Monte Carlo dose distribution calculation at nuclear level for Auger-emitting radionuclide energies

Maria, Salvatore Di; Belchior, Ana; Romanets, Y.; Paulo, António; Vaz, P.

doi:10.1016/j.apradiso.2018.01.013

Cited by 10 publications

(9 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Figure 5 shows representative models of reference man (A), the kidney (B), or cells (C) used in Monte Carlo Simulation of S-values (Stabin and Siegel 2018; Bouchet et al 2003; Cai et al 2017). Monte Carlo code used to calculate S-values includes MCNP6 (Di Maria et al 2018), PENELOPE (Falzone et al 2017; López-Coello et al 2019), Geant4 (López-Coello et al 2019) and GATE (López-Coello et al 2019). They all allow event-by-event simulation of electron and photon transport.…”

Section: Dosimetric Propertiesmentioning

confidence: 99%

Auger electrons for cancer therapy – a review

Facca

Cai

et al. 2019

EJNMMI radiopharm. chem.

240

207

View full text Add to dashboard Cite

Background: Auger electrons (AEs) are very low energy electrons that are emitted by radionuclides that decay by electron capture (e.g. 111 In, 67 Ga, 99m Tc, 195m Pt, 125 I and 123 I). This energy is deposited over nanometre-micrometre distances, resulting in high linear energy transfer (LET) that is potent for causing lethal damage in cancer cells. Thus, AE-emitting radiotherapeutic agents have great potential for treatment of cancer. In this review, we describe the radiobiological properties of AEs, their radiation dosimetry, radiolabelling methods, and preclinical and clinical studies that have been performed to investigate AEs for cancer treatment. Results: AEs are most lethal to cancer cells when emitted near the cell nucleus and especially when incorporated into DNA (e.g. 125 I-IUdR). AEs cause DNA damage both directly and indirectly via water radiolysis. AEs can also kill targeted cancer cells by damaging the cell membrane, and kill non-targeted cells through a cross-dose or bystander effect. The radiation dosimetry of AEs considers both organ doses and cellular doses. The Medical Internal Radiation Dose (MIRD) schema may be applied. Radiolabelling methods for complexing AE-emitters to biomolecules (antibodies and peptides) and nanoparticles include radioiodination (125 I and 123 I) or radiometal chelation (111 In, 67 Ga, 99m Tc). Cancer cells exposed in vitro to AE-emitting radiotherapeutic agents exhibit decreased clonogenic survival correlated at least in part with unrepaired DNA double-strand breaks (DSBs) detected by immunofluorescence for γH2AX, and chromosomal aberrations. Preclinical studies of AE-emitting radiotherapeutic agents have shown strong tumour growth inhibition in vivo in tumour xenograft mouse models. Minimal normal tissue toxicity was found due to the restricted toxicity of AEs mostly on tumour cells targeted by the radiotherapeutic agents. Clinical studies of AEs for cancer treatment have been limited but some encouraging results were obtained in early studies using 111 In-DTPAoctreotide and 125 I-IUdR, in which tumour remissions were achieved in several patients at administered amounts that caused low normal tissue toxicity, as well as promising improvements in the survival of glioblastoma patients with 125 I-mAb 425, with minimal normal tissue toxicity. Conclusions: Proof-of-principle for AE radiotherapy of cancer has been shown preclinically, and clinically in a limited number of studies. The recent introduction of many biologically-targeted therapies for cancer creates new opportunities to design novel AE-emitting agents for cancer treatment. Pierre Auger did not conceive of the application of AEs for targeted cancer treatment, but this is a tremendously exciting future that we and many other scientists in this field envision.

show abstract

Section: Dosimetric Propertiesmentioning

confidence: 99%

Auger electrons for cancer therapy – a review

Facca

Cai

et al. 2019

EJNMMI radiopharm. chem.

240

207

View full text Add to dashboard Cite

show abstract

“…The MIRD committee of the American Nuclear Society of Nuclear Medicine is often used in order to perform dosimetry calculations at subcellular level, by using semi-analytical methods (based on the continuous slowing-down approximation) to calculate the fraction of energy released from the source that is absorbed in the target zone (S-value) [ 25 ]. The radii of cell nucleus and cytoplasm considered in this study are respectively of 2 μm and 4 μm, corresponding to the average values obtained from fluorescence microscopy images of PC3 cells, as we have described previously [ 28 ].…”

Section: Methodsmentioning

confidence: 99%

“…Further discussions about models used to obtain ENDF/B-VI-8 data library can be found in reference [ 31 ]. Single-event mode is a relatively new feature of MCNP6 that was tested and validated in several works present in literature [ 28 , 32 , 33 ]. A validation of the MC model was made through MC S-values calculations (for several radionuclide spectra emission), and results showed agreement with MIRD values within 3% error [ 28 ].…”

Section: Methodsmentioning

confidence: 99%

“…Single-event mode is a relatively new feature of MCNP6 that was tested and validated in several works present in literature [28,32,33]. A validation of the MC model was made through MC S-values calculations (for several radionuclide spectra emission), and results showed agreement with MIRD values within 3% error [28]. Figure 2 shows the geometry setup chosen for MC simulations.…”

Section: Simulationsmentioning

confidence: 95%

See 1 more Smart Citation

Radiobiological and dosimetric assessment of DNA-intercalated 99mTc-complexes bearing acridine orange derivatives

et al. 2020

View full text Add to dashboard Cite

Background Recently, a new family of 99m Tc(I)-tricarbonyl complexes bearing an acridine orange (AO) DNA targeting unit and different linkers between the Auger emitter ( 99m Tc) and the AO moiety was evaluated for Auger therapy. Among them, 99m Tc-C 3 places the corresponding radionuclide at a shortest distance to DNA and produces important double strand breaks (DSB) yields in plasmid DNA providing the first evidence that 99m Tc can efficiently induce DNA damage when well positioned to the double helix. Here in, we have extended the studies to human prostate cancer PC3 cells using the 99m Tc-C 3 and 99m Tc-C 5 complexes, aiming to assess how the distance to DNA influences the radiation-induced biological effects in this tumoral cell line, namely, in which concerns early and late damage effects. Results Our results highlight the limited biological effectiveness of Auger electrons, as short path length radiation, with increasing distances to DNA. The evaluation of the radiation-induced biological effects was complemented with a comparative microdosimetric study based on intracellular dose values. The comparative study, between MIRD and Monte Carlo (MC) methods used to assess the cellular doses, revealed that efforts should be made in order to standardize the bioeffects modeling for DNA-incorporated Auger electron emitters. Conclusions 99m Tc might not be the ideal radionuclide for Auger therapy but can be useful to validate the design of new classes of Auger-electron emitting radioconjugates. In this context, our results highlight the crucial importance of the distance of Auger electron emitters to the target DNA and encourage the development of strategies for the fine tuning of the distance to DNA for other medical radionuclides (e.g., 111 In or 161 Tb) in order to enhance their radiotherapeutic effects within the Auger therapy of cancer.

show abstract

“…Multicellular dosimetry is also important for organs and tissue with microstructure (Sgouros et al, 2011). Several studies were performed for calculating the cellular S-coefficients based on analytical and Monte Carlo methods (Bousis et al, 2010;Chegeni et al, 2021;Di Maria et al, 2018;Fourie et al, 2015;Goddu et al, 1994a;Falzone et al, 2017;Ftáčniková and Böhm, 2000;Kouhkan et al, 2020;Lee et al, 2018;Moradi and Bidabadi, 2018;Salim and Taherparvar, 2020;Šefl et al, 2015;Siragusa et al, 2017;Tajik-Mansoury et al, 2017;Tang et al, 2021;Tung et al, 2004;Wu et al, 2012). For example, Goddu et al (1994a) evaluated the cellular S-coefficients for various α, β, and Auger electron emitters for the target←source combinations of cell←cell, cell←cell surface, nucleus←nucleus, nucleus←cytoplasm, and nucleus←cell surface.…”

Section: Radiopharmaceutical Therapymentioning

confidence: 99%

ICRU Report 98, Stochastic Nature of Radiation Interactions: Microdosimetry

Braby,

Conte,

Dingfelder

et al. 2023

J�ICRU

View full text Add to dashboard Cite

The Journal of the ICRU publishes reports on important and topical subjects within the field of radiation science and measurement. It is the successor to the series of reports published by or on behalf of the International Commission on Radiation Units and Measurements (ICRU) since 1927. The Commission continually reviews radiation science with the aim of identifying areas where the development of guidance and recommendations can make an important contribution.

show abstract

Monte Carlo dose distribution calculation at nuclear level for Auger-emitting radionuclide energies

Cited by 10 publications

References 20 publications

Auger electrons for cancer therapy – a review

Auger electrons for cancer therapy – a review

Radiobiological and dosimetric assessment of DNA-intercalated 99mTc-complexes bearing acridine orange derivatives

ICRU Report 98, Stochastic Nature of Radiation Interactions: Microdosimetry

Contact Info

Product

Resources

About