Radiation, Volume 1, Issue 1 (March 2021) – 7 articles

Richter transformation (RT) is a condition wherein B cell chronic lymphocytic leukemia (CLL) transforms into a more aggressive lymphoma variant. The incidence and the significance of RT detected by 2-[¹⁸F]-FDG PET/CT is a clinical challenge and it is not widely investigated in the literature. The aim of this systematic review was to analyze published data about the potential role of 2-[¹⁸F]-FDG PET/CT in detecting RT. A comprehensive computer literature search of the PubMed/MEDLINE, Embase and Cochrane library databases was conducted up to December 2020. Thirteen studies (1336 patients with CLL) were selected. The maximum standardized uptake value (SUVmax) was the most common metabolic parameter used to detect RT. An SUVmax of 5 had an average overall sensitivity of 87% (range: 71–96%), an average overall specificity of 49% (range: 4–80%), an average positive predictive value of 41% (range: 16–53%) and an average negative predictive value of 84% (range: 33–97%). Other metabolic variables were only marginally investigated, with promising results. 2-[¹⁸F]-FDG PET/CT imaging may play an important role in the detection of RT in CLL, based on the high metabolic activity of the nodal lesions that transformed into aggressive lymphomas. 2-[¹⁸F]-FDG PET/CT has high negative predictive value for evaluating RT. Full article

This is a study concerning the use of Machine Learning (ML) techniques to ascertain the impacts of particle ionizing radiation (IR) on cell survival and DNA damage. Current empirical models do not always take into account intrinsic complexities and stochastic effects of the interactions of IR and cell populations. Furthermore, these models often lack in biophysical interpretations of the irradiation outcomes. The linear quadratic (LQ) model is a common way to associate the biological response of a cell population with the radiation dose. The parameters of the LQ model are used to extrapolate the relation between the dosage and the survival fraction of a cell population. The goal was to create a ML-based model that predicts the $\alpha$ and $\beta$ parameters of the well known and established LQ model, along with the key metrics of DNA damage induction. The main target of this effort was, on the one hand, the development of a computational framework that will be able to assess key radiobiophysical quantities, and on the other hand, to provide meaningful interpretations of the outputs. Based on our results, as some metrics of the adaptability and training efficiency, our ML models exhibited 0.18 median error (relative root mean squared error (RRMSE)) in the prediction of the $\alpha$ parameter and errors of less than 0.01 for various DNA damage quantities; the prediction for $\beta$ exhibited a rather large error of 0.75. Our study is based on experimental data from a publicly available dataset of irradiation studies. All types of complex DNA damage (all clusters), and the number of double-stranded breaks (DSBs), which are widely accepted to be closely related to cell survival and the detrimental biological effects of IR, were calculated using the fast Monte Carlo Damage Simulation software (MCDS). We critically discussed the varying importance of physical parameters such as charge and linear energy transfer (LET); we also discussed the uncertainties of our predictions and future directions, and the dynamics of our approach. Full article

[⁶⁸Ga]Ga-RM2 is a promising innovative positron emission tomography (PET) tracer for patients with primary or metastatic prostate carcinoma. This study aims to analyze the biodistribution and radiation dosimetry of [⁶⁸Ga]Ga-RM2 in five prostate cancer patients. The percentages of injected activity in the source organs and blood samples were determined. Bone marrow residence time was calculated using an indirect blood-based method. OLINDA/EXM version 2.0 (Hermes Medical Solutions, Stockholm, Sweden) was used to determine residence times, organ absorbed and effective doses. Physiological uptake was seen in kidneys, urinary bladder, pancreas, stomach, spleen and liver. Blood clearance was fast and followed by rapid clearance of activity from kidneys resulting in high activity concentrations in the urinary bladder. The urinary bladder wall was the most irradiated organ with highest mean organ absorbed dose (0.470 mSv/MBq) followed by pancreas (0.124 mSv/MBq), stomach wall (0.063 mSv/MBq), kidneys (0.049 mSv/MBq) and red marrow (0.010 mSv/MBq). The effective dose was found to be 0.038 mSv/MBq. Organ absorbed doses were found to be comparable to other gallium-68 labelled GRPR antagonists and lower than [⁶⁸Ga]Ga-PSMA with the exception of the urinary bladder, pancreas and stomach wall. Remarkable interindividual differences were observed for the organ absorbed doses. Therefore, [⁶⁸Ga]Ga-RM2 is a safe diagnostic agent with a significantly lower kidney dose but higher pancreas and urinary bladder doses as compared to [⁶⁸Ga]Ga-PSMA. Full article

The new severe acute respiratory syndrome coronavirus (SARS-CoV-2) has caused more than 40 million human infections since December 2019, when a cluster of unexplained pneumonia cases was first reported in Wuhan, China. Just a few days after the coronavirus was officially recognized, it was identified as the causative agent of this mysterious pneumonia. This paper discusses the pros and cons of antiviral drugs from the selective pressure and possible drug resistance point of view. We also address the key advantages of potential selective pressure-free treatment methods such as the use of sparsely and densely ionizing low-dose radiation (LDR). It is known that LDR has the capacity to modulate excessive inflammatory responses, regulate lymphocyte counts and control bacterial co-infections in patients with COVID-19 and different modalities. Substantial evidence shows that viruses are constantly mutating and evolving. When an antiviral immune response is unable to eliminate a virus, viral evolution is promoted. Therefore, it is of crucial importance to limit the use of antivirals/vaccines against SARS-CoV-2 when their effects on viral fitness are not fully understood. Furthermore, to limit the spread of the virus, it is essential to develop a vaccine that is available for as many people as possible. However, with the advent of vaccines or new therapies, the new situation may force the virus to evolve. Given this consideration, selective pressure-free treatments for COVID-19 are of great importance. Full article

Photodynamic therapy (PDT) is a promising therapeutic strategy for cancers where surgery and radiotherapy cannot be effective. PDT relies on the photoactivation of photosensitizers, most of the time by lasers to produced reactive oxygen species and notably singlet oxygen. The major drawback of this strategy is the weak light penetration in the tissues. To overcome this issue, recent studies proposed to generate visible light in situ with radioactive isotopes emitting charged particles able to produce Cerenkov radiation. In vitro and preclinical results are appealing, but the existence of a true, lethal phototherapeutic effect is still controversial. In this article, we have reviewed previous original works dealing with Cerenkov-induced PDT (CR-PDT). Moreover, we propose a simple analytical equation resolution to demonstrate that Cerenkov light can potentially generate a photo-therapeutic effect, although most of the Cerenkov photons are emitted in the UV-B and UV-C domains. We suggest that CR-PDT and direct UV-tissue interaction act synergistically to yield the therapeutic effect observed in the literature. Moreover, adding a nanoscintillator in the photosensitizer vicinity would increase the PDT efficacy, as it will convert Cerenkov UV photons to light absorbed by the photosensitizer. Full article

Ionizing radiation (IR) is considered a traditional mutagen and genotoxic agent. Exposure to IR affects in all cases biological systems and living organisms from plants to humans mostly in a pernicious way. At low (<0.1 Gy) and low-to-medium doses (0.1–1 Gy), one can find in the literature a variety of findings indicating sometimes a positive-like anti-inflammatory effect or detrimental-like toxicity. In this Special Issue and in general in the current research, we would like to acquire works and more knowledge on the role(s) of DNA damage and its repair induced by ionizing radiations as instigators of the full range of biological responses to radiation. Emphasis should be given to advances offering mechanistic insights into the ability of radiations with different qualities to severely impact cells or tissues. High-quality research or review studies on different species projected to humans are welcome. Technical advances reporting on the methodologies to accurately measure DNA or other types of biological damage must be highly considered for the near future in our research community, as well. Last but not least, clinical trials or protocols with improvements to radiation therapy and radiation protection are also included in our vision for the advancement of research regarding biological effects of IR. Full article