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Beta and Alpha Particle Autoradiography
Published in Michael Ljungberg, Handbook of Nuclear Medicine and Molecular Imaging for Physicists, 2022
Anders Örbom, Brian W. Miller, Tom Bäck
Alpha-particle digital autoradiography has recently become important in the application of targeted alpha therapy (TAT). Due to their high linear energy transfer (LET) and short path length of α-particles in tissues, α-emitters are promising in cancer therapy, with recent trials showing remarkable success when other therapies have failed [78]. Alpha particles are potent at killing cancer cells, but are also toxic to normal tissues and organs, and understanding their biodistribution is key in development of new radiopharmaceuticals. Many of the α-emitters being considered for TAT are not suited for traditional imaging approaches such as scintigraphy or SPECT due to a combination of administered activities below detection limits, low photon emission efficiencies, and photon energies that are challenging or impractical to image. However, autoradiography with alphas is highly efficient with excellent spatial resolution making it an essential means for understanding biodistributions in pre-clinical TAT.
Radionuclide-based Diagnosis and Therapy of Prostate Cancer
Published in Michael Ljungberg, Handbook of Nuclear Medicine and Molecular Imaging for Physicists, 2022
Sven-Erik Strand, Mohamed Altai, Joanna Strand, David Ulmert
Alpha particle emitting radionuclides are also used for therapy as we will describe in the following text. However, for a comprehensive overview on alpha-emitters for radiotherapy, we refer the reader to a couple of reviews written by Poty and colleagues [22, 23].
Radiation Dose and Exposure Indicators
Published in Ken Holmes, Marcus Elkington, Phil Harris, Clark's Essential Physics in Imaging for Radiographers, 2021
When ionising radiation passes through tissue (a medium) it may interact with it and deposit energy along its path of travel. The average energy deposited per unit length is called the linear energy transfer (LET). The energy absorbed in tissue depends on the type of charged ionising particle which is travelling through the medium and the type of medium. LET is measured in kiloelectron volts (KeV) per micron (10−6 m) and is an important factor in assessing potential tissue damage. For diagnostic beams the LET is low. When diagnostic beams interact with tissue it causes damage by the production of free radicals which may cause damage to the DNA. High LET radiation eg alpha particles are more destructive to biological tissue as they lose their energy in a shorter length of tissue and are more ionising.
Modeling of dose and linear energy transfer homogeneity in cell nuclei exposed to alpha particles under various setup conditions
Published in International Journal of Radiation Biology, 2023
Adrianna Tartas, Mateusz Filipek, Marcin Pietrzak, Andrzej Wojcik, Beata Brzozowska
Alpha-irradiators have been used by many authors to study the effects of high LET radiation on cells in culture (Raju and Jett 1974; Edwards et al. 1980; Goodhead et al. 1991; Griffiths et al. 1994; Metting et al. 1995; Neti et al. 2004; Wang and Coderre 2005; Hakanen et al. 2006; Esposito et al. 2009; Tracy et al. 2015; Karthik et al. 2019; Thompson et al. 2019). The most common alpha emitters used in radiobiological experiments are Pu-238 and Am-241 which allow irradiation with alpha particle energy of about 5 MeV and lower. Generally, alpha particles are described by the average LET value. As demonstrated in the present investigation, the average LET parameter is not a sufficient quantity to characterize an alpha beam. Instead of using its averaged values, it is worth considering nanodosimetric variables that allow the interpretation of cellular response to ionizing radiation in the context of damage to a DNA molecule. Such a nanodosimetric quantity is the ionization cluster size distributions, which can be measured with the nanodosimeters, e.g. Jet Counter (Pszona et al. 2000). Based on these distributions, the probability of lethal cell damage can be calculated (Pietrzak et al. 2021), which is closer to the description of nanoscale phenomena than the averaged LET parameter. The use of nanodosimetric quantities also has a potential application in radiotherapy (Rucinski et al. 2021), but still requires further research.
Chromosome aberrations, micronucleus frequency, and catalase concentration in a population chronically exposed to high levels of radon
Published in International Journal of Radiation Biology, 2023
Dwi Ramadhani, Sofiati Purnami, Devita Tetriana, Irawan Sugoro, Viria Agesti Suvifan, Nastiti Rahadjeng, Septelia Inawati Wanandi, Heri Wibowo, Ikuo Kashiwakura, Tomisato Miura, Mukh Syaifudin
More than 60% of the total ionizing radiation a person gets each year can be attributed to natural sources; radon and its breakdown products account for more than 50% of these natural sources of radiation (Sinitsky and Druzhinin 2014). Radon, an odorless and colorless radioactive gas, is produced during the series of transformations in the uranium (U-238) decay chain. Specifically, radon (Rn-222) is the direct decay product of radium (Ra-226). As the decay chain continues, alpha (α) and beta (β) radioactive isotopes are produced. Alpha particles, have the ability to ionize and damage biomolecules in living cells (Walczak et al. 2019; Grzywa-Celińska et al. 2020). Ionizing radiation in the form of alpha particles can cause DNA damage, leading to double-strand DNA breaks and chromosomal aberrations (CA) (Robertson et al. 2013; Yanxiao et al. 2019). This type of radiation can also elicit damage to biomolecules (e.g. DNA, proteins, and lipids) indirectly by inducing the generation of reactive oxygen species (ROS). Several oxidant molecules are classified as ROS, including free radicals, such as superoxide (O2•–) and hydroxyl (OH•) radicals, and non-radical species, such as singlet oxygen (1O2) and hydrogen peroxide (H2O2). These highly reactive species are controlled by different mechanisms in the human body. One of them is the action of enzymatic antioxidants, such as superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT) (Kuciel-Lewandowska et al. 2018).
Emerging treatment options for prostate cancer
Published in Expert Review of Anticancer Therapy, 2023
Mohammad Atiq, Elias Chandran, Fatima Karzai, Ravi A. Madan, Jeanny B. Aragon-Ching
Alpha particles are attractive as these deliver high energy with fewer particle tracks to effect cell kill, have a short depth of penetration, and have shorter half-lives, potentially limiting toxicity to normal tissues. Additionally, from a practical perspective, the easier production of alpha particles lends for wider dissemination and use in the clinic [47]. The only alpha emitter approved thus far in prostate cancer is radium 223 dichloride. One alpha emitter being evaluated is actinium-225 (225Ac). A phase I study combining this with a PSMA-localizing antibody, J591, was recently presented by Tagawa et al. (NCT03276572) [48,49]. Thirty-two patients with mCRPC who progressed on at least 1 ARPI and chemotherapy were enrolled in the study. Interestingly, prior treatment with radium 223 and lutetium was allowed, and PSMA PET positivity was not required for enrollment. There was only one patient with dose-limiting toxicity (DLT) at all the planned dose levels: grade 4 anemia and thrombocytopenia. Grade 3 or higher AEs were hematologic. Lower grade AEs included fatigue, pain flare, nausea, and xerostomia (which occurred in 8 patients – 5 previously treated with lutetium – and was limited to grade 1). Clinical data presented included 22 out of 32 patients having any decline in PSA and 12 out of 32 patients experiencing ≥50% PSA reduction (PSA50 response).