Enhancement of IUdR Radiosensitization in Cancer Therapy by Low-Energy Transmission X Ray Irradiation

Chien Chih Ke; Jia Je Li; Hsueh Peng Wu; Wen Wang Kuo; Yi An Chen; Cheng Hsiu Lu; Hsin Ell Wang; Shih Ming Hsu; Ya Ju Hsieh; Ren Shyan Liu

doi:10.1007/s40846-021-00616-0

Enhancement of IUdR Radiosensitization in Cancer Therapy by Low-Energy Transmission X Ray Irradiation

Chien Chih Ke, Jia Je Li, Hsueh Peng Wu, Wen Wang Kuo, Yi An Chen, Cheng Hsiu Lu, Hsin Ell Wang, Shih Ming Hsu, Ya Ju Hsieh^*, Ren Shyan Liu

^*Corresponding author for this work

Department of Biomedical Imaging and Radiological Sciences

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

Purpose: 5-iododeoxyuridine (IUdR), a radiosensitizer able to be incorporated into nascent DNA during synthesis, makes the DNA easy to break upon irradiation. IUdR has been used together with low energy radiation in cancer treatments mechanistically by Auger electron induction to damage DNA. In this study, a small-sized transmission X-ray tube equipped with a Lanthalum target (La-tX ray) generating 33–40 keV-enriched photons was used in combination with IUdR for Auger cancer therapy, and the performance was evaluated by multiple assays in vitro and in vivo. Methods: Cytotoxicity, thymidine replacement and nuclear incorporation of IUdR were evaluated in NG4TL4 fibrosarcoma cells and SAS head and neck cancer cells. After treatment of IUdR + La-tX ray irradiation or IUdR + Co-60 irradiation, cell survival and DNA damages were evaluated by colony forming assay and comet assay/γH2AX staining, respectively. Growth of tumor xenografts receiving an intratumoral IUdR injection (45 μg) and/or La-tX ray irradiation were measured. Results: For NG4TL4 and SAS cells, the IC50 of IUdR were ~ 7 and ~ 10 μg/ml, respectively. As compared to IUdR + Co-60 irradiation, IUdR + La-tX ray resulted in higher DNA breaks in cancer cells. Also, IUdR + La-tX ray resulted in higher cell toxicity than IUdR + Co-60. In the in vivo study, tumor xenografts showed inhibited growth in the IUdR + La-tX ray treatment, compared to those in the IUdR or La-tX ray treatment alone. Conclusion: This study demonstrated the potential of cancer Auger electron therapy using a small-sized transmission X ray tube that generated enriched specific energy X rays for Auger electron induction.

Original language	English
Pages (from-to)	393-402
Number of pages	10
Journal	Journal of Medical and Biological Engineering
Volume	41
Issue number	3
DOIs	https://doi.org/10.1007/s40846-021-00616-0
State	Published - Jun 2021

Keywords

Auger electron
Cancer therapy
IUdR
Low energy X ray

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1007/s40846-021-00616-0

Cite this

@article{5456509ccbce46f1a8e9b3f3585119c0,

title = "Enhancement of IUdR Radiosensitization in Cancer Therapy by Low-Energy Transmission X Ray Irradiation",

abstract = "Purpose: 5-iododeoxyuridine (IUdR), a radiosensitizer able to be incorporated into nascent DNA during synthesis, makes the DNA easy to break upon irradiation. IUdR has been used together with low energy radiation in cancer treatments mechanistically by Auger electron induction to damage DNA. In this study, a small-sized transmission X-ray tube equipped with a Lanthalum target (La-tX ray) generating 33–40 keV-enriched photons was used in combination with IUdR for Auger cancer therapy, and the performance was evaluated by multiple assays in vitro and in vivo. Methods: Cytotoxicity, thymidine replacement and nuclear incorporation of IUdR were evaluated in NG4TL4 fibrosarcoma cells and SAS head and neck cancer cells. After treatment of IUdR + La-tX ray irradiation or IUdR + Co-60 irradiation, cell survival and DNA damages were evaluated by colony forming assay and comet assay/γH2AX staining, respectively. Growth of tumor xenografts receiving an intratumoral IUdR injection (45 μg) and/or La-tX ray irradiation were measured. Results: For NG4TL4 and SAS cells, the IC50 of IUdR were ~ 7 and ~ 10 μg/ml, respectively. As compared to IUdR + Co-60 irradiation, IUdR + La-tX ray resulted in higher DNA breaks in cancer cells. Also, IUdR + La-tX ray resulted in higher cell toxicity than IUdR + Co-60. In the in vivo study, tumor xenografts showed inhibited growth in the IUdR + La-tX ray treatment, compared to those in the IUdR or La-tX ray treatment alone. Conclusion: This study demonstrated the potential of cancer Auger electron therapy using a small-sized transmission X ray tube that generated enriched specific energy X rays for Auger electron induction.",

keywords = "Auger electron, Cancer therapy, IUdR, Low energy X ray",

author = "Ke, {Chien Chih} and Li, {Jia Je} and Wu, {Hsueh Peng} and Kuo, {Wen Wang} and Chen, {Yi An} and Lu, {Cheng Hsiu} and Wang, {Hsin Ell} and Hsu, {Shih Ming} and Hsieh, {Ya Ju} and Liu, {Ren Shyan}",

note = "Publisher Copyright: {\textcopyright} 2021, Taiwanese Society of Biomedical Engineering.",

year = "2021",

month = jun,

doi = "10.1007/s40846-021-00616-0",

language = "English",

volume = "41",

pages = "393--402",

journal = "Journal of Medical and Biological Engineering",

issn = "1609-0985",

publisher = "Springer Science and Business Media Deutschland GmbH",

number = "3",

}

TY - JOUR

T1 - Enhancement of IUdR Radiosensitization in Cancer Therapy by Low-Energy Transmission X Ray Irradiation

AU - Ke, Chien Chih

AU - Li, Jia Je

AU - Wu, Hsueh Peng

AU - Kuo, Wen Wang

AU - Chen, Yi An

AU - Lu, Cheng Hsiu

AU - Wang, Hsin Ell

AU - Hsu, Shih Ming

AU - Hsieh, Ya Ju

AU - Liu, Ren Shyan

PY - 2021/6

Y1 - 2021/6

N2 - Purpose: 5-iododeoxyuridine (IUdR), a radiosensitizer able to be incorporated into nascent DNA during synthesis, makes the DNA easy to break upon irradiation. IUdR has been used together with low energy radiation in cancer treatments mechanistically by Auger electron induction to damage DNA. In this study, a small-sized transmission X-ray tube equipped with a Lanthalum target (La-tX ray) generating 33–40 keV-enriched photons was used in combination with IUdR for Auger cancer therapy, and the performance was evaluated by multiple assays in vitro and in vivo. Methods: Cytotoxicity, thymidine replacement and nuclear incorporation of IUdR were evaluated in NG4TL4 fibrosarcoma cells and SAS head and neck cancer cells. After treatment of IUdR + La-tX ray irradiation or IUdR + Co-60 irradiation, cell survival and DNA damages were evaluated by colony forming assay and comet assay/γH2AX staining, respectively. Growth of tumor xenografts receiving an intratumoral IUdR injection (45 μg) and/or La-tX ray irradiation were measured. Results: For NG4TL4 and SAS cells, the IC50 of IUdR were ~ 7 and ~ 10 μg/ml, respectively. As compared to IUdR + Co-60 irradiation, IUdR + La-tX ray resulted in higher DNA breaks in cancer cells. Also, IUdR + La-tX ray resulted in higher cell toxicity than IUdR + Co-60. In the in vivo study, tumor xenografts showed inhibited growth in the IUdR + La-tX ray treatment, compared to those in the IUdR or La-tX ray treatment alone. Conclusion: This study demonstrated the potential of cancer Auger electron therapy using a small-sized transmission X ray tube that generated enriched specific energy X rays for Auger electron induction.

AB - Purpose: 5-iododeoxyuridine (IUdR), a radiosensitizer able to be incorporated into nascent DNA during synthesis, makes the DNA easy to break upon irradiation. IUdR has been used together with low energy radiation in cancer treatments mechanistically by Auger electron induction to damage DNA. In this study, a small-sized transmission X-ray tube equipped with a Lanthalum target (La-tX ray) generating 33–40 keV-enriched photons was used in combination with IUdR for Auger cancer therapy, and the performance was evaluated by multiple assays in vitro and in vivo. Methods: Cytotoxicity, thymidine replacement and nuclear incorporation of IUdR were evaluated in NG4TL4 fibrosarcoma cells and SAS head and neck cancer cells. After treatment of IUdR + La-tX ray irradiation or IUdR + Co-60 irradiation, cell survival and DNA damages were evaluated by colony forming assay and comet assay/γH2AX staining, respectively. Growth of tumor xenografts receiving an intratumoral IUdR injection (45 μg) and/or La-tX ray irradiation were measured. Results: For NG4TL4 and SAS cells, the IC50 of IUdR were ~ 7 and ~ 10 μg/ml, respectively. As compared to IUdR + Co-60 irradiation, IUdR + La-tX ray resulted in higher DNA breaks in cancer cells. Also, IUdR + La-tX ray resulted in higher cell toxicity than IUdR + Co-60. In the in vivo study, tumor xenografts showed inhibited growth in the IUdR + La-tX ray treatment, compared to those in the IUdR or La-tX ray treatment alone. Conclusion: This study demonstrated the potential of cancer Auger electron therapy using a small-sized transmission X ray tube that generated enriched specific energy X rays for Auger electron induction.

KW - Auger electron

KW - Cancer therapy

KW - IUdR

KW - Low energy X ray

UR - http://www.scopus.com/inward/record.url?scp=85106713202&partnerID=8YFLogxK

U2 - 10.1007/s40846-021-00616-0

DO - 10.1007/s40846-021-00616-0

M3 - Article

AN - SCOPUS:85106713202

SN - 1609-0985

VL - 41

SP - 393

EP - 402

JO - Journal of Medical and Biological Engineering

JF - Journal of Medical and Biological Engineering

IS - 3

ER -

Enhancement of IUdR Radiosensitization in Cancer Therapy by Low-Energy Transmission X Ray Irradiation

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this