Use Of Radioactive Isotopes Research Articles

The phenomenon of thermodiffusion in liquid and solid metals in the works of O. M. Skrebtsov

The year 2024 marks the 100th anniversary of a world-renowned scientist, our countryman, Professor Olexandr Mikhailovich Skrebtsov. In addition to research on the use of radioactive isotopes in metallurgy and the development of the theory of the liquid state of metal melts, he paid considerable attention to the phenomenon of thermodiffusion in liquid and solid metals. This paper is devoted to the analysis of this part of the scientific heritage of O. M. Skrebtsov. The movement of atoms under the action of a temperature gradient (thermodiffusion) occurs during various natural phenomena and in many technological processes. However, when studying the driving forces and mechanisms of thermodiffusion, as a rule, the academic approach prevailed. This allowed the theory of thermodiffusion to be well enough developed concerning gases, salt solutions, and solid metals. This article is focused on the analysis of research aimed at the possibility of practical use of this phenomenon to improve the service life of parts operating under conditions of a temperature gradient and optimize processes occurring with a temperature gradient. Such processes occur in metallurgical units, accompanying bimetallic casting, welding, surfacing, etc. Based on the analysis of the experimental data available in the literature, a relationship between the heat of thermodiffusion and the ratio of the atomic radii of the diffusing elements, Rd, and the base metal, Rb, was found. The fundamental possibility of using thermodiffusion for controlling the desulfurization processes in liquid cast iron and creating protective coatings on gray cast iron parts during their operation at high temperatures was also shown

Antibody-Drug Conjugates: A Review of Approved Drugs and Their Clinical Level of Evidence.

Antibody-drug conjugates (ADCs) are an innovative family of agents assembled through linking cytotoxic drugs (payloads) covalently to monoclonal antibodies (mAbs) to be delivered to tumor tissue that express their particular antigen, with the theoretical advantage of an augmented therapeutic ratio. As of June 2023, eleven ADCs have been approved by the Food and Drug Administration (FDA) and are on the market. These drugs have been added to the therapeutic armamentarium of acute myeloblastic and lymphoblastic leukemias, various types of lymphoma, breast, gastric or gastroesophageal junction, lung, urothelial, cervical, and ovarian cancers. They have proven to deliver more potent and effective anti-tumor activities than standard practice in a wide variety of indications. In addition to targeting antigen-expressing tumor cells, bystander effects have been engineered to extend cytotoxic killing to low-antigen-expressing or negative tumor cells in the heterogenous tumor milieu. Inevitably, myelosuppression is a common side effect with most of the ADCs due to the effects of the cytotoxic payload. Also, other unique side effects are specific to the tissue antigen that is targeted for, such as the cardiac toxicity with Her-2 targeting ADCs, and the hemorrhagic side effects with the tissue factor (TF) targeting Tisotumab vedotin. Further exciting developments are centered in the strategies to improve the tolerability and efficacy of the ADCs to improve the therapeutic window; as well as the development of novel payloads including (1) peptide-drug conjugates (PDCs), with the peptide replacing the monoclonal antibody, rendering greater tumor penetration; (2) immune-stimulating antibody conjugates (ISACs), which upon conjugation of the antigen, cause an influx of pro-inflammatory cytokines to activate dendritic cells and harness an anti-tumor T-cell response; and (3) the use of radioactive isotopes as a payload to enhance cytotoxic activity.

Applications of Radioactive Isotopes

Abstract The discovery of radioactivity, a fundamental property of certain atoms, is credited to several scientists, including Henri Becquerel and Marie and Pierre Curie, who together made ground-breaking discoveries that paved the way for the use of radioactive isotopes in various applications in fields such as medicine, agriculture, industry, or archaeology. In medicine especially, radioactivity plays a crucial role, with application in both diagnosis and treatment of various diseases, including cancer. However, radioisotopes also pose potential risks to human health and the environment if not handled properly, causing damage to cells and increase the risk of cancer and other health problems. Nevertheless, their uses are regulated and monitored to ensure safety and, therefore, their utilization has firmly increased in the last decades. Overall, radioactive isotopes are a valuable tool in a wide range of fields and their continued development and application will remain important for years to come.

Evaluation of the permissible 99Mo activity in the KL-15 cask in the design of transportation and process scheme

The demand for the use of radioactive isotopes in medicine is increasing with each coming year necessitating the increased output of radionuclide products. One of the most widely spread radionuclides used in medicine is technetium-99m (99mТс) (Feasibility of producing molybdenum-99 2015, NEA 2012, The Supply of Medical Radioisotopes 2015). The very short 99mТс life (6-hour half-life) requires its production directly on the site of medical treatment. This is achieved using molybdenum-technetium generators (Kodina and Krasikova 2014, Technical Reports No. NF-T-5.4. 2013, Technetium-99 Generator 2021) loaded with molybdenum-99 (99Мо), which uninterruptedly decays (half-life of 66 hours) yielding 99mTc. Close attention must be paid in the course of production of molybdenum-technetium generators to radiation safety during transportation of 99Мо on the territory of the manufacturing facility. The main measure for ensuring radiation safety during transportation of 99Мо is the application of special packaging kits. The Karpov Institute of Physical Chemistry JSC uses a wide range of packaging kits of types A and B for transportation of radioactive materials on the territory of the manufacturer with design features providing the required level of radiation safety. In particular, the KL-15 shipping cask loaded/unloaded from the top is used for onsite transportation of 99Мо for charging molybdenum-technetium generators. The maximum permissible activity of 99Мо is not specified in the passport of the KL-15 cask. Planned construction of a radionuclide production shop in accordance with GMP requirements will require the increase of output of target radionuclides by several times. The above considerations necessitated the evaluation of the maximum permissible activity of 99Мо planned to be transported in KL-15 casks. No other type of standard casks can be used because of their outside dimensions prohibiting the unloading of 99Мо inside the “hot” chamber. Calculation and experimental evaluation of permissible 99Мо activity during transportation inside the KL-15 cask was performed. The paper presents the calculated evaluation of the maximum permissible activity of 99Мо in a KL-15 cask to ensure the radiation exposure of personnel of group A working with the cask not exceeding the established level at the enterprise (80 μSv per shift) and not requiring the use of additional measures and means of protection. The results of the work allow us drawing the conclusion that the KL-15 cask ensures the required level of radiation safety with up to 241 Ki of 99Мо loaded in the cask.

From reactor to patient: an example of radioactive diagnostics and effective half-life in thyroid cancer treatment

We follow a radioactive sample from production in a reactor to its use in a biological application to model the complexities in the use of radioactive isotopes from a student’s perspective. Specifically, we describe a way to use gamma ray detection outside the body to estimate the clearance rate of these radioisotopes from the body and how that rate can be used to assess thyroid cancer remnant mass. This procedure has a long history in nuclear medicine and is well established. Classroom discussion questions are included to think more deeply about the proper (and improper) handling of radiopharmaceuticals as well as patient safety.

Radiation safety of food raw materials and food products

Intensive use of radioactive isotopes in industry, abnormal emissions of nuclear fission products into the environment gradually increase the level of natural background radiation. As a result, there is a problem of farming, the main producer of food for the population, raw materials for industry, associated with the control of the level of contamination of soil, water, and livestock products. It is necessary to constantly monitor the radiation situation, namely the content of cesium-137 in soil, water, as well as in animal products both in the North-Western region and in other subjects of the Russian Federation. Due care must be taken when organizing the feeding of productive animals (dairy cows, beef cattle in the final fattening period), whose products, without an additional processing stage, can be directed to consumption by the population.

Dr. Edith H. Quimby: A pioneering medical physicist and educator with outstanding contributions in radiation dosimetry

Dr. Edith H. Quimby: A pioneering medical physicist and educator with outstanding contributions in radiation dosimetry

A 3D-Printed Model That Simulates a Geiger–Müller Counter and the Radioactive Decay Experiment

The use of radioactive isotopes in radioactive decay studies can be a problem due to the manipulation of radioisotopes, expensive equipment, and the difficulty of finding samples with a reasonable half-life (between 1 and 10 min). In this paper, we present a mock-up of a Geiger–Müller counter plus three fictitious radioisotopes. They form an experimental kit that teachers and professors can use in laboratories of schools and universities. Inside the Geiger electronic box, an Arduino board can recognize the isotope specimen sample the student inserts in the Geiger–Müller tube support. Once the measuring process starts, the Arduino simulates the particle counting as a function of time for that chosen isotope. The complete kit presented here costs approximately US$ 20.00, and it can be an alternative to other simulations for radioactive decay lessons.

Technical Note: In vivo estimation of lipogenesis using a bolus injection of [U-13C]glucose in pigs.

The use of radioactive isotopes to measure de novo lipogenesis in pigs has been well established. Different from radioactive isotopes, stable isotopes present little or no risk to human and animal subjects. Therefore, the objective of this study was to adapt the method of bolus injection of radioactive glucose (14C) to use 13C-labeled glucose to estimate de novo lipogenesis in finishing pigs. Five vein-catheterized gilts received 3.0 kg/d of a commercial diet for 2 wk. On the last day, the pigs received a bolus injection of [U-13C]glucose (12 mg/kg body weight). A serial of blood samples was taken for 4 h to determine the glucose rate of disappearance (Rd) from plasma glucose isotopic enrichment (IE). The 13C IE of lipids was determined from adipose tissue biopsies collected at 1, 2, and 3 h after the bolus injection and from adipose tissue collected after pig euthanasia 4 h after the bolus. Lipogenesis was estimated from the incorporation of 13C from glucose into adipose tissue lipids. Glucose Rd, estimated using a double-exponential function, averaged 5.4 ± 1.4 mmol/min. The IE of lipids increased linearly during the 4 h following the bolus injection (P < 0.05). The rate of incorporation of glucose into lipids, estimating lipogenesis, averaged 9.0 µg glucose/(min × g of lipids) 4 h after the bolus injection. In conclusion, the in vivo method using a bolus injection of [U-13C]glucose allows a successful estimation of de novo lipogenesis in finishing pigs.

Real-Time Monitoring of APC /C-Mediated Substrate Degradation Using Xenopus laevis Egg Extracts.

The anaphase promoting complex/cyclosome (APC/C), a large E3 ubiquitin ligase, is a key regulator of mitotic progression. Upon activation in mitosis, the APC/C targets its two essential substrates, securin and cyclin B, for proteasomal destruction. Cyclin B is the activator of cyclin-dependent kinase 1 (Cdk1), the major mitotic kinase, and both cyclin B and securin are safeguards of sister chromatid cohesion. Conversely, the degradation of securin and cyclin B promotes sister chromatid separation and mitotic exit. The negative feedback loop between Cdk1 and APC/C-Cdk1 activating the APC/C and the APC/C inactivating Cdk1-constitutes the core of the biochemical cell cycle oscillator.Since its discovery three decades ago, the mechanisms of APC /C regulation have been intensively studied, and several in vitro assays exist to measure the activity of the APC /C in different activation states. However, most of these assays require the purification of numerous recombinant enzymes involved in the ubiquitylation process (e.g., ubiquitin, the E1 and E2 ubiquitin ligases, and the APC /C) and/or the use of radioactive isotopes. In this chapter, we describe an easy-to-implement method to continuously measure APC /C activity in Xenopus laevis egg extracts using APC /C substrates fused to fluorescent proteins and a fluorescence plate reader. Because the egg extract provides all important enzymes and proteins for the reaction, this method can be used largely without the need for recombinant protein purification. It can also easily be adapted to test the activity of APC /C mutants or investigate other mechanisms of APC /C regulation.

Measuring vitamin B-12 bioavailability with [13C]-cyanocobalamin in humans

Vitamin B-12deficiency is widespread inmany parts of the world,affecting all age groups and increasing with age.It is primarily due to a low intake of animalsourcefoodsor malabsorption. The measurement of bioavailability of vitamin B-12 is etiologically important in deficiency but is limited due to the use of radioactive isotopes like [57Co]- or [14C]-cyanocobalamin. The aim of this study was to measure the bioavailability of [13C]-cyanocobalamin in humans and to assess the effect of parenteral replenishment of vitamin B-12 on the bioavailability. We synthesized a stable isotope-labeled vitamin B-12, [13C]-cyanocobalamin, using Salmonella enterica by providing [13C2]-ethanolamine as a sole carbon source. After purification and mass spectrometry-based characterization, its oral bioavailability was measured in the fasted state with high and low oral doses, before and after parenteral replenishment of vitamin B-12 stores, fromthe kinetics of itsplasma appearancein a 2-compartment model. [13C]-cyanocobalamin was completely decyanated to [13C]-methylcobalamin describing metabolic utilization, and its plasma appearance showed early and late absorption phases. At a low dose of 2.3µg,themeanbioavailability was 46.2±12.8 (%, mean±SD, n = 11). At a higher dose of 18.3µg, the mean bioavailability was 7.6±1.7 (%, mean±SD, n=4). Parenteral replenishment of the vitaminB-12 store in deficient individuals prior to the measurement resulted in a 1.9-fold increase in bioavailability. VitaminB-12 bioavailability is dose dependent and at a low dose that approximates the normal daily requirement (46%). The stable isotope method described here couldbe used to define the etiology of deficiency and to informthe dietaryrequirement in different physiologic states as well asthe doserequired forsupplementationandfood fortification. This trial was registered at the Clinical Trials Registry of India as CTRI/2018/04/012957.

Application of Natural Radionuclide in the Subsurface Hydrogeology of Selected Two Local Governments in South Western Nigeria

This research investigated the use of radioactive isotopes to study the underground water characteristics of Ife South and Ife North Local governments area of Osun state in Southwestern Nigeria. The study aimed to determine the origin of water, the flow paths, residence time, and prediction of the geological formation of the study area. Twelve water samples were collected from the two local governments using standard methods for isotope study. Uranium 234U and 238U were analyzed for water samples using a gamma-ray spectrometer with Caesium Iodide (CsI) scintillation detector and physical analyses such as pH, electrical conductivity, total dissolved solids, and temperature were also determined. The specific activity of 238U ranged between 27.44±0.55 to 36.89±1.70 Bq/kg; activity ratio of water samples from the two LGA ranged from 0.83 to 1.07 with average activity ratio of 0.901. All the sample locations have an activity ratio of less than 1.00 except two locations in Ife South LGA (Ooni 1 and 2); a 234U value of 30.386747 Bq/kg was taken as constant. Ife North and Ife South have an average EC, turbidity, TDS, residence time of 493.3 (µs/cm), and 686.6 (µs/cm); 1.2 NTU and 3.33 NTU; 108.67 mg/l and 523.33 mg/l; 2.889 ma and 2.784 ma respectively. In conclusion, the groundwater of the two LGA originate from the same source and are in the oxidation state; aquifers within Ife North and Ife South are separated with a barrier; hence its groundwater does not flow through one another. The residence time of groundwater in the two LGA is over 2.8 ma; Ooni 1 and 2 area is underlain by rocks rich in Uranium (granite), rocks underlying Ife South is younger to Ife North, Ife North is underlying by old weathered rocks (sedimentary rocks).

Isotope Labeling to Study Phosphorus Uptake in the Arbuscular Mycorrhizal Symbiosis.

Isotope labeling enables the detection and quantification of nutrient fluxes between soil and plants through arbuscular mycorrhizal (AM) fungi. Here we describe the use of radioactive isotopes, 33P and 32P, to study the uptake of P from soil by AM fungal mycelium and its transfer to the host plant through the mycorrhizal pathway.

Analysis of Phosphorylation Status of Ectopically Expressed Proteins in Early Xenopus Embryos.

Xenopus embryos provide a rapid and accessible in vivo model, expressing a plethora of endogenous kinase and phosphatase enzymes that control protein phosphorylation and, in turn, affect physiological function. Traditionally, the detection of protein phosphorylation has been achieved by radioisotope phosphate labeling of proteins, sometimes with in vitro assays using recombinant proteins or with site-specific phospho-antibodies. However, the target phospho-sites and kinases responsible are often unknown, and the use of radioactive isotopes is not always desirable. Therefore, as a first step in determining the functional significance of potential phosphorylation, it is useful to show that a protein can be phosphorylated in vivo in Xenopus eggs and/or embryos. This protocol describes a nonradioactive method to visualize protein phosphorylation by exposing the protein to the egg/embryo kinase environment and then observing a difference in protein migration (as assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis [SDS-PAGE] and western blot analysis) with and without treatment with the lambda phosphatase enzyme. Subsequent investigation of the ability of site-specific phospho-mutant proteins to recapitulate the effect of phosphatase treatment can be used to explore the identity of the phosphorylated sites. Moreover, the detection of multiple bands of the protein of interest even after phosphatase treatment points to the presence of other types of posttranslational modifications.

ДИФУЗІЯ У ЗАЛІЗІ ТА ЙОГО СПЛАВАХ ПІСЛЯ НАСИЧЕННЯ ПОВЕРХНІ ІОНАМИ АРГОНУ ТА КРИПТОНУ ПРИ ВІДПАЛАХ ТА ІМПУЛЬСНИХ НАВАНТАЖЕННЯХ

The effect of the preliminary introduction of inert gases (argon and krypton) into iron and its alloys in a glow discharge plasma on diffusion (mass transfer) under various external influences was studied using methods based on the use of radioactive isotopes and xrays. The studies were carried out by methods of x-ray diffraction analysis, layered radiometric analysis of residual integral activity, macro-, micro-, electron-microscopic and activation autoradiography. Isotopes of iron 55Fe, nickel 63Ni, carbon 14C, argon 41Ar and krypton 85Kr were used. The following external effects were applied to the metal (alloy) in the initial state and after saturation with an inert gas: galvanic coating, isothermal annealing, athermal martensitic transformation with explosive kinetics and a large volume effect (~ 3%), ultrasonic impact treatment, compression due to deformation when the load falls, magnetic pulse deformation, etc. It is shown that the presence of a pre-introduced inert in iron and alloys based on it leads to a decrease in the mobility of atoms during annealing, low-temperature pulsed loading in a wide range of deformation rates, and further ion bombardment in a glow discharge. No difference was found in the effect of the type of inert gas — argon or krypton — on the change in atomic mobility, surface distribution, and the shape of the concentration profile. The barrier effect of the introduced gas is associated with structural-phase changes in the surface layers by the occurrence of gas-filled pores and a subtraction solid solution in the surface layers, which transforms into a substitutional solid solution away from the surface. Additional studies have shown that the barrier effect of the introduced inert gas on diffusion during subsequent exposures is observed not only on iron, but also on copper and aluminum. This effect is especially pronounced during the subsequent ion bombardment of copper and aluminum saturated with one or another inert gas in a krypton or argon medium as compared to the subsequent pulsed compression or deformation under martensitic transformations. This suggests the universal nature of the discovered regularity. It should be noted according to autoradiographic studies that the presence of an inert gas, which slows down the transfer of matter during subsequent treatments, does not change the nature of the distribution of atoms. There is diffusion over the grain volume with some depletion of the surface layer, and the concentration profiles are described by an exponential dependence on the square of the penetration depth. Therefore, the mechanism of volume diffusion is preserved over the entire range of temperatures and strain rates, and also does not depend on the type of external influence applied. This is true for native atoms and atoms forming solid solutions of various types: substitution (nickel), interstitial (carbon), subtraction (argon and krypton).

Improved Efficacy of Synthesizing *MIII-Labeled DOTA Complexes in Binary Mixtures of Water and Organic Solvents. A Combined Radio- and Physicochemical Study.

Typically, the synthesis of radiometal-based radiopharmaceuticals is performed in buffered aqueous solutions. We found that the presence of organic solvents like ethanol increased the radiolabeling yields of [68Ga]Ga-DOTA (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacatic acid). In the present study, the effect of organic cosolvents [ethanol (EtOH), isopropyl alcohol, and acetonitrile] on the radiolabeling yields of the macrocyclic chelator DOTA with several trivalent radiometals (gallium-68, scandium-44, and lutetium-177) was systematically investigated. Various binary water (H2O)/organic solvent mixtures allowed the radiolabeling of DOTA at a significantly lower temperature than 95 °C, which is relevant for the labeling of sensitive biological molecules. Simultaneously, much lower amounts of the chelators were required. This strategy may have a fundamental impact on the formulation of trivalent radiometal-based radiopharmaceuticals. The equilibrium properties and formation kinetics of [M(DOTA)]- (MIII= GaIII, CeIII, EuIII, YIII, and LuIII) complexes were investigated in H2O/EtOH mixtures (up to 70 vol % EtOH). The protonation constants of DOTA were determined by pH potentiometry in H2O/EtOH mixtures (0-70 vol % EtOH, 0.15 M NaCl, 25 °C). The log K1H and log K2H values associated with protonation of the ring N atoms decreased with an increase of the EtOH content. The formation rates of [M(DOTA)]- complexes increase with an increase of the pH and [EtOH]. Complexation occurs through rapid formation of the diprotonated [M(H2DOTA)]+ intermediates, which are in equilibrium with the kinetically active monoprotonated [M(HDOTA)] intermediates. The rate-controlling step is deprotonation (and rearrangement) of the monoprotonated intermediate, which occurs through H2O (*M(HL) kH2O) and OH- (*M(HL) kOH) assisted reaction pathways. The rate constants are essentially independent of the EtOH concentration, but the M(HL) kH2O values increase from CeIII to LuIII. However, the log KM(HL)H protonation constants, analogous to the log KH2 value, decrease with increasing [EtOH], which increases the concentration of the monoprotonated M(HDOTA) intermediate and accelerates formation of the final complexes. The overall rates of complex formation calculated by the obtained rate constants at different EtOH concentrations show a trend similar to that of the complexation rates determined with the use of radioactive isotopes.

Detection of Selenoproteins by Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP MS) in Immobilized pH Gradient (IPG) Strips.

In contrast to other trace elements that are cofactors of enzymes and removed from proteins under denaturing conditions, Se is covalently bound to proteins when incorporated into selenoproteins, since it is a component of selenocysteine aminoacid. It implies that selenoproteins can undergo several biochemical separation methods in stringent and chaotropic conditions and still maintain the presence of selenium in the primary sequence. This feature has been used to develop a method for the detection of trace levels of human selenoproteins in cell extracts without the use of radioactive isotopes. The selenoproteins are separated as a function of their isoelectric point (pI) using iso-electrofocusing (IEF) electrophoretic strips and detected by laser ablation-inductively coupled plasma mass spectrometry (LA-ICP MS). This method, therefore referred to as IEF-LA-ICP MS, allowed the detection of several selenoproteins in human cell lines, including Gpx1, Gpx4, TXNRD1, TXNRD2, and SELENOF.

Focal Cutaneous Squamous Cell Carcinoma Following Radium-223 Extravasation

Long-term sequelae due to extravasation of intravenous radioisotopes resulting in radiation injuries are rarely reported. As the use of radioactive isotopes for the treatment of osteoblastic metastases increases, information regarding the prevention, treatment, and long-term monitoring of suspected extravasation injury will become increasingly important. We present a patient with no previous history of skin cancer who developed an aggressive cutaneous squamous cell carcinoma at the site of prior radium-223 extravasation. We recommend that patients who experience extravasation of therapeutic radioisotopes be monitored by dermatologists for long-term sequelae. Cutaneous squamous cell carcinoma should be recognized as a rare but potential adverse event following cutaneous extravasation of radium-223 and is likely a side effect that is severely underreported.

Refinement of Mouse Protocols for the Study of Platelet Thromboembolic Responses In Vivo.

Mouse models of thromboembolism are frequently used to investigate platelet function in vivo and, according to European Union (EU) legislation, must be conducted in the context of replacement, refinement and reduction. We have previously developed a refined real-time mouse model of thromboembolism as an alternative to models of thromboembolic mortality which inflict considerable pain and suffering. Real-time monitoring involves infusion of radiolabelled platelets into the circulation of anaesthetized mice, and platelet aggregation is measured as increases in platelet-associated counts in the pulmonary vasculature following injection of platelet agonists. This gives a definitive data set on the tissue localization and extent of platelet activation. We developed an additional, more simplistic alternative to mortality models based on blood microsampling which entails the measurement of circulating platelet counts following agonist stimulation. Blood microsamples were collected from the tail vein of anaesthetized mice at three different time points leading to a reduction in animal numbers. Platelet counts significantly dropped 1 minute after stimulation with collagen or thrombin and were restored over 10 minutes. These results correlate with those obtained via real-time monitoring and were confirmed by immunohistochemistry. Pre-treatment of mice with aspirin significantly inhibited the decrease in platelet counts following collagen. These data suggest that blood microsampling may be implemented as a simplistic refined alternative to mortality models of thromboembolism when specialized monitoring equipment, or use of radioactive isotopes for real-time monitoring, which remains the ‘gold standard’, is not feasible. Microsampling refines and reduces animal procedures in compliance with current EU legislation.

The role of brachytherapy in the treatment of glioblastoma multiforme

Brachytherapy (BT) for glioblastoma multiforme (GBM) involves the use of radioactive isotopes to deliver ionizing radiation directly into the tumor bed. Its application as a means to prolong survival in GBM patients over the past few decades has come with variable success. The objective of this review is to describe the utility of BT in GBM, and to report the outcomes and adverse events associated with its use in different multimodal treatment approaches. A search of the literature was conducted using the PubMed database. The most recent search was performed in September 2015. Thirty-two series involving 1571 patients were included in our review. The longest median overall survival (MOS) following BT for newly diagnosed GBM reached 28.5months. Overall, 1-, 2-, and 3-year survival rates were 46-89%, 20-57%, and 14-27%. For recurrent GBM, the longest reported MOS after BT was 15.9months. One-, 2- and 3-year survival rates for recurrent GBM were 10-66%, 3-23%, and 9-15%. Adverse events were reported in 27% of patients. Reoperation for radiation necrosis occurred in 4 and 27% of patients following low- and high-dose rate BT, respectively. BT is a feasible option for extending survival in carefully selected GBM patients. As patient outcomes and overall survival improve with more aggressive radiotherapy, so does the risk of radiation-related complications. The most effective use of BT is likely as a part of multimodal treatment with other novel therapies.