Search Results (11)

The results of radiotherapy in patients with primary malignant brain tumors are extremely dissatisfactory: the overall survival after a diagnosis of glioblastoma is typically less than three years. The development of spatially fractionated radiotherapy techniques could help to improve this bleak prognosis. In order to develop technical equipment and organ-specific therapy plans, dosimetry studies as well as radiobiology studies are conducted. Although perfect spheres are considered optimal phantoms by physicists, this does not reflect the wide variety of head sizes and shapes in our patient community. Depth from surface and X-ray dose absorption by tissue between dose entry point and target, two key parameters in medical physics planning, are largely determined by the shape and thickness of the skull bone. We have, therefore, designed and produced a biomimetic tool to correlate measured technical dose and biological response in human cancer cells: a brain phantom, produced from tissue-equivalent materials. In a first pilot study, utilizing our phantom to correlate technical dose measurements and metabolic response to radiation in human cancer cell lines, we demonstrate why an anthropomorphic phantom is preferable over a simple spheroid phantom. Full article

Purpose: To investigate the impact of physiologically based pharmacokinetic (PBPK) parameters on physical, biological, and statistical measures in lutetium-177-labeled radiopharmaceutical therapies (RPTs) targeting the prostate-specific membrane antigen (PSMA). Methods: Using a clinically validated PBPK model, realistic time–activity curves (TACs) for tumors, salivary glands, and kidneys were generated based on various model parameters. These TACs were used to calculate the area-under-the-TAC (AUC), dose, biologically effective dose (BED), and figure-of-merit BED (fBED). The effects of these parameters on radiobiological, pharmacokinetic, time, and statistical features were assessed. Results: Manipulating PBPK parameters significantly influenced AUC, dose, BED, and fBED outcomes across four different BED models. Higher association rates increased AUC, dose, and BED values for tumors, with minimal impact on non-target organs. Increased internalization rates reduced AUC and dose for tumors and kidneys. Higher serum protein-binding rates decreased AUC and dose for all tissues. Elevated tumor receptor density and ligand amounts enhanced uptake and effectiveness in tumors. Larger tumor volumes required dosimetry adjustments to maintain efficacy. Setting the tumor release rate to zero intensified the impact of association and internalization rates, enhancing tumor targeting while minimizing the effects on salivary glands and kidneys. Conclusions: Optimizing PBPK parameters can enhance the efficacy of lutetium-177-labeled RPTs targeting PSMA, providing insights for personalized and effective treatment regimens to minimize toxicity and improve therapeutic outcomes. Full article

In the event of a radiological or nuclear accident, or when physical dosimetry is not available, the scoring of radiation-induced chromosomal aberrations in lymphocytes constitutes an essential tool for the estimation of the absorbed dose of the exposed individual and for effective triage. Cytogenetic biodosimetry employs different cytogenetic assays including the scoring of dicentrics, micronuclei, and translocations as well as analyses of induced premature chromosome condensation to define the frequency of chromosome aberrations. However, inherent challenges using these techniques include the considerable time span from sampling to result, the sensitivity and specificity of the various techniques, and the requirement of highly skilled personnel. Thus, techniques that obviate these challenges are needed. The introduction of telomere and centromere (TC) staining have successfully met these challenges and, in addition, greatly improved the efficiency of cytogenetic biodosimetry through the development of automated approaches, thus reducing the need for specialized personnel. Here, we review the role of the various cytogenetic dosimeters and their recent improvements in the management of populations exposed to genotoxic agents such as ionizing radiation. Finally, we discuss the emerging potentials to exploit these techniques in a wider spectrum of medical and biological applications, e.g., in cancer biology to identify prognostic biomarkers for the optimal triage and treatment of patients. Full article

Despite the unexpectedly high tumor responses and limited treatment-related toxicities observed with SFRT, prospective multi-institutional clinical trials of SFRT are still lacking. High variability of SFRT technologies and methods, unfamiliar complex dose and prescription concepts for heterogeneous dose and uncertainty regarding systemic therapies present major obstacles towards clinical trial development. To address these challenges, the consensus guideline reported here aimed at facilitating trial development and feasibility through a priori harmonization of treatment approach and the full range of clinical trial design parameters for SFRT trials in gynecologic cancer. Gynecologic cancers were evaluated for the status of SFRT pilot experience. A multi-disciplinary SFRT expert panel for gynecologic cancer was established to develop the consensus through formal panel review/discussions, appropriateness rank voting and public comment solicitation/review. The trial design parameters included eligibility/exclusions, endpoints, SFRT technology/technique, dose/dosimetric parameters, systemic therapies, patient evaluations, and embedded translational science. Cervical cancer was determined as the most suitable gynecologic tumor for an SFRT trial. Consensus emphasized standardization of SFRT dosimetry/physics parameters, biologic dose modeling, and specimen collection for translational/biological endpoints, which may be uniquely feasible in cervical cancer. Incorporation of brachytherapy into the SFRT regimen requires additional pre-trial pilot investigations. Specific consensus recommendations are presented and discussed. Full article

Theragnostic pairs of isotopes are used to infer radiation dosimetry for a therapeutic radiopharmaceutical from a diagnostic imaging study with the same tracer molecule labelled with an isotope better suited for the imaging task. We describe the transfer of radiation dosimetry from the diagnostic radioiodine isotope ¹²³I, labelled for the hypoxia tracer molecule iodoazomycin arabinoside ([¹²³I]IAZA), to isotopes ¹³¹I (therapeutic) and ¹²⁴I (PET imaging). Uncertainties introduced by the dissimilar isotope half-lives are discussed in detail. Radioisotope dosimetries for [¹²³I]IAZA were obtained previously. These data are used here to calculate residence times for ¹³¹I and ¹²⁴I and their uncertainties. We distinguish two cases when extrapolating to infinity: purely physical decay (case A) and physical decay plus biological washout (case B). Organ doses were calculated using the MIRD schema with the OLIDNA/EXM code. Significant increases in some organ doses (in mSv per injected activity) were found for ¹³¹I and ¹²⁴I. The most affected organs were the intestinal walls, thyroid, and urinary bladder wall. Uncertainty remained similar to ¹²³I for case A but considerably greater for case B, especially for long biological half-lives (GI tract). Normal tissue dosimetries for IAZA must be considered carefully when substituting isotope species. A long biological half-life can significantly increase dosimetric uncertainties. These findings are relevant when considering PET imaging studies with [¹²⁴I]IAZA or therapeutic administration of [¹³¹I]IAZA. Full article

External beam radiation therapy leads to cellular activation of the DNA damage response (DDR). DNA double-strand breaks (DSBs) activate the ATM/CHEK2/p53 pathway, inducing the transcription of stress genes. The dynamic nature of this transcriptional response has not been directly observed in vivo in humans. In this study we monitored the messenger RNA transcript abundances of nine DNA damage-responsive genes (CDKN1A, GADD45, CCNG1, FDXR, DDB2, MDM2, PHPT1, SESN1, and PUMA), eight of them regulated by p53 in circulating blood leukocytes at different time points (2, 6–8, 16–18, and 24 h) in cancer patients (lung, neck, brain, and pelvis) undergoing radiotherapy. We discovered that, although the calculated mean physical dose to the blood was very low (0.038–0.169 Gy), an upregulation of Ferredoxin reductase (FDXR) gene transcription was detectable 2 h after exposure and was dose dependent from the lowest irradiated percentage of the body (3.5% whole brain) to the highest, (up to 19.4%, pelvic zone) reaching a peak at 6–8 h. The radiation response of the other genes was not strong enough after such low doses to provide meaningful information. Following multiple fractions, the expression level increased further and was still significantly up-regulated by the end of the treatment. Moreover, we compared FDXR transcriptional responses to ionizing radiation (IR) in vivo with healthy donors’ blood cells exposed ex vivo and found a good correlation in the kinetics of expression from the 8-hours time-point onward, suggesting that a molecular transcriptional regulation mechanism yet to be identified is involved. To conclude, we provided the first in vivo human report of IR-induced gene transcription temporal response of a panel of p53-dependant genes. FDXR was demonstrated to be the most responsive gene, able to reliably inform on the low doses following partial body irradiation of the patients, and providing an expression pattern corresponding to the % of body exposed. An extended study would provide individual biological dosimetry information and may reveal inter-individual variability to predict radiotherapy-associated adverse health outcomes. Full article

Nuclear medicine staff are constantly exposed to low doses of ionizing radiation. This study investigated the level of genotoxic effects in hospital employees exposed to routinely used ¹³¹I and ^99mTc in comparison with a control group. The study compared the results of physical and biological monitoring in peripheral blood lymphocytes. The effects of confounding factors, such as smoking status and physical activity, were also considered. Physical dosimetry monitoring revealed differences in the individual annual effective dose as measured by finger ring dosimeter and whole-body dosimeter between the ¹³¹I- and ^99mTc-exposed groups. The DNA damage studies revealed differences between the groups in terms of excess premature chromosome condensation (PCC) fragments and tail DNA. Physical activity and smoking status differentiated the investigated groups. When assessed by the level of physical activity, the highest mean values of tail DNA were observed for the ^99mTc group. When assessed by work-related physical effort, excess PCC fragments were significantly higher in the ¹³¹I group than in the control group. In the investigated groups, the tail DNA values were significantly different between non-smokers and past or current smokers, but excess PCC fragments did not significantly differ by smoking status. It is important to measure exposure to low doses of ionizing radiation and assess the potential risk from this exposure. Such investigations support the need to continue epidemiological and experimental studies to improve our understanding of the mechanisms of the health effects of radionuclides and to develop predictive models of the behavior of these complex systems in response to low-dose radiation. Full article

Polymer gels and films, due to their near equivalence to biological tissue, are amongst the most promising future dosimetry tools for medical applications. The application of polymer dose gels is limited by the sensitivity of dose readout methods and dose gel properties. It is a challenge to find suitable dosimeters for registration of doses delivered to the target by orthovoltage therapy units. The application of metal-particle-enriched polymer composites for dose registration in X-ray therapy might be an elegant solution, especially if recent dose-reading technologies exploring advantages of different physical phenomena are involved. In this work, X-rays from the orthovoltage therapy range were used for the irradiation of experimental samples. In addition, radiation-induced processes of formation of silver nanoparticles in AgNO₃–PVA gels and in free standing AgNO₃PVA films, also containing some additional solvents, namely glycerol, ethanol, and isopropanol, have been investigated, with the aim to apply the developed composites for medical dosimetry purposes. A simple and environmentally friendly method for the formation of free-standing AgPVA films at room temperature was proposed and realized for preparing AgPVA films for investigation. Radiation-induced synthesis of silver nanoparticles in AgPVA composites was investigated, analyzing LPSR-based UV-VIS spectral changes to the irradiated films with respect to irradiation doses, and dose-related tendencies were also evaluated. It was shown that AgPVA films were more sensitive for detection of doses from the interval 0–1.0 Gy, thus indicating potential application of AgPVA films for dosimetry purposes. Full article

Medical workers are the largest group exposed to man-made sources of ionizing radiation. The annual doses received by medical workers have decreased over the last several decades, however for some applications, like fluoroscopically guided procedures, the occupational doses still remain relatively high. Studies show that for some procedures the operator and staff still use insufficient protective and dosimetric equipment, which might cause an underestimation of medical exposures. Physical dosimetry methods are a staple for estimating occupational exposures, although due to the inconsistent use of protection measures, an alternative method such as biological dosimetry might complement the physical methods to achieve a more complete picture. Such methods were used to detect exposures to doses as low as 0.1 mSv/year, and could be useful for a more accurate assessment of genotoxic effects of ionizing radiation in medical workers. Biological dosimetry is usually based on the measurement of the effects present in peripheral blood lymphocytes. Although some methods, such as chromosome aberration scoring or micronucleus assay, show promising results, currently there is no one method recognized as most suitable for dosimetric application in the case of chronic, low-dose exposures. In this review we decided to evaluate different methods used for biological dosimetry in assessment of occupational exposures of medical workers. Full article

Following recent developments, the RENEB network (Running the European Network of biological dosimetry and physical retrospective dosimetry) is in an excellent position to carry out large scale molecular epidemiological studies of ionizing radiation effects, with validated expertise in the dicentric, fluorescent in situ hybridization (FISH)-translocation, micronucleus, premature chromosome condensation, gamma-H2AX foci and gene expression assays. Large scale human health effects studies present complex challenges such as the practical aspects of sample logistics, assay costs, effort, effect modifiers and quality control/assurance measures. At Public Health England, the dicentric, automated micronucleus and gamma-H2AX radiation-induced foci assays have been tested for use in a large health effects study. The results of the study and the experience gained in carrying out such a large scale investigation provide valuable information that could help minimise random and systematic errors in biomarker data sets for health surveillance analyses going forward. Full article

Retrospective dosimetry is one of the most important tools of accident dosimetry for environmental dose estimation when large-scale radiological incidents and nuclear mass-casualty events occur. Electron paramagnetic resonance (EPR) dosimetry is a physical method for the retrospective assessment of absorbed dose based on the measurement of stable radiation-induced radicals in materials. Different from the fast disappearance of radials in aqueous systems, the radials can persist indefinitely in some organized matrices. Therefore, environmental materials contained in creatures from sea or land can be potentially used as environmental dosimeters for a retrospective dose analysis. This study aims to assess the EPR signals of free radicals from environmental biological samples, potentially for the retrospective dose estimation. The evaluated samples involve ox bone, cyclina shell, clam shell, chitin from squid, and human tissue (enamel and fingernail). First, we dehydrate and grind these materials to the powder with different sizes. Subsequently, all materials were irradiated with different doses ranging from 5 Gy to 50 Gy using 6 MV linear accelerator, and EPR spectra of these materials were obtained from the calculation of peak-to-peak amplitudes. The dose-response curve of EPR signals versus irradiated dose for the six materials shows good linearity (R²~0.99). For the grain-size experiment, the ox bone and tooth with 0.5 mm, the chitin with 0.1 mm, and the others with 1 mm have the strongest signal. For the storage temperature experiment, the optimal temperature of storage is at −20 °C for tooth, fingernail, ox bone, and chitin, at 45 °C for clam shell and cyclina shell where the signal fading is minimal. In conclusion, the developed dose-response curves of the six materials may potentially help a fast, rough retrospective dose reconstruction under the environment when radiation accidents occur. Full article