom Line: Determining dose-effect correlation is also a prerequisite for rigorous preclinical radiobiology studies because dosimetry provides the necessary referential to all TRT situations.However, conversely to EBRT where it is routinely used, dosimetry is still challenging in TRT.Therefore, it constitutes with radiobiology, one of the main challenges of TRT in the future.

View Article: PubMed Central - PubMed

Affiliation: Institut de Recherche en Cancérologie de Montpellier , Montpellier , France ; INSERM, U1194 , Montpellier , France ; Université de Montpellier , Montpellier , France ; Institut régional du Cancer de Montpellier , Montpellier , France.

ABSTRACT
During the last decades, new radionuclide-based targeted therapies have emerged as efficient tools for cancer treatment. Targeted radionuclide therapies (TRTs) are based on a multidisciplinary approach that involves the cooperation of specialists in several research fields. Among them, radiobiologists investigate the biological effects of ionizing radiation, specifically the molecular and cellular mechanisms involved in the radiation response. Most of the knowledge about radiation effects concerns external beam radiation therapy (EBRT) and radiobiology has then strongly contributed to the development of this therapeutic approach. Similarly, radiobiology and dosimetry are also assumed to be ways for improving TRT, in particular in the therapy of solid tumors, which are radioresistant. However, extrapolation of EBRT radiobiology to TRT is not straightforward. Indeed, the specific physical characteristics of TRT (heterogeneous and mixed irradiation, protracted exposure, and low absorbed dose rate) differ from those of conventional EBRT (homogeneous irradiation, short exposure, and high absorbed dose rate), and consequently the response of irradiated tissues might be different. Therefore, specific TRT radiobiology needs to be explored. Determining dose-effect correlation is also a prerequisite for rigorous preclinical radiobiology studies because dosimetry provides the necessary referential to all TRT situations. It is required too for developing patient-tailored TRT in the clinic in order to estimate the best dose for tumor control, while protecting the healthy tissues, thereby improving therapeutic efficacy. Finally, it will allow to determine the relative contribution of targeted effects (assumed to be dose-related) and non-targeted effects (assumed to be non-dose-related) of ionizing radiation. However, conversely to EBRT where it is routinely used, dosimetry is still challenging in TRT. Therefore, it constitutes with radiobiology, one of the main challenges of TRT in the future.

No MeSH data available.


Related in: MedlinePlus

Targeted and non-targeted effects in targeted radionuclide therapy. Targeted effects are caused by one or more particles crossing irradiated cells and can be due to self-irradiation and cross-fire irradiation. Non-targeted effects include effects observed in cells close to irradiated cells and also long-distance effects. The nature of the dose–effect relationship resulting from targeted and non-targeted effects needs to be determined. For more details, see the main text.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4362338&req=5

Figure 2: Targeted and non-targeted effects in targeted radionuclide therapy. Targeted effects are caused by one or more particles crossing irradiated cells and can be due to self-irradiation and cross-fire irradiation. Non-targeted effects include effects observed in cells close to irradiated cells and also long-distance effects. The nature of the dose–effect relationship resulting from targeted and non-targeted effects needs to be determined. For more details, see the main text.

Mentions: Beside EBRT improvements, TRT has emerged as an attractive approach for treating tumors during the twentieth century. In TRT, a radionuclide is coupled to a vector [for instance, monoclonal antibodies (mAbs) or peptides] directed against cancer cells or their environment to specifically irradiate only the tumor targets. Therefore, TRT is particularly attractive when conventional EBRT (CEBRT) cannot be used due to unacceptable toxicities toward healthy tissues. This is the case of disseminated disease, metastases, or tumors located in close vicinity of sensitive organs. Compared to chemotherapy, it offers the possibility to specifically target tumor cells, thereby reducing the side effects, and also to treat distant tumor cells (which cannot be directly reached by the drug) through cross-fire irradiation (i.e., energy deposition in cells that are not specifically targeted) (Figure 2).


Introduction to radiobiology of targeted radionuclide therapy.

Pouget JP, Lozza C, Deshayes E, Boudousq V, Navarro-Teulon I - Front Med (Lausanne) (2015)

Targeted and non-targeted effects in targeted radionuclide therapy. Targeted effects are caused by one or more particles crossing irradiated cells and can be due to self-irradiation and cross-fire irradiation. Non-targeted effects include effects observed in cells close to irradiated cells and also long-distance effects. The nature of the dose–effect relationship resulting from targeted and non-targeted effects needs to be determined. For more details, see the main text.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4362338&req=5

Figure 2: Targeted and non-targeted effects in targeted radionuclide therapy. Targeted effects are caused by one or more particles crossing irradiated cells and can be due to self-irradiation and cross-fire irradiation. Non-targeted effects include effects observed in cells close to irradiated cells and also long-distance effects. The nature of the dose–effect relationship resulting from targeted and non-targeted effects needs to be determined. For more details, see the main text.
Mentions: Beside EBRT improvements, TRT has emerged as an attractive approach for treating tumors during the twentieth century. In TRT, a radionuclide is coupled to a vector [for instance, monoclonal antibodies (mAbs) or peptides] directed against cancer cells or their environment to specifically irradiate only the tumor targets. Therefore, TRT is particularly attractive when conventional EBRT (CEBRT) cannot be used due to unacceptable toxicities toward healthy tissues. This is the case of disseminated disease, metastases, or tumors located in close vicinity of sensitive organs. Compared to chemotherapy, it offers the possibility to specifically target tumor cells, thereby reducing the side effects, and also to treat distant tumor cells (which cannot be directly reached by the drug) through cross-fire irradiation (i.e., energy deposition in cells that are not specifically targeted) (Figure 2).

Bottom Line: Determining dose-effect correlation is also a prerequisite for rigorous preclinical radiobiology studies because dosimetry provides the necessary referential to all TRT situations.However, conversely to EBRT where it is routinely used, dosimetry is still challenging in TRT.Therefore, it constitutes with radiobiology, one of the main challenges of TRT in the future.

View Article: PubMed Central - PubMed

Affiliation: Institut de Recherche en Cancérologie de Montpellier , Montpellier , France ; INSERM, U1194 , Montpellier , France ; Université de Montpellier , Montpellier , France ; Institut régional du Cancer de Montpellier , Montpellier , France.

ABSTRACT
During the last decades, new radionuclide-based targeted therapies have emerged as efficient tools for cancer treatment. Targeted radionuclide therapies (TRTs) are based on a multidisciplinary approach that involves the cooperation of specialists in several research fields. Among them, radiobiologists investigate the biological effects of ionizing radiation, specifically the molecular and cellular mechanisms involved in the radiation response. Most of the knowledge about radiation effects concerns external beam radiation therapy (EBRT) and radiobiology has then strongly contributed to the development of this therapeutic approach. Similarly, radiobiology and dosimetry are also assumed to be ways for improving TRT, in particular in the therapy of solid tumors, which are radioresistant. However, extrapolation of EBRT radiobiology to TRT is not straightforward. Indeed, the specific physical characteristics of TRT (heterogeneous and mixed irradiation, protracted exposure, and low absorbed dose rate) differ from those of conventional EBRT (homogeneous irradiation, short exposure, and high absorbed dose rate), and consequently the response of irradiated tissues might be different. Therefore, specific TRT radiobiology needs to be explored. Determining dose-effect correlation is also a prerequisite for rigorous preclinical radiobiology studies because dosimetry provides the necessary referential to all TRT situations. It is required too for developing patient-tailored TRT in the clinic in order to estimate the best dose for tumor control, while protecting the healthy tissues, thereby improving therapeutic efficacy. Finally, it will allow to determine the relative contribution of targeted effects (assumed to be dose-related) and non-targeted effects (assumed to be non-dose-related) of ionizing radiation. However, conversely to EBRT where it is routinely used, dosimetry is still challenging in TRT. Therefore, it constitutes with radiobiology, one of the main challenges of TRT in the future.

No MeSH data available.


Related in: MedlinePlus