Micro-dosimetry calculation of Auger-electron-emitting radionuclides mostly used in nuclear medicine using GEANT4-DNA

Moradi, Mahdi Seifi; Bidabadi, Babak Shirani

doi:10.1016/j.apradiso.2018.08.019

Cited by 9 publications

(5 citation statements)

References 26 publications

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“…Recent biodistribution studies with [ 123 I]MAPi in healthy athymic nude mice reported the estimated absorbed dose in liver and thyroid as 0.0044 Gy/MBq and 0.0041 Gy/MBq respectively, although the intracellular distribution of [ 123 I]MAPi was not taken into consideration [ 14 ]. The MIRD S-value for 125 I in a cell nucleus to nucleus was reported to be 6.60 × 10 −3 Gy/(Bq-s) [ 31 ]. Goddu et al ., reported a wide range of S-value for nucleus to nucleus radiation from 125 I ranging from 3.42 × 10 −1 Gy/(Bq-s) to 9.52 × 10 −4 Gy/(Bq-s), assuming a homogeneous distribution of 125 I in the nucleus with varying nucleus diameters [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

PARP targeted Auger emitter therapy with [125I]PARPi-01 for triple-negative breast cancer

et al. 2022

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Background Triple-negative breast cancer (TNBC) lacks biomarkers for targeted therapy. Auger emitters display the best therapeutic effect, if delivered directly into the nucleus proximal to DNA. The nuclear protein Poly (ADP-ribose)-Polymerase 1 (PARP1) is a suitable target against which few inhibitors (PARPi) are clinically approved for treatment of breast cancer with germline BRCA mutation (BRCAmut). In this study, a theranostic approach was investigated in a TNBC xenografted mouse model by radiolabelling a close derivative of a PARPi Olaparib (termed PARPi-01) with the Auger emitters 123/125I. Methods TNBC cell line MDA-MB-231 was subcutaneously implanted in female NOD/SCID mice. At a tumour size of ~ 500mm3, [123I]PARPi-01 was administered intravenously, and SPECT/CT images were obtained at 4 h or 24 h post injection (p.i). A therapy study was performed with [125I]PARPi-01 in 4 doses (10 MBq/dose, 10 days apart). Tumour growth was monitored by CT scans longitudinally once per week. Upon reaching study endpoint, tissues were harvested and stained with TUNEL assay for detection of apoptosis induction. Results SPECT/CT images showed rapid hepatobiliary tracer clearance at 4 h post injection (p.i.). Retention in thyroid at 24 h p.i. suggested tracer deiodination in vivo. The tumour and liver uptake were 0.2%ID/g and 2.5%ID/g, respectively. The tumour: blood ratio was 1.3. Endogenous therapy induced a significant delay in tumour growth (doubling time increased from 8.3 to 14.2 days), but no significant survival advantage. Significantly higher apoptosis ratio was observed in [125I]PARPi-01 treated tumour tissues. No radiotoxicity was detected in the liver and thyroid. Conclusion Considering the radio-cytotoxic effect in the tumour tissue and a delay on tumour doubling time, [125I]PARPi-01 presents a potential radiotherapeutics for treatment of TNBC. Improvements to overcome the suboptimal pharmacokinetics are necessary for its potential clinical application.

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Section: Discussionmentioning

confidence: 99%

PARP targeted Auger emitter therapy with [125I]PARPi-01 for triple-negative breast cancer

et al. 2022

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“…Moradi et al have reported the highest difference in the S-value between various radionuclides when radioactive source was localized in the nucleus, and there was not considerable difference in the nucleus dose when radionuclides were localized in cytoplasm and over the cell membrane. [ 19 ]…”

Section: Discussionmentioning

confidence: 99%

“…In most previous studies about cellular dosimetry, the effect of the nucleus size has been assessed employing the most commonly electron emitter radiopharmaceuticals in nuclear medicine which contain electrons with different energies and weighting factors and simulation codes. [ 18 19 20 ] However, the effect of electron energy has not been specifically addressed. In other words, the effect of the energy will not specially be provided by applying the electron emitter radionuclides with wide energy spectrum.…”

Section: Introductionmentioning

confidence: 99%

The effect of nucleus size on the cell dose in targeted radionuclide therapy – A monte carlo study

2020

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“…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

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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.

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Micro-dosimetry calculation of Auger-electron-emitting radionuclides mostly used in nuclear medicine using GEANT4-DNA

Cited by 9 publications

References 26 publications

PARP targeted Auger emitter therapy with [125I]PARPi-01 for triple-negative breast cancer

PARP targeted Auger emitter therapy with [125I]PARPi-01 for triple-negative breast cancer

The effect of nucleus size on the cell dose in targeted radionuclide therapy – A monte carlo study

ICRU Report 98, Stochastic Nature of Radiation Interactions: Microdosimetry

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