Targeted use of Alpha Particles: Current Status in Cancer Therapeutics

Maalouf, Bassam Nabih

doi:10.4172/2155-9619.1000136

Cited by 12 publications

(9 citation statements)

References 55 publications

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“…As exposure is primarily via inhalation, the largest dose of alpha-particles is received by lung cells, although other organs may also receive a significant dose [ 2 ]. Exposure to alpha-particles may also result from their use in targeted radiotherapy [ 3 ] as well as occupational exposures (e.g., in the nuclear industry) [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Induction of Genomic Instability in a Primary Human Fibroblast Cell Line Following Low-Dose Alpha-Particle Exposure and the Potential Role of Exosomes

Elbakrawy

Mayah

Hill

et al. 2020

Biology

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Purpose: To study the induction of genomic instability (GI) in the progeny of cell populations irradiated with low doses of alpha-particles and the potential role of exosome-encapsulated bystander signalling. Methods: The induction of GI in HF19 normal fibroblast cells was assessed by determining the formation of micronuclei (MN) in binucleate cells along with using the alkaline comet assay to assess DNA damage. Results: Low dose alpha-particle exposure (0.0001–1 Gy) was observed to produce a significant induction of micronuclei and DNA damage shortly after irradiation (assays performed at 5 and 1 h post exposure, respectively). This damage was not only still evident and statistically significant in all irradiated groups after 10 population doublings, but similar trends were observed after 20 population doublings. Exosomes from irradiated cells were also observed to enhance the level of DNA damage in non-irradiated bystander cells at early times. Conclusion: very low doses of alpha-particles are capable of inducing GI in the progeny of irradiated cells even at doses where <1% of the cells are traversed, where the level of response was similar to that observed at doses where 100% of the cells were traversed. This may have important implications with respect to the evaluation of cancer risk associated with very low-dose alpha-particle exposure and deviation from a linear dose response.

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Section: Introductionmentioning

confidence: 99%

Induction of Genomic Instability in a Primary Human Fibroblast Cell Line Following Low-Dose Alpha-Particle Exposure and the Potential Role of Exosomes

Elbakrawy

Mayah

Hill

et al. 2020

Biology

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“…This is especially true for alpha radionuclides which until recently have been considered of no medical use because of their strong ionizing properties. 27,30,31 The next part of the review considers already available scientific evidence that with the right scientific strategy alpha-radionuclides can not only find their medical application but also save lives where the weaker ionizing photon and beta radiations fail in the treatment of apoptosis-resistant tumors and even speed up the tumor growth with their weaker ionizing properties. 27,28,32…”

Section: Nature and Types Of Ionizing Radiation And Their Relation To The Elicited Intracellular Ionizing Effectsmentioning

confidence: 99%

“…The more research and clinical data accumulate, the more obvious it becomes how easily some tumor cells are able to overcome the cytotoxic effects of photon-and beta-emitters which are the predominating radio-therapeutics in the current clinical practice because of their weaker ionizing properties in comparison to alpha radiopharmaceuticals. 30,31 For example, MOLT-4 human T lymphoblasts, isolated from a patient with an acute lymphoblastic leukemia and irradiated with a 100 Gy proton beam, 24 h after the irradiation show no signs of induced apoptosis. Other cells famous for their resistance to treatment such as Head and Neck Squamous Cell Carcinoma (HNSCC) cells, also survive after repeated exposure to X-rays ionizing radiation with a total dose of 100 Gy and researchers are amazed to observe that the ionizing-resistant cells retained their radiation resistance even after 3 years of in vitro passaging.…”

Section: Tumor Cells Radioresistance As a Function Of Complex Factors-a Large Number Of Hidden Pro-survivalmechanisms In Tumor Cells Limimentioning

confidence: 99%

Prospects for Radiopharmaceuticals as Effective and Safe Therapeutics in Oncology and Challenges of Tumor Resistance to Radiotherapy

et al. 2021

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The rapid advances in nuclear medicine have resulted in significant advantages for the field of oncology. The focus is on the application of radiopharmaceuticals as therapeuticals. In addition, the latest developments in cell biology (the understanding of the cell structure, function, metabolism, genetics, signaling, transformation) have given a strong scientific boost to radiation oncology. In this regard, the article discusses what is soon going to be a new jump in radiation oncology based on the already accumulated considerable knowledge at the cellular level about the mechanisms of cell transformation and tumor progression, cell response to radiation, cell resistance to apoptosis and radiation and cell radio-sensitivity. The mechanisms of resistance of tumor cells to radiation and the genetically determined individual sensitivity to radiation in patients (which creates the risk of radiation-induced acute and late side effects) are the 2 major challenges to overcome in modern nuclear medicine. The paper focuses on these problems and makes a detailed summary of the significance of the differences in the ionizing properties of radiopharmaceuticals and the principle of their application in radiation oncology that will shed additional light on how to make the anti-cancer radiotherapies more efficient and safe, giving some ideas for optimizations.

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“…On the other hand, the range of alpha particles of 4-8 MeV in human tissue is about 50-100 μm [1,2]. Due to the short range and high kinetic energy, the alpha particles have about 500-times higher liner energy transfer (LET) than that of beta particles [1,3,4], so some of the alpha particle emitters are thought to be useful for the targeted radionuclide therapy, which is referred to as "targeted alpha-particle therapy" (TAT) [5,6]. Currently, only radium-223 (Ra-223) is clinically used for TAT, while other alpha particle emitters have been actively studied.…”

Section: Introductionmentioning

confidence: 99%

Monte Carlo approach to comparison of parallel-hole collimators of clinical scintillation camera system for imaging astatine-211 (At-211)

2022

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Astatine-211 (At-211) is a promising alpha particle emitter for targeted radionuclide therapy. Since its daughter isotope (polonium-211(Po-211)) emits characteristic X-rays of about 80 keV, the distribution of At-211 in the body can be imaged by detecting the X-rays with a scintillation camera. However, the isotopes also emit high-energy gamma photons that are collimated with difficulty for a parallel-hole collimator of a clinical scintillation camera system, and thus the selection of a collimator is important. In this study, we compared the performances of low-energy high-resolution (LEHR), low-energy all-purpose (LEAP), medium-energy (ME), and high-energy (HE) parallel-hole collimators for At-211 using Monte Carlo simulation. We simulated a clinical scintillation camera system with the collimators using the Geant4 toolkit. The energy spectra, sensitivities, and spatial resolutions for the point source of At-211 were evaluated. Moreover, we simulated imaging of six sphere sources of At-211 in a 1-cm-thick cylindrical phantom filled with At-211 solution to evaluate image contrast. All of the results in this study are simulation data. The spatial resolution with LEHR was 7.6 mm full width at half maximum (FWHM) and the highest between collimators, while the sensitivity with LEAP was 85 cps/MBq and the highest. The image contrast acquired with the ME collimator was superior to those with the other collimators. We concluded that the LEHR, LEAP, and ME collimators had their advantages, so an optimum collimator should be selected depending on the purpose of imaging of At-211, although there was no advantage in using the HE collimator for the imaging of At-211.

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Targeted use of Alpha Particles: Current Status in Cancer Therapeutics

Cited by 12 publications

References 55 publications

Induction of Genomic Instability in a Primary Human Fibroblast Cell Line Following Low-Dose Alpha-Particle Exposure and the Potential Role of Exosomes

Induction of Genomic Instability in a Primary Human Fibroblast Cell Line Following Low-Dose Alpha-Particle Exposure and the Potential Role of Exosomes

Prospects for Radiopharmaceuticals as Effective and Safe Therapeutics in Oncology and Challenges of Tumor Resistance to Radiotherapy

Monte Carlo approach to comparison of parallel-hole collimators of clinical scintillation camera system for imaging astatine-211 (At-211)

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