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1.
PLoS One ; 16(10): e0257605, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34648511

RESUMO

The objective of this study is to develop a skeleton model for assessing active marrow dose from bone-seeking beta-emitting radionuclides. This article explains the modeling methodology which accounts for individual variability of the macro- and microstructure of bone tissue. Bone sites with active hematopoiesis are assessed by dividing them into small segments described by simple geometric shapes. Spongiosa, which fills the segments, is modeled as an isotropic three-dimensional grid (framework) of rod-like trabeculae that "run through" the bone marrow. Randomized multiple framework deformations are simulated by changing the positions of the grid nodes and the thickness of the rods. Model grid parameters are selected in accordance with the parameters of spongiosa microstructures taken from the published papers. Stochastic modeling of radiation transport in heterogeneous media simulating the distribution of bone tissue and marrow in each of the segments is performed by Monte Carlo methods. Model output for the human femur at different ages is provided as an example. The uncertainty of dosimetric characteristics associated with individual variability of bone structure was evaluated. An advantage of this methodology for the calculation of doses absorbed in the marrow from bone-seeking radionuclides is that it does not require additional studies of autopsy material. The biokinetic model results will be used in the future to calculate individual doses to members of a cohort exposed to 89,90Sr from liquid radioactive waste discharged to the Techa River by the Mayak Production Association in 1949-1956. Further study of these unique cohorts provides an opportunity to gain more in-depth knowledge about the effects of chronic radiation on the hematopoietic system. In addition, the proposed model can be used to assess the doses to active marrow under any other scenarios of 90Sr and 89Sr intake to humans.


Assuntos
Partículas beta/efeitos adversos , Medula Óssea/efeitos da radiação , Osso e Ossos/efeitos da radiação , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Simulação por Computador , Feminino , Hematopoese/efeitos da radiação , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Método de Monte Carlo , Doses de Radiação , Radiometria , Processos Estocásticos , Adulto Jovem
2.
J Environ Radioact ; 237: 106720, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34454249

RESUMO

A hybrid extractive scintillating resin (HESR) was developed for the concentration and detection of radiocesium. The HESR comprised a cesium-selective potassium ferrierite ion-exchange powder embedded in porous polymeric scintillating beads. It was prepared by carrying out suspension polymerization of 4-methylstyrene with divinylbenzene, 2-(1-naphthyl)-4-vinyl-5-phenyloxazole fluor and ferrierite-K powder. A translucent column packed with the HESR was placed in a commercial flow-cell radiation detector for real-time detection of radiocesium. Measurements using the HESR detection system were compared with an on-line gamma-ray measurement using a NaI:Tl well detector containing a column of ferrierite-K powder/SiO2 or potassium-nickel ferrocyanate-polyacrylonitrile (KNiFC-PAN). The NaI:Tl well detector configuration quantified the gamma-ray from 137mBa, while the flow-cell detector primarily quantified the beta particles and conversion electrons of 137Cs. The minimum detectable concentration of the two detection modalities were calculated and shown to be lower than the maximum contaminant level in drinking water of 7.4 Bq/L (200 pCi/L).


Assuntos
Água Potável , Monitoramento de Radiação , Partículas beta , Césio , Dióxido de Silício
3.
Environ Health ; 20(1): 70, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-34126994

RESUMO

BACKGROUND: Exposure to ionizing radiation has been associated with insulin resistance and type 2 diabetes. In light of recent work showing an association between ambient particulate matter (PM) gross ß-activity and gestational diabetes mellitus (GDM) among pregnant women, we examined pregnancy glucose levels in relation to PM gross ß-activity to better understand this pathway. METHODS: Our study included 103 participants receiving prenatal care at Beth Israel Deaconess Medical Center in Boston, MA. PM gross ß-activity was obtained from US Environmental Protection Agency's RadNet program monitors, and blood glucose levels were obtained from the non-fasting glucose challenge test performed clinically as the first step of the 2-step GDM screening test. For each exposure window we examined (i.e., moving average same-day, one-week, first-trimester, and second-trimester PM gross ß-activity), we fitted generalized additive models and adjusted for clinical characteristics, socio-demographic factors, temporal variables, and PM with an aerodynamic diameter ≤ 2.5 µm (PM2.5). Subgroup analyses by maternal age and by body mass index were also conducted. RESULTS: An interquartile range increase in average PM gross ß-activity during the second trimester of pregnancy was associated with an increase of 17.5 (95% CI: 0.8, 34.3) mg/dL in glucose concentration. Associations were stronger among younger and overweight/obese participants. Our findings also suggest that the highest compared to the lowest quartile of one-week exposure was associated with 17.0 (95% CI: - 4.0, 38.0) mg/dL higher glucose levels. No associations of glucose were observed with PM gross ß-activity during same-day and first-trimester exposure windows. PM2.5 was not associated with glucose levels during any exposure window in our data. CONCLUSIONS: Exposure to higher levels of ambient PM gross ß-activity was associated with higher blood glucose levels in pregnant patients, with implications for how this novel environmental factor could impact pregnancy health.


Assuntos
Poluentes Atmosféricos/análise , Glicemia/análise , Exposição Materna , Material Particulado/análise , Adulto , Partículas beta , Feminino , Humanos , Gravidez
4.
Radiat Environ Biophys ; 60(2): 257-265, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33864119

RESUMO

The present paper proposes a novel method, based on Bayesian statistics, as a new approach in the field of thermoluminescence dosimetry for the assessment of personal doses in mixed beta-gamma radiation fields. The method can be utilized in situations when the classical way of dose calculation is insufficient or impossible. The proposed method uses a prior function which can be assigned to the unknown parameter and the likelihood function obtained from an experiment, which together can be transformed into the posterior probability distribution of the sought parameter. Finally, the distribution is converted to the value of the dose. The proposed method is supported by analytical and Monte Carlo calculations, which confirmed the results obtained through the Bayesian approach.


Assuntos
Dosimetria Termoluminescente/métodos , Teorema de Bayes , Partículas beta , Radioisótopos de Césio , Raios gama , Humanos , Método de Monte Carlo , Radioisótopos de Estrôncio
5.
Asian Pac J Cancer Prev ; 22(3): 801-809, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33773544

RESUMO

OBJECTIVE: To evaluate the potential radiological impact of atmospheric nuclear weapons tests conducted in 1966-1974 at Mururoa and Fangataufa atolls on populations in Oceania, South America and Africa. METHODS: Results of measurements of total beta(ß)-concentrations in filtered air and 131I activity concentrations in locally produced cow's milk in Oceania, South America and Africa after the tests were compared with those in French Polynesia. Radiation doses due to external irradiation and thyroid doses due to 131I intake with milk by local populations were also compared. RESULTS: Higher total ß-concentrations in filtered air, 131I activity concentrations in locally produced milk and radiation doses to local population were, in general, observed in French Polynesia than in other countries in the southern hemisphere. However, for specific years during the testing period, the radiological impact to South America was found to be similar or slightly higher than that to Tahiti. The resulting thyroid doses in the considered countries were lower than those in French Polynesia with two exceptions: thyroid doses due to 131I intake with cow's milk for 1-y old child in 1968 were higher in Peru (0.35 mGy) and in Madagascar (0.30 mGy) than in Tahiti (0.25 mGy). However, the populations outside French Polynesia received doses lower than those from the natural sources of radiation. CONCLUSION: According to the current knowledge in radiation epidemiology, it is very unlikely that nuclear fallout due to French nuclear tests had a measurable radiological and health impact outside French Polynesia.
.


Assuntos
Armas Nucleares , Doses de Radiação , Exposição à Radiação/estatística & dados numéricos , África , Animais , Partículas beta , França , Humanos , Radioisótopos do Iodo/análise , Madagáscar , Leite/química , Oceania , Peru , Polinésia , Monitoramento de Radiação , América do Sul
6.
J Radiol Prot ; 41(2)2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33690175

RESUMO

170Tm is being explored as a source for applications in brachytherapy. Although it has adequate physical properties, such as a short half-life (128.6 d), high specific activity and a mean photon energy of about 66 keV, it has a drawback of low photon yield (only about six photon emissions/100 beta emissions). The objective of this work is to study the dosimetric characteristics of a locally developed170Tm brachytherapy seed source using the Monte Carlo-based EGSnrc code system. In this study, we calculate the dose rate constant, air-kerma strength, radial dose function, anisotropic function and 2D dose-rate distributions in water. Separate simulations are carried out by considering the photon (gamma and characteristic x-ray) and beta spectra of the source. For regions close to the source (surface of the source

Assuntos
Braquiterapia , Partículas beta , Método de Monte Carlo , Fótons , Radiometria , Dosagem Radioterapêutica
7.
Cancer Biother Radiopharm ; 36(5): 397-406, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33601932

RESUMO

Background: In neuroendocrine tumor (NET), complete surgery could better the prognosis. Radioguided surgery (RGS) with ß--radioisotopes is a novel approach focused on developing a new probe that, detecting electrons and operating with low background, provides a clearer delineation of the lesions with low radiation exposition for surgeons. As a first step to validate this procedure, ex vivo specimens of tumors expressing somatostatin receptors, as small intestine neuroendocrine tumor (SI-NET), were tested. Materials and Methods: SI-NET presents a high uptake of a beta-emitting radiotracer, 90Y-DOTATOC. Five SI-NET patients were enrolled after performing a 68Ga-DOTATOC positron emission tomography/computed tomography (CT) and a CT enterography; 24 h before surgery, they received 5 mCi of 90Y-DOTATOC. Results: Surgery was performed as routine. Tumors and surrounding tissue were sectioned in different samples and examined ex vivo with the beta-detecting probe. All the tumor samples showed high counts of radioactivity that was up to a factor of 18 times higher than the corresponding cutoff value, with a sensitivity of 96% and a specificity of 100%. Conclusions: These first ex vivo RGS tests showed that this probe can discriminate very effectively between tumor and healthy tissues by the administration of low activities of 90Y-DOTATOC, allowing more precise surgery.


Assuntos
Neoplasias Intestinais/cirurgia , Tumores Neuroendócrinos/cirurgia , Octreotida/análogos & derivados , Idoso , Partículas beta , Feminino , Humanos , Neoplasias Intestinais/diagnóstico por imagem , Neoplasias Intestinais/patologia , Intestino Delgado , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/patologia , Compostos Organometálicos , Projetos Piloto , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Receptores de Somatostatina , Sensibilidade e Especificidade , Radioisótopos de Ítrio
8.
Sci Rep ; 11(1): 3341, 2021 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-33558553

RESUMO

This paper presents the first plasmid DNA irradiations carried out with Very High Energy Electrons (VHEE) over 100-200 MeV at the CLEAR user facility at CERN to determine the Relative Biological Effectiveness (RBE) of VHEE. DNA damage yields were measured in dry and aqueous environments to determine that ~ 99% of total DNA breaks were caused by indirect effects, consistent with other published measurements for protons and photons. Double-Strand Break (DSB) yield was used as the biological endpoint for RBE calculation, with values found to be consistent with established radiotherapy modalities. Similarities in physical damage between VHEE and conventional modalities gives confidence that biological effects of VHEE will also be similar-key for clinical implementation. Damage yields were used as a baseline for track structure simulations of VHEE plasmid irradiation using GEANT4-DNA. Current models for DSB yield have shown reasonable agreement with experimental values. The growing interest in FLASH radiotherapy motivated a study into DSB yield variation with dose rate following VHEE irradiation. No significant variations were observed between conventional and FLASH dose rate irradiations, indicating that no FLASH effect is seen under these conditions.


Assuntos
Partículas beta , Quebras de DNA de Cadeia Dupla , Modelos Químicos , Plasmídeos/química
9.
J Environ Radioact ; 228: 106527, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33421905

RESUMO

We evaluate the ability of the Canberra Alpha Beta Environmental Continuous Air Monitor (ECAM) to detect and quantify airborne radiological contamination. The ECAM essentially consists of a passively-implanted planar silicon (PIPS) detector near a particulate filter through which outside air is pulled. Three years' worth of background measurements on three different systems were assessed and calibrated to compensate for changing conditions and develop an average background response for the systems. The ECAM was also exposed to several radionuclides of interest, including 235U and 239Pu, to measure the response to alpha and beta particle sources. Both standard calibration sources and custom sources consisting of aqueous radioisotope solutions absorbed into clean filters. The ECAM responses to these sources were then scaled to quantities of interest and injected on the averaged background. Various alarm algorithms were evaluated on the source-injected spectra for minimum detectable air concentration for a given false alarm rate. Even in the worst case, the ECAM was able to detect radionuclides of interest at 10% of the Derived Response Level (DRL) for each isotope based on early-phase Protective Action Guides (PAG). Quantification of the radionuclides was also evaluated for the various algorithms, with mixed results, but overall clearly indicating the optimal algorithms for alpha and beta particle alarm and quantification. Finally, a limited evaluation of the beta particle detection efficiency points to a detection energy threshold of approximately 290 keV.


Assuntos
Poluentes Radioativos do Ar , Monitoramento Ambiental , Monitoramento de Radiação , Poluentes Radioativos do Ar/análise , Partículas beta , Calibragem , Radioisótopos
10.
Catheter Cardiovasc Interv ; 97(1): 47, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33460270

RESUMO

When a patient presents with restenosis and two layers of previously place drug eluting stents this is a true treatment dilemma for the interventionist. Beta radiation has proven its efficacy to decrease in-stent restenosis compared to standard PCI. No drug-coated balloons are currently available in the United States for treatment of in-stent restenosis.


Assuntos
Braquiterapia , Reestenose Coronária , Stents Farmacológicos , Intervenção Coronária Percutânea , Partículas beta , Braquiterapia/efeitos adversos , Reestenose Coronária/diagnóstico por imagem , Reestenose Coronária/etiologia , Reestenose Coronária/terapia , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Stents , Resultado do Tratamento
11.
Sci Rep ; 11(1): 2475, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33510222

RESUMO

Positron (ß+) emitting radionuclides have been used for positron emission tomography (PET) imaging in diagnostic medicine since its development in the 1950s. Development of a fluorinated glucose analog, fluorodeoxyglucose, labelled with a ß+ emitter fluorine-18 (18F-FDG), made it possible to image cellular targets with high glycolytic metabolism. These targets include cancer cells based on increased aerobic metabolism due to the Warburg effect, and thus, 18F-FDG is a staple in nuclear medicine clinics globally. However, due to its attention in the diagnostic setting, the therapeutic potential of ß+ emitters have been overlooked in cancer medicine. Here we show the first in vitro evidence of ß+ emitter cytotoxicity on prostate cancer cell line LNCaP C4-2B when treated with 20 Gy of 18F. Monte Carlo simulation revealed thermalized positrons (sub-keV) traversing DNA can be lethal due to highly localized energy deposition during the thermalization and annihilation processes. The computed single and double strand breakages were ~ 55% and 117% respectively, when compared to electrons at 400 eV. Our in vitro and in silico data imply an unexplored therapeutic potential for ß+ emitters. These results may also have implications for emerging cancer theranostic strategies, where ß+ emitting radionuclides could be utilized as a therapeutic as well as a diagnostic agent once the challenges in radiation safety and protection after patient administration of a radioactive compound are overcome.


Assuntos
Partículas beta , Elétrons , Tomografia por Emissão de Pósitrons , Neoplasias da Próstata , Linhagem Celular Tumoral , Fluordesoxiglucose F18/farmacologia , Humanos , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/radioterapia , Doses de Radiação , Compostos Radiofarmacêuticos/farmacologia
12.
J Nucl Med ; 62(6): 795-801, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33127621

RESUMO

Targeted therapies for multiple myeloma (MM) include the anti-CD38 antibody daratumumab, which, in addition to its inherent cytotoxicity, can be radiolabeled with tracers for imaging and with ß- and α-emitter radionuclides for radioimmunotherapy. Methods: We have compared the potential therapeutic efficacy of ß- versus α-emitter radioimmunotherapy using radiolabeled DOTA-daratumumab in a preclinical model of disseminated multiple myeloma. Multiple dose levels were investigated to find the dose with the highest efficacy and lowest toxicity. Results: In a dose­response study with the ß-emitter 177Lu-DOTA-daratumumab, the lowest tested dose, 1.85 MBq, extended survival from 37 to 47 d but did not delay tumor growth. Doses of 3.7 and 7.4 MBq extended survival to 55 and 58 d, respectively, causing a small equivalent delay in tumor growth, followed by regrowth. The higher dose, 11.1 MBq, eradicated the tumor but had no effect on survival compared with untreated controls, because of whole-body toxicity. In contrast, the α-emitter 225Ac-DOTA-daratumumab had a dose-dependent effect, in which 0.925, 1.85, and 3.7 kBq increased survival, compared with untreated controls (35 d), to 47, 52, and 73 d, respectively, with a significant delay in tumor growth for all 3 doses. Higher doses of 11.1 and 22.2 kBq resulted in equivalent survival to 82 d but with significant whole-body toxicity. Parallel studies with untargeted 225Ac-DOTA-trastuzumab conferred no improvement over untreated controls and resulted in whole-body toxicity. Conclusion: We conclude, and mathematic modeling confirms, that maximal biologic doses were achieved by targeted α-therapy and demonstrated 225Ac to be superior to 177Lu in delaying tumor growth and decreasing whole-body toxicity.


Assuntos
ADP-Ribosil Ciclase 1/imunologia , Partículas beta/uso terapêutico , Mieloma Múltiplo/patologia , Mieloma Múltiplo/radioterapia , Radioimunoterapia , Animais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/uso terapêutico , Partículas beta/efeitos adversos , Linhagem Celular Tumoral , Modelos Animais de Doenças , Humanos , Terapia de Alvo Molecular , Mieloma Múltiplo/imunologia , Segurança
13.
Health Phys ; 120(2): 177-190, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32833869

RESUMO

ABSTRACT: Pottery objects are presently more and more used for decoration in homes and hotels. To assess radiological hazards to potters, 238U, 232Th, 222Rn, and 220Rn radionuclides were analyzed in different clay body samples used for pottery production by means of CR-39 and LR-115 II track detectors. Data obtained were compared to those gotten by means of isotope dilution mass spectrometry. Annual equivalent doses to the skin of potters resulting from the energy loss of alpha-particles emitted by the radionuclides of the 238U and 232Th radioactive families were evaluated. Estimates of the annual equivalent doses to the skin of potters due to the emitted alpha-particles ranged between 6.45 mSy y-1 cm-2 and 17.50 mSy y-1 cm-2 and between 1.87 mSy y-1 cm-2 and 5.33 mSy y-1 cm-2, respectively. Annual equivalent doses received by the skin of potters due to beta-particles (ß-) emitted by the radionuclides of the 238U and 232Th series inside the studied clay body samples were determined. Alpha equivalent doses to the skin of potters resulting from the diffusion of 222Rn and 220Rn gases present in the studied clay body samples were calculated. A total maximum annual equivalent dose of 23.0 mSv y-1 cm-2, resulting from the energy loss of alpha and beta minus particles emitted by the radionuclides of the 238U and 232Th series, was found for potters working 8 h d-1(6 d wk-1, 49.28 wk y-1).


Assuntos
Partículas alfa , Partículas beta , Argila/química , Exposição Ocupacional/análise , Pele , Tório/análise , Urânio/análise , Humanos , Radioatividade , Radônio
14.
Phys Med Biol ; 66(3): 035016, 2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33321484

RESUMO

Acute hematologic toxicity is a frequent adverse effect of beta-emitter targeted radionuclide therapies (TRTs). Alpha emitters have the potential of delivering high linear energy transfer (LET) radiation to the tumor attributed to its shorter range. Antibody-based TRTs have increased blood-pool half-lives, and therefore increased marrow toxicity, which is a particular concern with alpha emitters. Accurate 3D absorbed dose calculations focusing on the interface region of blood vessels and bone can elucidate energy deposition patterns. Firstly, a cylindrical geometry model with a central blood vessel embedded in the trabecular tissue was modeled. Monte Carlo simulations in GATE were performed considering beta (177Lu, 90Y) and alpha emitters (211At, 225Ac) as sources restricted to the blood pool. Subsequently, the radioactive sources were added in the trabecular bone compartment in order to model bone marrow metastases infiltration (BMMI). Radial profiles, dose-volume histograms and voxel relative differences were used to evaluate the absorbed dose results. We demonstrated that alpha emitters have a higher localized energy deposition compared to beta emitters. In the cylindrical geometry model, when the sources are confined to the blood pool, the dose to the trabecular bone is greater for beta emitting radionuclides, as alpha emitters deposit the majority of their energy within 70 µm of the vessel wall. In the BMMI model, alpha emitters have a lower dose to untargeted trabecular bone. Our results suggest that when alpha emitters are restricted to the blood pool, as when labeled to antibodies, hematologic toxicities may be lower than expected due to differences in the microdistribution of delivered absorbed dose.


Assuntos
Partículas alfa/uso terapêutico , Partículas beta/uso terapêutico , Neoplasias da Medula Óssea/radioterapia , Medula Óssea/efeitos da radiação , Osso Esponjoso/efeitos da radiação , Método de Monte Carlo , Imagens de Fantasmas , Neoplasias da Medula Óssea/secundário , Meia-Vida , Humanos , Dosagem Radioterapêutica
15.
J Nucl Med ; 62(5): 669-674, 2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33008928

RESUMO

Treatment of advanced metastatic castration-resistant prostate cancer after failure of approved therapy options remains challenging. Prostate-specific membrane antigen (PSMA)-targeting ß- and α-emitters have been introduced, with promising response rates. Here, we present the first-to our knowledge-clinical data for PSMA-targeted α-therapy (TAT) using 225Ac-PSMA imaging and therapy (I&T). Methods: Fourteen patients receiving 225Ac-PSMA-I&T were included in this retrospective analysis. Eleven of the 14 had prior second-line antiandrogen treatment with abiraterone or enzalutamide, prior chemotherapy, and prior 177Lu-PSMA treatment. Patients were treated at bimonthly intervals until progression or intolerable side effects. Prostate-specific antigen (PSA) was measured for response assessment. Hematologic and nonhematologic side effects were recorded according to the Common Terminology Criteria for Adverse Events, version 5.0. Results: Thirty-four cycles of 225Ac-PSMA-I&T were applied (median dose, 7.8 MBq; range, 6.0-8.5), with 1 cycle in 3 patients, 2 cycles in 7 patients, 4 cycles in 3 patients, and 5 cycles in 1 patient. No acute toxicity was observed during hospitalization. Baseline PSA was 112 ng/mL (range, 20.5-818 ng/mL). The best PSA response after TAT (a PSA decline ≥ 50%) was observed in 7 patients, and a PSA decline of any amount was observed in 11 patients. Three patients had no PSA decline at any time. A subgroup analysis of 11 patients with prior 177Lu-PSMA treatment showed any PSA decline in 8 patients and a decline of at least 50% in 5 patients. After TAT, grade 3 anemia was observed in 3 of the 14 patients, with 2 of them presenting with grade 2 anemia already at baseline. Grade 3 leukopenia was observed in 1 patient. Eight patients with preexisting xerostomia after 177Lu-PSMA showed no worsening after TAT. Newly diagnosed grade 1 or 2 xerostomia after TAT was observed in 5 patients. One patient reported no xerostomia at all. Conclusion: Our first clinical data for TAT using 225Ac-PSMA-I&T showed a promising antitumor effect in advanced metastatic castration-resistant prostate cancer. These results are highly comparable to data on 225Ac-PSMA-617 TAT.


Assuntos
Actínio/uso terapêutico , Antígenos de Superfície/metabolismo , Partículas beta/uso terapêutico , Glutamato Carboxipeptidase II/metabolismo , Neoplasias de Próstata Resistentes à Castração/diagnóstico por imagem , Neoplasias de Próstata Resistentes à Castração/radioterapia , Humanos , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Metástase Neoplásica , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos , Resultado do Tratamento
16.
J Environ Radioact ; 225: 106437, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33011601

RESUMO

210Po and 210Pb represent the most abundant part of atmospheric aerosol long-lived natural radioactivity. Moreover, 210Pb-210Po monitoring in the atmosphere can be of interest for tracking extreme natural events that can enhance the level of alpha/beta radioactivity in air. In this paper, we question the possibility to use routine gross alpha/beta measurements in order to monitor 210Po, 210Pb and 210Po/210Pb ratio in the atmosphere. Based on joint gross alpha/beta measurement and 210Pb-210Po specific determination on 16 atmosphere samples, we show that (i) gross beta activity systematically overestimates 210Pb activity due to the presence of interfering beta emitters and (ii) gross alpha activity mostly reflects 210Po activity even if an underestimation is always observed due to alpha particle attenuation in the sample. In order to determine 210Po/210Pb ratio, we discuss the advantages of using gross alpha activity time variation compared to specific 210Po measurements. Finally, the gross alpha/beta ratio appear to be a good proxy of the 210Po/210Pb ratio when large-scale variations are to be monitored. We report a first reference level for the activity level of airborne 210Po in France of 13 ± 6 µBq/m3.


Assuntos
Poluentes Radioativos do Ar/análise , Radioisótopos de Chumbo/análise , Polônio/análise , Monitoramento de Radiação , Partículas alfa , Atmosfera/química , Partículas beta , França , Chumbo
17.
Mol Pharm ; 17(11): 4270-4279, 2020 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-33044830

RESUMO

Interest in the use of 225Ac for targeted alpha therapies has increased dramatically over the past few years, resulting in a multitude of new isotope production and translational research efforts. However, 225Ac radioimmunoconjugate (RIC) research is still in its infancy, with most prior experience in hematologic malignancies and only one reported preclinical solid tumor study using 225Ac RICs. In an effort to compare 225Ac RICs to other current antibody conjugates, a variety of RICs are tested against intractable small-cell lung cancer (SCLC). We directly compare, in vitro and in vivo, two promising candidates of each α or ß- category, 225Ac and 177Lu, versus pyrrolobenzodiazepine (PBD) nonradioactive benchmarks. The monoclonal antibody constructs are targeted to either delta like 3 protein (DLL3), a recently discovered SCLC target, or CD46 as a positive control. An immunocompromised maximum tolerated dose assay is performed on NOD SCID mice, along with tumor efficacy proof-of-concept studies in vivo. We overview the conjugation techniques required to create serum-stable RICs and characterize and compare in vitro cell killing with RICs conjugated to nonspecific antibodies (huIgG1) with either native or site-specific thiol loci against tumor antigen DLL3-expressing and nonexpressing cell lines. Using patient-derived xenografts of SCLC onto NOD SCID mice, solid tumor growth was controlled throughout 3 weeks before growth appeared, in comparison to PBD conjugate controls. NOD SCID mice showed lengthened survival using 225Ac compared to 177Lu RICs, and PBD dimers showed full tumor suppression with nine out of ten mice. The exploration of RICs on a variety of antibody-antigen systems is necessary to direct efforts in cancer research toward promising candidates. However, the anti-DLL3-RIC system with 225Ac and 177Lu appears to be not as effective as the anti-DLL3-PBD counterpart in SCLC therapy with matched antibodies and portrays the challenges in both SCLC therapy as well as the specialized utility of RICs in cancer treatment.


Assuntos
Actínio/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Imunoconjugados/administração & dosagem , Imunoglobulina G/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Lutécio/administração & dosagem , Radioisótopos/administração & dosagem , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Partículas alfa/uso terapêutico , Animais , Antígenos de Neoplasias/imunologia , Benzodiazepinas/administração & dosagem , Partículas beta/uso terapêutico , Feminino , Células HEK293 , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/imunologia , Neoplasias Pulmonares/patologia , Dose Máxima Tolerável , Proteínas de Membrana/imunologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Pirróis/administração & dosagem , Carcinoma de Pequenas Células do Pulmão/patologia , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Appl Radiat Isot ; 165: 109347, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32938536

RESUMO

Radioguided surgery (RGS) is a medical practice which thanks to a radiopharmaceutical tracer and a probe allows the surgeon to identify tumor residuals up to a millimetric resolution in real-time. The employment of ß- emitters, instead of γ or ß+, reduces background from healthy tissues, administered activity to the patient, and medical exposure. In a previous work the possibility of using a CMOS Imager (Aptina MT9V011), initially designed for visible light imaging, to detect ß- from 90Y or 90Sr sources has been established. Because of its possible application as counting probe in RGS, the performances of MT9V011 in clinical-like conditions were studied.1 Through horizontal scans on a collimated 90Sr source of different sizes (1, 3, 5, 7 mm), we have determined relationships between scan fit parameters and the source dimension, namely A quadratic correlation and a linear dependency of, respectively, signal integrated over scan interval, and maximum signal against source diameter, are determined. Horizontal scan measurements on a source, interposing collimators of different size, aim to determine relationships or correlations between scan fit parameters and source dimension. A quadratic correlation and a linear dependency of, respectively, signal integrated over scan interval, and maximum signal against source diameter are determined. In order to get closer to clinical conditions, agar-agar phantoms containing 90Y with different dimensions and activities were prepared. A 90Y phantom is characterized by a central spot and a ring all around, for simulating both signal (tumor) and background (surrounding healthy tissue). The relationship found between scan maximum and 90Sr source diameter is then exploited to extract the concentration ratio between spot and external ring of the 90Y phantom. This observable, defined as the ratio between the tumor and the nearby healthy tissues uptake simulates the Tumor-to-Non-tumor Ratio (TNR). With the aim of evaluating the sensor's ability to discriminate signal from background relying on the significance parameter, a further 90Y phantom, featuring a well-known and clinical-like activity will mimic the signal only condition. This result is used to extrapolate to different source sizes, after having estimated the background for various TNR. The obtained significance values suggest that the MT9V011 sensor is capable of distinguishing a signal from an estimated background, depending on the interplay among TNR, acquisition time and tumor diameter.


Assuntos
Partículas beta , Neoplasias/cirurgia , Compostos Radiofarmacêuticos/química , Cirurgia Assistida por Computador/métodos , Estudos de Viabilidade , Humanos
19.
Int J Mol Sci ; 21(18)2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32947870

RESUMO

The paper studies the combined effects of beta-emitting radionuclide tritium and Humic Substances (HS) on the marine unicellular microorganism-luminous bacteria-under conditions of low-dose radiation exposures (<0.04 Gy). Tritium was used as a component of tritiated water. Bacterial luminescence intensity was considered as a tested physiological parameter. The bioluminescence response of the marine bacteria to tritium corresponded to the "hormesis" model: it included stages of bioluminescence inhibition and activation, as well as the absence of the effect. HS were shown to decrease the inhibition and activation effects of tritium, similar to those of americium-241, alpha-emitting radionuclide, studied earlier. Correlations between the bioluminescence intensity and the content of Reactive Oxygen Species (ROS) were found in the radioactive bacterial suspensions. The results demonstrate an important role of HS in natural processes in the regions of low radioactive contamination: HS can mitigate radiotoxic effects and adaptive response of microorganisms to low-dose radioactive exposures. The involvement of ROS in these processes was demonstrated.


Assuntos
Organismos Aquáticos/efeitos da radiação , Bactérias/efeitos da radiação , Substâncias Húmicas , Luminescência , Espécies Reativas de Oxigênio/metabolismo , Trítio , Poluentes Radioativos da Água , Adaptação Fisiológica , Organismos Aquáticos/metabolismo , Bactérias/metabolismo , Partículas beta , Relação Dose-Resposta à Radiação , Hormese , Medições Luminescentes
20.
Pharmacol Res ; 160: 105070, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32659429

RESUMO

Targeted radionuclide therapy, known as molecular radiotherapy is a novel therapeutic module in cancer medicine. ß-radiating radionuclides have definite impact on target cells via interference in cell cycle and particular signalings that can lead to tumor regression with minimal off-target effects on the surrounding tissues. Radionuclides play a remarkable role not only in apoptosis induction and cell cycle arrest, but also in the amelioration of other characteristics of cancer cells. Recently, application of novel ß-radiating radionuclides in cancer therapy has been emerged as a promising therapeutic modality. Several investigations are ongoing to understand the underlying molecular mechanisms of ß-radiating elements in cancer medicine. Based on the radiation dose, exposure time and type of the ß-radiating element, different results could be achieved in cancer cells. It has been shown that ß-radiating radioisotopes block cancer cell proliferation by inducing apoptosis and cell cycle arrest. However, physical characteristics of the ß-radiating element (half-life, tissue penetration range, and maximum energy) and treatment protocol determine whether tumor cells undergo cell cycle arrest, apoptosis or both and to which extent. In this review, we highlighted novel therapeutic effects of ß-radiating radionuclides on cancer cells, particularly apoptosis induction and cell cycle arrest.


Assuntos
Partículas beta/uso terapêutico , Neoplasias/radioterapia , Radioisótopos/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos da radiação , Humanos
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