Targeted alpha therapies using 211At: A Geant4 simulation of dose and DNA damage

Chiara De Sio; Laura Ballisat; Lana M G Beck; Susanna Guatelli; Dousatsu Sakata; Yuyao Shi; Jinyan Duan; Lujin H S Abu Sabah; Jaap J Velthuis; Anatoly Rosenfeld

doi:10.1016/j.ejmp.2024.104860

Targeted alpha therapies using ²¹¹At: A Geant4 simulation of dose and DNA damage

Chiara De Sio^*
, Laura Ballisat
, Lana M G Beck
, Susanna Guatelli
, Dousatsu Sakata
, Yuyao Shi
, Jinyan Duan
, Lujin H S Abu Sabah
, Jaap J Velthuis
, Anatoly Rosenfeld

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

5 Citations (Scopus)

101 Downloads (Pure)

Abstract

Introduction:
Targeted alpha therapies show great potential for cancer treatment due to their high linear energy transfer (LET) and low range. ²¹¹At is currently employed in clinical trials. Targeted alpha therapies (TAT) are effective as an adjuvant treatment for cancer or to treat micrometastases and diffuse cancers. A deeper understanding of the induced initial damage is crucial to enhance treatment planning.

Methods:
This study shows Geant4(-DNA)-based simulations to calculate absorbed dose profiles and DNA damaging potential in intravenously administered TAT with ²¹¹At. It assumes radionuclide decay on the blood vessel wall, and calculates the DNA damage in the surrounding tissue.

Results:
The calculated dosimetric quantities show that the effect of such treatment is mainly due to the emitted alpha particles, and is localised in a region of up to 80 μm from the blood vessel. The RBE of the treatment is in the range 2.5 - 4, and is calculated as a function of the number of double-strand breaks.

Conclusions:
Targeted therapies with ²¹¹At are effective within the range of the emitted alpha particles. With its capacity to induce complex DNA damage in such a short range, it is very promising for localised treatment of small tumour cells or micrometastases.

Original language	English
Article number	104860
Number of pages	7
Journal	Physica Medica
Volume	129
Early online date	6 Dec 2024
DOIs	https://doi.org/10.1016/j.ejmp.2024.104860
Publication status	Published - 1 Jan 2025

Bibliographical note

Publisher Copyright:
© 2024 Published by Elsevier Ltd on behalf of Associazione Italiana di Fisica Medica e Sanitaria.

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

Targeted alpha therapies
Geant4-DNA
DNA damage
211At

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10.1016/j.ejmp.2024.104860

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Accepted author manuscript, 4.15 MBLicence: CC BY

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Cite this

@article{a0014e8256214e8192f0739ea0c5db7f,

title = "Targeted alpha therapies using 211At: A Geant4 simulation of dose and DNA damage",

abstract = "Introduction: Targeted alpha therapies show great potential for cancer treatment due to their high linear energy transfer (LET) and low range. 211At is currently employed in clinical trials. Targeted alpha therapies (TAT) are effective as an adjuvant treatment for cancer or to treat micrometastases and diffuse cancers. A deeper understanding of the induced initial damage is crucial to enhance treatment planning. Methods: This study shows Geant4(-DNA)-based simulations to calculate absorbed dose profiles and DNA damaging potential in intravenously administered TAT with 211At. It assumes radionuclide decay on the blood vessel wall, and calculates the DNA damage in the surrounding tissue. Results: The calculated dosimetric quantities show that the effect of such treatment is mainly due to the emitted alpha particles, and is localised in a region of up to 80 μm from the blood vessel. The RBE of the treatment is in the range 2.5 - 4, and is calculated as a function of the number of double-strand breaks. Conclusions: Targeted therapies with 211At are effective within the range of the emitted alpha particles. With its capacity to induce complex DNA damage in such a short range, it is very promising for localised treatment of small tumour cells or micrometastases.",

keywords = "Targeted alpha therapies, Geant4-DNA, DNA damage, 211At",

author = "\{De Sio\}, Chiara and Laura Ballisat and Beck, \{Lana M G\} and Susanna Guatelli and Dousatsu Sakata and Yuyao Shi and Jinyan Duan and \{Abu Sabah\}, \{Lujin H S\} and Velthuis, \{Jaap J\} and Anatoly Rosenfeld",

note = "Publisher Copyright: {\textcopyright} 2024 Published by Elsevier Ltd on behalf of Associazione Italiana di Fisica Medica e Sanitaria.",

year = "2025",

month = jan,

day = "1",

doi = "10.1016/j.ejmp.2024.104860",

language = "English",

volume = "129",

journal = "Physica Medica",

issn = "1120-1797",

publisher = "Associazione Italiana di Fisica Medica",

}

TY - JOUR

T1 - Targeted alpha therapies using 211At

T2 - A Geant4 simulation of dose and DNA damage

AU - De Sio, Chiara

AU - Ballisat, Laura

AU - Beck, Lana M G

AU - Guatelli, Susanna

AU - Sakata, Dousatsu

AU - Shi, Yuyao

AU - Duan, Jinyan

AU - Abu Sabah, Lujin H S

AU - Velthuis, Jaap J

AU - Rosenfeld, Anatoly

PY - 2025/1/1

Y1 - 2025/1/1

N2 - Introduction: Targeted alpha therapies show great potential for cancer treatment due to their high linear energy transfer (LET) and low range. 211At is currently employed in clinical trials. Targeted alpha therapies (TAT) are effective as an adjuvant treatment for cancer or to treat micrometastases and diffuse cancers. A deeper understanding of the induced initial damage is crucial to enhance treatment planning. Methods: This study shows Geant4(-DNA)-based simulations to calculate absorbed dose profiles and DNA damaging potential in intravenously administered TAT with 211At. It assumes radionuclide decay on the blood vessel wall, and calculates the DNA damage in the surrounding tissue. Results: The calculated dosimetric quantities show that the effect of such treatment is mainly due to the emitted alpha particles, and is localised in a region of up to 80 μm from the blood vessel. The RBE of the treatment is in the range 2.5 - 4, and is calculated as a function of the number of double-strand breaks. Conclusions: Targeted therapies with 211At are effective within the range of the emitted alpha particles. With its capacity to induce complex DNA damage in such a short range, it is very promising for localised treatment of small tumour cells or micrometastases.

AB - Introduction: Targeted alpha therapies show great potential for cancer treatment due to their high linear energy transfer (LET) and low range. 211At is currently employed in clinical trials. Targeted alpha therapies (TAT) are effective as an adjuvant treatment for cancer or to treat micrometastases and diffuse cancers. A deeper understanding of the induced initial damage is crucial to enhance treatment planning. Methods: This study shows Geant4(-DNA)-based simulations to calculate absorbed dose profiles and DNA damaging potential in intravenously administered TAT with 211At. It assumes radionuclide decay on the blood vessel wall, and calculates the DNA damage in the surrounding tissue. Results: The calculated dosimetric quantities show that the effect of such treatment is mainly due to the emitted alpha particles, and is localised in a region of up to 80 μm from the blood vessel. The RBE of the treatment is in the range 2.5 - 4, and is calculated as a function of the number of double-strand breaks. Conclusions: Targeted therapies with 211At are effective within the range of the emitted alpha particles. With its capacity to induce complex DNA damage in such a short range, it is very promising for localised treatment of small tumour cells or micrometastases.

KW - Targeted alpha therapies

KW - Geant4-DNA

KW - DNA damage

KW - 211At

U2 - 10.1016/j.ejmp.2024.104860

DO - 10.1016/j.ejmp.2024.104860

M3 - Article (Academic Journal)

C2 - 39644875

SN - 1120-1797

VL - 129

JO - Physica Medica

JF - Physica Medica

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