EANM guidelines for radionuclide therapy of bone metastases with beta-emitting radionuclides.
Ontology highlight
ABSTRACT:
SUBMITTER: Handkiewicz-Junak D
PROVIDER: S-EPMC5978928 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Brain metastases develop frequently in patients with breast cancer, and present a pressing therapeutic challenge. Expression of vascular cell adhesion molecule 1 (VCAM-1) is upregulated on brain endothelial cells during the early stages of metastasis and provides a target for the detection and treatment of early brain metastases. The aim of this study was to use a model of early brain metastasis to evaluate the efficacy of ?-emitting radionuclides, 149Tb, 211At, 212Pb, 213Bi and 225Ac; ?-emitting radionuclides, 90Y, 161Tb and 177Lu; and Auger electron (AE)-emitters 67Ga, 89Zr, 111In and 124I, for targeted radionuclide therapy (TRT). METHODS:Histologic sections and two photon microscopy of mouse brain parenchyma were used to inform a cylindrical vessel geometry using the Geant4 general purpose Monte Carlo (MC) toolkit with the Geant4-DNA low energy physics models. Energy deposition was evaluated as a radial function and the resulting phase spaces were superimposed on a DNA model to estimate double-strand break (DSB) yields for representative ?- and ?-emitters, 177Lu and 212Pb. Relative biological effectiveness (RBE) values were determined by only evaluating DNA damage due to physical interactions. RESULTS:177Lu produced 2.69 ± 0.08 DSB per GbpGy, without significant variation from the lumen of the vessel to a radius of 100 µm. The DSB yield of 212Pb included two local maxima produced by the 6.1 MeV and 8.8 MeV ?-emissions from decay products, 212Bi and 212Po, with yields of 7.64 ± 0.12 and 9.15 ± 0.24 per GbpGy, respectively. Given its higher DSB yield 212Pb may be more effective for short range targeting of early micrometastatic lesions than 177Lu. CONCLUSION:MC simulation of a model of early brain metastases provides invaluable insight into the potential efficacy of ?-, ?- and AE-emitting radionuclides for TRT. 212Pb, which has the attributes of a theranostic radionuclide since it can be used for SPECT imaging, showed a favorable dose profile and RBE.
| S-EPMC5743475 | biostudies-literature
Project description:Brain tumors are notoriously difficult to treat. The blood-brain barrier provides a sanctuary site where residual and metastatic cancer cells can evade most therapeutic modalities. The delicate nature of the brain further complicates the decision of eliminating as much tumorous tissue as possible while protecting healthy tissue. Despite recent advances in immunotherapy, radiotherapy and systemic treatments, prognosis of newly diagnosed patients remains dismal, and recurrence is still a universal problem. Several strategies are now under preclinical and clinical investigation to optimize delivery and maximize the cytotoxic potential of pharmaceuticals with regards to brain tumors. This review provides an overview of targeted radionuclide therapy approaches for the treatment of primary brain tumors and brain metastases, with an emphasis on biological targeting moieties that specifically target key biomarkers involved in cancer development.
| S-EPMC6723032 | biostudies-literature
Project description:The use of cardiac PET, and in particular of quantitative myocardial perfusion PET, has been growing during the last years, because scanners are becoming widely available and because several studies have convincingly demonstrated the advantages of this imaging approach. Therefore, there is a need of determining the procedural modalities for performing high-quality studies and obtaining from this demanding technique the most in terms of both measurement reliability and clinical data. Although the field is rapidly evolving, with progresses in hardware and software, and the near perspective of new tracers, the EANM Cardiovascular Committee found it reasonable and useful to expose in an updated text the state of the art of quantitative myocardial perfusion PET, in order to establish an effective use of this modality and to help implementing it on a wider basis. Together with the many steps necessary for the correct execution of quantitative measurements, the importance of a multiparametric approach and of a comprehensive and clinically useful report have been stressed.
| S-EPMC7603916 | biostudies-literature
Project description:Inflammatory musculoskeletal diseases represent a group of chronic and disabling conditions that evolve from a complex interplay between genetic and environmental factors that cause perturbations in innate and adaptive immune responses. Understanding the pathogenesis of inflammatory musculoskeletal diseases is, to a large extent, derived from preclinical and basic research experiments. In vivo molecular imaging enables us to study molecular targets and to measure biochemical processes non-invasively and longitudinally, providing information on disease processes and potential therapeutic strategies, e.g. efficacy of novel therapeutic interventions, which is of complementary value next to ex vivo (post mortem) histopathological analysis and molecular assays. Remarkably, the large body of preclinical imaging studies in inflammatory musculoskeletal disease is in contrast with the limited reports on molecular imaging in clinical practice and clinical guidelines. Therefore, in this EANM-endorsed position paper, we performed a systematic review of the preclinical studies in inflammatory musculoskeletal diseases that involve radionuclide imaging, with a detailed description of the animal models used. From these reflections, we provide recommendations on what future studies in this field should encompass to facilitate a greater impact of radionuclide imaging techniques on the translation to clinical settings.
| S-EPMC8421483 | biostudies-literature
Project description:RationaleThe development of consensus guidelines for interpretation of Prostate-Specific Membrane Antigen (PSMA)-Positron Emission Tomography (PET) is needed to provide more consistent reports in clinical practice. The standardization of PSMA-PET interpretation may also contribute to increasing the data reproducibility within clinical trials. Finally, guidelines in PSMA-PET interpretation are needed to communicate the exact location of findings to referring physicians, to support clinician therapeutic management decisions.MethodsA panel of worldwide experts in PSMA-PET was established. Panelists were selected based on their expertise and publication record in the diagnosis or treatment of PCa, in their involvement in clinical guidelines and according to their expertise in the clinical application of radiolabeled PSMA inhibitors. Panelists were actively involved in all stages of a modified, nonanonymous, Delphi consensus process.ResultsAccording to the findings obtained by modified Delphi consensus process, panelist recommendations were implemented in a structured report for PSMA-PET.ConclusionsThe E-PSMA standardized reporting guidelines, a document supported by the European Association of Nuclear Medicine (EANM), provide consensus statements among a panel of experts in PSMA-PET imaging, to develop a structured report for PSMA-PET in prostate cancer and to harmonize diagnostic interpretation criteria.
| S-EPMC8113168 | biostudies-literature
Project description:Targeted α-emitting drugs are promising for cancer therapy, but cannot be effectively imaged by conventional techniques. Cerenkov luminescence imaging (CLI) has previously been shown capable of imaging β(+)- and β(-)-emitting radionuclides in vivo and could have the potential to image α-emitters. Cerenkov light production from α-emitters is through Compton scattering and from farther down the decay chain. This causes the Cerenkov production to vary in time and depend on sample geometry, complicating the interpretation of CLI images. We used the simulation toolkit Geant4 to predict the Cerenkov light output from five α-emitting radionuclides that have therapeutic potential: (225)Ac, (230)U, (213)Bi, (212)Bi and (212)At. We found that (225)Ac, (213)Bi and (212)Bi produced an order of magnitude more Cerenkov light than (18)F. However, the light from (225)Ac is delayed from the initial decay, possibly decreasing the correlation of the drug and light source. This indicates that CLI will not be helpful in the development of some α-emitting drugs.
| S-EPMC5558792 | biostudies-other
Project description:Bone metastasis remains a major cause of death in cancer patients, and current therapies for bone metastatic disease are mainly palliative. Bone metastases arise after cancer cells have colonized the bone and co-opted the normal bone remodeling process. In addition to bone-targeted therapies (e.g., bisphosphonate and denosumab), hormone therapy, chemotherapy, external beam radiation therapy, and surgical intervention, attempts have been made to use systemic radiotherapy as a means of delivering cytocidal radiation to every bone metastatic lesion. Initially, several bone-seeking beta-minus-particle-emitting radiopharmaceuticals were incorporated into the treatment for bone metastases, but they failed to extend the overall survival in patients. However, recent clinical trials indicate that radium-223 dichloride (223RaCl2), an alpha-particle-emitting radiopharmaceutical, improves the overall survival of prostate cancer patients with bone metastases. This success has renewed interest in targeted alpha-particle therapy development for visceral and bone metastasis. This review will discuss (i) the biology of bone metastasis, especially focusing on the vicious cycle of bone metastasis, (ii) how bone remodeling has been exploited to administer systemic radiotherapies, and (iii) targeted radiotherapy development and progress in the development of targeted alpha-particle therapy for the treatment of prostate cancer bone metastasis.
| S-EPMC8070008 | biostudies-literature
Project description:Previous studies have shown that the mean absorbed dose to a tissue element may not be a suitable quantity for correlating with the biological response of cells in that tissue element. Cell survival can depend strongly on the distribution of radioactivity at the cellular and multicellular levels. Furthermore, when cellular absorbed doses are examined, the cross-dose from neighbor cells can be less radiotoxic than the self-dose component. To better understand how the nonuniformity of activity among cells can affect the dose response, a computer model of a 3D tissue culture was previously constructed and showed that activity distribution among cells is significantly more relevant than the mean absorbed dose for low-energy-electron emitters. The present work greatly expands upon those findings.In the present study, we used this same computer model but restricted the number of labeled cells to a fraction of the whole cell population (50%, 10%, and 1%, respectively). The labeled cells were randomly distributed among the whole cell population.While the activity distribution is an important factor in determining the tissue response for low-energy-electron emitters, the fraction of labeled cells has an even more pronounced effect on survival response. For all electron energies studied, reducing the percentage of cells labeled significantly increases the surviving fraction of the whole population.This study provides abundant information on killing tumor and normal cells under some conditions relevant to targeted radionuclide therapy of isolated tumor cells and micrometastases. The percentage of cells labeled, activity distribution among the labeled cells, and electron energy play key roles in determining their response. Most importantly, and not previously demonstrated, lognormal activity distributions can have a profound impact on the response of the tumor cells even when the radionuclide emits high-energy electrons.
| S-EPMC3543371 | biostudies-other
Project description:Auger-emitting radionuclides have potential application in targeted radiotherapy, particularly for metastatic cancers. This possibility, especially, is stemmed from their characteristic short-range (a few μm) in biological systems allowing localization of high dose within small tumours. To explore this potential application, a Geant4 Monte Carlo toolkit has been employed to simulate the energy deposition of different radionuclides in a water model. The Geant4 Monte Carlo toolkit has model packages to simulate the interaction of radiation with matter and with diverse applications such as studies in science and medicine. In this study, the Geant4-DNA package was used to simulate the radiolytic yields induced by some Auger electron-emitting (AE) radionuclides including; I-131, I-125 and Pd-103, In-111, Ru-97 and Rh-103 m in water model. The results showed that the transient yield of the radiolytic species is characterized by the kinetic energies of the emitted electrons. It was observed that almost all the radionuclides, except I-131, deposited more energy in their proximity thereby inducing a high density of spurs to interact in a short time. It is, therefore, important to consider the kinetic energies of the emitted particles in choosing a radionuclide for specified targeted radiotherapy. This means that apart from their toxicity, compatibility with chelator and carrier molecules, and method of production, we can predict radionuclides such as In-111, Ru-97, Pb-103 m and I-125 could be relevant for targeted radiotherapy for the treatment of metastasis lesions, or tiny tumours at the cellular level, and tumours after surgical resection.
| S-EPMC10036101 | biostudies-literature
Project description:Background:Best-practice guidelines recommend single-fraction (SFRT) instead of multi-fraction radiation therapy (MFRT) for uncomplicated symptomatic bone metastases. SFRT is comparable to MFRT in relieving pain, convenient for patients, and cost-effective. Patterns of practice in Canada reveal that SFRT is underused, with significant variability across the country. We audited SFRT use and studied factors that may influence treatment decisions at a large academic tertiary care center in Quebec, Canada. Methods:Patients who received radiotherapy for uncomplicated bone metastases between February 2014 and March 2015 were reviewed. Age, gender, primary histology, site of metastases and performance status were identified as potential factors affecting fractionation. These were explored by Fisher's test on univariate analysis and logistic regression for multivariate analysis. Retreatment rates were analyzed with cumulative incidence and compared with Gray's test. Results:254 radiotherapy courses were administered to 165 patients, 85.4% of which were delivered using a single fraction of 8?Gy. Patients age less than 70?years and those with breast histology were more likely to receive MFRT (p?=?0.04; p?=?0.0046). Performance status (ECOG) was a significant predictor of fractionation because of high correlations between young age, breast histology, and ECOG status (p?=?0.03). Follow-up was too short in 40% of patients to derive definitive conclusions on retreatment. Conclusions:In accordance with current guidelines, our audit confirms that use of SFRT in patients with uncomplicated bone metastases at our center is high. We identified that patient age, primary histology, and performance status influenced fractionation. Incorporation of this quality indicator into our performance dashboard will allow assessment of retreatment differences and other criteria that may also influence treatment choice.
| S-EPMC7033799 | biostudies-literature