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Sample records for alpha-particle-emitting radioimmunoconjugate 227th-rituximab

  1. Local energy deposited for alpha particles emitted from inhaled radon daughters

    International Nuclear Information System (INIS)

    Al-affan, I.A.M.; Haque, A.K.M.M.

    1989-01-01

    An analytical method has been developed to calculate the local energy deposited by alpha particles emitted from radon daughters deposited on the mucus surface in the lung airways. For the particular case of 218 Po (Ra A) and 214 Bi (Ra C'), microdose spectra have been evaluated in test spheres of 1 μm diameter which were taken to lie within airways of diameters 18 000, 3500 and 600 μm. In each case, the contributions of the near and far wall were computed separately. The average microdosimetric parameters y-bar F and y-bar D have also been calculated. For the two smaller airways, y-bar F and y-bar D values were found to be about 110 and 135 keV μm -1 for 218 Po and about 87 and 107 keV μm -1 for 214 Bi respectively. The corresponding values were about 10% higher for the largest airway. (author)

  2. Search for alpha particles emitted at rest in the break-up of the 12C-α-12C molecule-like configuration

    International Nuclear Information System (INIS)

    Scheurer, J.N.; Bertault, D.; Caussanel, M.; Quebert, J.L.; Fouan, J.P.

    1978-01-01

    A yield of alpha particles emitted at rest is clearly observed in 16 O+ 12 C at several incident energies. These alpha particles are detected by two methods: i) the alpha particle is considered as a missing mass in the detection of two 12 C nuclei in coincidence; ii) the alpha particle is detected at zero degree with a velocity due to centre of mass motion. Such a yield is assigned to a linear chain formation of the type 12 C-α- 12 C and an excitation function between 40 and 65 MeV is given. The emission due to Coulomb effects is emphasized in the discussion to give the chief explanation of the coincidence results

  3. Treatment of HER2-positive breast carcinomatous meningitis with intrathecal administration of {alpha}-particle-emitting {sup 211}At-labeled trastuzumab

    Energy Technology Data Exchange (ETDEWEB)

    Boskovitz, Abraham; McLendon, Roger E.; Okamura, Tatsunori [Department of Pathology, Duke University Medical Center, Durham, NC 27710 (United States); Sampson, John H. [Department of Surgery, Duke University Medical Center, Durham, NC 27710 (United States); Bigner, Darell D. [Department of Pathology, Duke University Medical Center, Durham, NC 27710 (United States); Zalutsky, Michael R. [Department of Radiology, Duke University Medical Center, Durham, NC 27710 (United States)], E-mail: zalut001@mc.duke.edu

    2009-08-15

    Introduction: Carcinomatous meningitis (CM) is a devastating disease characterized by the dissemination of malignant tumor cells into the subarachnoid space along the brain and spine. Systemic treatment with monoclonal antibody (mAb) trastuzumab can be effective against HER2-positive systemic breast carcinoma but, like other therapies, is ineffective against CM. The goal of this study was to evaluate the therapeutic effect of {alpha}-particle emitting {sup 211}At-labeled trastuzumab following intrathecal administration in a rat model of breast carcinoma CM. Methods: Athymic rats were injected intrathecally with MCF-7/HER2-18 breast carcinoma cells through a surgically implanted indwelling intrathecal catheter. In Experiment 1, animals received 33 or 66 {mu}Ci {sup 211}At-labeled trastuzumab, cold trastuzumab or saline. In Experiment 2, animals were inoculated with a lower tumor burden and received 46 or 92 {mu}Ci {sup 211}At-labeled trastuzumab or saline. In Experiment 3, animals received 28 {mu}Ci {sup 211}At-labeled trastuzumab, 30 {mu}Ci {sup 211}At-labeled TPS3.2 control mAb or saline. Histopathological analysis of the neuroaxis was performed at the end of the study. Results: In Experiment 1, median survival increased from 21 days for the saline and cold trastuzumab groups to 45 and 48 days for 33 and 66 {mu}Ci {sup 211}At-labeled trastuzumab, respectively. In Experiment 2, median survival increased from 23 days for saline controls to 68 and 92 days for 46 and 92 {mu}Ci {sup 211}At-labeled trastuzumab, respectively. In Experiment 3, median survival increased from 20 days to 29 and 36 days for animals treated with {sup 211}At-labeled TPS3.2 and {sup 211}At-labeled trastuzumab, respectively. Long-term survivors were observed exclusively in the {sup 211}At-trastuzumab-treated groups. Conclusion: Intrathecal {sup 211}At-labeled trastuzumab shows promise as a treatment for patients with HER2-positive breast CM.

  4. Pharmacotechnical development of a radioimmunoconjugate for non-Hodgkin Lymphoma therapy

    International Nuclear Information System (INIS)

    Massicano, Adriana Vidal Fernandes

    2016-01-01

    The radioimmunotherapy (RIT) has proven to be a promising therapeutic modality, especially for therapy of hematological malignancies, which has stimulated the development of this type of radiopharmaceutical. Currently, there is one radioimmunoconjugate approved by Food and Drug Administration (FDA) for refractory or relapsed non-Hodgkin lymphoma (NHL) therapy, 90 Y-ibritumomab tiuxetan (Zevalin®), and it has higher overall response and complete remission rates compared to conventional treatments. However, Zevalin® is not commercially available in Brazil. In this context, the goal of this work was to study the steps involved in the process of conjugation and radiolabeling with Lu-177 of anti-CD20 monoclonal antibody, in order to consolidate the in house methodology for development of this radioimmunoconjugate, contributing for the treatment of patients with NHL and also contributing for the future development of other radioimmunoconjugates. In the studies performed to determine the best antibody: chelator (DOTA) molar ratio, the molar ratio 1:50, showed high radiochemical purity (greater than 95% after purification) and the immunoreactivity was higher than many published studies. Additionally, the immunoconjugate was stable for, at least, 3 months under refrigeration when conjugated by two different methods. The study of radiolabeling parameters, produced a radioimmunoconjugate with specific activity of 740 MBq/mg, with adequate stability that allowed the transportation of the radiopharmaceutical to nuclear medicine centers. The biodistribution and pharmacokinetic profiles were consistent with other radioimmunoconjugates in the literature. The radioimmunoconjugate showed tumor uptake and in vivo stability appreciable, the latter evidenced by low bone uptake. The lyophilization studies were performed for the optimized formulation of immunoconjugate that allowed the lyophilization without structural damage, evidenced by polyacrylamide gel electrophoresis, and with

  5. Stability of a metabolizable ester bond in radioimmunoconjugates

    International Nuclear Information System (INIS)

    Arano, Yasushi; Wakisaka, Kouji; Mukai, Takahiro; Uezono, Takashi; Motonari, Hiroshi; Akizawa, Hiromichi; Kairiyama, Claudia; Ohmomo, Yoshiro; Tanaka, Chiaki; Ishiyama, Munetaka; Sakahara, Harumi; Konishi, Junji; Yokoyama, Akira

    1996-01-01

    suggested that while an introduction of an ester bond close to an antibody molecule stabilized the ester bond against esterase access, chemical structures of the linkages and radiolabels attached to the ester bonds play a significant role in the chemical stability of the ester bond. This may explain the different stability of the ester bonds in radioimmunoconjugates so far reported

  6. Assessment of gamma, beta and alpha-particle-emitting nuclides in marine samples

    International Nuclear Information System (INIS)

    Holm, E.

    1997-01-01

    Depending on the physical properties of radionuclides different systems must be used for their measurement. Most convenient is if gamma spectrometry can be used by germanium, Silicon or Scintillation detectors (eg. NaI). If, however, the main emission consists of beta or alpha particles or low-energy photons as is the case for radionuclides decaying by electron capture, radiochemical separation and specific source preparations must be undertaken. In such cases also the radiochemical yield must be determined. The radiochemical part mainly follows the lines presented by prof. T. Jaakkola, Department of Radiochemistry, Helsinki, Finland, at a course in radioecology in Lurid, 1991. For very long-lived radionuclides other methods such as mass spectrometry are superior although often associated with sophisticated expensive instrumentation. (author)

  7. Optimizing the Delivery of Short-Lived Alpha Particle-Emitting Isotopes to Solid Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Adams, Gregory P.

    2004-11-24

    The underlying hypothesis of this project was that optimal alpha emitter-based radioimmunotherapy (RAIT) could be achieved by pairing the physical half-life of the radioisotope to the biological half-life of the targeting vehicle. The project had two specific aims. The first aim was to create and optimize the therapeutic efficacy of 211At-SAPS-C6.5 diabody conjugates. The second aim was to develop bispecific-targeting strategies that increase the specificity and efficacy of alpha-emitter-based RAIT. In the performance of the first aim, we created 211At-SAPS-C6.5 diabody conjugates that specifically targeted the HER2 tumor associated antigen. In evaluating these immunoconjugates we determined that they were capable of efficient tumor targeting and therapeutic efficacy of established human tumor xenografts growing in immunodeficient mice. We also determined that therapeutic doses were associated with late renal toxicity, likely due to the role of the kidneys in the systemic elimination o f these agents. We are currently performing more studies focused on better understanding the observed toxicity. In the second aim, we successfully generated bispecific single-chain Fv (bs-scFv) molecules that co-targeted HER2 and HER3 or HER2 and HER4. The in vitro kinetics and in vivo tumor-targeting properties of these molecules were evaluated. These studies revealed that the bs-scFv molecules selectively localized in vitro on tumor cells that expressed both antigens and were capable of effective tumor localization in in vivo studies.

  8. Optimizing the Delivery of Short-Lived Alpha Particle-Emitting Isotopes to Solid Tumors

    International Nuclear Information System (INIS)

    Adams, Gregory P.

    2004-01-01

    The underlying hypothesis of this project was that optimal alpha emitter-based radioimmunotherapy (RAIT) could be achieved by pairing the physical half-life of the radioisotope to the biological half-life of the targeting vehicle. The project had two specific aims. The first aim was to create and optimize the therapeutic efficacy of 211At-SAPS-C6.5 diabody conjugates. The second aim was to develop bispecific-targeting strategies that increase the specificity and efficacy of alpha-emitter-based RAIT. In the performance of the first aim, we created 211At-SAPS-C6.5 diabody conjugates that specifically targeted the HER2 tumor associated antigen. In evaluating these immunoconjugates we determined that they were capable of efficient tumor targeting and therapeutic efficacy of established human tumor xenografts growing in immunodeficient mice. We also determined that therapeutic doses were associated with late renal toxicity, likely due to the role of the kidneys in the systemic elimination o f these agents. We are currently performing more studies focused on better understanding the observed toxicity. In the second aim, we successfully generated bispecific single-chain Fv (bs-scFv) molecules that co-targeted HER2 and HER3 or HER2 and HER4. The in vitro kinetics and in vivo tumor-targeting properties of these molecules were evaluated. These studies revealed that the bs-scFv molecules selectively localized in vitro on tumor cells that expressed both antigens and were capable of effective tumor localization in in vivo studies

  9. Alpha particles emitted from the surface of granite, clay, and its fired products, 1

    International Nuclear Information System (INIS)

    Aratani, Michi; Otsuka, Hideko

    1975-01-01

    As a part of an investigation on ''the effect of long-time irradiation from a trace amount of radioisotopes'', the emitting rate of alpha particles per unit surface area (apparent) coming from natural alpha-particle emitters has been measured. The samples measured were granite and its weathered product; clay, especially potter's clay, and its fired product; pottery ware. The values obtained were 39.1 +-0.9--0.73+-0.08 cpm/100 cm 2 in granite, 16.8+-0.4--6.4+-0.2 cpm/100cm 2 in potter's clay, and 1.36+-0.04--0.82+-0.04 cpm/100cm 2 in pottery ware on substrate, and 1.33+-0.05--0.32+-0.02 cpm/100cm 2 on glazer. (auth.)

  10. Development of radioimmunoconjugate for diagnosis and management of head-and-neck subclinical cancer and colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Raquel Benedetto

    2018-04-01

    Full Text Available ABSTRACT Scientific innovations in diagnostic methods are important drivers of cancer control and prevention. Noninvasive imaging of the epidermal growth factor receptor (EGFR in head-and-neck squamous, cell carcinoma and colorectal cancer could be valuable to select patients for EGFR-targeted therapy, as well as to monitor the efficacy and occurrence of resistance to immunotherapy. In order to develop the first Brazilian radioimmunoconjugate for diagnosis, Cetuximab has been conjugated to p-SCN-Bn-DTPA chelator and radiolabeled with Indium-111. The conjugation methodology was optimized using different mAb:DTPA molar ratios, time was then reduced for immunoconjugate preparation, besides the protein recovery’ percentage increased after purification (m = 83.8 ± 0.91 %. The stability of Cetuximab-DTPA at - 20 oC was evaluated for six months, and its integrity was greater than 90% (m =93.9 ± 1.5%, N = 24. The radioimmunoconjugate with specific activity of 185 MBq/mg showed radiochemical purity above 95% (m=96.8 ± 1.31 %, N = 15. We conclude that the radioimmunoconjugate 111In-DTPA-cetuximab is stable and may be applied to the diagnosis of EGFR-positive tumors.

  11. Development of [⁶⁴Cu]-DOTA-PR81 radioimmunoconjugate for MUC-1 positive PET imaging.

    Science.gov (United States)

    Alirezapour, Behrouz; Rasaee, Mohammad Javad; Jalilian, Amir Reza; Rajabifar, Saeed; Mohammadnejad, Javad; Paknejad, Malihe; Maadi, Ehsan; Moradkhani, Sedigheh

    2016-01-01

    Breast cancer radioimmunoscintigraphy targeting MUC1 expression is a growing field of work in nuclear medicine research. PR81 is a monoclonal antibody that binds with high affinity to MUC1, which is over expressed on breast tumors. In this study, we report production, quality control and preclinical qualifications of a copper-64 labeled PR81 for PET imaging of breast cancer. PR81 was conjugated with DOTA-NHS-ester and purified by molecular filtration followed by chelate:mAb ratio determination by spectrophotometric method. DOTA-PR81 was labeled with (64)Cu followed by radiochemical purity, in vitro stability, in vitro internalization and immunoreactivity determination. The tissue biodistribution of the (64)Cu-DOTA-PR81 and (64)Cu-DOTA-hIgG was evaluated in BALB/c mice with breast carcinoma tumors using tissue counting and imaging. The radiochemical purity of radioimmunoconjugate was >95±1.9% (ITLC) (specific activity; 4.6 μCi/μg). The average number of chelators per antibody was 3.4±0.3:1. The (64)Cu-DOTA-PR81 showed immunoreactivity towards MUC1 antigen and MCF7 cell line with significant in vitro stability (>89% in PBS and 78±0.5% in human serum) over 48 h. Maximum internalized activity of radiolabeled PR81 in 4-8 h was 81.5%. The biodistribution and scintigraphy studies showed the accumulation of the complex at the site of tumors with high sensitivity and specificity compared to control probes. The results showed that (64)Cu-DOTA-PR81 may be considered as a potential PET tracer for diagnosis and follow-up of MUC1 expression in oncology. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Preparation of (177Lu-DOTAn-PAMAM-[Nimotuzumab-F(ab’2] as a Therapeutic Radioimmunoconjugate for EGFR Overexpressed Cancer Treatment

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    Titis Sekar Humani

    2017-12-01

    Full Text Available Intact monoclonal antibodies with a high molecular weight tend to have a poor pharmacokinetic profile and tumor penetration, and potential for eliciting host antibody responses. F(ab’2 fragments smaller than intact monoclonal antibodies that still maintain antigen binding could solve this problem. The objective of this study was to optimize the digestion process of nimotuzumab, an anti-EGFR monoclonal antibody, into its F(ab’2 fragment and investigate its potential as a therapeutic radioimmunoconjugate. Optimal conditions for digestion of nimotuzumab to its F(ab’2 fragment were found to be 6 hours of digestion time with a pH of 3.5 and 1:100 mol ratio of pepsin to nimotuzumab. The purity of the F(ab’2-nimotuzumab was confirmed by SDS-PAGE and HPLC analysis. Prior to its labeling with lutetium-177 radionuclide, the nimotuzumab-F(ab’2 was conjugated to DOTA-PAMAM dendrimer [DOTA denotes 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, PAMAM denotes poly(amidoamine] to form conjugate of (DOTAn-PAMAM-[nimotuzumab-F(ab’2]. Radiolabeling of DOTA-PAMAM-[nimotuzumab-F(ab’2] conjugate with 177Lu resulted in (177Lu-DOTAn-PAMAM-[nimotuzumab-F(ab’2] with radiochemical purity > 99% after purification with a PD-10 column. Further studies still need to be performed in order to confirm the potential of this radioimmunoconjugate as a radioimmunotherapeutic agent for EGFR overexpressed cancers.

  13. In Vitro Cytotoxicity of Low-Dose-Rate Radioimmunotherapy by the Alpha-Emitting Radioimmunoconjugate Thorium-227-DOTA-Rituximab

    International Nuclear Information System (INIS)

    Dahle, Jostein; Krogh, Cecilie; Melhus, Katrine B.; Borrebaek, Jorgen; Larsen, Roy H.; Kvinnsland, Yngve

    2009-01-01

    Purpose: To determine whether the low-dose-rate α-particle-emitting radioimmunoconjugate 227 Th-1,4,7,10-p-isothiocyanato-benzyl-tetraazacyclododecane-1,4,7, 10-tetraacetic acid (DOTA)-rituximab can be used to inactivate lymphoma cells growing as single cells and small colonies. Methods and Materials: CD20-positive lymphoma cell lines were treated with 227 Th-DOTA-rituximab for 1-5 weeks. To simulate the in vivo situation with continuous but decreasing supply of radioimmunoconjugates from the blood pool, the cells were not washed after incubation with 227 Th-DOTA-rituximab, but half of the medium was replaced with fresh medium, and cell concentration and cell-bound activity were determined every other day after start of incubation. A microdosimetric model was established to estimate the average number of hits in the nucleus for different localizations of activity. Results: There was a specific targeted effect on cell growth of the 227 Th-DOTA-rituximab treatment. Although the cells were not washed after incubation with 227 Th-DOTA-rituximab, the average contribution of activity in the medium to the mean dose was only 6%, whereas the average contribution from activity on the cells' own surface was 78%. The mean dose rates after incubation with 800 Bq/mL 227 Th-DOTA-rituximab varied from 0.01 to 0.03 cGy/min. The average delay in growing from 10 5 to 10 7 cells/mL was 15 days when the cells were treated with a mean absorbed radiation dose of 2 Gy α-particle radiation from 227 Th-DOTA-rituximab, whereas it was 11 days when the cells were irradiated with 6 Gy of X-radiation. The relative biologic effect of the treatment was estimated to be 2.9-3.4. Conclusions: The low-dose-rate radioimmunoconjugate 227 Th-DOTA-rituximab is suitable for inactivation of single lymphoma cells and small colonies of lymphoma cells.

  14. Relativistic alpha-particles emitted in Fe-emulsion interactions at 1.7 A GeV

    International Nuclear Information System (INIS)

    Bhalla, K.B.; Chaudhry, M.; Lokanathan, S.; Grover, R.K.; Daftari, I.K.; Mangotra, L.L.; Rao, N.K.; Garpman, S.; Otterlund, I.

    1981-02-01

    Relativistic α-particles have been studied in 423 Fe-emulsion interactions at 1.7 A Gev. Comparisons of the observed angular distribution with that from 16 O-emulsion reactions at 2.1 A GeV reveal that more α particles are observed at large angles in the Fe-emulsion reactions. The α particles with large angles connot be explained by fragmentation from a clean cut spectator. Comparison of the experimental data with moving relativistic Boltzmann distributions shows that a single Boltzmann distribution cannot fit the fragmentation peak and the tail simultaneously. A thermal source (fireball) explaining the tail part of the distribution need to be formed by a mechanism other than simple clean cut participant-spectator picture. A large transverse momentum transfer to spectator before fragmentation may explain the tail. (author)

  15. Electron Microscopy Study of Stainless Steel Radiation Damage Due to Long-Term Irradation by Alpha Particles Emitted From Plutonium

    Energy Technology Data Exchange (ETDEWEB)

    Unlu, Kenan [Univ. of Texas, Austin, TX (United States); Rios-Martinez, Carlos [Univ. of Texas, Austin, TX (United States); Saglam, Mehmet [Univ. of Texas, Austin, TX (United States); Hart, Ron R. [Texas A & M Univ., College Station, TX (United States); Shipp, John D. [Texas A & M Univ., College Station, TX (United States); Rennie, John [Texas A & M Univ., College Station, TX (United States)

    1998-04-16

    Radiation damage and associated surface and microstructural changes produced in stainless steel encapsulation by high-fluence alpha particle irradiations from weapons-grade plutonium of 316-stainless steel are being investigated.

  16. Probability of bystander effect induced by alpha-particles emitted by radon progeny using the analytical model of tracheobronchial tree

    International Nuclear Information System (INIS)

    Jovanovic, B.; Nikezic, D.

    2010-01-01

    Radiation-induced biological bystander effects have become a phenomenon associated with the interaction of radiation with cells. There is a need to include the influence of biological effects in the dosimetry of the human lung. With this aim, the purpose of this work is to calculate the probability of bystander effect induced by alpha-particle radiation on sensitive cells of the human lung. Probability was calculated by applying the analytical model cylinder bifurcation, which was created to simulate the geometry of the human lung with the geometric distribution of cell nuclei in the airway wall of the tracheobronchial tree. This analytical model of the human tracheobronchial tree represents the extension of the ICRP 66 model, and follows it as much as possible. Reported probabilities are calculated for various targets and alpha-particle energies. Probability of bystander effect has been calculated for alpha particles with 6 and 7.69 MeV energies, which are emitted in the 222 Rn chain. The application of these results may enhance current dose risk estimation approaches in the sense of the inclusion of the influence of the biological effects. (authors)

  17. Synthesis and stability test of radioimmunoconjugate 177Lu-DOTA-F(ab′2-trastuzumab for theranostic agent of HER2 positive breast cancer

    Directory of Open Access Journals (Sweden)

    Sandra Hermanto

    2016-10-01

    Full Text Available The use of trastuzumab as intact IgG labeling radionuclide for HER2 positive breast cancer theranostic agent is not ideal because it is slowly eliminated from the blood and normal tissues resulting in low tumor/blood (T/B and tumor/normal tissue (T/NT ratios. To overcome this limitation, we developed the trastuzumab F(ab′2 fragments and radiolabeling of the fragments by β and γ-particle of Lutetium-177. F(ab2 fragments were produced by digestion of trastuzumab IgG (Herceptin with pepsin for 18 h at 37 °C. The F(ab′2 fragment fractionated in PD-10 column, followed by the conjugation with 2-(4-isothiocyanatobenzyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (p-SCN-Bn-DOTA as a metal chelator and radiolabeling with 177LuCl3. Molecular weight of fragments was calculated by LCMS (Liquid Chromatography Mass Spectroscopy and the radiochemical purity was evaluated by ITLC-SG (Instan Thin Layer Chromatography. Our study showed that the purity of F(ab′2 fragment generated by PD-10 fractions was >98% and the molecular weight of F(ab′2 was 98.35 kDa. The average numbers of pSCN-Bn-DOTA chelates per antibody fragment were 5.03 ± 1.5 and the optimum conjugation reactions was performed at molar ratio 20:1 (chelator to antibody. The stability test of the radioimmunoconjugate in the human serum albumin (HSA at 37 °C showed the radiochemical purity was 91.96 ± 0.26% after 96 h storage. This indicated that the radioimmunoconjugate is relatively stable when applied to the human body's physiological condition.

  18. Targeted Cancer Therapy with a Novel Anti-CD37 Beta-Particle Emitting Radioimmunoconjugate for Treatment of Non-Hodgkin Lymphoma.

    Directory of Open Access Journals (Sweden)

    Ada H V Repetto-Llamazares

    Full Text Available 177Lu-DOTA-HH1 (177Lu-HH1 is a novel anti-CD37 radioimmunoconjugate developed to treat non-Hodgkin lymphoma. Mice with subcutaneous Ramos xenografts were treated with different activities of 177Lu-HH1, 177Lu-DOTA-rituximab (177Lu-rituximab and non-specific 177Lu-DOTA-IgG1 (177Lu-IgG1 and therapeutic effect and toxicity of the treatment were monitored. Significant tumor growth delay and increased survival of mice were observed in mice treated with 530 MBq/kg 177Lu-HH1 as compared with mice treated with similar activities of 177Lu-rituximab or non-specific 177Lu-IgG1, 0.9% NaCl or unlabeled HH1. All mice injected with 530 MBq/kg of 177Lu-HH1 tolerated the treatment well. In contrast, 6 out of 10 mice treated with 530 MBq/kg 177Lu-rituximab experienced severe radiation toxicity. The retention of 177Lu-rituximab in organs of the mononuclear phagocyte system was longer than for 177Lu-HH1, which explains the higher toxicity observed in mice treated with 177Lu-rituximab. In vitro internalization studies showed that 177Lu-HH1 internalizes faster and to a higher extent than 177Lu-rituximab which might be the reason for the better therapeutic effect of 177Lu-HH1.

  19. 177Lu-DOTA-HH1, a novel anti-CD37 radio-immunoconjugate: a study of toxicity in nude mice.

    Directory of Open Access Journals (Sweden)

    Ada H V Repetto-Llamazares

    Full Text Available CD37 is an internalizing B-cell antigen expressed on Non-Hodgkin lymphoma (NHL and chronic lymphocytic leukemia cells (CLL. The anti-CD37 monoclonal antibody HH1 was conjugated to the bifunctional chelator p-SCN-Bn-DOTA and labelled with the beta-particle emitting radionuclide 177Lu creating the radio-immunoconjugate (RIC 177Lu-DOTA-HH1 (177Lu-HH1, trade name Betalutin. The present toxicity study was performed prior to initiation of clinical studies with 177Lu-HH1.Nude mice with or without tumor xenografts were treated with 50 to 1000 MBq/kg 177Lu- HH1 and followed for clinical signs of toxicity up to ten months. Acute, life threatening bone marrow toxicity was observed in animals receiving 800 and 1000 MBq/kg 177Lu-HH1. Significant changes in serum concentrations of liver enzymes were evident for treatment with 1000 MBq/kg 177Lu-HH1. Lymphoid depletion, liver necrosis and atrophy, and interstitial cell hyperplasia of the ovaries were also observed for mice in this dose group.177Lu-DOTA-HH1 was well tolerated at dosages about 10 times above those considered relevant for radioimmunotherapy in patients with B-cell derived malignancies.The toxicity profile was as expected for RICs. Our experimental results have paved the way for clinical evaluation of 177Lu-HH1 in NHL patients.

  20. High treatment efficacy by dual targeting of Burkitt's lymphoma xenografted mice with a {sup 177}Lu-based CD22-specific radioimmunoconjugate and rituximab

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Tobias; Boetticher, Benedikt; Keller, Armin; Schlegelmilch, Anne; Jaeger, Dirk; Krauss, Juergen [Heidelberg University Hospital, Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg (Germany); Mier, Walter; Kraemer, Susanne; Leotta, Karin [Heidelberg University Hospital, Department of Nuclear Medicine, Heidelberg (Germany); Sauter, Max; Haberkorn, Uwe [Heidelberg University Hospital, Department of Nuclear Medicine, Heidelberg (Germany); German Cancer Research Center (DKFZ), Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); Grosse-Hovest, Ludger [University of Tuebingen, Department of Immunology, Tuebingen (Germany); Arndt, Michaela A.E. [Heidelberg University Hospital, Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg (Germany); German Cancer Research Center (DKFZ), Immunotherapy Program, National Center for Tumor Diseases, Heidelberg (Germany)

    2016-03-15

    Dual-targeted therapy has been shown to be a promising treatment option in recurrent and/or refractory B-cell non-Hodgkin's lymphoma (B-NHL). We generated radioimmunoconjugates (RICs) comprising either a novel humanized anti-CD22 monoclonal antibody, huRFB4, or rituximab, and the low-energy β-emitter {sup 177}Lu. Both RICs were evaluated as single agents in a human Burkitt's lymphoma xenograft mouse model. To increase the therapeutic efficacy of the anti-CD22 RIC, combination therapy with unlabelled anti-CD20 rituximab was explored. The binding activity of CHX-A''-DTPA-conjugated antibodies to target cells was analysed by flow cytometry. To assess tumour targeting of {sup 177}Lu-labelled antibodies, in vivo biodistribution experiments were performed. For radioimmunotherapy (RIT) studies, non-obese diabetic recombination activating gene-1 (NOD-Rag1{sup null}) interleukin-2 receptor common gamma chain (IL2r γ {sup null}) null mice (NRG mice) were xenografted subcutaneously with Raji Burkitt's lymphoma cells. {sup 177}Lu-conjugated antibodies were administered at a single dose of 9.5 MBq per mouse. For dual-targeted therapy, rituximab was injected at weekly intervals (0.5 - 1.0 mg). Tumour accumulation of RICs was monitored by planar scintigraphy. Conjugation of CHX-A''-DTPA resulted in highly stable RICs with excellent antigen-binding properties. Biodistribution experiments revealed higher tumour uptake of the {sup 177}Lu-labelled anti-CD22 IgG than of {sup 177}Lu-labelled rituximab. Treatment with {sup 177}Lu-conjugated huRFB4 resulted in increased tumour growth inhibition and significantly longer survival than treatment with {sup 177}Lu-conjugated rituximab. The therapeutic efficacy of the anti-CD22 RIC could be markedly enhanced by combination with unlabelled rituximab. These findings suggest that dual targeting with {sup 177}Lu-based CD22-specific RIT in combination with rituximab is a promising new treatment option for

  1. Radioimmunotherapy (I): development of radioimmunoconjugates

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Tea Hyun; Lim, Sang Moo [Korea Institute of Radiological and Medicine, Seoul (Korea, Republic of)

    2006-04-15

    Monoclonal antibodies are designed to bind specifically to certain antigen, give therapeutic effect to the target and to be produced in large scale with homogeneity. The monoclonal conjugated with radionuclide can deliver therapeutic irradiation to the target, and showed successful results in certain malignancies, which is known as radioimmunotherapy. The target-to-background ratio depends on the antigen expression in the target and normal tissues, which is related to the therapeutic efficacy and toxicity in radioimmunotherapy. For the solid tumor beta-ray energy should be high, but lower beta energy is better for the hematological malignancies. I-131 is widely used in thyroid cancer with low cost and high availability. Labeling monoclonal antibody with I-131 is relatively simple and reproducible. Some preclinical data for the I-131 labeled monoclonal antibodies including acute toxicity and efficacy are available from already published literatures. In KIRAMS, physician sponsored clinical trial protocols using Rituximab, KFDA approved anti-CD20 chimeric monoclonal antibody and I-131 were approved by KFDA and currently are ongoing.

  2. Auger electron-emitting "1"1"1In-DTPA-NLS-CSL360 radioimmunoconjugates are cytotoxic to human acute myeloid leukemia (AML) cells displaying the CD123"+/CD131"− phenotype of leukemia stem cells

    International Nuclear Information System (INIS)

    Gao, Catherine; Leyton, Jeffrey V.; Schimmer, Aaron D.; Minden, Mark; Reilly, Raymond M.

    2016-01-01

    Chimeric IgG_1 monoclonal antibody CSL360 recognizes the CD123"+/CD131"− phenotype expressed by leukemic stem cells (LSC). Auger electron-emitting "1"1"1In-DTPA-NLS-CSL360 radioimmunoconjugates incorporating nuclear translocation sequence (NLS) peptides bound specifically to Raji cells transfected with CD123 and exhibited a K_D of 11 nmols/L in a competition receptor-binding assay using CD123-transfected CHO cells. "1"1"1In-DTPA-NLS-CSL360 was bound, internalized and transported to the nucleus of human AML-5 myeloid leukemia cells. The clonogenic survival of AML-5 cells was reduced by "1"1"1In-DTPA-NLS-CSL360 up to 3.7-fold. Isotype control "1"1"1In-DTPA-chIgG_1 was 2-fold less cytotoxic, and unlabeled CSL360, DTPA-NLS-CSL360 or free "1"1"1In acetate did not decrease cell survival. These results are promising for further evaluation of "1"1"1In-DTPA-NLS-CSL360 for Auger electron radioimmunotherapy of AML targeting the critical LSC subpopulation. - Highlights: • "1"1"1In-DTPA-NLS-CSL360 the CD123"+/CD131"− phenotype of leukemic stem cells (LSC). • "1"1"1In-DTPA-NLS-CSL360 was bound, internalized and imported into the nucleus of AML-5 leukemia cells. • "1"1"1In-DTPA-NLS-CSL360 reduced the clonogenic survival of AML-5 leukemia cells by 4-fold.

  3. Methods and instruments available for the measurement and study of radium, radon and other alpha-particle-emitting radioisotopes of the 238U radioactive decay chain in soils, rocks and solutions

    International Nuclear Information System (INIS)

    McCorkell, R.

    1980-01-01

    The author describes methods used in his laboratory to determine radon, radon daughter, uranium and radium concentrations in air, soil gas, and aqueous solutions. These methods include emanometry, the use of track detectors or collectors, filtration, and autoradiography

  4. 64Cu-Labeled Trastuzumab Fab-PEG24-EGF Radioimmunoconjugates Bispecific for HER2 and EGFR: Pharmacokinetics, Biodistribution, and Tumor Imaging by PET in Comparison to Monospecific Agents.

    Science.gov (United States)

    Kwon, Luke Yongkyu; Scollard, Deborah A; Reilly, Raymond M

    2017-02-06

    Heterodimerization of EGFR with HER2 coexpressed in breast cancer (BC) promotes tumor growth, and increased EGFR expression is associated with trastuzumab resistance. Our aim was to construct 64 Cu-labeled bispecific radioimmunoconjugates (bsRIC) composed of trastuzumab Fab, which binds HER2 linked through a polyethylene glycol (PEG 24 ) spacer to EGF, and to compare their pharmacokinetic, biodistribution, and tumor imaging characteristics by positron-emission tomography (PET). bsRICs were generated by linking maleimide modified trastuzumab Fab with thiolated EGF through a thioether bond. HER2 and EGFR binding were assessed in vitro in MDA-MB-231 (EGFR mod /HER2 low ), MDA-MB-468 (EGFR high /HER2 neg ), MDA-MB-231-H2N (EGFR mod /HER2 mod ), and SKOV3 (EGFR low /HER2 high ) cells by competition and saturation cell binding assays to estimate the dissociation constant (K d ). The elimination of the 64 Cu-NOTA-trastuzumab Fab-PEG 24 -EGF bsRICs from the blood of Balb/c mice was compared to monospecific 64 Cu-NOTA-trastuzumab Fab and 64 Cu-NOTA-EGF. MicroPET/CT imaging was performed in NOD/SCID mice bearing subcutaneous MDA-MB-468, MDA-MB-231/H2N, or SKOV3 human BC xenografts at 24 and 48 h postinjection (p.i.) of bsRICs. Tumor and normal tissue uptake were quantified by biodistribution studies and compared to monospecific agents. The binding of bsRICs to MDA-MB-231 cells was decreased to 24.5 ± 5.2% by excess EGF, while the binding of bsRICs to SKOV3 cells was decreased to 38.6 ± 5.4% by excess trastuzumab Fab, demonstrating specific binding to both EGFR and HER2. 64 Cu-labeled bsRICs incorporating the PEG 24 spacer were eliminated more slowly from the blood than 64 Cu-bsRICs without the PEG spacer and were cleared much more slowly than 64 Cu-NOTA-Fab or 64 Cu-NOTA-EGF. All three tumor xenografts were visualized by microPET/CT at 24 and 48 h p.i. of bsRICs. Biodistribution studies at 48 h p.i. in NOD/SCID mice with MDA-MB-231/H2N tumors demonstrated significantly

  5. The human polynucleotide kinase/phosphatase (hPNKP) inhibitor A12B4C3 radiosensitizes human myeloid leukemia cells to Auger electron-emitting anti-CD123 111In-NLS-7G3 radioimmunoconjugates

    International Nuclear Information System (INIS)

    Zereshkian, Arman; Leyton, Jeffrey V.; Cai, Zhongli; Bergstrom, Dane; Weinfeld, Michael; Reilly, Raymond M.

    2014-01-01

    Introduction: Leukemia stem cells (LSCs) are believed to be responsible for initiating and propagating acute myeloid leukemia (AML) and for causing relapse after treatment. Radioimmunotherapy (RIT) targeting these cells may improve the treatment of AML, but is limited by the low density of target epitopes. Our objective was to study a human polynucleotide kinase/phosphatase (hPNKP) inhibitor that interferes with DNA repair as a radiosensitizer for the Auger electron RIT agent, 111 In-NLS-7G3, which recognizes the CD123 + /CD131 - phenotype uniquely displayed by LSCs. Methods: The surviving fraction (SF) of CD123 + /CD131 - AML-5 cells exposed to 111 In-NLS-7G3 (33–266 nmols/L; 0.74 MBq/μg) or to γ-radiation (0.25-5 Gy) was determined by clonogenic assays. The effect of A12B4C3 (25 μmols/L) combined with 111 In-NLS-7G3 (16–66 nmols/L) or with γ-radiation (0.25–2 Gy) on the SF of AML-5 cells was assessed. The density of DNA double-strand breaks (DSBs) in the nucleus was measured using the γ-H2AX assay. Cellular dosimetry was estimated based on the subcellular distribution of 111 In-NLS-7G3 measured by cell fractionation. Results: Binding of 111 In-NLS-7G3 to AML-5 cells was reduced by 2.2-fold in the presence of an excess (1 μM) of unlabeled NLS-7G3, demonstrating specific binding to the CD123 + /CD131 - epitope. 111 In-NLS-7G3 reduced the SF of AML-5 cells from 86.1 ± 11.0% at 33 nmols/L to 10.5 ± 3.6% at 266 nmols/L. Unlabeled NLS-7G3 had no significant effect on the SF. Treatment of AML-5 cells with γ-radiation reduced the SF from 98.9 ± 14.9% at 0.25 Gy to 0.03 ± 0.1% at 5 Gy. A12B4C3 combined with 111 In-NLS-7G3 (16–66 nmols/L) enhanced the cytotoxicity up to 1.7-fold compared to treatment with radioimmunoconjugates alone and was associated with a 1.6-fold increase in DNA DSBs in the nucleus. A12B4C3 enhanced the cytotoxicity of γ-radiation (0.25–0.5 Gy) on AML-5 cells by up to 1.5-fold, and DNA DSBs were increased by 1.7-fold. Exposure to

  6. Paradoxical effects of Auger electron-emitting 111In-DTPA-NLS-CSL360 radioimmunoconjugates on hCD45+ cells in the bone marrow and spleen of leukemia-engrafted NOD/SCID or NRG mice

    International Nuclear Information System (INIS)

    Bergstrom, Dane; Leyton, Jeffrey V.; Zereshkian, Arman; Chan, Conrad; Cai, Zhongli; Reilly, Raymond M.

    2016-01-01

    Introduction: 111 In-DTPA-NLS-CSL360 radioimmunoconjugates (RIC) recognize the overexpression of the interleukin-3 receptor α-subchain (CD123) relative to the β-subchain (CD131) on leukemia stem cells (LSC). Our aim was to study Auger electron radioimmunotherapy (RIT) of acute myeloid leukemia (AML) with 111 In-DTPA-NLS-CSL360 in non-obese diabetic severe combined immunodeficiency (NOD/SCID) mice or NOD-Rag1 null IL2rγ null (NRG) mice engrafted with CD123 + human AML-5 cells. Methods: The toxicity of three doses of 111 In-DTPA-NLS-CSL360 (3.3–4.8 MBq; 11–15 μg each) injected i.v. every two weeks was studied in non-engrafted NOD/SCID or NRG mice pre-treated with 200 cGy of γ-radiation required for AML engraftment. Engraftment efficiency of (1–5) × 10 6 cells AML-5 cells inoculated i.v. into NOD/SCID or NRG mice was assessed by flow cytometric analysis for human CD45 + (hCD45 + ) cells in the bone marrow (BM) and spleen. AML-5 engrafted mice were treated with two or three doses (3.7 MBq; 10 μg each) every two weeks of 111 In-DTPA-NLS-CSL360, non-specific 111 In-DTPA-NLS-hIgG, unlabeled CSL360 (10 μg) or normal saline. The percentage of hCD45 + cells in the BM and spleen were measured at one week after completion of treatment. Results: 111 In-DTPA-NLS-CSL360 in combination with 200 cGy of γ-radiation caused an initial transient decrease in body weight in NOD/SCID but not in NRG mice. There were no hematological, liver or kidney toxicities. The spleen exhibited 13-fold lower engraftment efficiency than the BM in NOD/SCID mice inoculated with 1 × 10 6 cells but both organs were highly (>85%) engrafted in NRG mice. Unexpectedly, 111 In-DTPA-NLS-CSL360 or non-specific 111 In-DTPA-NLS-hIgG caused a paradoxical 1.5-fold increase (P < 0.0001) in the proportion of hCD45 + cells in the BM of NOD/SCID mice compared to normal saline treated mice. 111 In-DTPA-NLS-CSL360 reduced hCD45 + cells in the spleen by 3.0-fold compared to 111 In-DTPA-NLS-hIgG (P = 0

  7. Experimental Treatment of Bladder Cancer with Bi-213-anti-EGFR MAb

    International Nuclear Information System (INIS)

    Seidl, Christof; Pfost, Birgit; Müller, Felix

    2013-01-01

    Therapy of non-muscle-invasive bladder cancer (carcinoma in situ) comprises transurethral resection of the tumour and subsequent instillation of the chemotherapeutic drug mitomycin C in order to eradicate remaining tumour cells. Yet 15 – 40% of treated patients relapse within 5 years. Therefore, new therapeutic strategies to combat tumour recurrence are needed. Alpha-particle emitting radionuclides efficiently kill single tumour cells or small tumour cell clusters. Because the epidermal growth factor receptor (EGFR) is overexpressed on bladder cancer cells, conjugates composed of the alpha-emitter Bi-213 and the anti-EGFR antibody matuzumab should provide a powerful drug to eliminate disseminated bladder cancer cells. Therefore, the aims of our study were (i) to analyse the cytotoxic effects of Bi-213-anti-EGFR radioimmunoconjugates at the cellular level, (ii) to evaluate therapeutic efficacy of intravesically applied Bi-213- anti-EGFR-Mab in a nude mouse model with intravesical human bladder cancer xenografts, (iii) to compare Bi- 213-anti-EGFR-Mab efficacy with chemotherapy using mitomycin C and (iv) to demonstrate that radioimmunotherapy is not toxic to cells of the bladder wall and of the kidneys

  8. Preparation of a pure 99mTc-F(ab')2 radioimmunoconjugate by direct labeling methods

    International Nuclear Information System (INIS)

    Griffiths, G.L.; Jones, A.L.; Hansen, H.J.; Goldenberg, D.M.

    1994-01-01

    Intact IgG and Fab' can be labeled directly with 99m Tc to give quantitative incorporation of radioactivity into the protein. With F(ab') 2 the reductive conditions yield a mixture of 99m Tc-F(ab') 2 and 99m Tc-Fab'. We now report a direct labeling method to produce only 99m Tc-F(ab') 2 in quantitative yield and contaminated with 99m Tc-Fab'. The properties, stability and biodistribution of the 99m Tc-F(ab') 2 have been compared to 99m Tc-Fab'. This new technology will allow us to compare technetium direct-labeled IgG, F(ab') 2 and Fab' derivatives of the same antibody for radioimmunodetection. (author)

  9. Bismuth 213-labeled anti-CD45 radioimmunoconjugate to condition dogs for nonmyeloablative allogeneic marrow grafts

    Energy Technology Data Exchange (ETDEWEB)

    Sandmaier, B M.(Fred Hutchinson Cancer Research Center, Seattle, WA); Bethge, W A.(Fred Hutchinson Cancer Research Center, Seattle, WA); Wilbur, D. Scott (Washington, Univ Of); Hamlin, Donald K.(Washington, Univ Of); Santos, E B.(Fred Hutchinson Cancer Research Center, Seattle, WA); Brechbiel, M W.(National Cancer Institute, National Institutes of Health, Bethesda, MD); Fisher, Darrell R.(BATTELLE (PACIFIC NW LAB)); Storb, R. (Fred Hutchinson Cancer Research Center)

    2002-01-01

    To lower treatment-related mortality and toxicity of conventional marrow transplantation, a nonmyeloablative regimen using 200 cGy total-body irradiation (TBI) and mycophenolate mofetil (MMF) combined with cyclosporine (CSP) for postgrafting immunosuppression was developed. To circumvent possible toxic effects of external- beam gamma irradiation, strategies for targeted radiation therapy were investigated. We tested whether the short-lived (46 minutes) alpha-emitter Bi-213 conjugated to an anti-CD45 monoclonal antibody (mAb) could replace 200 cGy TBI and selectively target hematopoietic tissues in a canine model of nonmyeloablative DLA-identical marrow transplantation. Biodistribution studies using iodine 123-labeled anti-CD45 mAb showed uptake in blood, marrow, lymph nodes, spleen, and liver. In a dose-escalation study, 7 dogs treated with the Bi-213-anti-CD45 conjugate (Bi-213 dose, 0.1-5.9 mCi/kg[3.7-218 MBq/kg]) without marrow grafts had no toxic effects other than a mild, reversible suppression of blood counts. On the basis of these studies, 3 dogs were treated with 0.5 mg/kg Bi-213-labeled anti-CD45 mAb (Bi-213 doses, 3.6, 4.6, and 8.8 mCi/kg[133, 170, and 326 MBq/kg]) given in 6 injections 3 and 2 days before grafting of marrow from DLA-identical littermates. The dogs also received MMF (10 mg/kg subcutaneously twice daily the day of transplantation until day 27 afterward) and CSP (15 mg/kg orally twice daily the day before transplantation until 35 days afterward). Therapy was well tolerated except for transient elevations in levels of transaminases in 3 dogs, followed by, in one dog, ascites. All dogs achieved prompt engraftment and stable mixed hematopoietic chimerism, with donor contributions ranging from 30% to 70% after more than 27 weeks of follow-up. These results form the basis for additional studies in animals and the design of clinical trials using Bi-213 as a nonmyeloablative conditioning regimen with minimal toxicity.

  10. 78 FR 15358 - DOE's Preferred Alternative for Certain Tanks Evaluated in the Final Tank Closure and Waste...

    Science.gov (United States)

    2013-03-11

    ... SUPPLEMENTARY INFORMATION.) \\1\\ Transuranic (TRU) waste is waste that contains alpha particle-emitting... Document Manager, Office of River Protection, U.S. Department of Energy, P.O. Box 1178, Richland...

  11. Pramana – Journal of Physics | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    Open problems in formation and decay of composite systems in heavy ion ... Heavy ion reactions; measured energetic gamma-rays; light charged particle spectra. ... data the emission barrier of alpha particles emitted from highly excited nuclei ...

  12. Alpha particles, are they really a problem

    International Nuclear Information System (INIS)

    Waddell, J.M.

    1980-01-01

    Soft errors are nonrepetitive errors generated in systems employing dynamic Random Access Memories, and specially by alpha particles emitted by uranium on thorium occurring as impurities in the casings. Special attention was given to this problem by ITT Semiconductors, a 16 K dynamic range being considered. The results of these studies are given in this article [fr

  13. Experimental assessment of absorbed dose to mineralized bone tissue from internal emitters: An electron paramagnetic resonance study

    International Nuclear Information System (INIS)

    Desrosiers, M.F.

    1994-01-01

    EPR resonances attributable to radiation-induced centers in hydroxyapatite were not detectable in bone samples supplied by the USTUR. These centers are the basis for imaging and dose assessment. Presumable, the short range of the alpha particles emitted precluded the formation of appreciable amounts of hydroxyapatite centers. However, one bone sample did offer a suggestion of hydroxyapatite centers and newly-developed methods to extract this information will be pursued

  14. Conventional sources of fast neutrons in 'cold fusion' experiments

    International Nuclear Information System (INIS)

    Cribier, M.; Spiro, M.; Favier, J.

    1989-04-01

    In 'cold fusion' experiments with heavy water a source of neutrons is the dissociation of deuterium induced by alpha particles emitted by natural occurring radioisotopes. We evaluate the rate of fast neutron emission as a function of the concentration of U, Th, Rn in contact with deuterium and discuss the possibility that the neutrons claimed to have been observed in 'cold fusion' experiments could be due to this conventional source

  15. Earthquake prediction research with plastic nuclear track detectors

    International Nuclear Information System (INIS)

    Woith, H.; Enge, W.; Beaujean, R.; Oschlies, K.

    1988-01-01

    Since 1984 a German-Turkish project on earthquake prediction research has been operating at the North Anatolian fault zone in Turkey. Among many other parameters changes in Radon emission have also been investigated. Plastic nuclear track detectors (Kodak cellulose nitrate LR 115) are used to record alpha-particles emitted from Radon and Thoron atoms and their daughter isotopes. The detectors are replaced and analyzed every 3 weeks. Thus a quasi-continuous time sequence of the Radon soil gas emission is recorded. We present a comparison between measurements made with electronic counters and plastic track detectors. (author)

  16. Pulsed neutron source well logging system

    International Nuclear Information System (INIS)

    Dillingham, M.E.

    1975-01-01

    A pulsed neutron source arrangement is provided in which a sealed cylindrical chamber encloses a rotatable rotor member carrying a plurality of elongated target strips of material which emits neutrons when bombarded with alpha particles emitted by the plurality of source material strips. The rotor may be locked in a so-called ON position by an electromagnetic clutch drive mechanism controllable from the earth's surface so as to permit the making of various types of logs utilizing a continuously emitting neutron source. (Patent Office Record)

  17. Alpha emitters activity measurement using the defined solid angle method

    International Nuclear Information System (INIS)

    Blanchis, P.

    1983-01-01

    The defined solid angle counting method can reach a very high accuracy, specially for heavy ions as alpha particles emitted by a radioactive source. The activity measurement of such sources with a relative uncertainty of the order of 0.01% is investigated. Such an accuracy is available only under suitable conditions: the radiation emitted by the source must be isotropic and all the particles emitted in the effective solid angle must be detected. The efficiency detection value must be equal to unity and phenomena such as absorption or scattering must be null. It is shown that corrections often become necessary. All parameters which can influence the measurements are studied [fr

  18. Laser and alpha particle characterization of floating-base BJT detector

    Energy Technology Data Exchange (ETDEWEB)

    Tyzhnevyi, V., E-mail: tyzhnevyi@disi.unitn.i [Universita di Trento and INFN Trento, Trento (Italy); Batignani, G. [Dipartimento di Fisica, Universita di Pisa and INFN Pisa, Pisa (Italy); Bosisio, L. [Dipartimento di Fisica, Universita di Trieste and INFN Trieste, Trieste (Italy); Dalla Betta, G.-F. [Universita di Trento and INFN Trento, Trento (Italy); Verzellesi, G. [Universita di Modena e Reggio Emilia and INFN Trento, Reggio Emilia (Italy); Zorzi, N. [Fondazione Bruno Kessler (FBK), Trento (Italy)

    2010-05-21

    In this work, we investigate the detection properties of existing prototypes of BJT detectors operated with floating base. We report about results of two functional tests. The charge-collection properties of BJT detectors were evaluated by means of a pulsed laser setup. The response to {alpha}-particles emitted from radioactive {sup 241}Am source are also presented. Experimental results show that current gains of about 450 with response times in the order of 50 {mu}s are preserved even in this non-standard operation mode, in spite of a non-optimized structure.

  19. 2016 Research Outreach Program report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hye Young [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Kim, Yangkyu [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-10-13

    This paper is the research activity report for 4 weeks in LANL. Under the guidance of Dr. Lee, who performs nuclear physics research at LANSCE, LANL, I studied the Low Energy NZ (LENZ) setup and how to use the LENZ. First, I studied the LENZ chamber and Si detectors, and worked on detector calibrations, using the computer software, ROOT (CERN developed data analysis tool) and EXCEL (Microsoft office software). I also performed the calibration experiments that measure alpha particles emitted from a Th-229 source by using a S1-type detector (Si detector). And with Dr. Lee, we checked the result.

  20. Correction of Doppler broadening of {gamma}-ray lines induced by particle emission in heavy-ion induced fusion-evaporation reactions

    Energy Technology Data Exchange (ETDEWEB)

    Nyberg, J; Seweryniak, D; Fahlander, C; Insua-Cao, P [Uppsala Univ. (Sweden). Dept. of Radiation Sciences; Johnson, A; Cederwall, B [Manne Siegbahn Inst. of Physics, Stockholm (Sweden); [Royal Inst. of Tech., Stockholm (Sweden); Adamides, E; Piiparinen, M [National Centre for Scientific Research, Ag. Paraskevi, Attiki (Greece); Atac, A; Norlin, L O [Niels Bohr Inst., Copenhagen (Denmark); Ideguchi, E; Mitarai, S [Kyushu Univ., Fukuoka (Japan). Dept. of Physics; Julin, R; Juutinen, S; Tormanen, S; Virtanen, A [Jyvaeskylae Univ. (Finland). Dept. of Physics; Karczmarczyk, W; Kownacki, J [Warsaw Univ. (Poland); Schubart, R [Hahn-Meitner-Institut Berlin GmbH (Germany)

    1992-08-01

    The effect of particle emission on the peak shape of {gamma}-ray lines have been investigated using the NORDBALL detector system. By detecting neutrons, protons and {alpha} particles emitted in the {sup 32}S (95 MeV) + {sup 27}Al reaction, the energy and direction of emission of the residual nuclei could be determined and subsequently used for an event-by -event Doppler correction of the detected {gamma} rays. Extensive Monte Carlo simulations were performed to study how the different Doppler phenomena influence the peak shape and in particular which particle detector properties are important for the Doppler correction. (author). 2 refs., 1 tab., 4 figs.

  1. Range measurements and track kinetics in Dielectric Nuclear Track Detectors (DNTDs)

    Energy Technology Data Exchange (ETDEWEB)

    Aframian, A

    1981-01-01

    Observations of nuclear track development profiles and the kinetics of etched tracks in sensitive dielectric nuclear track detectors indicate three separate phases: the inception phase or the cone phase, the transition phase and the sphere phase. Continued etching of the sphere phase to through-tracks yields accurate range data for particles of different masses and energies and minimum critical angles of registration for each particle. The present results show an energy resolution of 40 keV (fwhm) for 5.48 MeV alpha-particles emitted from Am-241.

  2. Cellular lung dosimetry for inhaled thoron progeny: comparison with radon progeny

    International Nuclear Information System (INIS)

    Abd El-Hady, M.; Hofmann, W.; Balashazy, I.

    1998-01-01

    Recently an analytical method was developed to compute radiation doses deposited by 222 Rn progeny alpha particles in 1 μm spheres located at different depths in bronchial epithelium. The same method was now applied to alpha particles emitted from 220 Rn progeny deposited in bronchial airway surfaces. Results of the computations are presented in graphs. The mean cellular doses imparted by 220 Rn progeny to basal and secretory cell nuclei were compared with those produced by 222 Rn progeny; due to differences in alpha energies, radon progeny doses were found to be generally higher than those for thoron progeny. (A.K.)

  3. Development of low level alpha particle counting system

    International Nuclear Information System (INIS)

    Minobe, Masao; Kondo, Hiraku; Chinuki, Takashi; Hirano, Hiromichi

    1987-01-01

    Much attention has been paid to the trace analysis of uranium and thorium contained in the base material of LSI or VLSI, since the so-called ''soft-error'' of the memory device was known to be due to alpha particles emitted from these radioactive elements. We have developed an apparatus to meet the needs of estimating such a very small quantity of U and Th of the level of ppb, by directly counting alpha particles using a gas-flow type proportional counter. This method requires no sophisticated analytical skill, and the accuracy of the result is satisfactory. The instrumentation and some application of this apparatus are described. (author)

  4. Detection of fission fragments and alpha particles using the solid trace detector CR-39

    International Nuclear Information System (INIS)

    Santos, R.C.

    1988-01-01

    The technique of detecting charged particles using the solid track detector CR-39 is employed to establish some characteristics of fission fragments and alpha particles emitted from a Cf-252 source. Results are presented and discussed on the following aspects i) distribution of the track diameters; ii) variations on the track diameters to the chemical attack; iii) variations of the chemical attack velocity with respect to concentration and temperature. iv) activation energy of the developping process; v) induction time; vi) critical angle and efficiency on track developping. (A.C.A.S.) [pt

  5. Which radionuclide, carrier molecule and clinical indication for alpha-immunotherapy?

    International Nuclear Information System (INIS)

    Guerard, F.; Barbet, J.; Cherel, M.; Chatal, J.-F.; Haddad, F.; Kraeber-Bodere, F.

    2015-01-01

    Beta-emitting radionuclides are not able to kill isolated tumor cells disseminated in the body, even if a high density of radiolabeled molecules can be targeted at the surface of these cells because the vast majority of emitted electrons deliver their energy outside the targeted cells. Alpha-particle emitting radionuclides may overcome this limitation. It is thus of primary importance to test and validate the radionuclide of choice, the most appropriate carrier molecule and the most promising clinical indication. Four α-particle emitting radionuclides have been or are clinically tested in phase I studies namely 213 Bi, 225 Ac, 212 Pb and 211 At. Clinical safety has been documented and encouraging efficacy has been shown for some of them ( 213 Bi and 211 At). 211 At has been the most studied and could be the most promising radionuclide but 225 Ac and 212 Pb are also of potential great interest. Any carrier molecule that has been labeled with β-emitting radionuclides could be labeled with alpha particle-emitting radionuclide using, for some of them, the same chelating agents. However, the physical half-life of the radionuclide should match the biological half-life of the radioconjugate or its catabolites. Finally everybody agrees, based on the quite short range of alpha particles, on the fact that the clinical indications for alpha-immunotherapy should be limited to the situation of disseminated minimal residual diseases made of small clusters of malignant cells or isolated tumor cells.

  6. Preparation and bioevaluation of {sup 177}Lu-labelled anti-CD44 for radioimmunotherapy of colon cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, So Young; Hong, Young Don; Jung, Sung Hee; Choi, Sun Ju [Radioisotope Research Division, Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2015-12-15

    CD44 is a particular adhesion molecule and facilitates both cell-cell and cell-matrix interactions. In particular, splice variants of CD44 are particularly overexpressed in a large number of malignancies and carcinomas. In this study, the {sup 177}Lu-labelled CD44 targeting antibody was prepared and bioevaluated in vitro and in vivo. Anti-CD44 was immunoconjugated with the equivalent molar ratio of cysteine-based dtPA-ncS and radioimmunoconjugated with {sup 177}Lu at room temperature within 15 minutes. the stability was tested in human serum. An in vitro study was carried out in Ht-29 human colon cancer cell lines. For the biodistribution study {sup 177}Lu-labelled anti-CD44 was injected in xenograft mice. Anti-CD44 was immunoconjugated with cysteinebased dtPA-ncS and purified by a centricon filter system having a molecular cut-off of 50 kda. radioimmunoconjugation with {sup 177}Lu was reacted for 15 min at room temperature. the radiolabeling yield was >99%, and it was stable in human serum without any fragmentation or degradation. The radioimmunoconjugate showed a high binding affinity on HT-29 colon cancer cell surfaces. In a biodistribution study, the tumor-to-blood ratio of the radioimmunoconjugate was 43 : 1 at 1 day post injection (p.i) in human colon cancer bearing mice. the anti-CD44 monoclonal antibody for the targeting of colon cancer was effectively radioimmunoconjugated with {sup 177}Lu. the in vitro high immunoactivity of this radioimmunoconjugate was determined by a cell binding assay. In addition, the antibody's tumor targeting ability was demonstrated with very high uptake in tumors. this radioimmunoconjugate is applicable to therapy in human colon cancer with highly expressed CD44.

  7. Self-absorption and self-scattering in emitter source of alpha particles

    International Nuclear Information System (INIS)

    Terini, R.A.

    1990-01-01

    This paper describes preliminary results on spectrometric analysis and activity measurements of alpha-emitting sources prepared by evaporation on mylar. The measurements were made with a Si surface barrier detector. By the analysis of the angular distribuition of the alpha particles emitted, it was possible to observe that the width of the spectrum low energy tail increases with the emission angle θ, due to the energy degradation in the source material, which affects the measured particles energy. The source activity was also measured from detection solid angles of approx. 10 -1 and aprox. 10 -3 Sr, as a function of θ. The absolute activity of the alpha source was determined and a discussion is present on the ideal conditions necessary for such measurements. (author) [pt

  8. Low-cost radon detector

    International Nuclear Information System (INIS)

    Simon, W.E.; Powers, T.L.; Ernsberger, G.W.

    1989-01-01

    This patent describes a detector for alpha particles produced by radioactive decay in a test medium. It comprises: a solid state diode having a depletion layer disposed close enough to the test medium that alpha particles emitted in the test medium deposit energy in the depletion layer; a first amplifier connected to amplify a signal produced by the diode. The first amplifier being operable to produce an output pulse upon energy being deposited in the depletion layer; a second amplifier having at least one connection in common with the first amplifier. The second amplifier having inputs connected other than to the signal produced by the diode. Both the first and second amplifiers produce output pulses due to transients and only the first amplifier produces output pulses due to alpha particles; and means to sense output pulses occurring on the first amplifier only, and to ignore output pulses occurring on both the first and second amplifiers

  9. Concept design of a time-of-flight spectrometer for the measurement of the energy of alpha particles.

    Science.gov (United States)

    García-Toraño, E

    2018-04-01

    The knowledge of the energies of the alpha particles emitted in the radioactive decay of a nuclide is a key factor in the construction of its decay scheme. Virtually all existing data are based on a few absolute measurements made by magnetic spectrometry (MS), to which most other MS measurements are traced. An alternative solution would be the use of time-of-flight detectors. This paper discusses the main aspects to be considered in the design of such detectors, and the performances that could be reasonably expected. Based on the concepts discussed here, it is estimated that an energy resolution about 2.5keV may be attainable with a good quality source. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Evaluation of soft errors rate in a commercial memory EEPROM

    International Nuclear Information System (INIS)

    Claro, Luiz H.; Silva, A.A.; Santos, Jose A.

    2011-01-01

    Soft errors are transient circuit errors caused by external radiation. When an ion intercepts a p-n region in an electronic component, the ionization produces excess charges along the track. These charges when collected can flip internal values, especially in memory cells. The problem affects not only space application but also terrestrial ones. Neutrons induced by cosmic rays and alpha particles, emitted from traces of radioactive contaminants contained in packaging and chip materials, are the predominant sources of radiation. The soft error susceptibility is different for different memory technology hence the experimental study are very important for Soft Error Rate (SER) evaluation. In this work, the methodology for accelerated tests is presented with the results for SER in a commercial electrically erasable and programmable read-only memory (EEPROM). (author)

  11. A new method for evaluating annual absorbed gamma dose rates in an archaeological site by combining the SSNTD technique with Monte Carlo simulations

    CERN Document Server

    Misdaq, M A; Erramli, H; Mikdad, A; Rzama, A; Yousif-Charif, M L

    1998-01-01

    Uranium and thorium contents in different layers of an archaeological site have been determined by using CR-39 and LR-115 type II solid state nuclear track detectors (SSNTD) and calculating the probabilities for alpha-particles emitted by the uranium and thorium series to reach and be registered on the SSNTD films. A new method has been developed based on calculating the self-absorption coefficient of the gamma-photons emitted by the uranium ( sup 2 sup 3 sup 8 U), thorium ( sup 2 sup 3 sup 2 Th) and their corresponding decay products as well as the potassium-40 ( sup 4 sup 0 K) isotope for evaluating the annual absorbed gamma dose rates in the considered material samples. Results obtained have been compared with data obtained by using the TL dosimetry and Bell's methods. Ceramic samples belonging to the studied archaeological site have been dated.

  12. Study of the odd-${A}$, high-spin isomers in neutron-deficient trans-lead nuclei with ISOLTRAP

    CERN Multimedia

    Herfurth, F; Blaum, K; Beck, D; Kowalska, M; Schwarz, S; Stanja, J; Huyse, M L; Wienholtz, F

    We propose to measure the excitation energy of the $\\frac{13^{+}}{2}$ isomers in the neutron-deficient isotopes $^{193,195,197}$Po with the ISOLTRAP mass spectrometer. The assignment of the low- and high-spin isomers will be made by measuring the energy of the $\\alpha$- particles emitted in the decay of purified beams implanted in a windmill system. Using $\\alpha$-decay information, it is then also possible to determine the excitation energy of the similar isomers in the $\\alpha$-daughter nuclei $^{189,191,193}$Pb, $\\alpha$-parent nuclei $^{197,199,201}$Rn, and $\\alpha$-grand-parent nuclei $^{201,203,205}$Ra. The polonium beams are produced with a UC$_{\\textrm{x}}$ target and using the RILIS.

  13. Traversal of cells by radiation and absorbed fraction estimates for electrons and alpha particles

    International Nuclear Information System (INIS)

    Eckerman, K.F.; Ryman, J.C.; Taner, A.C.; Kerr, G.D.

    1986-01-01

    Consideration of the pathlength which radiation traverses in a cell is central to algorithms for estimating energy deposition on a cellular level. Distinct pathlength distributions occur for radionuclides: (1) uniformly distributed in space about the cell (referred to as μ-randomness); (2) uniformly distributed on the surface of the cell (S-randomness); and (3) uniformly distributed within the cell volume (I-randomness). For a spherical cell of diameter d, the mean pathlengths are 2/3d, and 3/4d, respectively, for these distributions. Algorithms for simulating the path of radiation through a cell are presented and the absorbed fraction in the cell and its nucleus are tabulated for low energy electrons and alpha particles emitted on the surface of spherical cells. The algorithms and absorbed fraction data should be of interest to those concerned with the dosimetry of radionuclide-labeled monoclonal antibodies. 8 references, 3 figures, 2 tables

  14. Traversal of cells by radiation and absorbed fraction estimates for electrons and alpha particles

    International Nuclear Information System (INIS)

    Eckerman, K.F.; Ryman, J.C.; Taner, A.C.; Kerr, G.D.

    1985-01-01

    Consideration of the pathlength which radiation traverses in a cell is central to algorithms for estimating energy deposition on a cellular level. Distinct pathlength distributions occur for radionuclides: (1) uniformly distributed in space about the cell (referred to as μ-randomness); (2) uniformly distributed on the surface of the cell (S-randomness); and (3) uniformly distributed within the cell volume (I-randomness). For a spherical cell of diameter d, the mean pathlengths are 2/3d, 1/2d, and 3/4d, respectively, for these distributions. Algorithms for simulating the path of radiation through a cell are presented and the absorbed fraction in the cell and its nucleus are tabulated for low energy electrons and alpha particles emitted on the surface of spherical cells. The algorithms and absorbed fraction data should be of interest to those concerned with the dosimetry of radionuclide-labeled monoclonal antibodies. 8 refs., 3 figs., 2 tabs

  15. Effect of various etching conditions on the response of Cr-39 plastic track detector applied for radon dosimetry in environment

    International Nuclear Information System (INIS)

    Maged, A.F.; Ashraf, F.A.

    1997-01-01

    A solid state nuclear track detector Cr-39 has been used for measuring the radon concentration in the soil air and indoor concentration. The bulk etch rate, C B of Cr-39 has been measured in various concentrations of NaOH in the range (6-8 mole) at temperature 70 degree C. In addition, the track etch rate, V T , and the ratio V = V T /V B , of alpha particles emitted from radon gas exists in nature have been measured in a similar range of etching conditions. This study shows that 8 M NaOH at 70 degree C represent the optimum etching conditions for Cr-39, with the range of the present study. The equilibrium factor and gamma-dose equivalent were calculated by using the track densities of open and filtered solid state nuclear track detectors

  16. Microdosimetry computation code of internal sources - MICRODOSE 1

    International Nuclear Information System (INIS)

    Li Weibo; Zheng Wenzhong; Ye Changqing

    1995-01-01

    This paper describes a microdosimetry computation code, MICRODOSE 1, on the basis of the following described methods: (1) the method of calculating f 1 (z) for charged particle in the unit density tissues; (2) the method of calculating f(z) for a point source; (3) the method of applying the Fourier transform theory to the calculation of the compound Poisson process; (4) the method of using fast Fourier transform technique to determine f(z) and, giving some computed examples based on the code, MICRODOSE 1, including alpha particles emitted from 239 Pu in the alveolar lung tissues and from radon progeny RaA and RAC in the human respiratory tract. (author). 13 refs., 6 figs

  17. Compact Raman Lidar Measurement of Liquid and Vapor Phase Water Under the Influence of Ionizing Radiation

    Directory of Open Access Journals (Sweden)

    Shiina Tatsuo

    2016-01-01

    Full Text Available A compact Raman lidar has been developed for studying phase changes of water in the atmosphere under the influence of ionization radiation. The Raman lidar is operated at the wavelength of 349 nm and backscattered Raman signals of liquid and vapor phase water are detected at 396 and 400 nm, respectively. Alpha particles emitted from 241Am of 9 MBq ionize air molecules in a scattering chamber, and the resulting ions lead to the formation of liquid water droplets. From the analysis of Raman signal intensities, it has been found that the increase in the liquid water Raman channel is approximately 3 times as much as the decrease in the vapor phase water Raman channel, which is consistent with the theoretical prediction based on the Raman cross-sections. In addition, the radius of the water droplet is estimated to be 0.2 μm.

  18. Apparatus for detecting alpha radiation in difficult access areas

    International Nuclear Information System (INIS)

    Steadman, P.; MacArthur, D.W.

    1997-01-01

    An electrostatic alpha radiation detector for measuring alpha radiation emitted from inside an enclosure comprising an electrically conductive expandable electrode for insertion into the enclosure is disclosed. After insertion, the electrically conductive expandable electrode is insulated from the enclosure and defines a decay cavity between the electrically conductive expandable electrode and the enclosure so that air ions generated in the decay cavity are electrostatically captured by the electrically conductive expandable electrode and the enclosure when an electric potential is applied between the electrically conductive expandable electrode and the enclosure. Indicator means are attached to the electrically conductive expandable electrode for indicating an electrical current produced by generation of the air ions generated in the decay cavity by collisions between air molecules and the alpha particles emitted from the enclosure. A voltage source is connected between the indicator means and the electrically conductive enclosure for creating an electric field between the electrically conductive expandable electrode and the enclosure. 4 figs

  19. Angular correlation between the heavy fragments and the light charged particles in tripartition of 236U and 252Cf

    International Nuclear Information System (INIS)

    Sowinski, M.

    1975-05-01

    The energy distributions and relative intensities of protons, deuterons, tritons and alpha-particles emitted along the fission axis during thermal neutron fission of 236 U are measured simultaneously with the energies of the two fission fragments. The mass distributions of the fragments, the total kinetic energy (TKE), the dependence of the mean TKE on the fragment mass, as well as the mean kinetic energy dependence of polar particles on the fragment mass and energy are deduced from these data. Although some experimental results agree remarkably well with the hypothesis that polar particles are evaporated in-flight from fission fragments, the general conclusion is that these particles are emitted according to some other mechanism

  20. Measurement of 222Rn in soil concentrations in interstitial air

    International Nuclear Information System (INIS)

    Duenas, C.; Fernandez, M.C.; Carretero, J.; Liger, E.

    1996-01-01

    Measurements of 222 Rn soil concentrations were made by inserting stainless-steel sampling tubes into the soil. The samples of the soil interstitial air were taken in to pre-evacuated 1 L glass flasks. The glass flasks are cylindrical and coated with a film of ZnS(Ag). 222 Rn was measured by counting the alpha particles emitted by 222 Rn and its daughter products, 218 Po and 214 Bi, when they reached radioactive equilibrium. Measurements of 222 Rn gas concentrations in the soil air interstices by the method at different depths were used to calculate the diffusion coefficient of the 222 Rn in the soil air. This study has been carried out for diverse soils. (Author)

  1. On determining dead layer and detector thicknesses for a position-sensitive silicon detector

    Science.gov (United States)

    Manfredi, J.; Lee, Jenny; Lynch, W. G.; Niu, C. Y.; Tsang, M. B.; Anderson, C.; Barney, J.; Brown, K. W.; Chajecki, Z.; Chan, K. P.; Chen, G.; Estee, J.; Li, Z.; Pruitt, C.; Rogers, A. M.; Sanetullaev, A.; Setiawan, H.; Showalter, R.; Tsang, C. Y.; Winkelbauer, J. R.; Xiao, Z.; Xu, Z.

    2018-04-01

    In this work, two particular properties of the position-sensitive, thick silicon detectors (known as the "E" detectors) in the High Resolution Array (HiRA) are investigated: the thickness of the dead layer on the front of the detector, and the overall thickness of the detector itself. The dead layer thickness for each E detector in HiRA is extracted using a measurement of alpha particles emitted from a 212Pb pin source placed close to the detector surface. This procedure also allows for energy calibrations of the E detectors, which are otherwise inaccessible for alpha source calibration as each one is sandwiched between two other detectors. The E detector thickness is obtained from a combination of elastically scattered protons and an energy-loss calculation method. Results from these analyses agree with values provided by the manufacturer.

  2. Detection of genomic instability in normal human bronchial epithelial cells exposed to 238Pu

    International Nuclear Information System (INIS)

    Kennedy, C.H.; Fukushima, N.H.; Neft, R.E.; Lechner, J.F.

    1994-01-01

    Alpha particle-emitting radon daughters constitute a risk for development of lung cancer in humans. The development of this disease involves multiple genetic alterations. These changes and the time course they follow are not yet defined despite numerous in vitro endeavors to transform human lung cells with various physical or chemical agents. However, genomic instability, characterized both by structural and numerical chromosomal aberrations and by elevated rates of point mutations, is a common feature of tumor cells. Further, both types of genomic instability have been reported in the noncancerous progeny of normal murine hemopoietic cells exposed in vitro to α-particles. The purpose of this investigation was to determine if genomic instability is also a prominent feature of normal human bronchial epithelial cells exposed to α-particle irradiation from the decay of inhaled radon daughters

  3. Development of the MICROMEGAS Detector for Measuring the Energy Spectrum of Alpha Particles by using a 241-Am Source

    CERN Document Server

    Kim, Do Yoon; Shin, Jae Won; Park, Tae-Sun; Hong, Seung-Woo; Andriamonje, Samuel; Kadi, Yacine; Tenreiro, Claudio

    2016-01-01

    We have developed MICROMEGAS (MICRO MEsh GASeous) detectors for detecting {\\alpha} particles emitted from an 241-Am standard source. The voltage applied to the ionization region of the detector is optimized for stable operation at room temperature and atmospheric pressure. The energy of {\\alpha} particles from the 241-Am source can be varied by changing the flight path of the {\\alpha} particle from the 241 Am source. The channel numbers of the experimentally-measured pulse peak positions for different energies of the {\\alpha} particles are associated with the energies deposited by the alpha particles in the ionization region of the detector as calculated by using GEANT4 simulations; thus, the energy calibration of the MICROMEGAS detector for {\\alpha} particles is done. For the energy calibration, the thickness of the ionization region is adjusted so that {\\alpha} particles may completely stop in the ionization region and their kinetic energies are fully deposited in the region. The efficiency of our MICROMEGA...

  4. Radiation studies in Lens culinaris: impact of absorbed polonium on microsporogenesis

    International Nuclear Information System (INIS)

    Singh, V.K.; Tauheed, Nusrat; Jha, V.N.; Tripathi, R.M.

    2008-01-01

    The root systems of fully grown plants of Lens culinaris (2n=14) were exposed to solutions of different concentrations of polonium (mixture of 208 Po and 209 Po Energy of alpha being 5.1 MeV and 4.9 MeV respectively). Variability in duration of exposure was also maintained. The controlled samples showed normal behavior of chromosomes forming seven bivalents with varying numbers of chiasmata. However, the pollen grain mother cells (PMC) of treated plants harbored a broad spectrum of chromosomal aberrations viz. Clumped configurations, multivalent formation, sticky anaphase bridge and laggards. Clumped configurations following surface stickiness was the most prominent manifestation. It appeared that the alpha particles emitted by the polonium atoms, logged in different organs including the anthers, created a situation akin to chronic internal radiation and inflicting injuries of different extent on the chromosome surface. (author)

  5. Distribution of radioactive minerals in a granite

    Energy Technology Data Exchange (ETDEWEB)

    Coppens, R

    1949-04-04

    The study, by means of a photographic plate, of the radioactivity of a Brittany granite, both of a pulverized sample and of a polished sample, has resulted in a complete determination of the radioactivity present. The ratio of the concentration of Th to that of U i.e., C/sub Th/C/sub U/, was determined as approximately 2.8 using the relationship between the concentration of these elements and the number of ..beta.. particles in a particular range which were detected. Using this ratio and measuring the average number of ..cap alpha.. particles emitted/cm/sup 2//sec, the average activities were found to correspond to concentrations of the order of 10/sup -5/ of both metals. The lack of uniformity in the distribution of the radioactivity within the crystal is noted.

  6. Flow-cytometric measurements of somatic cell mutations in Thorotrast patients

    International Nuclear Information System (INIS)

    Umeki, Shigeko; Kyoizumi, Seishi; Kusunoki, Yoichiro; Nakamura, Nori; Sasaki, Masao; Mori, Takesaburo; Ishikawa, Yuichi; Cologne, J.B.; Akiyama, Mitoshi.

    1992-10-01

    Exposure to ionizing radiation is a well-recognized risk factor for cancer development. Because ionizing radiation can induce mutations, an accurate way of measuring somatic mutation frequencies could be a useful tool for evaluating cancer risk. In the present study, we have examined in vivo somatic mutation frequencies at the erythrocyte glycophorin A and T-cell receptor loci in 18 Thorotrast patients. These persons have been continuously irradiated with alpha particles emitted from the internal deposition of thorium dioxide and thus have increased risks of certain malignant tumors. When compared with controls, the Thorotrast patients showed a significantly higher frequency of mutants at the lymphocyte T-cell receptor loci but not at the erythrocyte glycophorin A loci. (author)

  7. Application of X-ray imagery with coded aperture to laser-produced plasmas

    International Nuclear Information System (INIS)

    Fleurot, N.; Gex, J.P.; Sauneuf, R.; Beaucoudray, N. de.

    1981-05-01

    The analysis of the phenomena occurring inside microplasmas generated by laser techniques is often performed with images obtained by the X-rays or alpha particles emitted. Pinhole chambers are extensively used for this type of diagnostic. The number of photons or particles collected, however, decreases with increasing resolution as does the signal-to-noise (S/B) ratio. The coding schema shows that the coder and detector are both flat and parallel to one another. Each object point projects the shadow of the coder onto the detector. The coder shadow is a homothetic figure of the coder. The dimensions and the position of this shadow depend on the position of the point in space, which gives three dimensional information [fr

  8. Determination of uranium and thorium contents inside different materials using track detectors and mean critical angles

    CERN Document Server

    Misdaq, M A; Ktata, A; Merzouki, A; Youbi, N

    1999-01-01

    The critical angles of the CR-39 (theta sub c) and LR-115 type II (theta sub c ') solid state nuclear track detectors (SSNTD) for detecting alpha-particles emitted by the uranium and thorium series have been evaluated by calculating the corresponding ranges of the emitted alpha-particles in different material samples and in the SSNTD studied. The influence of the emitted alpha-particles initial and residual energies on the critical angles of the SSNTD studied has been investigated. The uranium and thorium contents of different geological samples have been evaluated by exploiting data obtained for the critical angles of the CR-39 and LR-115 type II solid state nuclear track detectors and measuring the corresponding densities of tracks.

  9. Development of an integrated sampler based on direct 222Rn/220Rn progeny sensors in flow-mode for estimating unattached/attached progeny concentration

    International Nuclear Information System (INIS)

    Mishra, Rosaline; Sapra, B.K.; Mayya, Y.S.

    2009-01-01

    A flow-mode integrated sampler consisting of a wire-mesh and filter-paper array along with passive solid state nuclear track detectors has been developed for estimating unattached and attached fraction of 222 Rn/ 220 Rn progeny concentration. The essential element of this sampler is the direct 222 Rn/ 220 Rn progeny sensor (DRPS/DTPS), which is an absorber-mounted-LR115 type nuclear track detector that selectively registers the alpha particles emitted from the progeny deposited on its surface. During sampling at a specified flow-rate, the unattached progeny is captured on the wire-mesh; while the attached progeny gets transmitted and is captured on the filter-paper. The alpha particles emitted by the deposited progeny atoms are registered on the sensors placed at a specified distance facing the wire-mesh and the filter-paper, respectively. The various steps involved in the development of this flow-mode direct progeny sampler such as the optimization of the sampling rate and the distance between the sensor and the deposition substrate are discussed. The sensitivity factor of the DTPS-loaded sampler for 220 Rn progeny deposited on the wire-mesh and filter-paper is found to be 23.77 ± 0.64 (track cm -2 h -1 ) (Bq m -3 ) -1 and 22.30 ± 0.18 (track cm -2 h -1 ) (Bq m -3 ) -1 , respectively; while that of DRPS-loaded sampler for 222 Rn progeny deposition, is 3.03 ± 0.14 (track cm -2 h -1 ) (Bq m -3 ) -1 and 2.08 ± 0.07 (track cm -2 h -1 ) (Bq m -3 ) -1 , respectively. The highlight of this flow-mode sampler is its high sensitivity and that it utilizes the passive technique for estimating the unattached and attached progeny concentration, thus doing away with the alpha counting procedures.

  10. Improved radioimmunotherapy of hematologic malignancies. Final technical report

    International Nuclear Information System (INIS)

    Press, O.W.

    1996-01-01

    Experiments were performed to study the rates of endocytosis, intracellular routing, and metabolic degradation of radiolabeled monoclonal antibodies targeting tumor-associated antigens on human leukemia and lymphoma cells. An attempt was made to examine in vivo the effects of lysosomotropic amines and thioamides on the retention of radiolabeled monoclonal antibodies by tumor cells. Experiments also examined the impact of newer radioiodination techniques on the metabolic degradation of radioiodinated antibodies, and on the radioimmunoscintigraphy and radioimmunotherapy of neoplasms. The endocytosis, intracellular routing, and degradation of radioimmunoconjugates prepared with I-131, In-111, and Y-90 were compared. The utility of radioimmunoconjugates targeting oncogene products for the radioimmunotherapy and radioimmunoscintigraphy of cancer was investigated

  11. Alpha particle emitters in cancer therapy: establishing the rationale and overcoming the difficulties

    International Nuclear Information System (INIS)

    Sgouros, G.

    1996-01-01

    Full text: Once a tumor has metastasized, the possibility of cure is significantly diminished, if not excluded. Since metastatic spread arises due to the release of single tumor cells or tumor cell clusters, treatment regimens following an overt metastasis must include agents that eradicate individual tumor cells and cell clusters or that prevent their dissemination. Alpha particles may be highly effective in eradicating rapidly accessible disease. The effectiveness of alpha particles arises because the amount of energy deposited per unit distance traveled (linear energy transfer or LET) is approximately 400 times greater than that of beta particles (80 keV/μm vs. 0.2 keV/μm). Each traversal of an alpha particle through a cell nucleus results in a very highly ionizing track. Cell survival studies have shown that alpha-particle killing is independent of oxygenation state or cell-cycle during irradiation and that as few as 1 to 6 tracks across the nucleus may result in cell death. Most studies with alpha-particle emitting radionuclides for therapy have examined either bismuth-212 or astatine-211. Both radionuclides are short-lived with 61 minute and 7.2 hour half-lives, respectively, yielding intermediates with 3-minute and 32 year half-lives, respectively. Both emit alpha particles whose range is 40 to 80 μm. Alpha-particle emitting radionuclides have been attached to antibodies against tumor cell associated antigen. Antibodies have been the most widely used vehicle for delivery of alpha particles due to their specificity. Bismuth-212 has demonstrated a significant curative potential with minimal toxicity. In an ascites tumor mouse model, specific targeting and 80% cure following injection of Bi-212-labeled antibody has been observed (Macklis RM et al, Science, 240:1024-1026, 1988). It is important to define the realm of applicability for alpha particle emitting radionuclides. The short half-life of most currently available radionuclides, limits their use to

  12. Preparation and radiolabeling of a lyophilized (kit) formulation of DOTA-rituximab with ⁹⁰Y and ¹¹¹In for domestic radioimmunotherapy and radioscintigraphy of non-Hodgkin's lymphoma.

    Science.gov (United States)

    Gholipour, Nazila; Jalilian, Amir Reza; Khalaj, Ali; Johari-Daha, Fariba; Yavari, Kamal; Sabzevari, Omid; Khanchi, Ali Reza; Akhlaghi, Mehdi

    2014-07-29

    On the basis of results of our previous investigations on 90Y-DTPA-rituximab and in order to fulfil national demands to radioimmunoconjugates for radioscintigraphy and radioimmunotherapy of Non-Hodgkin's Lymphoma (NHL), preparation and radiolabeling of a lyophilized formulation (kit) of DOTA-rituximab with 111In and 90Y was investigated. 111In and 90Y with high radiochemical and radionuclide purity were prepared by 112Cd (p,2n)111In nuclear reaction and a locally developed 90Sr/90Y generator, respectively. DOTA-rituximab immunoconjugates were prepared by the reaction of solutions of p-SCN-Bz-DOTA and rituximab in carbonate buffer (pH = 9.5) and the number of DOTA per molecule of conjugates were determined by transchelation reaction between DOTA and arsenaso yttrium(III) complex. DOTA-rituximab immunoconjugates were labeled with 111In and 90Y and radioimmunoconjugates were checked for radiochemical purity by chromatography methods and for immunoreactivity by cell-binding assay using Raji cell line. The stability of radiolabeled conjugate with the approximate number of 7 DOTA molecules per one rituximab molecule which was prepared in moderate yield and showed moderate immunoreactivity, compared to two other prepared radioimmunoconjugates, was determined at different time intervals and against EDTA and human serum by chromatography methods and reducing SDS-polyacrylamide gel electrophoresis, respectively. The biodistribution of the selected radioimmunoconjugate in rats was determined by measurement of the radioactivity of different organs after sacrificing the animals by ether asphyxiation. The radioimmunoconjugate with approximate DOTA/rituximab molar ratio of 7 showed stability after 24 h at room temperature, after 96 h at 4°C, as the lyophilized formulation after six months storage and against EDTA and human serum. This radioimmunoconjugate had a biodistribution profile similar to that of 90Y-ibritumomab, which is approved by FDA for radioimmunotherapy of NHL

  13. 188Re-Labeled Nimotuzumab in the Locoregional Treatment of Malignant Gliomas

    International Nuclear Information System (INIS)

    Montana, R. Leyva; Barrabi, M. Zamora; Casaco, A.; Torres, L.; Perera, A.; Lopez, G.

    2009-01-01

    A new formulation of 188 Re-Nimotuzumab was developed to evaluate the biodistribution, internal radiation dosimetry and safety in the locoregional treatment of malignant gliomas. A phase I clinical trial was performed to evaluate the toxicity and clinical effect of an intracavitary administration of single dose of Nimotuzumab labeled with 188 Re. Nimotuzumab is a humanized monoclonal antibody directed against epidermal growth factor receptors. Nine patients with anaplastic astrocytoma or glioblastoma multiforme were intended to be treated with 3 mg of mAb labeled with 10 or 15 mCi of 188 Re. The radioimmunoconjugated showed a high retention in the surgical created resection cavity and the brain adjacent tissues with a mean value of 85.5% of the injected dose one hour post- administration. No patient developed human anti-mouse antibody response. This radioimmunoconjugate may be relatively safe and a promising therapeutic approach for treating high grade gliomas. (author)

  14. Monoclonal Antibodies Radiolabeling with Rhenium-188 for Radioimmunotherapy

    Science.gov (United States)

    Martini, Petra; Pasquali, Micol

    2017-01-01

    Rhenium-188, obtained from an alumina-based tungsten-188/rhenium-188 generator, is actually considered a useful candidate for labeling biomolecules such as antibodies, antibody fragments, peptides, and DNAs for radiotherapy. There is a widespread interest in the availability of labeling procedures that allow obtaining 188Re-labeled radiopharmaceuticals for various therapeutic applications, in particular for the rhenium attachment to tumor-specific monoclonal antibodies (Mo)Abs for immunotherapy. Different approaches have been developed in order to obtain 188Re-radioimmunoconjugates in high radiochemical purity starting from the generator eluted [188Re]ReO4−. The aim of this paper is to provide a short overview on 188Re-labeled (Mo)Abs, focusing in particular on the radiolabeling methods, quality control of radioimmunoconjugates, and their in vitro stability for radioimmunotherapy (RIT), with particular reference to the most important contributions published in literature in this topic. PMID:28951872

  15. Design and synthesis of {sup 225}Ac radioimmunopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    McDevitt, Michael R.; Ma, Dangshe; Simon, Jim; Frank, R. Keith; Scheinberg, David A. E-mail: d-scheinberg@ski.mskcc.org

    2002-12-01

    The alpha-particle-emitting radionuclides {sup 213}Bi, {sup 211}At, {sup 224}Ra are under investigation for the treatment of leukemias, gliomas, and ankylosing spondylitis, respectively. {sup 213}Bi and {sup 211}At were attached to monoclonal antibodies and used as targeted immunotherapeutic agents while unconjugated {sup 224}Ra chloride selectively seeks bone. {sup 225}Ac possesses favorable physical properties for radioimmunotherapy (10 d half-life and 4 net alpha particles), but has a history of unfavorable radiolabeling chemistry and poor metal-chelate stability. We selected functionalized derivatives of DOTA as the most promising to pursue from out of a group of potential {sup 225}Ac chelate compounds. A two-step synthetic process employing either MeO-DOTA-NCS or 2B-DOTA-NCS as the chelating moiety was developed to attach {sup 225}Ac to monoclonal antibodies. This method was tested using several different IgG systems. The chelation reaction yield in the first step was 93{+-}8% radiochemically pure (n=26). The second step yielded {sup 225}Ac-DOTA-IgG constructs that were 95{+-}5% radiochemically pure (n=27) and the mean percent immunoreactivity ranged from 25% to 81%, depending on the antibody used. This process has yielded several potential novel targeted {sup 225}Ac-labeled immunotherapeutic agents that may now be evaluated in appropriate model systems and ultimately in humans.

  16. Correlations between the alpha particles and ejectiles in the 208 MeV 14N on 93Nb reaction at three different ejectile angles

    International Nuclear Information System (INIS)

    Fukuda, T.; Ishihara, M.; Tanaka, M.; Ogata, H.; Miura, I.; Inoue, M.; Shimoda, T.; Katori, K.; Nakayama, S.

    1983-01-01

    The in plane correlations between alpha particles and various ejectiles were investigated in the reaction of 208 MeV 14 N on 93 Nb at theta/sub HI/ = +22 0 , +50 0 , and +80 0 . There were three sources of coincident alpha particles: (i) the sequential alpha decay of the excited ejectiles, (ii) the equilibrium alpha emission from the targetlike fragments, and (iii) the nonequilibrium process. Process (i) contributed mainly to the cross sections with the angular range of theta/sub α/ close to theta/sub HI/. Process (ii) contributed to the lowest part of the alpha energy spectra irrespectively of theta/sub HI/ and theta/sub α/. The remaining part was ascribed to process (iii). For this process the differential coincidence cross section of the lower energy part of the alpha particles was approximately factorized as d 4 sigma/dΩ/sub HI/dΩ/sub α/dE/sub HI/dE/sub α/ = K (d 2 sigma/dΩ/sub HI/dE/sub HI/)/sub singles/ (d 2 sigma/dΩ/sub α/dE/sub α/)/sub singles/ with Kapprox.0.4/b, whereas the higher energy part of the alpha particles emitted at the forward angles had a tendency to coincide weakly with the ejectiles emitted at the backward angles (theta/sub HI/ = +50 0 and +80 0 ) as compared to the lower energy part of the alpha particles

  17. Preparation of thin {alpha}-particle sources using poly-pyrrole films functionalized by a chelating agent; Preparation de sources minces d'emetteurs alpha a l'aide de films de polypyrrole fonctionnalises par un ligand chelatant

    Energy Technology Data Exchange (ETDEWEB)

    Mariet, C. [CEA Saclay, INSTN, Institut National des Sciences et Techniques Nucleaires, 91 - Gif-sur-Yvette (France); Universite Pierre et Marie Curie, 75 - Paris (France)

    2000-07-01

    This work takes place in the scope of analysis of the {alpha}-particle emitting elements U, Pu and Am present in compound environmental matrix like sols and sediments. The samples diversity and above all the {alpha}-ray characteristics require the analyst to implement a sequence of chemical steps in which the more restricting is the actinides concentration in a uniform and thin layer en allowing an accurately measure of alpha activity. On this account, we studied a new technique for radioactive sources preparation based on tow steps: preparation of a thin film as source support; incorporation of radioactive elements by a chelating extraction mechanism. The thin films were obtained through electro-polymerization of pyrrole monomer functionalized by an chelating ligand able to extract actinides from concentrated acidic solutions. Polymerization conditions of this monomer were perfected, then obtained films were characterized from a physico-chemical point of view. We point out their extracting properties were comparable to (retention capacity, distribution coefficient) to those of usual ion-exchange resins. The underscore of uranyl and americium nitrate complexes formed in the thin layer allowed to calculate the extraction constants in case acid extraction is negligible. Thanks to this results, the values of the coefficients distribution D{sub U} and D{sub Am} could be provided for all nitric solutions in which acid extraction is negligible. Optimal actinides retention conditions in the polymer were defined and used to settle a protocol for plutonium analysis in environmental samples. (author)

  18. Validation of an in vitro model of rat p53 regulation and function

    International Nuclear Information System (INIS)

    Carpenter, T.R.; Groch, R.P.; Hickman, A.W.; Johnson, N.F.

    1994-01-01

    Public and governmental concern about the cancer risks associated with indoor exposure to alpha particle-emitting radon progeny is growing. Such concern arises from the exposure-dependent elevation in cancer risk seen in underground miners, most notably uranium miners. Risk estimates for the general population are derived from extrapolations of risk estimates for the uranium miners. The ability to compare data from the numerous retrospective population studies, animal model experiments, and in vitro experiments is based upon dose-conversion factors that indicate equivalent detrimental endpoints due to certain exposure levels. Recently, efforts to use cytotoxic endpoints such as cell survival, micronucleus formation, and mitotic delay as biologic dosimeters have been compared in vivo and in vitro to obtain dose conversion ratios. While these efforts are successful in cumulative exposure levels of 75-1000 working level months (WLM), such biological dosimeters are insensitive to the cumulative exposure levels found in indoor environments (1-50 WLM). More sensitive indicators of radiation damage/effect are needed to improve dose conversion factors and to better understand how alpha-emitters such as radon cause cancer

  19. A new method for determining uranium and thorium contents in mineral mining materials

    International Nuclear Information System (INIS)

    Khalil, A.; Membry, A.; Chambaudet, A.; Fromm, M.

    1994-01-01

    The method is based on the quantitative analysis of solid state nuclear track detectors (SSNTD). A mathematical model taking into account the variability of the critical angle of registration for the etching of the tracks generated by the incoming alpha projectiles is described. Complementarity of laboratory experiments and theoretical track etching model enables the relationship between critical angle and alpha particles energy to be determined. The formalism of the dosimetric method is based on the calculation of the probability P sub i for an alpha particle emitted in the phosphate to generate an observable etched track in the CR39 SSNTD. The determination of these probabilities cannot be achieved without a good knowledge of the relation expressing the critical angle as a function of particle energy. Supposing a secular equilibrium, we first propose a bulk relation giving the number of parent nuclides of a given family per unit volume of material. By taking the probabilities as P sub i into account, the content of uranium and thorium in the material (phosphates) can be estimated. The results obtained are compared to those cited in the literature. 1 tab., 6 refs. (author)

  20. Evaluation of internal/external exposure from interior building materials

    International Nuclear Information System (INIS)

    Furuta, Etsuko; Morita-Murase, Yuko; Yoshizawa, Yukio

    2008-01-01

    Internal exposure to alpha particles emitted from 222 Rn (radon) and its daughters is the second leading cause of lung cancer. As a source of indoor radon in home, there are interior building materials that contain radioactive minerals. These radioactive consumer products have been claimed by distributors to have effect of 'minus-ion' or 'radon spring' for healthy promotion. We analyzed radioactive nuclides contained in the interior building materials, and measured radon levels released from them. The results of gamma-ray spectrometry revealed that these interior building materials contain U- and Th-series nuclides. The densities of some radioactive nuclides in the tile used for a bathroom exceeded the exempt limits of International Basic Safety Standards. However, the radon densities released from the tile was lower than detectable limit. In contrast, one of the wallpaper released 34 Bq·m -3 of radon gas in a 50-liter container. This value is two times higher than the average radon level in Japanese homes. The minus-ion effect' wallpapers are thought to be a cause of residential exposure to radon. (author)

  1. Osteosarcoma induction by plutonium-239, americium-241 and neptunium-237 : the problem of deriving risk estimates for man

    International Nuclear Information System (INIS)

    Taylor, D.M.

    1988-01-01

    Spontaneous bone cancer (osteosarcoma) represents only about 0.3% of all human cancers, but is well known to be inducible in humans by internal contamination with radium-226 and radium-224. plutonium-239, americium-241 and neptunium-237 form, or will form, the principal long-lived alpha particle emitting components of high activity waste and burnt-up nuclear fuel elements. These three nuclides deposit extensively in human bone and although, fortunately, no case of a human osteosarcoma induced by any of these nuclides is known, evidence from animal studies suggests that all three are more effective than radium-226 in inducing osteosarcoma. The assumption that the ratio of the risk factors, the number of osteosarcoma expected per 10000 person/animal Gy, for radium-226 and any other bone-seeking alpha-emitter will be independent of animal species has formed the basis of all the important studies of the radiotoxicity of actinide nuclides in experimental animals. The aim of this communication is to review the risk factors which may be calculated from the various animal studies carried out over the last thirty years with plutonium-237, americium-241 and neptunium-237 and to consider the problems which may arise in extrapolating these risk factors to homo sapiens

  2. Calculating CR-39 Response to Radon in Water Using Monte Carlo Simulation

    International Nuclear Information System (INIS)

    Razaie Rayeni Nejad, M. R.

    2012-01-01

    CR-39 detectors are widely used for Radon and progeny measurement in the air. In this paper, using the Monte Carlo simulation, the possibility of using the CR-39 for direct measurement of Radon and progeny in water is investigated. Assuming the random position and angle of alpha particle emitted by Radon and progeny, alpha energy and angular spectrum that arrive at CR-39, the calibration factor, and the suitable depth of chemical etching of CR-39 in air and water was calculated. In this simulation, a range of data were obtained from SRIM2008 software. Calibration factor of CR-39 in water is calculated as 6.6 (kBq.d/m 3 )/(track/cm 2 ) that is corresponding with EPA standard level of Radon concentration in water (10-11 kBq/m 3 ). With replacing the skin instead of CR-39, the volume affected by Radon and progeny was determined to be 2.51 mm 3 for one m 2 of skin area. The annual dose conversion factor for Radon and progeny was calculated to be between 8.8-58.8 nSv/(Bq.h/m 3 ). Using the CR-39 for Radon measurement in water can be beneficial. The annual dose conversion factor for Radon and progeny was calculated to be between 8.8-58.8 nSv/ (Bq.h/m 3 ).

  3. Phase I Final Report: Ultra-Low Background Alpha Activity Counter

    International Nuclear Information System (INIS)

    Warburton, W.K.

    2005-01-01

    In certain important physics experiments that search for rare-events, such as neutrino or double beta decay detections, it is critical to minimize the number of background events that arise from alpha particle emitted by the natural radioactivity in the materials used to construct the experiment. Similarly, the natural radioactivity in materials used to connect and package silicon microcircuits must also be minimized in order to eliminate ''soft errors'' caused by alpha particles depositing charges within the microcircuits and thereby changing their logic states. For these, and related reasons in the areas of environmental cleanup and nuclear materials tracking, there is a need that is important from commercial, scientific, and national security perspectives to develop an ultra-low background alpha counter that would be capable of measuring materials' alpha particle emissivity at rates well below 0.00001 alpha/cm 2 /hour. This rate, which corresponds to 24 alpha particles per square meter per day, is essentially impossible to achieve with existing commercial instruments because the natural radioactivity of the materials used to construct even the best of these counters produces background rates at the 0.005 alpha/cm 2 /hr level. Our company (XIA) had previously developed an instrument that uses electronic background suppression to operate at the 0.0005 0.005 alpha/cm 2 /hr level. This patented technology sets up an electric field between a large planar sample and a large planar anode, and fills the gap with pure Nitrogen. An alpha particle entering the chamber ionizes the Nitrogen, producing a ''track'' of electrons, which drift to the anode in the electric field. Tracks close to the anode take less than 10 microseconds (us) to be collected, giving a preamplifier signal with a 10 us risetime. Tracks from the sample have to drift across the full anode-sample gap and produce a 35 us risetime signal. By analyzing the preamplifier signals with a digital signal

  4. Simulation study on the measurements of diffusion coefficients in solid materials by short-lived radiotracer beams

    CERN Document Server

    Jeong, S C; Kawakami, H

    2003-01-01

    We have examined, by a computer simulation, an on-line measurement of diffusion coefficients by using a short-lived alpha particle emitter, sup 8 Li (half life of 0.84s), as a radiotracer. The energy spectra of alpha particles emitted from diffusing sup 8 Li primarily implanted in the sample of LiAl ar simulated as a measure of the diffusion of sup 8 Li in the sample. As a possible time sequence for the measurement, a time cycle of 6s, i.e. the implantation of sup 8 Li for 1.5s and subsequent diffusion for 4.5s, is supposed. The sample is primarily set on a given temperature for the measurement. The time-dependent yields of alpha particles during the time cycle reveal the possibility to measure the diffusion coefficient with an accuracy of 10% if larger than 1 x 10 sup - sup 9 cm sup 2 /s, by the comparison with the experimental spectra measured at the temperature, i.e. at a certain diffusion coefficient. (author)

  5. Bulk GaN alpha-particle detector with large depletion region and improved energy resolution

    Science.gov (United States)

    Xu, Qiang; Mulligan, Padhraic; Wang, Jinghui; Chuirazzi, William; Cao, Lei

    2017-03-01

    An alpha-particle detector was fabricated using a freestanding n-type bulk GaN wafer with a Au/Ni/GaN sandwich Schottky structure. Current-voltage measurements at room temperature revealed a Schottky contact with a leakage current of 7.53±0.3 nA at a reverse bias of 200 V. The detector had a large depletion depth that can capture much of the energy from 5.486 MeV alpha particles emitted from a 241Am source. The resolution of its alpha-particle energy spectrum was improved to 2.2±0.2% at 5.486 MeV under a bias of 550 V. This superior resolution was attributed to the shortening of the carrier transit time and the large energy deposition within the large depletion depth, i.e., 27 μm at -550 V, which all resulted in a more complete charge collection. A model developed using the ATLAS simulation framework from Silvaco Inc. was employed to study the charge collection process. The simulation results were found to agree closely with the experimental results. This detector will be beneficial for research at neutron scattering facilities, the International Thermonuclear Experimental Reactor, and the Large Hadron Collider, among other institutions, where the Si-based charged particle detectors could be quickly degraded in an intense radiation field.

  6. Updated estimates of the proportion of childhood leukaemia incidence in Great Britain that may be caused by natural background ionising radiation

    International Nuclear Information System (INIS)

    Little, Mark P; Wakeford, Richard; Kendall, Gerald M

    2009-01-01

    The aetiology of childhood leukaemia remains generally unknown, although exposure to moderate and high levels of ionising radiation, such as was experienced during the atomic bombings of Japan or from radiotherapy, is an established cause. Risk models based primarily upon studies of the Japanese A-bomb survivors imply that low-level exposure to ionising radiation, including to ubiquitous natural background radiation, also raises the risk of childhood leukaemia. In a recent paper (Wakeford et al 2009 Leukaemia 23 770-6) we estimated the proportion of childhood leukaemia incidence in Great Britain attributable to natural background radiation to be about 20%. In this paper we employ the two sets of published leukaemia risk models used previously, but use recently published revised estimates of natural background radiation doses received by the red bone marrow of British children to update the previous results. Using the newer dosimetry we calculate that the best estimate of the proportion of cases of childhood leukaemia in Great Britain predicted to be attributable to this source of exposure is 15-20%, although the uncertainty associated with certain stages in the calculation (e.g. the nature of the transfer of risk between populations and the pertinent dose received from naturally occurring alpha-particle-emitting radionuclides) is significant. The slightly lower attributable proportions compared with those previously derived by Wakeford et al (Leukaemia 2009 23 770-6) are largely due to the lower doses (and in particular lower high LET doses) for the first year of life.

  7. Inverse-kinematics study of 78Kr + 40Ca at 10 AMeV

    Directory of Open Access Journals (Sweden)

    Henry E.

    2015-01-01

    Full Text Available The CHIMERA multi-detector array at LNS Catania has been used to study the inverse-kinematics reaction of 78Kr + 40Ca at a bombarding energy of 10 A MeV. Analysis of the experimental data focused on a class of selected events consistent with the complete fusion and subsequent binary split of the of the reacting system. This class of events features a broad A, Z distribution of fission fragments centered about symmetric fission while exhibiting relative velocities significantly higher than given by Viola systematics. The center-of-mass angular distribution (dσ/dΘ of the fission fragments exhibit an unexpected anisotropy inconsistent with a compound-nucleus reaction and indicates a dynamic fusion-fission like process. The observed angular distribution features an asymmetric forward-backward peaking most prevalent for mass-asymmetric events. Furthermore, the more massive fragment of mass-asymmetric events appears to emerge preferentially in the forward direction, along the beam axis, in analogy to dynamic fragmentation of projectile-like fragments. Analysis of the angular distribution of alpha particles emitted from these fission fragments suggests the events are associated mostly with central collisions.

  8. Risk Assessment from Radon Gas in the Greenhouses

    International Nuclear Information System (INIS)

    Fahmi, N.M.; El-Khatib, A.M.; Abd El-Zaher, M

    2009-01-01

    Radon is a naturally occurring radioactive gas found in varying amounts in all soils. Therefore, it is very important to study radon emanation from different soils in different circumstances; especially, in green houses which widely used to propagate and cultivate of plants. In greenhouses radon comes from either soil or the substances which make suitable flooring in the greenhouse. Radon and its progeny are accumulated in the air and on the plants themselves, which causes hazard for workers and customers in a later stage. Radon gas is measured in two kinds of greenhouses, one of them is constructed from plastic sheet and the other from glass (Agriculture Research Center - Horticulture Research Institute) using CR-39 NTDs as a passive technique. It based on the production of track in the detector due to alpha-particles emitted from radon and its progeny. The observed track densities are then converted to annual radon dose to be 12.36 mSv and 8.3 mSv for the plastic and glass greenhouses under investigation, respectively. It is also found that the workers have been subject to regulatory control

  9. Evaluation of {sup 211}At-labelled monodisperse polymer particles in vivo: comparison of different specific activities

    Energy Technology Data Exchange (ETDEWEB)

    Larsen, R.H.; Hoff, Per; Alstad, Jorolf [Oslo Univ., Chemistry Dept., Oslo (Norway); Varaas, Tone; De Vos, L.N.; Nustad, Kjell [Norwegian Radium Hospital, Central Lab., Oslo (Norway); Vergote, I.B. [Norwegian Radium Hospital, Gynecologic Oncology Dept., Oslo (Norway)

    1996-09-01

    The {alpha}-particle emitter {sup 211}At was covalently coupled to 1.8 {mu}m aminated monodisperse polymer particles (MDPP) and used to irradiate the intraperitoneal cavity in mice with disseminated tumour cells. Specific activity has previously been shown to influence the therapeutic efficacy of {alpha}-particle emitting compounds and the therapeutic efficacy of {sup 211}At-MDPP with various specific activity was therefore investigated. Groups of mice (10 animals per group) were treated with intraperitoneal injections of 100 kBq of {sup 211}At-MDPP with specific activities of 0.19, 0.55, 1.7, 5.0, 15, and 45 MBq/mg. A significantly prolonged survival was observed in the treated groups compared to the control group (from 19 to 26 days vs. 12 days, median). The difference in survival between the {sup 211}At-MDPP treated groups was not significant, but some animals with short survival were observed in the groups that had received the 0.19, 15 and 45 MBq/mg preparations. K13 monoclonal antibody values, which are an indicator of tumour growth, were high in some animals in the 15 and 45 MBq/mg groups (day 7 values). (author).

  10. Design and synthesis of 225Ac radioimmunopharmaceuticals

    International Nuclear Information System (INIS)

    McDevitt, Michael R.; Ma, Dangshe; Simon, Jim; Frank, R. Keith; Scheinberg, David A.

    2002-01-01

    The alpha-particle-emitting radionuclides 213 Bi, 211 At, 224 Ra are under investigation for the treatment of leukemias, gliomas, and ankylosing spondylitis, respectively. 213 Bi and 211 At were attached to monoclonal antibodies and used as targeted immunotherapeutic agents while unconjugated 224 Ra chloride selectively seeks bone. 225 Ac possesses favorable physical properties for radioimmunotherapy (10 d half-life and 4 net alpha particles), but has a history of unfavorable radiolabeling chemistry and poor metal-chelate stability. We selected functionalized derivatives of DOTA as the most promising to pursue from out of a group of potential 225 Ac chelate compounds. A two-step synthetic process employing either MeO-DOTA-NCS or 2B-DOTA-NCS as the chelating moiety was developed to attach 225 Ac to monoclonal antibodies. This method was tested using several different IgG systems. The chelation reaction yield in the first step was 93±8% radiochemically pure (n=26). The second step yielded 225 Ac-DOTA-IgG constructs that were 95±5% radiochemically pure (n=27) and the mean percent immunoreactivity ranged from 25% to 81%, depending on the antibody used. This process has yielded several potential novel targeted 225 Ac-labeled immunotherapeutic agents that may now be evaluated in appropriate model systems and ultimately in humans

  11. Radiation quality and effective dose equivalent of alpha particles from radon decay products indoors: uncertainties in risk estimation

    Energy Technology Data Exchange (ETDEWEB)

    Al-Affan, I.A. (Velindre Hospital, Whitchurch, Cardiff (United Kingdom))

    1994-01-01

    In order to make a better estimate of cancer risk due to radon the radiation quality of alpha particles emitted from the element and its daughters has been re-assessed. In particular, uncertainties in all components involved in the calculations of the effective dose E, have been investigated. This has been done in the light of the recent draft report of the ICRU on quantities and units for use in radiation protection (Allisy et al (1991) ICRU NEWS 2). On the assumption of an indoor radon concentration of 30 Bq.m[sup -3], microdose spectra have been calculated for alpha particles hitting lung cells at different depths. Then the mean quality factor Q-bar in the lung, dose equivalent H[sub T] to the lung and the effective dose have been calculated. A comparison between lung cancer risk from radon and that arising from diagnostic X rays to the chest is made. A suggestion to make the lung weighting factor w[sub T] a function of the fraction of lung cells hit is discussed. (Author).

  12. Pulse shape discrimination of plastic scintillator EJ 299-33 with radioactive sources

    Science.gov (United States)

    Pagano, E. V.; Chatterjee, M. B.; De Filippo, E.; Russotto, P.; Auditore, L.; Cardella, G.; Geraci, E.; Gnoffo, B.; Guazzoni, C.; Lanzalone, G.; De Luca, S.; Maiolino, C.; Martorana, N. S.; Pagano, A.; Papa, M.; Parsani, T.; Pirrone, S.; Politi, G.; Porto, F.; Quattrocchi, L.; Rizzo, F.; Trifirò, A.; Trimarchi, M.

    2018-05-01

    The present study has been carried out in order to investigate about the possibility of using EJ 299-33 scintillator in a multi-detector array to detect neutrons along with light charged particles. In a reaction induced by stable and exotic heavy-ions beams, where copious production of neutrons and other light charged particles occurs, discrimination with low identification threshold of these particles are of great importance. In view of this, EJ 299-33 scintillator having dimension of 3 cm × 3 cm × 3 cm backed by a photomultiplier tube was tested and used under vacuum to detect neutrons, gamma-rays and alpha particles emitted by radioactive sources. Anode pulses from the photomultiplier tube were digitized through GET electronics, recorded and stored in a data acquisition system for the purpose of an off-line analysis. The measurements, under vacuum and low background conditions, show good pulse shape discrimination properties characterized by low identification threshold for neutrons, gamma-rays and alpha particles. The Figures of Merit for neutron-gamma and alpha particles-gamma discriminations have been evaluated together with the energy resolution for gamma-ray and alpha particles.

  13. Measurement of radon-222 concentration in environment sampled within short time using charcoal detector

    International Nuclear Information System (INIS)

    Yamasaki, Tadashi; Sekiyama, Shigenobu; Tokin, Mina; Nakayasu, Yumiko; Watanabe, Tamaki.

    1994-01-01

    The concentration of 222 Rn in air sampled within a very short period of time was measured using activated charcoal as the adsorber. The detector is the plastic canister containing mixture of the activated charcoal and the silica gel. The radon gas was adsorbed in the charcoal in the radon chamber at the temperature of 25degC. A little amount of liquid scintillation cocktail was added into the vial of liquid scintillation counter with the canister. The radon in the charcoal was extracted in the liquid scintillation cocktail. Alpha particles emitted from radon and its daughter nuclei in the cocktail were detected using the liquid scintillation counter. Present method has advantages of not only short sampling time of air but also adsorption of radon in charcoal under a constant temperature. The concentration of radon in air down to 2 Bq/m 3 could be detected. A kinetic model for adsorption of radon in the charcoal is also presented. The ratio of radon concentration in the charcoal to that in air under the equilibrium state of adsorption was estimated to be from 6.1 to 6.8 m 3 /kg at the temperature of 25degC. (author)

  14. Room-temperature particle detectors with guard rings based on semi-insulating InP co-doped with Ti and Zn

    International Nuclear Information System (INIS)

    Yatskiv, R.; Zdansky, K.; Pekarek, L.

    2009-01-01

    Particle detectors made with a guard-ring (GR) electrode, operating at room temperature, have been studied. The detectors were fabricated on a semi-insulating InP crystal co-doped with Ti and Zn, grown using the Liquid-Encapsulated Czochralski technique. The detection performance of the particle detectors was evaluated using alpha particles emitted from a 241 Am source. Good detector performance has been achieved with measured charge-collection efficiencies of 99.9% and 98.2% and FWHM energy resolutions of 0.9% and 2.1%. The measurements were carried out at 230 K for negative and positive bias voltages of the irradiated electrode. The good performance is due to the SI properties of the material which has been achieved by doping with suitable Ti atoms and co-doping with a low concentration of Zn acceptors, sufficient to fully compensate shallow donors. Electron and hole charge-collection efficiencies (CCEs) were measured at various temperatures. At room temperature, unlike at low temperature (T<250 K), the hole CCE was better than the electron CCE, which can be explained by the presence of electron-trapping centres in InP with a temperature-dependent capture rate.

  15. Application of CR-39 microfilm for rapid discrimination between alpha-particle sources

    Energy Technology Data Exchange (ETDEWEB)

    Dwaikat, Nidal; Al-karmi, Anan M. [Dept. of Physics, King Fahd University of Petroleum and Minerals, Dhahran (Saudi Arabia)

    2017-06-15

    This work presents a new technique for discriminating between alpha particles of different energy levels. In a first study, two groups of alpha particles emitted from radium-226 and americium-241 sources were successfully separated using a CR-39 microfilm of appropriate thickness. This thickness was adjusted by chemical etching before and after irradiation so that lower-energy particles were stopped within the detector, while higher-energy particles were revealed on the back side of the detector. The number of tracks on the front side of the microfilm represented all alpha particles incident on that side from the two sources. However, the number of tracks on the back side of the microfilm represented only the long-range alpha particles of higher energy that arrived at that side. Therefore, by subtracting the number of tracks on the back side from the number of tracks on the front side, one could easily determine the number of tracks for the short-range alpha particles of lower energy that remained embedded in the microfilm. Discrimination of the two energy levels is thus achieved in a simple, fast, and reliable process.

  16. Cancer hazard from inhaled plutonium

    International Nuclear Information System (INIS)

    Gofman, J.W.

    1975-01-01

    The best estimate of the lung cancer potential in humans for inhaled insoluble compounds of plutonium (such as PuO 2 particles) has been grossly underestimated by such authoritative bodies as the International Commission on Radiological Protection and the British Medical Research Council. Calculations are presented of lung cancer induction by 239 Pu as insoluble particles and for deposited reactor-grade Pu. The reason for the gross underestimate of the carcinogenic effects of Pu by ICRP or the British Medical Research Council (BMRC) is their use of a totally unrealistic idealized model for the clearance of deposited Pu from the lungs and bronchi plus their non-recognition of the bronchi as the true site for most human lung cancers. The erroneous model used by such organizations also fails totally to take into account the effect of cigarette-smoking upon the physiological function of human lungs. Plutonium nuclides, such as 239 Pu, or other alpha particle-emitting nuclides, in an insoluble form represent an inhalation cancer hazard in a class some 100,000 times more potent than the potent chemical carcinogens, weight for weight. The already-existing lung cancer data for beagle dogs inhaling insoluble PuO 2 particles is clearly in order of magnitude agreement with calculations for humans

  17. A new method for studying the transport of gamma photons in various geological materials by combining the SSNTD technique with Monte Carlo simulations

    International Nuclear Information System (INIS)

    Misdaq, M.A.; Merzouki, A.; Bourzik, W.; Sfairi, T.

    2000-01-01

    The gamma dose rate due to the uranium and thorium series as well as the potassium 40 nuclei represents a large fraction of the total dose rate from the natural background. Natural gamma-activities of rock and soil samples collected from volcanic areas have been determined using gamma-ray spectrometry. The corresponding gamma dose rates in air have been measured by means of thermoluminescence (TL) dosimeters. Annual absorbed gamma dose rates have been evaluated in different soil samples belonging to an archaeological site by using experimental and calculational methods. Uranium and thorium contents in different geological samples have been determined by using CR-39 and LR-115 type II solid state nuclear track detectors (SSNTD) and calculating the probabilities for alpha particles emitted by the uranium and thorium series to reach and be registered on the SSNTD films. A new method has been developed based on calculating the self-absorption and transmission coefficients of the gamma photons emitted by the uranium and thorium families as well as the potassium 40 isotope for evaluating the gamma dose rate in the considered geological samples. Transport of gamma-photons across parallelepipedic blocks of the geological materials studied has been investigated. Gamma dose rates have been evaluated in the atmosphere of different geological deposits. (author)

  18. A new method for determining the uranium and thorium distribution in volcanic rock samples using solid state nuclear track detectors

    International Nuclear Information System (INIS)

    Misdaq, M.A.; Bakhchi, A.; Ktata, A.; Koutit, A.; Lamine, J.; Ait nouh, F.; Oufni, L.

    2000-01-01

    A method based on using solid state nuclear track detectors (SSNTD) CR- 39 and LR-115 type II and calculating the probabilities for the alpha particles emitted by the uranium and thorium series to reach and be registered on these films was utilized for uranium and thorium contents determination in various geological samples. The distribution of uranium and thorium in different volcanic rocks has been investigated using the track fission method. In this work, the uranium and thorium contents have been determined in different volcanic rock samples by using CR-39 and LR-115 type II solid state nuclear track detectors (SSNTD). The mean critical angles of etching of the solid state nuclear track detectors utilized have been calculated. A petrographical study of the volcanic rock thin layers studied has been conducted. The uranium and thorium distribution inside different rock thin layers has been studied. The mechanism of inclusion of the uranium and thorium nuclei inside the volcanic rock samples studied has been investigated. (author)

  19. Continuous particle spectra and their angular distributions

    International Nuclear Information System (INIS)

    Sastry, Ch.V.; Jain, R.K.; Rama Rao, J.; Ernst, J.; Machner, H.

    1996-01-01

    The angular distribution of continuous particle spectra in pre-equilibrium reactions is still an unsolved problem, particularly so at forward angles. In the present work, the angular distributions of alpha particles emitted in (α, α',x) reactions in the target elements gold and rhodium have been studied in detail. Alpha particle beams of energy 60 MeV from the Variable Energy Cyclotron of Calcutta were used in these experiments. The theoretical calculations were done using an extended exciton model of Kalbach incorporated into the Computer Code PRECO-D2. The formalism used in the exciton model was modified to include division of pre equilibrium cross section into multi-step direct (MSD) and multi-step compound (MSC) components. These MSD and MSC cross sections were used to calculate the angular distributions in terms of Legendre polynomials whose coefficients are given by simple phenomenological relations. Even with a reasonable set of parameters, the agreement between theory and experiment was far from satisfactory at forward angles. Similar conclusion was also drawn in the case of continuous particle spectra of deuterons in (d, d'x) reactions at 25 MeV in various targets. (author). 10 refs., 2 figs

  20. Depleted uranium instead of lead in munitions: the lesser evil.

    Science.gov (United States)

    Jargin, Sergei V

    2014-03-01

    Uranium has many similarities to lead in its exposure mechanisms, metabolism and target organs. However, lead is more toxic, which is reflected in the threshold limit values. The main potential hazard associated with depleted uranium is inhalation of the aerosols created when a projectile hits an armoured target. A person can be exposed to lead in similar ways. Accidental dangerous exposures can result from contact with both substances. Encountering uranium fragments is of minor significance because of the low penetration depth of alpha particles emitted by uranium: they are unable to penetrate even the superficial keratin layer of human skin. An additional cancer risk attributable to the uranium exposure might be significant only in case of prolonged contact of the contaminant with susceptible tissues. Lead intoxication can be observed in the wounded, in workers manufacturing munitions etc; moreover, lead has been documented to have a negative impact on the intellectual function of children at very low blood concentrations. It is concluded on the basis of the literature overview that replacement of lead by depleted uranium in munitions would be environmentally beneficial or largely insignificant because both lead and uranium are present in the environment.

  1. Depleted uranium instead of lead in munitions: the lesser evil

    International Nuclear Information System (INIS)

    Jargin, Sergei V

    2014-01-01

    Uranium has many similarities to lead in its exposure mechanisms, metabolism and target organs. However, lead is more toxic, which is reflected in the threshold limit values. The main potential hazard associated with depleted uranium is inhalation of the aerosols created when a projectile hits an armoured target. A person can be exposed to lead in similar ways. Accidental dangerous exposures can result from contact with both substances. Encountering uranium fragments is of minor significance because of the low penetration depth of alpha particles emitted by uranium: they are unable to penetrate even the superficial keratin layer of human skin. An additional cancer risk attributable to the uranium exposure might be significant only in case of prolonged contact of the contaminant with susceptible tissues. Lead intoxication can be observed in the wounded, in workers manufacturing munitions etc; moreover, lead has been documented to have a negative impact on the intellectual function of children at very low blood concentrations. It is concluded on the basis of the literature overview that replacement of lead by depleted uranium in munitions would be environmentally beneficial or largely insignificant because both lead and uranium are present in the environment. (opinion)

  2. Radon exhalation rates from slate stone samples in Aravali Range in Haryana

    International Nuclear Information System (INIS)

    Upadhyay, S.B.; Kant, K.; Chakarvarti, S.K.

    2012-01-01

    The slate stone tiles are very popular in covering the walls of the rooms. Radon is released into ambient air from slate stones due to ubiquitous uranium and radium in them, thus increasing the airborne radon concentration. The radioactivity in slates stones is related to radioactivity in the rocks from which the slate stone tiles are formed. In the present investigation, the radon emanated from slate stone samples collected from different slate mines in Aravali range of hills in the Haryana state of Northern India has been estimated. For the measurement of radon concentration emanated from these samples, alpha-sensitive LR-115 type II plastic track detectors have been used. The alpha particles emitted from the radon form tracks in these detectors. After chemical etching the track density of registered tracks is used to calculate radon concentration and exhalation rates of radon using required formulae. The measurements indicate normal to some higher levels of radon concentration emanated from the slat stone samples collected from Aravali range of hills in north India. The results will be discussed in full paper. (author)

  3. Low-level radon measurements by nuclear track detectors

    International Nuclear Information System (INIS)

    Koksal, E. M.; Goksel, S. A.; Alkan, H.

    1985-01-01

    In the work to be described here we have developed a passive nuclear track dosimeter to measure the integrated value of indoor radon (Rn-222) over a long period of time. Passive radon dosimeter which we have developed in our laboratories makes use of two small pieces of CR-39 plastic (Allyl diglycol carbonate) as detectors for registering tracks of alpha particles emitted by radon. These CR-39 plastic detectors are fixed on the inside bottom of a cup-shaped polystrene enclosure which is closed at the top by a tissue permeable for gases only. CR-39 detectors exposed to radon gas in the indoor air for a period of six months then are removed and chemically etched to make the alpha particle tracks visible under the microscope. The counts of tracks are evaluated to determine the radon concentration in the air in comparison with the number of tracks produced by a known concentration of radon gas. By using the passive dosimeters developed and the chemical etching procedure descriped here, measurements of indoor radon concentrations were carried out in 45 houses in different districts of the city of Istanbul. In this pilot experiment mean radon concentrations between 0.7 and 3.5 pCi/l have been found in these houses. In order to improve the counting of alpha tracks produced on the detectors a prototype electrochemical etching system in addition to chemical etching, is being developed. (author)

  4. Radon in the Houses of Slavonski Brod-Posavina County

    International Nuclear Information System (INIS)

    Poleto, Z.; Varga, M.; Radolic, V.; Poje, M.; Vukovic, B.

    2008-01-01

    Radon is a noble alpha-emitting radioactive gas produced by the decay od radium. The aim of this study was to measure radon concentrations in the houses of Slavonski Brod-Posavina county. The measurements were performed by means of the passive track etching method with strippable LR-115 SSNDT film, type II (Kodak-Pathe, France). The cylindrical plastic vessel of detector, with the diameter and the length of 11 and 7 cm, respectively, was covered with a paper filter of 0.078 kg/m 3 surface density. Inside, of the bottom of the vessel, a LR-115 film that presented a diffusion detector was fixed.Outside, on the cylindrical shell of the vessel, another film, that presented the open detector was fixed. The open LR-115 detector registers the total number of alpha-particles of radon and its short-lived progeny, while the diffusion detector registers tracks only of alpha particles emitted by radon. Measurements gave radon concentrations in the range of 14-404 Bq m -3 . Average annual effective radon dose for population of Slavonski Brod-Posavina county is 2.91 mSv

  5. Development of Reagents for Application of At-211 to Targeted Radionuclide Therapy of Cancer

    International Nuclear Information System (INIS)

    Wilbur, D. Scott

    2011-01-01

    This grant covered only a period of 4 months as the major portion of the award was returned to DOE due to an award of funding from NIH that covered the same research objectives. A letter regarding the termination of the research is attached as the last page of the Final Report. The research conducted was limited due to the short period of this grant, but the results obtained in that period are outlined in the Final Report. The studies addressed in the research effort were directed at a problem that is of critical importance to the in vivo application of the alpha-particle emitting radionuclide At-211. That problem, low in vivo stability of many astatinated molecules, severely limits the use of At-211 in therapeutic applications. The advances sought in the studies were expected to expand the types of biomolecules that can be used as carriers of At-211, and provide improved in vivo targeting of the radiation dose compared with the dose delivered to normal tissue.

  6. Radon as a medicine. Therapeutic effectiveness, biological mechanism and comparative risk assessment

    International Nuclear Information System (INIS)

    Deetjen, Peter; Falkenbach, Albrecht; Harder, Dietrich; Joeckel, Hans; Kaul, Alexander; Philipsborn, Henning von

    2014-01-01

    Proofs of the therapeutic efficiency of balneological radon applications administered to patients suffering from rheumatic diseases, investigations into the biological action mechanism associated with the alpha particles emitted by radon and its radioactive daughter products, and the comparative risk assessment of radon treatment and medicinal pain therapy have been the research projects whose results are summarized in this book. Controlled clinical studies, if possible performed as prospective, randomized and placebo-controlled double blind studies, have given evidence that the therapeutic effects of balneological radon applications - long-lasting pain reduction and reduced consumption of medicines compared with controls - are significantly persisting over many post-treatment months. The molecular and cellular mechanism of action underlying these long-lasting therapeutic effects has been identified as the down-regulation of cellular immune responses, initiated by cellular apoptosis sequential to low alpha particle doses and by the subsequent release of anti-inflammatory cytokines. The unwanted side-effects of non-steroidal anti-rheumatic drug treatments have to be compared with the absence of side effects from the balneological radon applications which merely involve radiation doses well below the mean value and the fluctuation width of the annual doses attributable to everybody's natural radiation exposure.

  7. Measurement of the 235 U absolute activity

    International Nuclear Information System (INIS)

    Bueno, C.C.; Santos, M.D.S.

    1993-01-01

    The absolute activity of 235 U contained in a sample was measured utilizing a sum-coincidence circuit which selects only the alpha particles emitted simultaneously with the 143 KeV gamma radiations from the 231 Th (product nucleus). The alpha particles were detected by means of a new type of a gas scintillating chamber, in which the light emitted by excitation of the gas atoms, due to the passage of a charged incoming particle, has its intensity increased by the action of an applied electric field. The gamma radiations were detected by means of a 1'x 1 1/2 Nal (TI) scintillation detector. The value obtained for the half-life of 235 U, (7.04+-0.01)10 8 y, was compared with the data available from various observers with used different experimental techniques. It is shown that our results are in excellent agreement with the best data available on the subject. (author) 15 refs, 5 figs, 1 tab

  8. Radon as a medicine. Therapeutic effectiveness, biological mechanism and comparative risk assessment

    Energy Technology Data Exchange (ETDEWEB)

    Deetjen, Peter; Falkenbach, Albrecht; Harder, Dietrich; Joeckel, Hans; Kaul, Alexander; Philipsborn, Henning von

    2014-07-01

    Proofs of the therapeutic efficiency of balneological radon applications administered to patients suffering from rheumatic diseases, investigations into the biological action mechanism associated with the alpha particles emitted by radon and its radioactive daughter products, and the comparative risk assessment of radon treatment and medicinal pain therapy have been the research projects whose results are summarized in this book. Controlled clinical studies, if possible performed as prospective, randomized and placebo-controlled double blind studies, have given evidence that the therapeutic effects of balneological radon applications - long-lasting pain reduction and reduced consumption of medicines compared with controls - are significantly persisting over many post-treatment months. The molecular and cellular mechanism of action underlying these long-lasting therapeutic effects has been identified as the down-regulation of cellular immune responses, initiated by cellular apoptosis sequential to low alpha particle doses and by the subsequent release of anti-inflammatory cytokines. The unwanted side-effects of non-steroidal anti-rheumatic drug treatments have to be compared with the absence of side effects from the balneological radon applications which merely involve radiation doses well below the mean value and the fluctuation width of the annual doses attributable to everybody's natural radiation exposure.

  9. Proceedings of transuranium elements

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    The identification of the first synthetic elements was established by chemical evidence. Conclusive proof of the synthesis of the first artificial element, technetium, was published in 1937 by Perrier and Segre. An essential aspect of their achievement was the prediction of the chemical properties of element 43, which had been missing from the periodic table and which was expected to have properties similar to those of manganese and rhenium. The discovery of other artificial elements, astatine and francium, was facilitated in 1939-1940 by the prediction of their chemical properties. A little more than 50 years ago, in the spring of 1940, Edwin McMillan and Philip Abelson synthesized element 93, neptunium, and confirmed its uniqueness by chemical means. On August 30, 1940, Glenn Seaborg, Arthur Wahl, and the late Joseph Kennedy began their neutron irradiations of uranium nitrate hexahydrate. A few months later they synthesized element 94, later named plutonium, by observing the alpha particles emitted from uranium oxide targets that had been bombarded with deuterons. Shortly thereafter they proved that is was the second transuranium element by establishing its unique oxidation-reduction behavior. The symposium honored the scientists and engineers whose vision and dedication led to the discovery of the transuranium elements and to the understanding of the influence of 5f electrons on their electronic structure and bonding. This volume represents a record of papers presented at the symposium

  10. On the detection of low-energy 4He, 12C, 14N, 16O ions in PC foils and its use in nuclear reaction measurements

    International Nuclear Information System (INIS)

    Somogyi, G.; Hunyadi, I.; Koltay, E.; Zolnai, L.

    1977-01-01

    It is shown that by using a proper etching reagent the registration sensitivity of polycarbonate foils can be enhanced and they prove to be very suitable track recorders for alpha-particles emitted from nuclear reactions. At 6 MeV an energy resolution of 0.2 MeV can be achieved when using the track diameters as a measure of the particle energy. A theoretical way to calculate the track parameters important in nuclear reaction measurements involving alpha-particles recorded in polycarbonate foils is given. For this purpose the track etch rate vs residual range curve was determined by a parameter optimization procedure. The energy resolution of the track-diameter method as a function of the particle energy was predicted. In earlier studies the track-diameter method was mostly used in angular distribution measurements of (d, α) nuclear reactions. In this work it is shown that with polycarbonate foils it can be well applied to excitation function measurements, as well. Such studies are presented for the α 0 and α 1 groups of the 27 Al(p, α) 24 Mg reaction in an energy interval between 1540 and 1920 keV. Finally, preliminary results of the track etching properties of low-energy O + , N + , C + and He + ions accelerated with a 5 MV Van de Graaff generator are given. (Auth.)

  11. Contribution of waterborne radon to home air quality

    International Nuclear Information System (INIS)

    Deb, A.K.

    1994-01-01

    Radon-222 is a member of the uranium decay chain and is formed from the decay of radium-226. Radon and its decay products emit alpha particles during the decay process. If radon is inhaled, alpha particles emitted from inhaled radon and its daughters increase the risk of lung cancer. Radon is soluble in water; thus when radon comes in contact with groundwater it dissolves. The radon concentration in groundwater may range from 100 pCi/L to 1,000,000 pCi/L. When water with a high radon level is used in the home, radon is released from the water to the air and thus can increase indoor air radon concentration. Considering the estimated health risk from radon in public water supply systems, EPA has proposed a maximum contaminant level (MCL) of 300 pCi/L for radon in public drinking water supplies. To address the health risks of radon in water and the proposed regulations, the American Water Works Association Research Foundation (AWWARF) initiated a study to determine the contribution of waterborne radon to radon levels in indoor household air

  12. Nuclear physics experiments with low cost instrumentation

    Science.gov (United States)

    Oliveira Bastos, Rodrigo; Adelar Boff, Cleber; Melquiades, Fábio Luiz

    2016-11-01

    One of the difficulties in modern physics teaching is the limited availability of experimental activities. This is particularly true for teaching nuclear physics in high school or college. The activities suggested in the literature generally symbolise real phenomenon, using simulations. It happens because the experimental practices mostly include some kind of expensive radiation detector and an ionising radiation source that requires special care for handling and storage, being subject to a highly bureaucratic regulation in some countries. This study overcomes these difficulties and proposes three nuclear physics experiments using a low-cost ion chamber which construction is explained: the measurement of 222Rn progeny collected from the indoor air; the measurement of the range of alpha particles emitted by the 232Th progeny, present in lantern mantles and in thoriated welding rods, and by the air filter containing 222Rn progeny; and the measurement of 220Rn half-life collected from the emanation of the lantern mantles. This paper presents the experimental procedures and the expected results, indicating that the experiments may provide support for nuclear physics classes. These practices may outreach wide access to either college or high-school didactic laboratories, and the apparatus has the potential for the development of new teaching activities for nuclear physics.

  13. Improved radioimmunotherapy of hematologic malignancies

    International Nuclear Information System (INIS)

    Press, O.W.

    1992-01-01

    This research project proposes to develop novel new approaches of improving the radioimmunodetection and radioimmunotherapy of malignancies by augmenting retention of radioimmunoconjugates by tumor cells. The approaches shown to be effective in these laboratory experiments will subsequently be incorporated into out ongoing clinical trials in patients. Specific project objectives include: to study the rates of endocytosis, intracellular routing, and metabolic degradation of radiolabeled monoclonal antibodies targeting tumor-associated antigens on human leukemia and lymphoma cells; To examine the effects of lysosomotropic amines (e.g. chloroquine, amantadine), carboxylic ionophores (monensin, nigericin), and thioamides (propylthiouracil), on the retention of radiolabeled MoAbs by tumor cells; to examine the impact of newer radioiodination techniques (tyramine cellobiose, paraiodobenzoyl) on the metabolic degradation of radioiodinated antibodies; to compare the endocytosis, intracellular routing, and degradation of radioimmunoconjugates prepared with different radionuclides ( 131 Iodine, 111 Indium, 90 Yttrium, 99m Technetium, 186 Rhenium); and to examine the utility of radioimmunoconjugates targeting oncogene products for the radioimmunotherapy and radioimmunoscintigraphy of cancer

  14. Improved radioimmunotherapy of hematologic malignancies. [Final report

    Energy Technology Data Exchange (ETDEWEB)

    Press, O.W.

    1992-03-24

    This research project proposes to develop novel new approaches of improving the radioimmunodetection and radioimmunotherapy of malignancies by augmenting retention of radioimmunoconjugates by tumor cells. The approaches shown to be effective in these laboratory experiments will subsequently be incorporated into out ongoing clinical trials in patients. Specific project objectives include: to study the rates of endocytosis, intracellular routing, and metabolic degradation of radiolabeled monoclonal antibodies targeting tumor-associated antigens on human leukemia and lymphoma cells; To examine the effects of lysosomotropic amines (e.g. chloroquine, amantadine), carboxylic ionophores (monensin, nigericin), and thioamides (propylthiouracil), on the retention of radiolabeled MoAbs by tumor cells; to examine the impact of newer radioiodination techniques (tyramine cellobiose, paraiodobenzoyl) on the metabolic degradation of radioiodinated antibodies; to compare the endocytosis, intracellular routing, and degradation of radioimmunoconjugates prepared with different radionuclides ({sup 131}Iodine, {sup 111}Indium, {sup 90}Yttrium, {sup 99m}Technetium, {sup 186}Rhenium); and to examine the utility of radioimmunoconjugates targeting oncogene products for the radioimmunotherapy and radioimmunoscintigraphy of cancer.

  15. Improved radioimmunotherapy of hematologic malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Press, O.W.

    1992-03-24

    This research project proposes to develop novel new approaches of improving the radioimmunodetection and radioimmunotherapy of malignancies by augmenting retention of radioimmunoconjugates by tumor cells. The approaches shown to be effective in these laboratory experiments will subsequently be incorporated into out ongoing clinical trials in patients. Specific project objectives include: to study the rates of endocytosis, intracellular routing, and metabolic degradation of radiolabeled monoclonal antibodies targeting tumor-associated antigens on human leukemia and lymphoma cells; To examine the effects of lysosomotropic amines (e.g. chloroquine, amantadine), carboxylic ionophores (monensin, nigericin), and thioamides (propylthiouracil), on the retention of radiolabeled MoAbs by tumor cells; to examine the impact of newer radioiodination techniques (tyramine cellobiose, paraiodobenzoyl) on the metabolic degradation of radioiodinated antibodies; to compare the endocytosis, intracellular routing, and degradation of radioimmunoconjugates prepared with different radionuclides ({sup 131}Iodine, {sup 111}Indium, {sup 90}Yttrium, {sup 99m}Technetium, {sup 186}Rhenium); and to examine the utility of radioimmunoconjugates targeting oncogene products for the radioimmunotherapy and radioimmunoscintigraphy of cancer.

  16. Air alpha monitoring device and system for the calibration of the track detectors

    International Nuclear Information System (INIS)

    Danis, A; Oncescu, M.; Ciubotariu, M.

    2001-01-01

    The radon measurement plays a critical role: - in monitoring the human health and safety, due to radon destructive health effects. Sustained exposures of humans to high concentration of radon, in fact to high concentrations of its decay products, can produce lung cancer; - in a variety of geophysical, geochemical, hydrological and atmospheric investigations, such as exploring resources of uranium or hydrocarbons. The transport of radon within the earth, waters and atmosphere makes it a useful tracer in these purposes. in both cases, the reliable long-term measurements are required because usual short-term variations in concentration need to be averaged. These variations are caused by factors such as relative humidity, temperature, atmospheric pressure and their seasonal variations, moisture content in the air, or ventilation in the dwelling or working places. The integrating measurement methods meet these requirements. Among them, the alpha track method is one of the adequate and useful method and it is used by authors in radon measurements in dwelling and working places including mines and house cellars. The best etched track alpha detector for radon measurements proved to be the detector CR-39 due to: - its sensitivity to alpha particles emitted by radon decay products; - its stability against various environmental factors; - its high degree of optical clarity, was used in a proper device for alpha monitoring in air. Its calibration for radon measurements was performed in the proper calibration system. The general descriptions and specifications were given previously. Only some characteristics of these devices are given here. For air alpha monitoring device: i) equipped with filter, during alpha exposure, the alpha particles of radon are registered in the etched track detector mounted inside (ρ Rn - track density); ii) without filter, the alpha particles emitted by radon + its alpha decay products/their aerosols are registered in the detector (ρ tot - track

  17. Radiation effects in moist-air systems and the influence of radiolytic product formation on nuclear waste glass corrosion

    International Nuclear Information System (INIS)

    Wronkiewicz, D.J.; Bates, J.K.; Buck, E.C.; Hoh, J.C.; Emery, J.W.; Wang, L.M.

    1997-07-01

    Ionizing radiation may affect the performance of glass in an unsaturated repository site by interacting with air, water vapor, or liquid water to produce a variety of radiolytic products. Tests were conducted to examine the effects of radiolysis under high gas/liquid ratios. Results indicate that nitrate is the predominant radiolytic product produced following both gamma and alpha radiation exposure, with lesser amounts of nitrite and carboxylic acids. The formation of nitrogen acids during exposure to long-lived, alpha-particle-emitting transuranic elements indicates that these acids may play a role in influencing nuclear waste form reactions in a long-term unsaturated disposal scenario. Experiments were also conducted with samples that simulate the composition of Savannah River Plant nuclear waste glasses. Radiolytic product formation in batch tests (340 m -1 , 90 C) resulted in a small increase in the release rates of many glass components, such as alkali and alkaline earth elements, although silicon and uranium release rates were slightly reduced indicating an overall beneficial effect of radiation on waste form stability. The radiolytic acids increased the rate of ion exchange between the glass and the thin film of condensate, resulting in accelerated corrosion rates for the glass. The paragenetic sequence of alteration phases formed on both the irradiated and nonirradiated glass samples reacted in the vapor hydration tests matches closely with those developed during volcanic glass alteration in naturally occurring saline-alkaline lake systems. This correspondence suggests that the high temperatures used in these tests have not changed the underlying glass reaction mechanism relate to that which controls glass reactions under ambient surficial conditions

  18. Radon integral measurement system

    International Nuclear Information System (INIS)

    Garcia H, J.M.

    1994-01-01

    The Radon Integral Measurement System (SMIR) is a device designed specially to detect, to count and to store the data of the acquisition of alpha particles emitted by Radon-222 coming from the underground. The system includes a detection chamber, a radiation detector, a digital system with bateries backup and an auxiliary photovoltaic cell. A personal computer fixes the mode in which the system works, transmitting the commands to the system by the serial port. The heart of the system is a microprocesor working with interrupts by hardware. Every external device to the microprocessor sends his own interrupt request and the microprocessor handles the interrupts with a defined priority. The system uses a real time clock, compatible with the microprocessor, to take care of the real timing and date of the acquisition. A non volatile RAM is used to store data of two bytes every 15 minutes along 41 days as a maximum. After the setting up to the system by the computer, it can operate in stand alone way for up 41 days in the working place without the lose of any data. If the memory is full the next data will be written in the first locations of the memory. The memory is divided in pages corresponding every one of this to a different day of the acquisition. The counting time for every acquisition can be programmed by the user from 15 minutes to 65535 minutes but it is recommended to use a small time not to reach the limit of 65535 counts in every acquisition period. We can take information of the system without affecting the acquisition process in the field by using a lap top computer, then the information can be stored in a file. There is a program in the computer that can show the information in a table of values or in a bar graph. (Author)

  19. Final Report for grant entitled "Production of Astatine-211 for U.S. Investigators"

    Energy Technology Data Exchange (ETDEWEB)

    Wilbur, Daniel Scott

    2012-12-12

    Alpha-particle emitting radionuclides hold great promise in the therapy of cancer, but few alpha-emitters are available to investigators to evaluate. Of the alpha-emitters that have properties amenable for use in humans, 211At is of particular interest as it does not have alpha-emitting daughter radionuclides. Thus, there is a high interest in having a source of 211At for sale to investigators in the US. Production of 211At is accomplished on a cyclotron using an alpha-particle beam irradiation of bismuth metal. Unfortunately, there are few cyclotrons available that can produce an alpha particle beam for that production. The University of Washington has a cyclotron, one of three in the U.S., that is currently producing 211At. In the proposed studies, the things necessary for production and shipment of 211At to other investigators will be put into place at UW. Of major importance is the efficient production and isolation of 211At in a form that can be readily used by other investigators. In the studies, production of 211At on the UW cyclotron will be optimized by determining the best beam energy and the highest beam current to maximize 211At production. As it would be very difficult for most investigators to isolate the 211At from the irradiated target, the 211At-isolation process will be optimized and automated to more safely and efficiently obtain the 211At for shipment. Additional tasks to make the 211At available for distribution include obtaining appropriate shipping vials and containers, putting into place the requisite standard operating procedures for Radiation Safety compliance at the levels of 211At activity to be produced / shipped, and working with the Department of Energy, Isotope Development and Production for Research and Applications Program, to take orders, make shipments and be reimbursed for costs of production and shipment.

  20. Construction of a bi parametric analysis system. Application to the study of the decay of the 16.11 MeV level of {sup 12}C; Realisation d'un ensemble d'analyse biparametrique. Application a l'etude de la desintegration du niveau de 16,11 MeV du {sup 12}C

    Energy Technology Data Exchange (ETDEWEB)

    Engelhardt, H D [Commissariat a l' Energie Atomique, Grenoble (France). Centre d' Etudes Nucleaires

    1966-11-15

    A baroreceptor analysis system has been assembled to measure {alpha}-{alpha} spectra in coincidence (resolution 2 {tau} = 10 ns). The correlations in energy and angle of the {alpha}-particles emitted from the reaction {sup 11}B(p,{alpha}) have been studied using 163 keV protons produced by a Van-de-Graaff accelerator. Evidence has been obtained for the sequential decay of {sup 12}C{sup *} (16.11 MeV) via the 0{sup +} and 2{sup +} states of {sup 8}Be. Contributions from the {sup 8}Be{sup *}(4{sup +}) level or from the simultaneous break-up of {sup 12}C{sup *} (16.11 MeV) into three {alpha}-particles cannot be excluded. (author) [French] On a mis au point un dispositif d'analyse biparametrique de spectres {alpha}-{alpha} en coincidences (resolution 2 {tau} = 10 ns). On a etudie, a l'aide de ce dispositif et d'un accelerateur Van de Graaff la correlation d'energie et angulaire entre les particules a de la reaction {sup 11}B(p,{alpha}) a une energie de protons E{sub p} = 163 keV. On a mis en evidence la desintegration sequentielle du {sup 12}C{sup *} (16.11 MeV) par les etats (0{sup +} et 2{sup +}) du {sup 8}Be. La contribution d'un niveau (4{sup +}) du {sup 8}Be{sup *} ou d'une desintegration simultanee du {sup 12}C{sup *} (16,11 MeV) en 3 {alpha} ne peut pas etre exclue. (auteur)

  1. Alpha detection in pipes using an inverting membrane scintillator

    International Nuclear Information System (INIS)

    Kendrick, D.T.; Cremer, C.D.; Lowry, W.; Cramer, E.

    1995-01-01

    Characterization of surface alpha emitting contamination inside enclosed spaces such as piping systems presents an interesting radiological measurement challenge. Detection of these alpha particles from the exterior of the pipe is impossible since the alpha particles are completely absorbed by the pipe wall. Traditional survey techniques, using hand-held instruments, simply can not be used effectively inside pipes. Science and Engineering Associates, Inc. is currently developing an enhancement to its Pipe Explorer trademark system that will address this challenge. The Pipe Explorer trademark uses a unique sensor deployment method where an inverted tubular membrane is propagated through complex pipe runs via air pressure. The inversion process causes the membrane to fold out against the pipe wall, such that no part of the membrane drags along the pipe wall. This deployment methodology has been successfully demonstrated at several DOE sites to transport specially designed beta and gamma scintillation detectors into pipes ranging in length up to 250 ft. The measurement methodology under development overcomes the limitations associated with conventional hand-held survey instruments by remotely emplacing an alpha scintillator in direct contact with the interior pipe surface over the entire length to be characterized. This is accomplished by incorporating a suitable scintillator into the otherwise clear membrane material. Alpha particles emitted from the interior pipe surface will intersect the membrane, resulting in the emission of light pulses from the scintillator. A photodetector, towed by the inverting membrane, is used to count these light pulses as a function of distance into the pipe, thereby producing a log of the surface alpha contamination levels. It is anticipated that the resulting system will be able to perform measurements in pipes as small as two inches in diameter, and several hundred feet in length

  2. Bulk GaN alpha-particle detector with large depletion region and improved energy resolution

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Qiang; Mulligan, Padhraic [Nuclear Engineering Program, Department of Mechanical and Aerospace Engineering, The Ohio State University, Columbus, OH 43210 (United States); Wang, Jinghui [Department of Radiology, Stanford University, 1201 Welch Rd, Stanford, CA 94305 (United States); Chuirazzi, William [Nuclear Engineering Program, Department of Mechanical and Aerospace Engineering, The Ohio State University, Columbus, OH 43210 (United States); Cao, Lei, E-mail: cao.152@osu.edu [Nuclear Engineering Program, Department of Mechanical and Aerospace Engineering, The Ohio State University, Columbus, OH 43210 (United States)

    2017-03-21

    An alpha-particle detector was fabricated using a freestanding n-type bulk GaN wafer with a Au/Ni/GaN sandwich Schottky structure. Current–voltage measurements at room temperature revealed a Schottky contact with a leakage current of 7.53±0.3 nA at a reverse bias of 200 V. The detector had a large depletion depth that can capture much of the energy from 5.486 MeV alpha particles emitted from a {sup 241}Am source. The resolution of its alpha-particle energy spectrum was improved to 2.2±0.2% at 5.486 MeV under a bias of 550 V. This superior resolution was attributed to the shortening of the carrier transit time and the large energy deposition within the large depletion depth, i.e., 27 µm at −550 V, which all resulted in a more complete charge collection. A model developed using the ATLAS simulation framework from Silvaco Inc. was employed to study the charge collection process. The simulation results were found to agree closely with the experimental results. This detector will be beneficial for research at neutron scattering facilities, the International Thermonuclear Experimental Reactor, and the Large Hadron Collider, among other institutions, where the Si-based charged particle detectors could be quickly degraded in an intense radiation field. - Highlights: • An alpha-particle detector based on a Schottky-structured GaN wafer was tested. • The detector's large depletion depth enables fuller energy spectra to be obtained. • The best resolution yet attained in GaN alpha-particle spectrometry was achieved. • The detector's short carrier transit time resulted in improved charge collection. • This detector is usable in extreme conditions, including intense radiation fields.

  3. Calibration of SSNDT detectors for radon measurements; Calibração de detectores SSNDT para medição de radônio

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Laura C.; Santos, Talita O.; Pinheiro, Rose Mary M.; Rocha, Zildete, E-mail: lauratakahashi@hotmail.com, E-mail: talitaolsantos@yahoo.com.br, E-mail: rosepin@cdtn.br, E-mail: rochaz@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

    2017-07-01

    The methods and instrumentation used to measure the concentration of radon need to be calibrated to obtain accurate results. The Nuclear Track Detector is considered the main method of analysis of radon research. Thus, the Natural Radioactivity Laboratory of the Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG, Brazil) uses the detector CR-39 (Landauer) to measure the concentration of radon in homes, workplaces, underground mines, soils and in environment. Epidemiological studies reveal the strong relationship between lung cancer and radon exposure. Therefore, it is important to monitor this gas and its progeny in order to assess the radiological risk. The alpha particles emitted by radon and its progeny leave traces on CR-39 due to Coulombian interactions with the atoms of the material. The liquid density of traces is converted to radon concentration by means of a calibration factor obtained in calibrated systems. This work aims to determine the LRN / CDTN calibration factor. To do so, the CR-39 detectors were placed inside the calibration chambers, along with two AlphaGUARD (Saphymo GmbH) detectors and Ra-266 sources with activities of 3,379 kBq or 0.483 kBq, referenced by NIST. From this, six levels of exposure were obtained, which were: 44 kBq.d.m{sup 3}, 4 kBq.d.m{sup 3}, 3 kBq.d.m{sup 3}, 15 kBq.d.m{sup 3}, 30 kBq.d.m{sup 3} , 26 kBq.d.m {sup 3}. The conversion factor between the liquid density of traces and the total exposure time obtained was K = 52.028 ± 0.752 [(trace density.cm{sup -2}) / (kBq.d.m{sup -3})]. After the determination of the conversion factor, it was used to measure the concentration of radon in underground mines, obtaining concentration results between 122 ± 24 and 7384 ± 517 kBq.m{sup -3}.

  4. Cellular dosimetry for radon progeny alpha particles in bronchial tissue

    International Nuclear Information System (INIS)

    Mohamed, A.; Hofmann, W.; Balashazy, I.

    1996-01-01

    Inhaled radon progeny are deposited in different regions of the human bronchial tree as functions of particle size and flow rate. Following deposition and mucociliary clearance, the sensitive bronchial basal and secretory cells are irradiated by two different alpha particle sources: (i) radon progeny in the sol and/or gel phase of the mucous layer, and (ii) radon progeny within the bronchial epithelium. In the case of internally deposited radionuclides, direct measurement of the energy absorbed from the ionizing radiation emitted by the decaying radionuclides is rarely, if ever, possible. Therefore, one must rely on dosimetric models to obtain estimates of the spatial and temporal patterns of energy deposition in tissues and organs of the body. When the radionuclide is uniformly distributed throughout the volume of a tissue of homogeneous composition and when the size of the tissue is large compared to the range of the particulate emissions of the radionuclide, then the dose rate within the tissue is also uniform and the calculation of absorbed dose can proceed without complication. However, if non-uniformities in the spatial and temporal distributions of the radionuclide are coupled with heterogeneous tissue composition, then the calculation of absorbed dose becomes complex and uncertain. Such is the case with the dosimetry of inhaled radon and radon progeny in the respiratory tract. There are increasing demands to obtain a definitive explanation of the role of alpha particles emitted from radon daughters in the induction of lung cancer. Various authors have attempted to evaluate the dose to the bronchial region of the respiratory tract due to the inhalation of radon daughters

  5. Individual variation in p53 and Cip1 expression profiles in normal human fibroblast strains following exposure to high-let radiation

    Energy Technology Data Exchange (ETDEWEB)

    Carpenter, T.R.; Johnson, N.F.; Gilliland, F.D. [Univ. of New Mexico, Albuquerque, NM (United States)] [and others

    1995-12-01

    Exposure to {alpha}-particles emitted by radon progeny appears to be the second-leading cause of lung cancer mortality. However, individual susceptibility to the carcinogenic effects of {alpha}-particles remains poorly characterized. Variation in susceptibility to cancer produced by certian classes of DNA-damaging chemicals is suspected to involve differences in metabolic activation and detoxication. Susceptibility to {alpha}-particle-induced cancer may involve variations in capacity or opportunity to repair DNA damage. Subtle variations in DNA repair capacity would more likely explain radon-related lung cancer susceptibility. The p53 tumor suppressor protein accumulates as a cellular response to DNA damage from ionizing radiation and regulates arrest in the G{sub 1} portion of the cell cycle. Arrest in G{sub 1} portion of the cell cycle. While upstream regulation of p53 protein stability is poorly understood, variations in the ability to accumulate p53 following DNA damage represent potential variations in lung cancer susceptibility related to radon progeny. Further, transcription of the cell-cycle regulatory gene Cip1 is regulated by p53 and increases following ionizing radiation. Therefore, variations in the expression of Cip1 following {alpha}-particle exposure may also be a susceptibility factor in radon-related lung cancers. The purpose of the present investigation was to measure p53 and Cip1 protein induction following {alpha}-particle exposure of fibroblast lines from nine individuals to determine if there were significant variations. The expression of Cip1 protein indicates the differences in response are biologically relevant.

  6. Enhanced efficacy of combined {sup 213}Bi-DTPA-F3 and paclitaxel therapy of peritoneal carcinomatosis is mediated by enhanced induction of apoptosis and G2/M phase arrest

    Energy Technology Data Exchange (ETDEWEB)

    Vallon, Mario; Seidl, Christof; Blechert, Birgit; Li, Zhoulei; Gaertner, Florian C.; Senekowitsch-Schmidtke, Reingard; Essler, Markus [Technische Universitaet Muenchen, Department of Nuclear Medicine, Munich (Germany); Gilbertz, Klaus-Peter [German Armed Forces, Institute of Radiobiology, Munich (Germany); Baumgart, Anja [Technische Universitaet Muenchen, III. Medical Department, Munich (Germany); Aichler, Michaela; Feuchtinger, Annette; Walch, Axel K. [Helmholtz Zentrum Muenchen, Institute of Pathology, Neuherberg (Germany); Bruchertseifer, Frank; Morgenstern, Alfred [Institute for Transuranium Elements, European Commission, Joint Research Centre, Karlsruhe (Germany)

    2012-12-15

    Targeted therapy with {alpha}-particle emitting radionuclides is a promising new option in cancer therapy. Stable conjugates of the vascular tumour-homing peptide F3 with the {alpha}-emitter {sup 213}Bi specifically target tumour cells. The aim of our study was to determine efficacy of combined {sup 213}Bi-diethylenetriaminepentaacetic acid (DTPA)-F3 and paclitaxel treatment compared to treatment with either {sup 213}Bi-DTPA-F3 or paclitaxel both in vitro and in vivo. Cytotoxicity of treatment with {sup 213}Bi-DTPA-F3 and paclitaxel, alone or in combination, was assayed towards OVCAR-3 cells using the alamarBlue assay, the clonogenic assay and flow cytometric analyses of the mode of cell death and cell cycle arrest. Therapeutic efficacy of the different treatment options was assayed after repeated treatment of mice bearing intraperitoneal OVCAR-3 xenograft tumours. Therapy monitoring was performed by bioluminescence imaging and histopathologic analysis. Treatment of OVCAR-3 cells in vitro with combined {sup 213}Bi-DTPA-F3 and paclitaxel resulted in enhanced cytotoxicity, induction of apoptosis and G2/M phase arrest compared to treatment with either {sup 213}Bi-DTPA-F3 or paclitaxel. Accordingly, i.p. xenograft OVCAR-3 tumours showed the best response following repeated (six times) combined therapy with {sup 213}Bi-DTPA-F3 (1.85 MBq) and paclitaxel (120 {mu}g) as demonstrated by bioluminescence imaging and histopathologic investigation of tumour spread on the mesentery of the small and large intestine. Moreover, mean survival of xenograft mice that received combined therapy with {sup 213}Bi-DTPA-F3 and paclitaxel was significantly superior to mice treated with either {sup 213}Bi-DTPA-F3 or paclitaxel alone. Combined treatment with {sup 213}Bi-DTPA-F3 and paclitaxel significantly increased mean survival of mice with peritoneal carcinomatosis of ovarian origin, thus favouring future therapeutic application. (orig.)

  7. Effects of alpha-particles on survival and chromosomal aberrations in human mammary epithelial cells

    Science.gov (United States)

    Durante, M.; Grossi, G. F.; Gialanella, G.; Pugliese, M.; Nappo, M.; Yang, T. C.

    1995-01-01

    We have studied the radiation responses of a human mammary epithelial cell line, H184B5 F5-1 M/10. This cell line was derived from primary mammary cells after treatment with chemicals and heavy ions. The F5-1 M/10 cells are immortal, density-inhibited in growth, and non-tumorigenic in athymic nude mice and represent an in vitro model of the human epithelium for radiation studies. Because epithelial cells are the target of alpha-particles emitted from radon daughters, we concentrated our studies on the efficiency of alpha-particles. Confluent cultures of M/10 cells were exposed to accelerated alpha-particles [beam energy incident at the cell monolayer = 3.85 MeV, incident linear energy transfer (LET) in cell = 109 keV/microns] and, for comparison, to 80 kVp x-rays. The following endpoints were studied: (1) survival, (2) chromosome aberrations at the first postirradiation mitosis, and (3) chromosome alterations at later passages following irradiation. The survival curve was exponential for alpha-particles (D0 = 0.73 +/- 0.04 Gy), while a shoulder was observed for x-rays (alpha/beta = 2.9 Gy; D0 = 2.5 Gy, extrapolation number 1.6). The relative biological effectiveness (RBE) of high-LET alpha-particles for human epithelial cell killing was 3.3 at 37% survival. Dose-response curves for the induction of chromosome aberrations were linear for alpha-particles and linearquadratic for x-rays. The RBE for the induction of chromosome aberrations varied with the type of aberration scored and was high (about 5) for chromosome breaks and low (about 2) for chromosome exchanges.(ABSTRACT TRUNCATED AT 250 WORDS).

  8. Determine concentration radon 222Rn in the air inside and outside the buildings at the summer province of Baghdad

    International Nuclear Information System (INIS)

    Al-Ataby, N.R.; Aisa, B.H.; Jebir, H.M.; Hatem, J.N.

    2010-01-01

    In this study, Was use of solid-state nuclear track detectors in the measurement of concentrations of radon 222 Rn inside and outside of the buildings in the summer and winter of the Baghdad province and because of the high features of the technical sensitivity and efficiency to record track of charged particles (such as protons and alpha particles and fission fragments) . Is the radon of Environmental Pollutions that is caused health problems , that was seemed the concern at the problem of pollution, radon gas 222 Rn and thoron gas 220 Rn and the considerable risk resulting from exposure to these isotopes by alpha particles emitted which have proved the relationship between exposure to emitted alpha particles with the incidence of disease of lung cancer. In this study, measured the concentration of radon 222 Rn inside and outside buildings in the summer and winter in several areas from the Baghdad province and as showed in the attached tables. Been studied the environmental radioactivity and measurement of the concentration of radon gas in the air in different parts of the city of Baghdad. the highest concentration was Found in the second Orf ali (A) (of the Sadr City) for the summer and was (37.973 Bq/m3) outside the building and ((53.400 Bq/m3 inside the building, either for the winter season was (55.773 Bq/m3) outside the building and (Bq/m3 58.148) inside the building for the same region and This is the concentration within the limits allowed

  9. I. Fission Probabilities, Fission Barriers, and Shell Effects. II. Particle Structure Functions

    Energy Technology Data Exchange (ETDEWEB)

    Jing, Kexing [Univ. of California, Berkeley, CA (United States)

    1999-05-01

    In Part I, fission excitation functions of osmium isotopes 185,186, 187, 189 Os produced in 3He +182,183, 184, 186W reactions, and of polonium isotopes 209,210, 211, 212Po produced in 3He/4He + 206, 207, 208Pb reactions, were measured with high precision. These excitation functions have been analyzed in detail based upon the transition state formalism. The fission barriers, and shell effects for the corresponding nuclei are extracted from the detailed analyses. A novel approach has been developed to determine upper limits of the transient time of the fission process. The upper limits are constrained by the fission probabilities of neighboring isotopes. The upper limits for the transient time set with this new method are 15x 10–21 sec and 25x 10–21 sec for 0s and Po compound nuclei, respectively. In Part II, we report on a search for evidence of the optical modulations in the energy spectra of alpha particles emitted from hot compound nuclei. The optical modulations are expected to arise from the ~-particle interaction with the rest of the nucleus as the particle prepares to exit. Some evidence for the modulations has been observed in the alpha spectra measured in the 3He-induced reactions, 3He + natAg in particular. The identification of the modulations involves a technique that subtracts the bulk statistical background from the measured alpha spectra, in order for the modulations to become visible in the residuals. Due to insufficient knowledge of the background spectra, however, the presented evidence should only be regarded as preliminary and tentative.

  10. Concentrations Of Radon In Kindergartens And Schools In Like - Sen And Karlovac Counties

    International Nuclear Information System (INIS)

    Radolic, V.; Stanic, D.; Miklavcic, I.; Poje, M.; Muzevic, M.; Krpan, I.; Vukovic, B.

    2015-01-01

    Measurements of radon concentrations in schools and kindergartens were performed by means of passive, strippable, nuclear track etched detectors LR - 115 type II (Kodak - Pathe, France). The detectors are paired in the way that one detector (open detector), placed on the circumferential side of the plastic detector vessel, registers total number of alpha particles from radon and its short-lived progenies. At the same time, the other detector (diffusion detector) is placed inside the vessel and it registers only alpha particles emitted by radon. The average radon concentrations in kindergartens and schools of Lika-Senj County are 318 and 317 Bq m -3 while for Karlovac County they are 228 and 304 Bq m -3 respectively. Moreover, there are three schools in Karlovac County with the average radon concentration higher than 1000 Bq m -3 , which represents the action level for intervention measures in Croatia. Even more, there are 2.5 percent of rooms in kindergartens and 4 percent of rooms in schools in Lika - Senj County with measured radon concentrations higher than 1000 Bq m -3 . In Karlovac County there are 2.4 percent of such rooms in kindergartens and 7 percent in schools. Maps of spatial distribution of indoor radon concentrations for homes as well as for kindergartens and schools were created by using the Inverse Distance Weighting interpolation method. This is one of the useful methods for identifying radon prone areas. The authors propose a repetition of measurements in those kindergartens, schools and homes with higher radon concentrations in coordination with the local government. (author).

  11. A kinematically complete, interdisciplinary, and co-institutional measurement of the 19F(α,n) cross section for nuclear safeguards science

    Energy Technology Data Exchange (ETDEWEB)

    Peters, W. A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Univ. of Tennessee, Knoxville, TN (United States); Smith, M. S. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Pittman, S. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Thompson, S. J. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Clement, R. R. C. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Cizewski, J. A. [Rutgers Univ., New Brunswick, NJ (United States); Pain, S. D. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Febbraro, M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Univ. of Michigan, Ann Arbor, MI (United States); Chipps, K. A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Burcher, S. [Rutgers Univ., New Brunswick, NJ (United States); Manning, B. [Rutgers Univ., New Brunswick, NJ (United States); Reingold, C. [Rutgers Univ., New Brunswick, NJ (United States); Avetisyan, R. [Univ. of Notre Dame, IN (United States); Battaglia, A. [Univ. of Notre Dame, IN (United States); Chen, Y. [Univ. of Notre Dame, IN (United States); Long, A. [Univ. of Notre Dame, IN (United States); Lyons, S. [Univ. of Notre Dame, IN (United States); Marley, S. T. [Univ. of Notre Dame, IN (United States); Seymour, C. [Univ. of Notre Dame, IN (United States); Siegl, K. T. [Univ. of Notre Dame, IN (United States); Smith, M. K. [Univ. of Notre Dame, IN (United States); Strauss, S. [Univ. of Notre Dame, IN (United States); Talwar, R. [Univ. of Notre Dame, IN (United States); Bardayan, D. W. [Univ. of Notre Dame, IN (United States); Gyurjinyan, A. [Univ. of Notre Dame, IN (United States); Smith, K. [Univ. of Tennessee, Knoxville, TN (United States); Thornsberry, C.; Thompson, P.; Madurga, M. [Univ. of Tennessee, Knoxville, TN (United States); Stech, E. [Univ. of Notre Dame, IN (United States); Tan, W. P. [Univ. of Notre Dame, IN (United States); Wiescher, M. [Univ. of Notre Dame, IN (United States); Ilyushkin, S. [Colorado School of Mines, Golden, CO (United States); Tully, Z. [Tennessee Technological Univ., Cookeville, TN (United States); Grinder, M. M. [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2016-05-01

    Alpha particles emitted from the decay of uranium in a UF6 matrix can interact with fluorine and generate neutrons via the 19F(α,n)22Na reaction. These neutrons can be used to determine the uranium content in a UF6 storage cylinder. The accuracy of this self-interrogating, non-destructive assay (NDA) technique is, however, limited by the uncertainty of the 19F(α,n)22Na cross section. We have performed complementary measurements of the 19F(α,n)22Na reaction with both 4He and 19F beams to improve the precision of the 19F(α,n)22Na cross section over the alpha energy range that encompasses common actinide alpha decay needed for NDA studies. We have determined an absolute cross section for the 19F(α,n)22Na reaction to an average precision of 7.6% over the alpha energy range of 3.9 – 6.7 MeV. We utilized this cross section in a simulation of a 100 g spherical UF6 assembly and obtained a change in neutron emission rate values of approximately 10-12%, and a significant (factor of 3.6) decrease in the neutron emission rate uncertainty (from 50-51% to 13-14%), compared to simulations using the old cross section. Our new absolute cross section enables improved interpretations of NDAs of containers of arbitrary size and configuration.

  12. Multi-parametric approach towards the assessment of radon and thoron progeny exposures

    Energy Technology Data Exchange (ETDEWEB)

    Mishra, Rosaline, E-mail: rosaline@barc.gov.in, E-mail: rosaline.mishra@gmail.com; Sapra, B. K. [Radiological Physics and Advisory Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India); Mayya, Y. S. [Indian Institute of Technology, Mumbai (India)

    2014-02-15

    Conventionally, the dosimetry is carried out using radon and thoron gas concentration measurements and doses have been assigned using assumed equilibrium factors for the progeny species, which is inadequate pertaining to the variations in equilibrium factors and possibly due to significant thoron. In fact, since the true exposures depend upon the intricate mechanisms of progeny deposition in the lung, therefore an integrated approach for the assessment of progeny is essential. In this context, the recently developed deposition based progeny concentration measurement techniques (DTPS: Direct Thoron progeny sensors and DRPS: Direct Radon progeny sensors) appear to be best suited for radiological risk assessments both among occupational workers and general study populations. DTPS and DRPS consist of aluminized mylar mounted LR115 type passive detectors, which essentially detects the alpha particles emitted from the deposited progeny atoms on the detector surface. It gives direct measure of progeny activity concentrations in air. DTPS has a lower limit of detection limit of 0.1 Bq/m{sup 3} whereas that for DRPS is 1 Bq/m{sup 3}, hence are perfectly suitable for indoor environments. These DTPS and DRPS can be capped with 200-mesh type wire-screen to measure the coarse fraction of the progeny concentration and the corresponding coarse fraction deposition velocities as well as the time integrated fine fraction. DTPS and DRPS can also be lodged in an integrated sampler wherein the wire-mesh and filter-paper are arranged in an array in flow-mode, to measure the fine and coarse fraction concentration separately and simultaneously. The details are further discussed in the paper.

  13. Radiation effects in moist-air systems and the influence of radiolytic product formation on nuclear waste glass corrosion

    Energy Technology Data Exchange (ETDEWEB)

    Wronkiewicz, D.J.; Bates, J.K.; Buck, E.C.; Hoh, J.C.; Emery, J.W. [Argonne National Lab., IL (United States). Chemical Technology Div.; Wang, L.M. [Univ. of New Mexico, Albuquerque, NM (United States). Dept. of Geology

    1997-07-01

    Ionizing radiation may affect the performance of glass in an unsaturated repository site by interacting with air, water vapor, or liquid water to produce a variety of radiolytic products. Tests were conducted to examine the effects of radiolysis under high gas/liquid ratios. Results indicate that nitrate is the predominant radiolytic product produced following both gamma and alpha radiation exposure, with lesser amounts of nitrite and carboxylic acids. The formation of nitrogen acids during exposure to long-lived, alpha-particle-emitting transuranic elements indicates that these acids may play a role in influencing nuclear waste form reactions in a long-term unsaturated disposal scenario. Experiments were also conducted with samples that simulate the composition of Savannah River Plant nuclear waste glasses. Radiolytic product formation in batch tests (340 m{sup {minus}1}, 90 C) resulted in a small increase in the release rates of many glass components, such as alkali and alkaline earth elements, although silicon and uranium release rates were slightly reduced indicating an overall beneficial effect of radiation on waste form stability. The radiolytic acids increased the rate of ion exchange between the glass and the thin film of condensate, resulting in accelerated corrosion rates for the glass. The paragenetic sequence of alteration phases formed on both the irradiated and nonirradiated glass samples reacted in the vapor hydration tests matches closely with those developed during volcanic glass alteration in naturally occurring saline-alkaline lake systems. This correspondence suggests that the high temperatures used in these tests have not changed the underlying glass reaction mechanism relate to that which controls glass reactions under ambient surficial conditions.

  14. Contribution to the study of radon risk assessment - Use of Solid State Nuclear Tracks Detectors (SSNTD) for the measurement of radon in buildings

    International Nuclear Information System (INIS)

    RALAIARISOA, H.L

    2004-01-01

    222 Rn is a natural radioactive gas, originating from the decay of 226 Ra. Both of these radionuclides are elements of 238 U series. Uranium is naturally present in the rocks and soils, therefore radon is always present too because it is a soil gas. Radon takes the most important part in man exposure to natural sources of ionizing radiations. Moreover, it causes lung cancer. It can accumulate in confined environments such as buildings, so that its inhalation is a potential risk for human health. Thus radon measurement is necessary for radiation protection. Integrated measurement using Solid State Nuclear Tracks Detector (SSNTD) is a very common method for radon measurement in buildings because of the low cost of the detectors and their easy application. The measurement technics are based on the interaction of alpha particles emitted by radon with a polymer. Alpha particles produce in the polymer latent tracks, which need chemical revelation to be observable with optical microscopy. The number of revealed tracks is proportionnal to the average volumic activity of 222 Rn corresponding to the time exposure of the detectors.The aim of this thesis work is the continuation of previous study on the preliminary investigations of radon levels in the city of Antananarivo, and to extend this study in Antsirabe, which has been shown as a region of interest. The levels of radon measured in buildings in Antananarivo and Antsirabe are typical values of indoor radon concentration. The average values of concentrations are inferior to 60 Bq.m - 3. The health risk is negligible but not nul. A typical protocol of radon level measurement in Malagasy buildings is suggested to allow the implementation of a risk management policy related to radon within the Malagasy context. [fr

  15. Radon in the Houses of Virovitica and Podravina County

    International Nuclear Information System (INIS)

    Varga Pajtler, M.; Miklavcic, I.; Poje, M.; Radolic, V.; Vukovic, B.; Ivkovic, I.; Jurisic, D.

    2011-01-01

    222Ra is the gaseous radioactive product of the decay of radium isotope 226Ra which is present in soil. Radon atoms that are released from the ground are transported by diffusion and then released in the atmosphere. Radon entries into buildings by advection that is driven by the pressure difference between the building and the ground around the foundation. The aim of this study was to measure radon concentrations in the houses of Virovitica and Podravina county. The measurements were performed by means of two passive track detectors LR-115 (Kodak-Pathe, France), one of which (the open detector) detected total number of alpha-particles of radon and its short-lived progeny, while the other (diffusion detector) registerd tracks only of alpha particles emitted by radon. After being exposed to radiation, the LR-115 detectors were etched in 10 % NaOH aqueous solution at 60 degrees of C for 120 minutes and the detector tracks were counted. Radon concentrations in air were determined according to equation (1), where D 0 was the number of tracks per one day of exposure of the open detector and k is the sensitivity coefficient od the person that counted the tracks. For the track densities D and D 0 of the open and diffusion detectors, respectively, the equilibrium factor was calculated according to equation (2), with the parameters a = 0,50, and b = -0,53. Obtained value for the equilibrium factor was 0,85. Measurements gave radon concentrations in the range of 5.7 - 187.7 Bq m -3 . Average annual effective radon dose for population of Virovitica and Podravina county is 1,5 mSv. (author)

  16. In vitro experimental (211)At-anti-CD33 antibody therapy of leukaemia cells overcomes cellular resistance seen in vivo against gemtuzumab ozogamicin.

    Science.gov (United States)

    Petrich, Thorsten; Korkmaz, Zekiye; Krull, Doris; Frömke, Cornelia; Meyer, Geerd J; Knapp, Wolfram H

    2010-05-01

    Monoclonal anti-CD33 antibodies conjugated with toxic calicheamicin derivative (gemtuzumab ozogamicin, GO) are a novel therapy option for acute myeloid leukaemia (AML). Key prognostic factors for patients with AML are high CD33 expression on the leukaemic cells and the ability to overcome mechanisms of resistance to cytotoxic chemotherapies, including drug efflux or other mechanisms decreasing apoptosis. Alpha particle-emitting radionuclides overwhelm such anti-apoptotic mechanisms by producing numerous DNA double-stranded breaks (DSBs) accompanied by decreased DNA repair. We labelled anti-CD33 antibodies with the alpha-emitter (211)At and compared survival of leukaemic HL-60 and K-562 cells treated with the (211)At-labelled antibodies, GO or unlabelled antibodies as controls. We also measured caspase-3/7 activity, DNA fragmentation and necrosis in HL-60 cells after treatment with the different antibodies or with free (211)At. The mean labelling ratio of (211)At-labelled antibodies was 1:1,090 +/- 364 (range: 1:738-1:1,722) in comparison to 2-3:1 for GO. Tumour cell binding of (211)At-anti-CD33 was high in the presence of abundant CD33 expression and could be specifically blocked by unlabelled anti-CD33. (211)At-anti-CD33 decreased survival significantly more than did GO at comparable dilution (1:1,000). No significant differences in induction of apoptosis or necrosis or DNA DSB or in decreased survival were observed after (211)At-anti-CD33 (1:1,090) versus GO (1:1) treatment. Our results suggest that (211)At is a promising, highly cytotoxic radioimmunotherapy in CD33-positive leukaemia and kills tumour cells more efficiently than does calicheamicin-conjugated antibody. Labelling techniques leading to higher chemical yield and specific activities must be developed to increase (211)At-anti-CD33 therapeutic effects.

  17. Experimental models in the rat for the assessment of local and systemic behaviour and decorporation of MOX after contamination by wounding

    International Nuclear Information System (INIS)

    Griffiths, N.M.; Van der Meeren, A.; Abram, M.C.; Chau, Q.; Coudert, S.; Renault, D.; Wilk, J.C.; Guichet, C.; Helfer, N.; Angulo-Mora, J.

    2013-11-01

    Accidental contamination of nuclear industry workers by alpha particle-emitting actinides (plutonium; Pu, americium; Am) can occur after wounding. Transfer from the wound depends on contaminant physicochemical properties, wound type and anatomical location. These factors and wound activity levels direct the ensuing medical approaches. The principal objective of this research program, carried out in the Laboratoire de Radio-Toxicologie (CEA/DSV) in collaboration with AREVA NC, was to establish models of actinide-contaminated wounds in the rat using multidisciplinary approaches. Rats were contaminated by MOX (7.1% Pu by mass) or Pu nitrate or Am nitrate, either by subcutaneous implantation of an agarose gel containing the radioelement or following incision of the hind limb muscles. Actinide urinary excretion, wound, tissue levels and effects of decorporant regimens including wound excision were evaluated. In both experimental models following MOX contamination, urinary Am excretion was greater than Pu, and bone Pu and Am retention increased significantly with time. Moreover after Pu or Am nitrate contamination, Am excretion and tissue retention was greater than Pu again reflecting the higher solubility of Am. Coherent with the insoluble nature of oxide forms, tissue Am or Pu levels were much lower after MOX compared to those seen after nitrates. Wound site actinide retention was also much higher after MOX contamination. Repeated systemic DTPA increased actinide urinary excretion and decreased tissue retention, as did single or repeated local DTPA. Pu urinary excretion was transiently increased after wound excision but no further Pu organ retention was observed. In conclusion, several different experimental models have been developed in the rat to simulate actinide wound contamination. Information obtained on Pu and Am behavior either at the wound site or at distant organs allowed the discrimination between different physicochemical actinide forms and evaluation of

  18. Calibration of SSNDT detectors for radon measurements

    International Nuclear Information System (INIS)

    Takahashi, Laura C.; Santos, Talita O.; Pinheiro, Rose Mary M.; Rocha, Zildete

    2017-01-01

    The methods and instrumentation used to measure the concentration of radon need to be calibrated to obtain accurate results. The Nuclear Track Detector is considered the main method of analysis of radon research. Thus, the Natural Radioactivity Laboratory of the Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG, Brazil) uses the detector CR-39 (Landauer) to measure the concentration of radon in homes, workplaces, underground mines, soils and in environment. Epidemiological studies reveal the strong relationship between lung cancer and radon exposure. Therefore, it is important to monitor this gas and its progeny in order to assess the radiological risk. The alpha particles emitted by radon and its progeny leave traces on CR-39 due to Coulombian interactions with the atoms of the material. The liquid density of traces is converted to radon concentration by means of a calibration factor obtained in calibrated systems. This work aims to determine the LRN / CDTN calibration factor. To do so, the CR-39 detectors were placed inside the calibration chambers, along with two AlphaGUARD (Saphymo GmbH) detectors and Ra-266 sources with activities of 3,379 kBq or 0.483 kBq, referenced by NIST. From this, six levels of exposure were obtained, which were: 44 kBq.d.m 3 , 4 kBq.d.m 3 , 3 kBq.d.m 3 , 15 kBq.d.m 3 , 30 kBq.d.m 3 , 26 kBq.d.m 3 . The conversion factor between the liquid density of traces and the total exposure time obtained was K = 52.028 ± 0.752 [(trace density.cm -2 ) / (kBq.d.m -3 )]. After the determination of the conversion factor, it was used to measure the concentration of radon in underground mines, obtaining concentration results between 122 ± 24 and 7384 ± 517 kBq.m -3

  19. Determination of radon in soil and water in parts of Accra, and generation of preliminary radon map for Ghana

    International Nuclear Information System (INIS)

    Osei, Peter

    2016-07-01

    The research was focused on determining the radon levels in soil and water in parts of Accra, generate a preliminary radon map for Ghana and estimate a pilot reference level for the country, using the data obtained from this research and collated data from other researchers. The radon gas measurement was done with the passive method, using the SSNTDs which are sensitive to alpha particles emitted by radon. Cellulose nitrate LR – 115 type II alpha particle detectors were used. The detectors were chemically etched in a 2.5 M NaOH solution at a temperature of 60 °C for 90 minutes, after two weeks and two months of exposure to soil and water respectively. The images of the etched detectors were acquired by means of a scanner and then tracks counted with ImageJ software. Inverse Distance Weighing (IDW) method of ArcGIS 10.2 was used to spatially distribute the radon concentration on a map. The average soil radon concentration in the study area ranges from 0.191 kBqm"-"3 to 3.416 kBqm"-"3 with a mean of 1.193 kBqm"-"3. The radon concentration in water from the study area ranges from 0.00346 BqL"-"1 to 0.00538 BqL"-"1 with an average of 0.00456 BqL"-"1. A strong negative correlation has been established between radon in soil and water in the study area. The preliminary national average indoor, water and soil radon concentrations are 137 Bqm"-"3, 361.93 Bqm"-"3 and 3716.74 Bqm"-"3 respectively. The average levels of water and indoor radon exceeded WHO’s reference level of 100 Bqm"-"3. Accordingly, the pilot national indoor radon reference level for Ghana is set as 200 Bqm"-"3. (au)

  20. In vitro experimental {sup 211}At-anti-CD33 antibody therapy of leukaemia cells overcomes cellular resistance seen in vivo against gemtuzumab ozogamicin

    Energy Technology Data Exchange (ETDEWEB)

    Petrich, Thorsten; Korkmaz, Zekiye; Krull, Doris; Meyer, Geerd J.; Knapp, Wolfram H. [Hanover University School of Medicine, Department of Nuclear Medicine, Hanover (Germany); Froemke, Cornelia [Hanover University School of Medicine, Department of Biometry, Hanover (Germany)

    2010-05-15

    Monoclonal anti-CD33 antibodies conjugated with toxic calicheamicin derivative (gemtuzumab ozogamicin, GO) are a novel therapy option for acute myeloid leukaemia (AML). Key prognostic factors for patients with AML are high CD33 expression on the leukaemic cells and the ability to overcome mechanisms of resistance to cytotoxic chemotherapies, including drug efflux or other mechanisms decreasing apoptosis. Alpha particle-emitting radionuclides overwhelm such anti-apoptotic mechanisms by producing numerous DNA double-stranded breaks (DSBs) accompanied by decreased DNA repair. We labelled anti-CD33 antibodies with the alpha-emitter {sup 211}At and compared survival of leukaemic HL-60 and K-562 cells treated with the {sup 211}At-labelled antibodies, GO or unlabelled antibodies as controls. We also measured caspase-3/7 activity, DNA fragmentation and necrosis in HL-60 cells after treatment with the different antibodies or with free {sup 211}At. The mean labelling ratio of {sup 211}At-labelled antibodies was 1:1,090 {+-} 364 (range: 1:738-1:1,722) in comparison to 2-3:1 for GO. Tumour cell binding of {sup 211}At-anti-CD33 was high in the presence of abundant CD33 expression and could be specifically blocked by unlabelled anti-CD33. {sup 211}At-anti-CD33 decreased survival significantly more than did GO at comparable dilution (1:1,000). No significant differences in induction of apoptosis or necrosis or DNA DSB or in decreased survival were observed after {sup 211}At-anti-CD33 (1:1,090) versus GO (1:1) treatment. Our results suggest that {sup 211}At is a promising, highly cytotoxic radioimmunotherapy in CD33-positive leukaemia and kills tumour cells more efficiently than does calicheamicin-conjugated antibody. Labelling techniques leading to higher chemical yield and specific activities must be developed to increase {sup 211}At-anti-CD33 therapeutic effects. (orig.)

  1. Lutetium 177-Labeled Cetuximab Evaluation for Radioimmunotherapeutic Applications

    Directory of Open Access Journals (Sweden)

    Kamal Yavari

    2012-06-01

    Full Text Available Background & Objectives: The monoclonal antibody cetuximab binds to EGFR and thus provides an opportunity to create both imaging and therapeutic modalities that target this receptor. The potential of cetuximab as a radioimmunoconjugate was investigated and quality control tests (in vitro and in vivo were performed as a first step in the production of a new radiopharmaceutical.   Methods : Cetuximab solution was dialyzed and concentrated using an Amicon Ultra-15 filter. Purified antibody was labeled with lutetium-177 using the acyclic bifunctional chelator, DOTA-NHS, and radioimmunoconjugates were purified by PD10 columns. Radiochemical purity and stability in buffer and human blood serum were determined using thin layer chromatography. Integrity of the radiolabeled complex was checked by SDS-PAGE. Preliminary biodistribution studies in normal mice model performed to determine radioimmunoconjugates distribution up to 72h.   Results: The radiochemical purity of the complex was 98±1%. The stabilities in phosphate buffer and in human blood serum at 96 hours post-preparation were 96±2 % and 78±4%, respectively. All of the samples, controls and radiolabeled antibodies, showed a similar pattern of migration in the gel electrophoresis. Biodistribution of Lu177-cetuximab was evaluated in normal mice and the highest ID/g% was observed in the blood (13.2±1.3% at 24 hours and the liver (9.1±1.3% at 24 hours.   Conclusion: Our results show that DOTA-cituximab can be labeled with 177Lu. Lu177-cetuximab has sufficient stability and retains its integrity. The new complex could be considered for further evaluation in animals and possibly in humans as a new radiopharmaceutical for use in radioimmunotherapy of cancers.

  2. Modeling of biodistribution of 90 Y-DOTA-hR3 by using artificial intelligence techniques

    International Nuclear Information System (INIS)

    Ondarse, Dianelys; Quiza, Ramon; Leyva, Rene; Zamora, Minely; Ducat, Luis; Hernandez, Ignacio; Alonso, Luis Michel

    2011-01-01

    In this work the biodistribution of radioimmunoconjugate 9 0Y-DOTA-hR3 was modeled by using an artificial neural network. In vivo stability of 9 0Y-DOTA-hR3 was determined in healthy male Wistar rats at 4, 24 and 48 hours, in different organs. A model describing the relationship between, by one hand, the incorporated dose and, by the other hand, organ and time was developed by using a multilayer perceptron neural network. Adjusted model was analyzed by several statistical tests. Outcomes shown that proposed neural model describes the relationship between the studied variables in a proper way. (Author)

  3. Pharmacokinetics and dose estimates following intrathecal administration of 131I-monoclonal antibodies for the treatment of central nervous system malignancies

    International Nuclear Information System (INIS)

    Papanastassiou, Varnavus; Pizer, Barry L.; Chandler, Christopher L.; Zananiri, Tony F.; Kemshead, John T.; Hopkins, Kirsten I.

    1995-01-01

    Purpose: Treatment of malignant disease in the central nervous system (CNS) with systemic radiolabeled monoclonal antibodies (MoAbs) is compromised by poor penetration into the cerebrospinal fluid (CSF), limited diffusion into solid tumors, and the generation of anti-mouse antibodies. To attempt to avoid these problems we have treated patients with diffuse neoplastic meningitis with radioimmunoconjugates injected directly into the intrathecal space. Methods and Materials: Tumor-specific MoAbs were conjugated to Iodine-131 ( 131 I) (629-3331 MBq) by the Iodogen technique, and administered via an intraventricular reservoir. A clinical response rate of approximately 33% was achieved, with better results in more radiosensitive tumors. Here, we present detailed pharmacodynamic data on patients receiving this intracompartmental targeted therapy. Results: Elimination from the ventricular CSF appeared biphasic, with more rapid clearance occurring in the first 24 h. Radioimmunoconjugate entered the subarachnoid space and subsequently the vascular compartment. From this information, the areas under the effective activity curves for ventricular CSF, blood, and subarachnoid CSF were calculated to permit dosimetry. Critical organ doses were calculated using conventional medical internal radiation dose (MIRD) formalism. Where available, S-values were taken from standard tables. To calculate the doses to CSF, brain, and spinal cord, S-values were evaluated using the models described in the text. Conclusion: A marked advantage could be demonstrated for the dose delivered to tumor cells within the CSF as compared to other neural elements

  4. Development and evaluation of copper-67 and samarium-153 labeled conjugates for tumor radioimmunotherapy

    International Nuclear Information System (INIS)

    Srivastava, S.C.; Mausner, L.F.; Mease, R.C.; Meinken, G.E.; Joshi, V.; Kolsky, K.; Sweet, M.; Steplewski, Z.

    1995-01-01

    The potential of utilizing receptor-specific agents such as monoclonal antibodies (MAb), and MAb-derived smaller molecules, as carriers of radionuclides for the selective destruction of tumors has stimulated much research activity. The success of such applications depends on many factors, especially the tumor binding properties of the antibody reagent, the efficiency of labeling and in-vivo stability of the radioconjugate and, on the careful choice of the radionuclide best suited to treat the tumor under consideration. The radiolabeled antibody technique for radioimmunotherapy (RIT), however, has experienced many limitations, and its success has not matched the expectations that were raised more than a decade ago. The problems that have been identified include: (i) degradation of antibody immunoreactivity resulting from chemical manipulations required for labeling; (ii) lack of suitable radioisotopes and methods for stable attachment of the radiolabel; (iii) in-vivo instability of the radioimmunoconjugates; (iv) excessive accumulation of activity in non-target locations; and (v) lack of radioimmunoconjugate accessibility to cells internal to a tumor mass. A careful choice of the radionuclide(s) best suited to treat the tumor under consideration is one of the most important requirements for successful radioimmunotherapy. This study evaluates copper 67 and samarium 153 for tumor radioimmunotherapy

  5. Development of radioinmunoconjugate 90Y-DOTA-nimotuzumab-Fab for therapy of EGFR over expressing tumors

    International Nuclear Information System (INIS)

    Rodriguez, A. M.; Alonso, L. M.; Gongora, M.; Leyva, R.; Solana, A.

    2015-01-01

    Many monoclonal antibodies conjugated with 1,4,7,10-tetraaza cyclododecane-N, N', N'', N'''-tetraacetic acid (DOTA) and radiolabeled with 90 Y, have been used for radioimmunotherapy. As know IgG molecules are heavy proteins with a molecular weight of approximately 150 kDa. Accordingly, intact IgG antibodies may have significant slow kinetics biodistribution and severely limited properties of tissue penetration. Antibody fragments labeled with radio metals could be promising radiopharmaceuticals for imaging and non-invasive therapy due to its high affinity to the tumor, the lack of effector function and rapid pharmacokinetic. In this work, the nimotuzumab Fab fragment was obtained by cleavage with papain in molar excess. After separating the reaction mixture in three steps using affinity, size exclusion and ion exchange chromatography; the Fab fragment showed high values of purity, integrity and identity. The Fab fragment was derivatized with DOTA and labeled with 90 Y. The radioimmunoconjugate with high radiochemical yield was assessed by in vitro stability with an excess of 50mM DTPA. The development of 90 Y-DOTA-Nimotuzumab-Fab radioimmunoconjugate allows to count on as a potential agent for radioimmunotherapy. (Author)

  6. Improved radioimmunotherapy of hematologic malignancies

    International Nuclear Information System (INIS)

    Press, O.W.

    1989-01-01

    In the seven months which have elapsed since initial funding of this project, considerable progress has been made towards achieving the objectives of this research. These objectives include: to study the relative rates of metabolic degradation of radiolabeled monoclonal antibodies (mAbs) targeting tumor associated antigens; to examine the effects of lysomotropic amines (ammonium chloride, chloroquine, amantadine), carboxylic ionophores (monensin), and thionamides (propylthiouracil), on the retention of radiolabeled mAbs by tumor cells; to identify the subcellular site of radioimmunoconjugate degradation, and to quantify the sizes of the fragments generated by intracellular metabolism of radiolabeled mAbs; to examine the effects of lysomotropic agents on the quality of external gamma camera imaging and radiation dosimetry generated in tumor-bearing mice injected with radiolabeled mAbs; to examine the effects of lysomotropic agents on the radiotherapeutic efficacy of radiolabeled mAbs in murine tumors and human tumors xenografted to nude mice; and to compare the effects of lysomotropic agents on the degradation of radioimmunoconjugates made with different radionuclides and different conjugation methods

  7. Therapeutic efficacy and toxicity of {sup 225}Ac-labelled vs. {sup 213}Bi-labelled tumour-homing peptides in a preclinical mouse model of peritoneal carcinomatosis

    Energy Technology Data Exchange (ETDEWEB)

    Essler, Markus; Gaertner, Florian C.; Blechert, Birgit; Senekowitsch-Schmidtke, Reingard; Seidl, Christof [Technische Universitaet Muenchen, Department of Nuclear Medicine, Munich (Germany); Neff, Frauke [Helmholtz Zentrum Muenchen, Institute of Pathology, Neuherberg (Germany); Bruchertseifer, Frank; Morgenstern, Alfred [Institute for Transuranium Elements, European Commission, Joint Research Centre, Karlsruhe (Germany)

    2012-04-15

    Targeted delivery of alpha-particle-emitting radionuclides is a promising novel option in cancer therapy. We generated stable conjugates of the vascular tumour-homing peptide F3 both with {sup 225}Ac and {sup 213}Bi that specifically bind to nucleolin on the surface of proliferating tumour cells. The aim of our study was to determine the therapeutic efficacy of {sup 225}Ac-DOTA-F3 in comparison with that of {sup 213}Bi-DTPA-F3. ID{sub 50} values of {sup 213}Bi-DTPA-F3 and {sup 225}Ac-DOTA-F3 were determined via clonogenic assays. The therapeutic efficacy of both constructs was assayed by repeated treatment of mice bearing intraperitoneal MDA-MB-435 xenograft tumours. Therapy was monitored by bioluminescence imaging. Nephrotoxic effects were analysed by histology. ID{sub 50} values of {sup 213}Bi-DTPA-F3 and {sup 225}Ac-DOTA-F3 were 53 kBq/ml and 67 Bq/ml, respectively. The median survival of control mice treated with phosphate-buffered saline was 60 days after intraperitoneal inoculation of 1 x 10{sup 7} MDA-MB-435 cells. Therapy with 6 x 1.85 kBq of {sup 225}Ac-DOTA-F3 or 6 x 1.85 MBq of {sup 213}Bi-DTPA-F3 prolonged median survival to 95 days and 97 days, respectively. While F3 labelled with short-lived {sup 213}Bi (t{sub 1/2} 46 min) reduced the tumour mass at early time-points up to 30 days after treatment, the antitumour effect of {sup 225}Ac-DOTA-F3 (t{sub 1/2} 10 days) increased at later time-points. The difference in the fraction of necrotic cells after treatment with {sup 225}Ac-DOTA-F3 (43%) and with {sup 213}Bi-DTPA-F3 (36%) was not significant. Though histological analysis of kidney samples revealed acute tubular necrosis and tubular oedema in 10-30% of animals after treatment with {sup 225}Ac-DOTA-F3 or {sup 213}Bi-DTPA-F3, protein casts were negligible (2%), indicating only minor damage to the kidney. Therapy with both {sup 225}Ac-DOTA-F3 and {sup 213}Bi-DTPA-F3 increased survival of mice with peritoneal carcinomatosis. Mild renal toxicity of both

  8. Alpha radioactivity in Indian cement samples

    International Nuclear Information System (INIS)

    Nain, M.; Chauhan, R. P.; Chakarvarti, S. K.

    2006-01-01

    The essential constituents of radioactive and each of cements like lime, silica and alumina are derived from earth's crust in which radioactive elements like uranium, thorium etc are also present in varying amounts almost everywhere. These two elements are considered as the parent elements of uranium and thorium radioactive decay series in which radon and thoron are produced respectively as decay products. In the present study the samples of ordinary Portland cement , Portland pozzolana cement and some other cementious finishing materials like white cement, Plaster of Paris , cement putty etc were collected and analysed for radium and radon concentrations along with radon exhalation rates. Materials and Methods: Alpha sensitive LR-115 Type II plastic track detectors commonly known as S olid State Nuclear Track Detectors w ere used to measure the radium and radon concentration. The alpha particles emitted from the radon causes the radiation damaged tracks. The Chemical etching in NaOH at 60 C for about 90 minutes was done to reveal these latent tracks, which were then scanned and counted by an optical microscope of suitable magnification. By calculating the track density of registered tracks, the radon and radium concentrations along with exhalation rate of radon, were determined using required formulae. Results: The radon and radium concentration in various brands of cements found to vary from 333±9.9 to 506±13.3 Bq m-3 and from 3.7±0.1 to 5.6±0.2 Bq k g-1 while in various cementious finishing materials used in the construction, these were found to vary from 378±19.7 to 550±9.8 Bq m-3 and from 4.2±0.2 to 6.1±0.1 Bq Kg-1, respectively. Based on the data the mass and surface exhalation rates were also calculated Conclusion: The measurements indicate that there is marginal variation of the concentration of radium and radon in various brands of cements in India with lower levels in the cement samples having red oxide and higher levels in fly ash based cement

  9. Fetal dosimetry from natural alpha emitters

    Energy Technology Data Exchange (ETDEWEB)

    Purnell, S.J

    1999-09-01

    The size of marrow cavities in fetal vertebra, rib and sternum was investigated using an image analysis system. The average chord lengths through marrow spaces in the vertebrae were found to increase approximately linearly with gestational age from 140 {mu}m at 20 weeks to 300 {mu}m at 40 weeks. Average chord lengths through marrow spaces in fetal rib and sternum were 330 {mu}m at 35 weeks in both cases. These results can be compared with an average chord length across marrow spaces in adult vertebra of 1172 {mu}m. At natural background UK exposure, activity concentrations of supported {sup 210}Po in fetal bone of 0.075 Bq kg{sup -1} and 0.15 Bq kg{sup -1} at mid- and late gestation respectively were calculated. Monte Carlo simulations modelling the paths of alpha-particles in fetal vertebra gave a total alpha-radiation dose to marrow over the second and third trimesters of 32.0 {+-} 0.8 {mu}Sv with the {sup 210}Po in bone contributing 8.9 {+-} 0.9 {mu}Sv. The dose to primitive haemopoietic stem cells, the target cells for acute lymphoblastic leukaemia, and the survival of these stem cells following a hit by an alpha-particle was investigated, also using Monte Carlo simulations. Alpha-particles emitted from bone and marrow contributed an average dose of 1.9 Gy to stem cells with a nuclear diameter of 3.8 {mu}m. This study has estimated that 1% of babies born each year are born with a mutated primitive haemopoietic stem cell due to in utero irradiation from high LET radiation. That is 7,320 babies compared to an estimated 300 incidences of cALL each year initiated in utero. The probability that a mutated cell will go on to give rise to leukaemia is unknown but it would seem not unlikely that irradiation in utero plays a substantial part in the induction of childhood leukaemia. (author)

  10. Skeletal dosimetry models for alpha-particles for use in molecular radiotherapy

    Science.gov (United States)

    Watchman, Christopher J.

    Molecular radiotherapy is a cancer treatment methodology whereby a radionuclide is combined with a biologically active molecule to preferentially target cancer cells. Alpha-particle emitting radionuclides show significant potential for use in molecular radiotherapy due to the short range of the alpha-particles in tissue and their high rates of energy deposition. Current radiation dosimetry models used to assess alpha emitter dose in the skeleton were developed originally for occupational applications. In medical dosimetry, individual variability in uptake, translocation and other biological factors can result in poor correlation of clinical outcome with marrow dose estimates determined using existing skeletal models. Methods presented in this work were developed in response to the need for dosimetry models which account for these biological and patient-specific factors. Dosimetry models are presented for trabecular bone alpha particle dosimetry as well as a model for cortical bone dosimetry. These radiation transport models are the 3D chord-based infinite spongiosa transport model (3D-CBIST) and the chord-based infinite cortical transport model (CBICT), respectively. Absorbed fraction data for several skeletal tissues for several subjects are presented. Each modeling strategy accounts for biological parameters, such as bone marrow cellularity, not previously incorporated into alpha-particle skeletal dosimetry models used in radiation protection. Using these data a study investigating the variability in alpha-particle absorbed fractions in the human skeleton is also presented. Data is also offered relating skeletal tissue masses in individual bone sites for a range of ages. These data are necessary for dose calculations and have previously only been available as whole body tissue masses. A revised 3D-CBIST model is also presented which allows for changes in endosteum thickness to account for revised target cell location of tissues involved in the radiological

  11. Radiobiological effects on transcriptome in mouse thyroid after irradiation with AT-211

    International Nuclear Information System (INIS)

    Rudqvist, N.; Parris, T.; Nemes, S.; Helou, K.; Forssell-Aronsson, E.

    2013-01-01

    The full text of the publication follows. At-211 is an alpha particle emitting halogen used in radiation therapy, and is accumulated in the thyroid gland. Knowledge of biological processes that occur after irradiation is of high value in radiation therapy. Also, the behavior of thyrocytes after At-211 irradiation is to a high degree unknown. Female BALB/c nude mice were i.v. injected with At-211; absorbed dose to the thyroid was 0.05-32 Gy. Total RNA was extracted from pooled thyroids that were removed 24 hours after injection and processed in triplicate using Illumina Mouse Ref-8 Whole-Genome Expression Bead-chips. Nexus Expression 2.0 was used for data analysis. Compared with non-irradiated controls, 1225 (887 Down, 338 Up), 1636 (1156 Down, 480 Up), 544 (260 Down, 284 Up), 575 (163 Down, 412 Up) and 425 (132 Down, 293 Up) transcripts were affected for 0.05, 0.5, 1.4, 11 and 32 Gy, respectively. A total of 130 transcripts were altered in all groups (40 Down, 46 Up). For apoptosis, 36, 56, 11, 17 and 10 transcripts were differently regulated for 0.05, 0.5, 1.4, 11 and 32 Gy, respectively. Overall, 20, 23, 26, 21 and 14 biological processes were affected for 0.05, 0.5, 1.4, 11 and 32 Gy, respectively. Of these, only 2 were shared by all irradiated groups. Many similarities were obtained between 0.05 and 0.5 Gy and between 11 and 32 Gy, while the effects at 1.4 Gy deviated more from the other groups. Conclusively, high absorbed doses that mediate larger DNA damages altered genes involved in cytoskeleton reorganization. In contrast, low doses which produce few DNA damages altered more genes involved in cellular maintenance and metabolism. Interestingly, there seemed to be a transition phase around 1.4 Gy in the type of cellular response to DNA damages. Further work is needed in order to gain a complete understanding of the processes involved. (authors)

  12. Determination of alpha dose rate profile at the HLW nuclear glass/water interface

    Energy Technology Data Exchange (ETDEWEB)

    Mougnaud, S., E-mail: sarah.mougnaud@cea.fr [CEA Marcoule, DEN/DTCD/SECM, BP 17171, 30207 Bagnols-sur-Cèze cedex (France); Tribet, M.; Rolland, S. [CEA Marcoule, DEN/DTCD/SECM, BP 17171, 30207 Bagnols-sur-Cèze cedex (France); Renault, J.-P. [CEA Saclay, NIMBE UMR 3685 CEA/CNRS, 91191 Gif-sur-Yvette cedex (France); Jégou, C. [CEA Marcoule, DEN/DTCD/SECM, BP 17171, 30207 Bagnols-sur-Cèze cedex (France)

    2015-07-15

    Highlights: • The nuclear glass/water interface is studied. • The way the energy of alpha particles is deposited is modeled using MCNPX code. • A model giving dose rate profiles at the interface using intrinsic data is proposed. • Bulk dose rate is a majoring estimation in alteration layer and in surrounding water. • Dose rate is high in small cracks; in larger ones irradiated volume is negligible. - Abstract: Alpha irradiation and radiolysis can affect the alteration behavior of High Level Waste (HLW) nuclear glasses. In this study, the way the energy of alpha particles, emitted by a typical HLW glass, is deposited in water at the glass/water interface is investigated, with the aim of better characterizing the dose deposition at the glass/water interface during water-induced leaching mechanisms. A simplified chemical composition was considered for the nuclear glass under study, wherein the dose rate is about 140 Gy/h. The MCNPX calculation code was used to calculate alpha dose rate and alpha particle flux profiles at the glass/water interface in different systems: a single glass grain in water, a glass powder in water and a water-filled ideal crack in a glass package. Dose rate decreases within glass and in water as distance to the center of the grain increases. A general model has been proposed to fit a dose rate profile in water and in glass from values for dose rate in glass bulk, alpha range in water and linear energy transfer considerations. The glass powder simulation showed that there was systematic overlapping of radiation fields for neighboring glass grains, but the water dose rate always remained lower than the bulk value. Finally, for typical ideal cracks in a glass matrix, an overlapping of irradiation fields was observed while the crack aperture was lower than twice the alpha range in water. This led to significant values for the alpha dose rate within the crack volume, as long as the aperture remained lower than 60 μm.

  13. Radioactive contamination and health risk assessment due to burning of coal in thermal energy generation

    International Nuclear Information System (INIS)

    Kant, K.

    2008-01-01

    Full text: Radon being a ubiquitous air pollutant has global impact and its monitoring in the environment at work places is essential from health and hygiene point of view. In thermal power plants, a lot of coal is burnt which contains radionuclides which are released into the environment and are hazardous. Radon is the main culprit in the local radioactive contamination of the environment due to burning of coal in thermal energy generation. It has been reported by several researchers (Nikl and Vegvari 1992, Bodizs et al. 1992) that the concentrations of the isotopes U 238 and Ra 226 become 3-5 times more than those in the coal itself in the coal slag and fly ash obtained by burning the coal in coal fired power plants. Several researchers have reported radon levels in thermal power plants (Bodizs et al. 1992, Rawat et al. 1991, Nikl and Vevgari 1992, Papastefanou and Charalanbous 1979, Kant et al. 2001). Keeping in view the environmental pollution caused due to the burning of coal in thermal power stations, there is an upsurge in the establishment of nuclear and gas turbine power stations in recent times. An increased share of gas and nuclear in power generation could lead to lower emissions. Also, considerable emphasis is being laid on developing non-polluting and renewable energy sources like water, air, solar energy and others. In this study, measurement of radon and its progeny levels was carried out over long integrated times in thermal power plant in Haryana by using LR-115, Type- II (Kodak Pathe, France), plastic track detectors commonly known as solid state nuclear track detectors (SS NTDs). Alpha particles emitted from radon cause radiation damage tracks, which were subsequently revealed by chemical etching in NaOH. These alpha tracks registered were counted by optical microscope at suitable magnification and converted into radon concentration. The findings indicate that it is very important to carry out these studies and the results of the full study will

  14. WE-FG-BRA-10: Radiodosimetry of a Novel Alpha Particle Therapy Targeted to Uveal Melanoma: Absorbed Dose to Organs in Mice

    Energy Technology Data Exchange (ETDEWEB)

    Tichacek, Christopher J.; Tafreshi, Narges K.; Budzevich, Mikalai M.; Ruiz, Epifanio [Small Animal Imaging Core, Tampa, FL (United States); Wadas, Thaddeus J. [Wake Forest School of Medicine, Departments of Radiology and Cancer Biology, Winston-Salem, NC (United States); McLaughlin, Mark L. [Department of Chemistry, Tampa, FL (United States); H. Lee Moffitt Cancer Center & Research Institute (United States); Modulation Therapeutics, Inc., Tampa, FL (United States); Moros, Eduardo G.; Morse, David L.

    2016-06-15

    Purpose: The melanocortin-1 receptor (MC1R) is expressed in 94% of uveal melanomas and is described as an ideal target for this untreatable disease. MC1RL is a high affinity MC1R specific peptidomimetic ligand that can serve as a scaffold for therapeutic conjugates such as alpha particle emitting isotopes. The purpose of this study was to assess normal tissue distribution and risk as a result of using the DOTA chelator conjugated to MC1RL to deliver {sup 225}Ac: MC1RL-DOTA-{sup 225}Ac. Methods: 17 non-tumor bearing BALB/c mice were intravenously injected with the novel MC1RL-DOTA-{sup 225}Ac radiopharmaceutical with an average initial administered activity of 2.5 µCi. After the injection, three groups of animals (6, 6, and 5 per group) were euthanized at 24, 48, and 96 hour time points. A total of 11 organs of interest were harvested at each time point including kidneys and liver. Since the emitted alpha particles from {sup 225}Ac and its daughter products are not easy to detect directly, the isomeric gamma spectra were measured instead in the tissue samples using a modified Atomlab™ Gamma Counter (Biodex Medical Systems, Inc) and converted using factors for gamma ray abundance per alpha decay. Dosimetry was performed using measured radioactivity distribution in organs and the generalized internal dosimetry schema of MIRD pamphlet #21. Results: Our calculations have shown that the maximum absorbed dose was delivered to the liver with a total of 47 cGy per 96 hour period. The average dose per kidney was calculated to be 21 cGy. Heart, brain, lung, spleen, skin doses ranged from 0.01 to 1 cGy over the same time period. All animals gained weight over the 110 day decay period and no organ damage was observed by pathology. Conclusion: Based on our results, the risk of using the MC1RL-DOTA-{sup 225}Ac compound is relatively small in terms of deterministic radiation effects. Funding Support: NIH/NCI P50CA168536-03 Skin SPORE; NIH/NCI Phase I SBIR Contract #HHSN

  15. Radon exhalation study from cement, cement slabs and concrete slabs with variation in fly ash

    International Nuclear Information System (INIS)

    Sharma, Nisha; Singh, Jaspal

    2012-01-01

    Fly ash is a waste product from coal-fired power plants. Fly ash has become a subject of world-wide interest in recent years because of its diverse uses, e.g. in the manufacture of concrete for building purposes, for the filling of underground cavities, or as a component of building material. The fly ash may contain enhanced levels of the natural radionuclides in the uranium and thorium series and by using the fly ash in building materials, the radiation levels in houses may thus be technologically enhanced. Because of its relatively high radionuclide contents (including 226 Ra), fly ash may, however, present a potential hazard to the population through its radon emanation, which would be highly undesirable. Since fly ash is frequently used as a building material, the idea of the experiment was to mix fly ash in different proportions in the cement in the powder form, cemented slabs and concrete slabs to study the combined behaviors. Alpha sensitive LR-115 type II plastic track detector, commonly known as Solid State Nuclear Track Detectors (SSNTDs), were used to measure the radon concentration. The alpha particles emitted from the radon causes the radiation damaged tracks. The chemical etching in NaOH at 60°C for about 90 minutes was done to reveal these latent tracks, which were then scanned and counted by an optical microscope of suitable magnification. By calculating the track density of registered tracks, the radon concentrations were determined. In case of cement in the powder form and in cemented slab, starting from the pure cement, fly ash was added up to 70% by weight. In this case the radon exhalation rate has increased by addition of fly ash in the cement and in case of concrete slabs by the addition of fly ash in the cement the radon exhalation increases up to 60% and then decreases. Therefore, on the basis of our investigations we concluded that in general radon exhalation rate increases with the addition of fly ash. (author)

  16. Cell death triggered by alpha-emitting {sup 213}Bi-immunoconjugates in HSC45-M2 gastric cancer cells is different from apoptotic cell death

    Energy Technology Data Exchange (ETDEWEB)

    Seidl, Christof; Schroeck, Hedwig; Seidenschwang, Sabine; Beck, Roswitha; Schwaiger, Markus; Senekowitsch-Schmidtke, Reingard [Technische Universitaet Muenchen, Department of Nuclear Medicine, Munich (Germany); Schmid, Ernst [National Research Center for Environment and Health, Institute of Radiation Biology, GSF, Neuherberg (Germany); Abend, Michael [German Armed Forces, Institute of Radiobiology, Munich (Germany); Becker, Karl-Friedrich [Technische Universitaet Muenchen, Institute of Pathology, Munich (Germany); National Research Center for Environment and Health, Institute of Pathology, GSF, Neuherberg (Germany); National Research Center for Environment and Health, Institute of Molecular Immunology, GSF, Munich (Germany); Apostolidis, Christos; Nikula, Tuomo K. [European Commission, Institute for Transuranium Elements, Karlsruhe (Germany); Kremmer, Elisabeth [National Research Center for Environment and Health, Institute of Molecular Immunology, GSF, Munich (Germany)

    2005-03-01

    Radioimmunotherapy with {alpha}-particle-emitting nuclides, such as{sup 213}Bi, is a promising concept for the elimination of small tumour nodules or single disseminated tumour cells. The aim of this study was to investigate cellular damage and the mode of cell death triggered by {sup 213}Bi-immunoconjugates. Human gastric cancer cells (HSC45-M2) expressing d9-E-cadherin were incubated with different levels of activity of {sup 213}Bi-d9MAb targeting d9-E-cadherin and {sup 213}Bi-d8MAb, which does not bind to d9-E-cadherin. Micronucleated (M) cells, abnormal (A) cells and apoptotic (A) [(MAA)] cells were scored microscopically in the MAA assay following fluorescent staining of nuclei and cytoplasm. Chromosomal aberrations were analysed microscopically following Giemsa staining. The effect of z-VAD-fmk, known to inhibit apoptosis, on the prevention of cell death was investigated following treatment of HSC45-M2 cells with sorbitol as well as {sup 213}Bi-d9MAb. Activation of caspase 3 after incubation of HSC45-M2 cells with both sorbitol and {sup 213}Bi-d9MAb was analysed via Western blotting. Following incubation of HSC45-M2 human gastric cancer cells expressing d9-E-cadherin with {sup 213}Bi-d9MAb the number of cells killed increased proportional to the applied activity concentration. Microscopically visible effects of {alpha}-irradiation of HSC45-M2 cells were formation of micronuclei and severe chromosomal aberrations. Preferential induction of these lesions with specific {sup 213}Bi-d9MAb compared with unspecific {sup 213}Bi-d8MAb (not targeting d9-E-cadherin) was not observed if the number of floating, i.e. unbound {sup 213}Bi-immunoconjugates per cell exceeded 2 x 10{sup 4}, most likely due to intense crossfire. In contrast to sorbitol-induced cell death, cell death triggered by {sup 213}Bi-immunoconjugates was independent of caspase 3 activation and could not be inhibited by z-VAD-fmk, known to suppress the apoptotic pathway. {sup 213}Bi-immunoconjugates seem

  17. تصميم هيكل التكاليف ونمذجته باستخدام تقنية ""CBS لقياس تكاليف معالجة غاز الرادون المشع في مياه الآبار الجوفية وتكاليف الامتثال لمستويات تلوث وكالة حماية البيئة الأمريكية باستخدام"منظومة الدائرة التكاملية المغلقة "

    Directory of Open Access Journals (Sweden)

    إيمان محمد عبدالله

    2017-09-01

    Full Text Available Logic of Accounting has been changing, as a result of changing in business logic. All the trends are moving towards restructure the Costs, to be a guide for Cost Reduction efforts, and using the Costs in analyzing business rather than income followed in a traditional Accounting. This changes were reflected in searching a new techniques for measuring the values of activities can not be measured by a traditional Accounting measuring, as a measure of pollution in values in environmental activity, Which Accounting thought efforts to be restructured and modeled under a new Accounting measuring techniques, called (CBS Cost Breakdown Structure technique. that USEPA decided in 2014 to used it as a costs measuring approach and modeling for restructure the components of unit cost to contamination drinking water for three types of drinking water treatment techniques are(Packed tower aeration, Multistage bubble aeration, and granular activated carbon. Although, US EPA used this technique in measuring treatment costs for various contaminants, but it focus on aeration or liquid phase of treatment process, and did not worked on radiological properties of Radon. The dangerous nature of Radon need a special technology to dialing with it, because of its a radioactive nature. The alpha particles emitting from radon during its decay, and the exposure for the radioactive Radon particles by inhalation or ingestion causes cancer. So, there is a need for a technique to controlling, treating contaminate levels of Radon to a achieve the safety levels, as well as study the economic feasibility of treatment costs and Compliance Costs. By using a new innovative treatment technique called (CICS "Closed Integrated Circuit System", to measuring treatment costs of Radon pollution, with compliance cost, by designing a special CBS" Cost Breakdown Structure" to achieve the safety a contaminant levels issued by US EPA. The results indicated high accuracy measurements, and the

  18. [Research programs in radiotherapy]. DOE final report, 1996

    International Nuclear Information System (INIS)

    DeNardo, S.J.

    1996-01-01

    Results which have not yet been published in detail are reported here on the following associated studies: Progress in the area of macrocyclic chelates for targeted therapy; Progress in biologic activation with radioimmunoconjugate therapy: Association of molecular receptor increase and tumor response in ChL6/L6 protocol patients; Progress in genetically engineered Lym-1 single chain molecules; Progress in analysis of molecular genetic coded messages to enhance tumor response; Progress on development and validation of planar imaging for therapy planning systems; Progress in development of a 3-D treatment planning system using SPECT; Progress in development of methods to evaluate enhancement of tumor penetration in a murine model; and Progress in clinical applications

  19. [Research programs in radiotherapy]. DOE final report, 1996

    Energy Technology Data Exchange (ETDEWEB)

    DeNardo, S.J.

    1996-12-31

    Results which have not yet been published in detail are reported here on the following associated studies: Progress in the area of macrocyclic chelates for targeted therapy; Progress in biologic activation with radioimmunoconjugate therapy: Association of molecular receptor increase and tumor response in ChL6/L6 protocol patients; Progress in genetically engineered Lym-1 single chain molecules; Progress in analysis of molecular genetic coded messages to enhance tumor response; Progress on development and validation of planar imaging for therapy planning systems; Progress in development of a 3-D treatment planning system using SPECT; Progress in development of methods to evaluate enhancement of tumor penetration in a murine model; and Progress in clinical applications.

  20. Development of 177Lu-DOTA-anti-CD20 for radioimmunotherapy

    International Nuclear Information System (INIS)

    Hassan Yousefnia; Amir Reza Jalilian; Ali Bahrami-Samani; Simindokht Shirvani-Arani; Mohammad Ghannadi-Maragheh; Azim Arbabi; Edalat Radfar

    2011-01-01

    Rituximab was successively labeled with 177 Lu-lutetium chloride. 177 Lu chloride was obtained by thermal neutron flux (4 x 1013 n cm -2 s -1 ) of natural Lu 2 O 3 sample with a specific activity of 2.6-3 GBq/mg. The macrocyclic bifunctional chelating agent, N-succinimidyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA-NHS) was prepared at 25 deg C using DOTA, N-hydroxy succinimide (NHS) in CH 2 Cl 2 . DOTA-rituximab was obtained by the addition of 1 mL of a rituximab pharmaceutical solution (5 mg/mL, in phosphate buffer, pH 7.8) to a glass tube pre-coated with DOTA-NHS (0.01-0.1 mg) at 25 deg C with continuous mild stirring for 15 h. Radiolabeling was performed at 37 deg C in 24 h. Radio-thin layer chromatography showed an overall radiochemical purity of >98% at optimized conditions (specific activity = 444 MBq/mg, labeling efficacy; 82%). The final isotonic 177 Lu-DOTA-rituximab complex was checked by gel electrophoresis for structure integrity control. Radio-TLC was performed to ensure that only one species was present after filtration through a 0.22 μm filter. Preliminary biodistribution studies in normal rats were carried out to determine complex distribution of the radioimmunoconjugate up to 168 h. The biodistribution data were in accordance with other antiCD20 radioimmunoconjugates already reported. (author)

  1. A Pretargeted Approach for the Multimodal PET/NIRF Imaging of Colorectal Cancer.

    Science.gov (United States)

    Adumeau, Pierre; Carnazza, Kathryn E; Brand, Christian; Carlin, Sean D; Reiner, Thomas; Agnew, Brian J; Lewis, Jason S; Zeglis, Brian M

    2016-01-01

    The complementary nature of positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging makes the development of strategies for the multimodal PET/NIRF imaging of cancer a very enticing prospect. Indeed, in the context of colorectal cancer, a single multimodal PET/NIRF imaging agent could be used to stage the disease, identify candidates for surgical intervention, and facilitate the image-guided resection of the disease. While antibodies have proven to be highly effective vectors for the delivery of radioisotopes and fluorophores to malignant tissues, the use of radioimmunoconjugates labeled with long-lived nuclides such as 89 Zr poses two important clinical complications: high radiation doses to the patient and the need for significant lag time between imaging and surgery. In vivo pretargeting strategies that decouple the targeting vector from the radioactivity at the time of injection have the potential to circumvent these issues by facilitating the use of positron-emitting radioisotopes with far shorter half-lives. Here, we report the synthesis, characterization, and in vivo validation of a pretargeted strategy for the multimodal PET and NIRF imaging of colorectal carcinoma. This approach is based on the rapid and bioorthogonal ligation between a trans -cyclooctene- and fluorophore-bearing immunoconjugate of the huA33 antibody (huA33-Dye800-TCO) and a 64 Cu-labeled tetrazine radioligand ( 64 Cu-Tz-SarAr). In vivo imaging experiments in mice bearing A33 antigen-expressing SW1222 colorectal cancer xenografts clearly demonstrate that this approach enables the non-invasive visualization of tumors and the image-guided resection of malignant tissue, all at only a fraction of the radiation dose created by a directly labeled radioimmunoconjugate. Additional in vivo experiments in peritoneal and patient-derived xenograft models of colorectal carcinoma reinforce the efficacy of this methodology and underscore its potential as an innovative and useful

  2. Standardization of Procedures for the Preparation of (177)Lu- and (90)Y-labeled DOTA-Rituximab Based on the Freeze-dried Kit Formulation.

    Science.gov (United States)

    Wojdowska, Wioletta; Karczmarczyk, Urszula; Maurin, Michal; Garnuszek, Piotr; Mikołajczak, Renata

    2015-01-01

    Rituximab when radiolabelled with (177)Lu or (90)Y has been investigated for the treatment of patients with Non-Hodgkin's Lymphoma. In this study, we optimized the preparation of antibody conjugates with chelating agent in the freeze-dried kit. It shortens procedures needed for the successful radiolabeling with lutetium-177 and yttrium-90 and assures reproducible labelling yields. Various molar ratios of Rituximab:DOTA (from 1:5 to 1:100) were used at the conjugation step and different purification method to remove unbound DOTA were investigated (size-exclusion chromatography, dialysis, ultrafiltration). The final monoclonal antibody concentration was quantified by Bradford method, and the number of DOTA molecules was determined by radiolabeling assay using (64)Cu. The specific activity of (177)Lu-DOTA-Rituximab and (90)Y-DOTA-Rituximab were optimized using various amounts of radiometal. Quality control (SE-HPLC, ITLC) and stability study were performed. An average of 4.2 ± 0.8 p-SCN-Bz-DOTA molecules could be randomly conjugated to a single molecule of Rituximab. The ultrafiltration system was the most efficient for purification and resulted in the highest recovery efficiency (77.2%). At optimized conditions the (177)Lu-DOTARituximab and (90)Y-DOTA-Rituximab were obtained with radiochemical purity >99% and specific activity ca. 600 MBq/mg. The radioimmunoconjugates were stable in human serum and 0.9% NaCl. After 72 h of incubation the radiochemical purity of (177)Lu-DOTA-Rituximab decreased to 94% but it was still more than 88% for (90)Y-DOTA-Rituximab. The radioimmunoconjugate showed stability after six months storage at 2 - 8(0)C, as a lyophilized formulation. Our study shows that Rituximab-DOTA can be efficiently radiolabeled with (177)Lu and (90)Y via p-SCN-Bn-DOTA using a freezedried kit.

  3. From academy to industry

    International Nuclear Information System (INIS)

    Chatal, J.F.

    2015-01-01

    Full text of publication follows. Clinical efficacy of radioimmunotherapy (RIT) has been clearly documented in the consolidation situation, such as first line treatment of indolent Non Hodgkin Lymphoma after induction chemotherapy [1] or after salvage resection of liver metastases from colon carcinoma [2], when tumor targets have a small, preferably microscopic, size. In this favorable situation RIT, which is a targeted therapy with toxicity limited to hematological toxicity, has a great potential and could be competitive with chemotherapy in particular for solid tumors. Such potential has been recently demonstrated in prostate cancer [3]. A lot of academic preclinical studies have been performed using multiple antibodies and antibody formats labeled with varied beta-emitting and more recently alpha particle-emitting radionuclides. With regard to other targeted therapies, the efficacy of RIT has been fully recognized and academic preclinical studies have been extended to a lot of clinical phase I/II studies but a limited number of phase II studies. Paradoxically, despite quite encouraging results, the number of industrially implemented phase III studies has been limited to the fingers of one hand illustrating a gap between academy and industry. For the last ten years only 2 ARCs (Antibody Radio Conjugates) (Zevalin and Bexxar) have been approved. The reasons for such a gap are complex and multiple but they could be summarized in one word: Money. The cost for a phase III study, enrolling hundreds of patients, exceeds the financial capabilities of most radiopharmaceutical companies and, up to now, Big Pharmas did not dare to invest in this field of RIT in part because they are not familiar with the use of radionuclides and prefer to develop ADCs (Antibody Drug Conjugates) even if they are generally more toxic and no more efficient than ARCs. For the future of RIT it is crucial to succeed in convincing Big Pharmas to invest in this field of ARCs. For this purpose it

  4. Production of Actinium-225 via High Energy Proton Induced Spallation of Thorium-232

    Energy Technology Data Exchange (ETDEWEB)

    Harvey, James T.; Nolen, Jerry; Vandergrift, George; Gomes, Itacil; Kroc, Tom; Horwitz, Phil; McAlister, Dan; Bowers, Del; Sullivan, Vivian; Greene, John

    2011-12-30

    The science of cancer research is currently expanding its use of alpha particle emitting radioisotopes. Coupled with the discovery and proliferation of molecular species that seek out and attach to tumors, new therapy and diagnostics are being developed to enhance the treatment of cancer and other diseases. This latest technology is commonly referred to as Alpha Immunotherapy (AIT). Actinium-225/Bismuth-213 is a parent/daughter alpha-emitting radioisotope pair that is highly sought after because of the potential for treating numerous diseases and its ability to be chemically compatible with many known and widely used carrier molecules (such as monoclonal antibodies and proteins/peptides). Unfortunately, the worldwide supply of actinium-225 is limited to about 1,000mCi annually and most of that is currently spoken for, thus limiting the ability of this radioisotope pair to enter into research and subsequently clinical trials. The route proposed herein utilizes high energy protons to produce actinium-225 via spallation of a thorium-232 target. As part of previous R and D efforts carried out at Argonne National Laboratory recently in support of the proposed US FRIB facility, it was shown that a very effective production mechanism for actinium-225 is spallation of thorium-232 by high energy proton beams. The base-line simulation for the production rate of actinium-225 by this reaction mechanism is 8E12 atoms per second at 200 MeV proton beam energy with 50 g/cm2 thorium target and 100 kW beam power. An irradiation of one actinium-225 half-life (10 days) produces {approx}100 Ci of actinium-225. For a given beam current the reaction cross section increases slightly with energy to about 400 MeV and then decreases slightly for beam energies in the several GeV regime. The object of this effort is to refine the simulations at proton beam energies of 400 MeV and above up to about 8 GeV. Once completed, the simulations will be experimentally verified using 400 MeV and 8 Ge

  5. Theoretical estimation of absorbed dose to organs in radioimmunotherapy using radionuclides with multiple unstable daughters

    International Nuclear Information System (INIS)

    Hamacher, K.A.; Sgouros, G.

    2001-01-01

    The toxicity and clinical utility of long-lived alpha emitters such as Ac-225 and Ra-223 will depend upon the fate of alpha-particle emitting unstable intermediates generated after decay of the conjugated parent. For example, decay of Ac-225 to a stable element yields four alpha particles and seven radionuclides. Each of these progeny has its own free-state biodistribution and characteristic half-life. Therefore, their inclusion for a more accurate prediction of absorbed dose and potential toxicity requires a formalism that takes these factors into consideration as well. To facilitate the incorporation of such intermediates into the dose calculation, a previously developed methodology (model 1) has been extended. Two new models (models 2 and 3) for allocation of daughter products are introduced and are compared with the previously developed model. Model 1 restricts the transport to a function that yields either the place of origin or the place(s) of biodistribution depending on the half-life of the parent radionuclide. Model 2 includes the transient time within the bloodstream and model 3 incorporates additional binding at or within the tumor. This means that model 2 also allows for radionuclide decay and further daughter production while moving from one location to the next and that model 3 relaxes the constraint that the residence time within the tumor is solely based on the half-life of the parent. The models are used to estimate normal organ absorbed doses for the following parent radionuclides: Ac-225, Pb-212, At-211, Ra-223, and Bi-213. Model simulations are for a 0.1 g rapidly accessible tumor and a 10 g solid tumor. Additionally, the effects of varying radiolabled carrier molecule purity and amount of carrier molecules, as well as tumor cell antigen saturation are examined. The results indicate that there is a distinct advantage in using parent radionuclides such as Ac-225 or Ra-223, each having a half-life of more than 10 days and yielding four alpha

  6. Design and fabrication of a novel self-powered solid-state neutron detector

    Science.gov (United States)

    LiCausi, Nicholas

    There is a strong interest in intercepting special nuclear materials (SNM) at national and international borders and ports for homeland security applications. Detection of SNM such as U and Pu is often accomplished by sensing their natural or induced neutron emission. Such detector systems typically use thermal neutron detectors inside a plastic moderator. In order to achieve high detection efficiency gas filled detectors are often used; these detectors require high voltage bias for operation, which complicates the system when tens or hundreds of detectors are deployed. A better type of detector would be an inexpensive solid-state detector that can be mass-produced like any other computer chip. Research surrounding solid-state detectors has been underway since the late 1990's. A simple solid-state detector employs a planar solar-cell type p-n junction and a thin conversion material that converts incident thermal neutrons into detectable alpha-particles and 7Li ions. Existing work has typically used 6LiF or 10B as this conversion layer. Although a simple planar detector can act as a highly portable, low cost detector, it is limited to relatively low detection efficiency (˜10%). To increase the efficiency, 3D perforated p-i-n silicon devices were proposed. To get high efficiency, these detectors need to be biased, resulting in increased leakage current and hence detector noise. In this research, a new type of detector structure was proposed, designed and fabricated. Among several detector structures evaluated, a honeycomb-like silicon p-n structure was selected, which is filled with natural boron as the neutron converter. A silicon p+-n diode formed on the thin silicon wall of the honeycomb structure detects the energetic alpha-particles emitted from the boron conversion layer. The silicon detection layer is fabricated to be fully depleted with an integral step during the boron filling process. This novel feature results in a simplified fabrication process. Three

  7. Localization of alpha emitters by damage production in a thin film. Application to the study of alpha emitter diffusion in irradiated samples; Localisation des emetteurs alpha par creation de dommages dans un film mince. Application a l'etude de la diffusion des emetteurs alpha dans des echantillons irradies

    Energy Technology Data Exchange (ETDEWEB)

    Houdaille, B; Perrot, M [Commissariat a l' Energie Atomique, 91 - Saclay (France). Centre d' Etudes Nucleaires

    1968-07-01

    The process of recording {alpha} particles on cellulose nitrate films, called alpha-graphy, is applied to the study of the diffusion of {alpha}-emitting elements in irradiated alloys. The existence of diffusion is shown by attacking the film with concentrated caustic soda after exposition. The insensitivity of the recorder to {beta} {gamma} radiation emitted by the sample after passing in the reactor makes it possible to operate with long exposure times and to detect small diffusions. The concentration-penetration curves are drawn up after carrying out a densitometric analysis of the alpha-graphies. - As the cellulose nitrate is affected only by {alpha} particles of energies of between 0.5 and 4 MeV, it was first necessary to determine the yield of the recorder for {alpha} particles emitted by a thick source, i.e. whose energy varies between 0 and E{sub 0}, E{sub 0} being the energy of the alpha emitter. - The concentration C of the {alpha}-emitter, as a function of the optical density D of the alpha-graphy, and of the exposure time t is given by a simple relationship: C = D/at where a is an experimental constant determined by calibration. It depends on the nature of the cellulose nitrate, of the {alpha}-emitting element and of the alloy studied. (authors) [French] Le procede d'enregistrement des particules alpha sur film de nitrate de cellulose, ou alphagraphie, est applique a l'etude de la diffusion d'elements emetteurs alpha dans des alliages irradies. La diffusion est mise en evidence par une attaque du film de nitrate, apres exposition, dans de la soude concentree. L'insensibilite de l'enregistreur au rayonnement {beta} {gamma}, emis par l'echantillon apres son sejour en pile, permet d'operer sur de longs temps de pose et de detecter des diffusions faibles. Les courbes concentration - penetration sont etablies par exploitation densitometrique des alphagraphies. - Comme le nitrate de cellulose n'est impressionne que par des particules alpha dont l'energie est

  8. Radiobiological Effects of Alpha-Particles from Astatine-211: From DNA Damage to Cell Death

    Energy Technology Data Exchange (ETDEWEB)

    Claesson, Kristina

    2011-05-15

    In recent years, the use of high linear energy transfer (LET) radiation for radiotherapeutic applications has gained increased interest. Astatine-211 (211At) is an alpha-particle emitting radionuclide, promising for targeted radioimmunotherapy of isolated tumor cells and microscopic clusters. To improve development of safe radiotherapy using 211At it is important to increase our knowledge of the radiobiological effects in cells. During radiotherapy, both tumors and adjacent normal tissue will be irradiated and therefore, it is of importance to understand differences in the radio response between proliferating and resting cells. The aim of this thesis was to investigate effects in fibroblasts with different proliferation status after irradiation with alpha-particles from 211At or X-rays, from inflicted DNA damage, to cellular responses and biological consequences. Throughout this work, irradiation was performed with alpha-particles from 211A or X-rays. The induction and repair of double-strand breaks (DSBs) in human normal fibroblasts were investigated using pulsed-field gel electrophoresis and fragment analysis. The relative biological effectiveness (RBE) of 211At for DSB induction varied between 1.4 and 3.1. A small increase of DSBs was observed in cycling cells compared to stationary cells. The repair kinetics was slower after 211At and more residual damage was found after 24 h. Comparison between cells with different proliferation status showed that the repair was inefficient in cycling cells with more residual damage, regardless of radiation quality. Activation of cell cycle arrests was investigated using immunofluorescent labeling of the checkpoint kinase Chk2 and by measuring cell cycle distributions with flow cytometry analysis. After alpha-particle irradiation, the average number of Chk2-foci was larger and the cells had a more affected cell cycle progression for several weeks compared with X-irradiated cells, indicating a more powerful arrest after 211At

  9. Therapy with high LET Radioisotopes: Can sufficient levels of attractive Auger and alpha emitters be produced to make their use practical?

    International Nuclear Information System (INIS)

    Knapp, F.F. Jr.; Mirzadeh, S.; Stabin, M.; Brill, A.B.

    2005-01-01

    Because of localized energy deposition within a very small volume, cellular targeted therapy with high linear energy transfer (LET) Auger-electron and alpha-particle emitting radioisotopes is of great interest. While the energy deposition from alpha particles usually encompasses several cell diameters, the dose from Auger electrons is confined to a single cell. Two major challenges for broader use of Alpha and Auger emitters are the efficient and cost effective routine production of sufficient levels of these radioisotopes, and the availability of targeting molecules to which the radioisotopes can be attached for cellular delivery of sufficient levels of activity for effective therapy. Examples of several Alpha-and Auger-emitting radioisotopes of current interest are presented. Alpha- and Auger electron-emitting radioisotopes can be produced in accelerators (A) and nuclear reactors (R), and several alpha emitter congeners (i.e. thorium-229) can be obtained from uranium decay products. The challenge for reactor production, is the availability and exploitation of methods - other then the usual radiative (n,γ) production route which will provide no-carrier-added (nca) or the high specific activity radioisotopes of interest. The submitted manuscript has been authored by a contractor of the U.S. Government under contract DE-AC05-00OR22725. Accordingly, the U.S. Government retains a nonexclusive, royalty-free license to publish or reproduce the published form of this contribution, or allow others to do so, for U.S. Government purposes High LET radioisotopes of current interest which are in the initial stages of development and/or which demonstrate practical use in clinical trials include several alpha-emitters, in particular bismuth-213 - and also the actinium-225 parent - astatine-211 and bismuth-212. Extensive experimental studies have been reported with Auger iododeoxyuridine (IdUR) radiolabeled with the iodine-125 emitter-labeled. However, development of production

  10. Cuban Monoclonal Antibodies for Radioimmunodiagnosis and Radioimmunotherapy of Cancer Diseases

    International Nuclear Information System (INIS)

    Casaco, A.

    2009-01-01

    The Centre of Molecular Immunology produces monoclonal antibodies for treating cancer diseases. We are mainly focus on two target systems; one is the epidermal growth factor receptor (EGF-R) because there is a tremendous relationship between the EGF/EGF-R system and several human tumours such as lung, head and neck, ovarian breast and brain cancers; the second one is the ganglioside system, the relevance of certain gangliosides in tumour growth and metastatic dissemination has been well documented, GM3(NeuGc) ganglioside is particularly interesting due to its restrictive expression in normal human tissues. Nimotuzumab (h-R3) is a humanized monoclonal antibody (mAb) that was obtained by complementarity-determining regions grafting of a murine mAb (ior egf/r3) to a human framework having remarkable antiproliferative, pro-apoptotic, and antiangiogenic effects. A Phase I clinical trial was performed to evaluate the toxicity and clinical effect of an intracavitary (intracerebral) administration of a single dose of nimotuzumab (h-R3) labelled with increasing doses of 188Re. All patients bearing astrocytomas grade III/IV should be treated previously with conventional therapies and have an EGF-R overexpression in the tumour, demonstrated by immunohistochemical study. Maximal tolerated dose was 3 mg of the h-R3 labelled with 10 mCi of 188 Re. The radioimmunoconjugate showed a high retention in the surgical created resection cavity and the brain adjacent tissues with a mean value of 85.5% of the injected dose one hour post-administration. This radioimmunoconjugate may be relatively safe and a promising therapeutic approach for treating high grade gliomas. GM3(NeuGc) ganglioside is particularly interesting due to its restrictive expression in normal human tissues according to immunohistochemical studies, using either polyclonal or monoclonal antibodies. But both immunohistochemical and biochemical methods have strongly suggested its over-expression in human breast and colon

  11. Optimized preparation and preliminary evaluation of [64Cu]-DOTA-trastuzumab for targeting ErbB2/Neu expression

    International Nuclear Information System (INIS)

    Behrooz Alirezapour; Mohammad Javad Rasaee

    2013-01-01

    Breast cancer radioimmunoscintigraphy targeting HER2/neu expression is a growing field of work in nuclear medicine research. Trastuzumab is a monoclonal antibody that binds with high affinity to HER2/neu, which is over expressed on breast and other tumors. Developing new tracers for the detection of this cancer is of great interest. In this study, trastuzumab was successively labeled with [ 64 Cu]CuCl 2 after conjugation with DOTA-NHS-ester. The conjugate was purified by molecular filtration, the average number of DOTA conjugated per mAb was calculated and total concentration was determined by spectrophotometric method. DOTA-trastuzumab was labeled with 64 Cu produced by 68 Zn(p,αn) 64 Cu nuclear reaction (30 MeV protons at 180 μA). Radiochemical purity, integrity of protein after radiolabeling and immunoreactivity of radiolabeled mAb trastuzumab with HER2/neu antigen and SkBr3 cell line were performed by RIA. In vitro stability of radiolabeled mAb in human serum was determined by thin layer chromatography. In vitro internalization studies were performed with the SkBr3 cell line and the tissue biodistribution of the 64 Cu-DOTA-trastuzumab was evaluated in wild-type rat (90 ± 5.5 μCi, 2, 6, 12, 24 h p.i.). The radioimmunoconjugate was prepared with a radiochemical purity of higher than 96 ± 0.5 % (ITLC) and specific activity as high as 5.3 μCi/μg. The average number of chelators per antibody for the conjugate used in this study was 5.8/1. The sample was showed to have similar patterns of migration in the gel electrophoresis. The 64 Cu-DOTA-trastuzumab showed high immunoreactivity towards HER2/neu antigen and SkBr3 cell line. In vitro stability of the labeled product was found to be more than 94 % in PBS and 82 ± 0.5 % in human serum over 48 h. In vitro internalization studies of the 64 Cu-DOTA-trastuzumab showed that up to 11.5 % of the radioimmunoconjugate internalized after 10 h. The accumulation of the radiolabeled mAb in liver, skin, intestine, lung

  12. Preparation and radiolabeling of humanized anti-HER1 monoclonal antibody nimotuzumab Fab' fragment with 68Ga and 90Y

    International Nuclear Information System (INIS)

    Alonso Martinez, L. M.; Xiques Castillo, A.; Leyva Montanna, R.; Perez-Malo Cruz, M.; Zamora Barrabi, M.; Manresa Sanchez, Y.

    2013-01-01

    Antibody-based targeted delivery of radioisotopes to malignant tissues is a promising approach in cancer diagnostics and therapy. However, intact antibody molecules are large glycoproteins (∼150 kDa) that have limited application in molecular imaging and therapy due to their relatively slow clearance from the circulation leading to a high background signal rather both cases the sensitivity can be increased with the use of enzymatically produced Fab' fragments. In this work, the ability to get labeled with 62 Ga and 90 Y of a monoclonal antibody (mAb) Fab' fragment against the transmembrane receptor tyrosine kinase HER-1 was studied for future applications in PET imaging and radioimmunotherapy of tumors. In order to obtain the Fab' fragment the mAb was cleaved with pepsin in molar excess. After separating the reaction mixture in two steps using affinity and ion-exchange chromatography, the Fab' fragment was finally obtained by reduction of the F(ab') 2 with a molar excess of 2-mercaptoethanol followed by a size exclusion purification step. The Fab' fragment was derivatized with 1,4,7,10-tetraaza cyclododecane-1,4,7,10-tetraacetic acid mono N-hydroxysuccinimide commercial ester (DOTA-NHS-ester) applying a simple procedure and the number of DOTA groups linked to Fab' were determinate. The labeling of the conjugate with 68 Ga and 90 Y from 'in-house generators yielded radiochemically pure probes that can become a suitable radioimmunoconjugated in a near future. (Author)

  13. In vitro stability of EDTA and DTPA immunoconjugates of monoclonal antibody 2G3 labeled with indium-111

    Energy Technology Data Exchange (ETDEWEB)

    Reilly, R.; Lee, N.; Houle, S. (The Toronto Hospital (Canada)); Law, J.; Marks, A. (Toronto Univ., ON (Canada))

    1992-08-01

    Monoclonal antibody 2G3 directed against a high molecular weight glycoprotein on breast and ovarian cancer cells was conjugated with bicyclic DTPA (or EDTA) anhydride or benzyl isothiocyanate DTPA (benzyl DTPA) and labeled with {sup 111}In. DTPA anhydride was more reactive with the antibody than benzyl DTPA, and kinetics of labeling with {sup 111}In were more rapid for DTPA substituted 2G3 than for benzyl DTPA substituted 2G3. On the other hand, {sup 111}In-2G3 conjugates prepared using DTPA anhydride were subject to more extensive dimerization and higher losses in immunoreactivity than those prepared using benzyl DTPA. On the basis of measurement of transchelation to transferrin, the stability of {sup 111}In-2G3 prepared using DTPA anhydride or benzyl DTPA did not differ during incubation in human plasma for 6 days at 37{sup o}C. These results suggest that an important advantage of benzyl DTPA over DTPA anhydride for preparing {sup 111}In-labeled antibodies is the prevention of intermolecular (and intramolecular) crosslinking during conjugation which ultimately leads to alterations in conformation and losses in immunoreactivity of the radioimmunoconjugate. (author).

  14. Development of 111In-DTPA-human polyclonal antibody complex for long-term inflammation/infection detection

    International Nuclear Information System (INIS)

    Jalilian, A.R.; Rowshanfarzad, P.; Kamali-Dehghan, M.; Moafian, J.; Akhlaghi, M.; Rajabifar, S.; Mirzaii, M.; Shafaii, K.; Babaii, M.

    2005-01-01

    Human polyclonal antibody (HIgG) was successively labeled with 111-indium chloride after residulation with freshly prepared cyclic DTPA-dianhydride. The best results of the conjugation were obtained by the addition of solid DTPA-dianhydride (0.1-0.3 mg) to 100 μl of the HIgG solution (0.2-0.4 mg/ml) at pH = 6 in phosphate buffer media at 25 o C with continuous stirring for 30 min. Radio-thin-layer chromatography showed an overall radiochemical yield of 96-99% at optimized conditions (specific activity = 300-500 MBq/mg, radiochemical purity >98%). The final isotonic 111 In-DTPA-HIgG complex was checked by radio-TLC to ensure the formation of only one species followed by filtration through a 0.22 μ filter. Preliminary long-term in vivo studies in turpentine-oil induced inflammation in rat model was performed to determine late complex distribution of the radioimmunoconjugate. The target/skin and target/blood ratios were 27 and 51 after 24 h, and 23 and 51 after 110 h, showing a high selectivity of the radiopharmaceutical for inflammatory lesions. (author)

  15. Synthesis of a novel bicyclic bifunctional chelating agent

    International Nuclear Information System (INIS)

    Sweet, M.P.; Mease, R.C.; Joshi, V.; Srivastava, S.C.

    1994-01-01

    Semi-rigid ligands such as cyclohexyl EDTA (CDTA) and 4-isothiocyanato-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid (4-ICE) form chelates that are more stable in vivo compared to those of EDTA or DTPA. The authors have synthesized a new class of ligands in which the metal-binding polyaminocarboxylate groups are incorporated onto the rigid bicyclo[2.2.2]octane ring system. These ligands are expected to contribute to even higher in vivo stability of radiometal complexes. The synthesis of the first in this series of ligands (2.3-diaminobicyclo[2.2.2]octane-N,N,N',N'-tetraacetic acid, BODTA) began with a Diels-Alder reaction of 1,3-diacetylimidazolin-2-one and 1,3-cyclohexadiene. Base hydrolysis afforded the diamine. Following alkylation of the diamine with ethyl iodoacetate and hydrogenation of the double bond, hydrolysis of the esters gave BODTA. For initial conjugation with proteins, an average of one carboxylic acid of BODTA was converted into an NHS ester. In vivo testing of radioimmunoconjugates, prepared using this method, is in progress

  16. PET imaging of osteosarcoma in dogs using a fluorine-18-labeled monoclonal antibody fab fragment

    International Nuclear Information System (INIS)

    Page, R.L.; Garg, P.K.; Gard, S.

    1994-01-01

    Four dogs with histologically confirmed osteogenic sarcoma were studied with PET following intravenous injection of the 18 F-labeled Fab fragment of TP-3, a monoclonal antibody specific for human and canine osteosarcomas. The antibody fragment was labeled using the N-succinimidyl (8-(4'-( 18 F)fluorobenzyl)amino)suberate acylation agent. Blood clearance of activity was biphasic in all dogs but half-times were variable (T 1/2β = 2-13 hr). Catabolism of labeled Fab was reflected by the decrease in protein-associated activity in serum from more than 90% at 1 min to 60%-80% at 4 hr. PET images demonstrated increased accumulation of 18 F at the primary tumor site relative to normal contralateral bone in one dog as early as 15 min after injection. Biopsies obtained after euthanasia indicated higher uptake at the edges of the tumor as observed on the PET scans. Tumor uptake was 1-3 x 10 -3 % injected dose/g, a level similar to that reported for other Fab fragments in human tumors. In the three dogs with metastatic disease, early PET images reflected activity in the blood pool but later uptake was observed in suspected metastatic sites. These results, although preliminary, suggest that PET imaging of 18 F-labeled antibody fragments is feasible and that dogs with spontaneous tumors could be a valuable model for preclinical research with radioimmunoconjugates. 34 refs., 6 figs., 2 tabs

  17. Monte Carlo Simulations of Necrotic Cell Targeted Alpha Therapy

    International Nuclear Information System (INIS)

    Penfold, S.N.; Brown, M.P.; Bezak, E.

    2011-01-01

    Full text: Hypoxic tumour cells are radioresistant and are significant contributors to the locoregional recurrences and distant metastases that mark treatment failure. Due to restricted circulatory supply, hypoxic tumor cells frequently become necrotic and thus necrotic areas often lie near hypoxic tumour areas. In this study we investigate the feasibility of binding an alpha-emitting conjugate to necrotic cells located in the proximity of hypoxic, viable tumour cells. Monte Carlo radiation transport simulations were performed to investigate the dose distribution resulting from the thorium 227 (Th227) decay chain in a representative tumour geometry. The Geant4 software toolkit was used to simulate the decay and interactions of the Th227 decay chain. The distribution of Th227 was based on a study by Thomlinson and Gray of human lung cancer histological samples (Thomlinson RH, Gray LH. Br J Cancer 1955; 9:539). The normalized dose distribution obtained with Geant4 from a cylindrical Th227 source in water is illustrated in Fig. I. The relative contribution of the different decay channels is displayed, together with a profile through the centre of the accumulated dose map. The results support the hypothesis that significant α-particle doses will be deposited in the hypoxic tumor tissue immediately surrounding the necrotic core (where the majority of Th227 will be located). As an internal a-particle generator, the Th227-radioimmunoconjugate shows potential as an efficient hypoxic tumour sterilizer.

  18. PET imaging of osteosarcoma in dogs using a fluorine-18-labeled monoclonal antibody fab fragment

    Energy Technology Data Exchange (ETDEWEB)

    Page, R.L.; Garg, P.K.; Gard, S. [North Carolina State Univ., Raleigh, NC (United States)]|[Duke Univ. Medical Center, Durham, NC (United States)]|[North Carolina and Norke Radium Hospital, Oslo (Norway)] [and others

    1994-09-01

    Four dogs with histologically confirmed osteogenic sarcoma were studied with PET following intravenous injection of the {sup 18}F-labeled Fab fragment of TP-3, a monoclonal antibody specific for human and canine osteosarcomas. The antibody fragment was labeled using the N-succinimidyl (8-(4{prime}-({sup 18}F)fluorobenzyl)amino)suberate acylation agent. Blood clearance of activity was biphasic in all dogs but half-times were variable (T{sub 1/2{beta}} = 2-13 hr). Catabolism of labeled Fab was reflected by the decrease in protein-associated activity in serum from more than 90% at 1 min to 60%-80% at 4 hr. PET images demonstrated increased accumulation of {sup 18}F at the primary tumor site relative to normal contralateral bone in one dog as early as 15 min after injection. Biopsies obtained after euthanasia indicated higher uptake at the edges of the tumor as observed on the PET scans. Tumor uptake was 1-3 x 10{sup -3}% injected dose/g, a level similar to that reported for other Fab fragments in human tumors. In the three dogs with metastatic disease, early PET images reflected activity in the blood pool but later uptake was observed in suspected metastatic sites. These results, although preliminary, suggest that PET imaging of {sup 18}F-labeled antibody fragments is feasible and that dogs with spontaneous tumors could be a valuable model for preclinical research with radioimmunoconjugates. 34 refs., 6 figs., 2 tabs.

  19. Preparation, biodistribution, and dosimetry of 188Re-Labeled MoAb ior cea1 and its f(ab')2 fragments by avidin-biotin strategy

    International Nuclear Information System (INIS)

    Ferro-Flores, Guillermina; Pimentel-Gonzalez, Gilmara; Gonzalez-Zavala, Maria Antonia; Murphy, Consuelo Arteaga de; Melendez-Alafort, Laura; Tendilla, Jose I.; Croft, Barbara Y.

    1999-01-01

    The biotinylated monoclonal antibody (MoAb) ior cea1 and its F(ab') 2 fragments were labeled with Re-188 by combination of avidin-biotin strategy. 188 Re-MoAb, 188 Re-MoAb-biotin, 188 Re-F(ab') 2 , and 188 Re-F(ab') 2 -biotin preparations were produced for these studies with specific activities of 1.30±0.18 GBq/mg and from instant freeze-dried kit formulations using ethane-1-hydroxy-1,1-diphosphonic acid (EHDP) as a weak competing ligand. There were no significant differences (p>0.05) between the biodistribution in mice of biotinylated and unbiotinylated 188 Re-labeled immunoconjugates. When avidin was injected as a chase after injection of 188 Re-MoAb-biotin or 188 Re-F(ab') 2 -biotin, the blood radioactivity level decreased approximately 75% (cumulated activity) and the effective dose decreased almost 25% with respect to that of the radioimmunoconjugates in which the chase effect was not used. Our results suggest that 188 Re-labeled biotinylated MoAb ior cea1 and its F(ab') 2 fragments prepared by this method are stable complexes in vivo

  20. Preclinical evaluation of intravenously administered 111In-and 90Y-labeled B72.3 immunoconjugate (GYK-DTPA) in beagle dogs

    International Nuclear Information System (INIS)

    Quadri, S.M.; Vriesendorp, H.M.; Yi Shao; Blum, J.E.; Leichner, P.K.; Williams, J.R.

    1993-01-01

    B72.3, a monoclonal antibody with reactivity against human adenocarcinomas was obtained from the Cytogen Corporation in the form of an immunoconjugate coupled with linker-chelator GYK-DTPA by using proprietary carbohydrate directed site specific chemistry. The immunoconjugate was radiolabeled with indium-111 or yttrium-90. A preclinical analysis was performed in 10 normal beagle dogs. The pharmacokinetics of intravenously administered indium- and yttrium-labeled immunoconjugates were compared serially in blood, bone marrow and urine samples. Compared to 90 Y less of the 111 In label ended up in urine and more was found in blood and bone marrow. Indium-labeled B72.3 GYK-DTPA had relatively higher uptake in most glandular tissues than 111 In-labeled antiferritin immunoconjugate. Bone marrow toxicity was the dose limiting side effect after intravenous infusion of 90 Y-labeled B72.3 GYK-DTPA. Toxicity was also observed in the liver but not in other organ systems. Recently other investigators obtained similar results with these immunoconjugates in human patients. A preclinical pharmacokinetic analysis of radioimmunoconjugates in beagle dogs provided useful information regarding bone marrow toxicity, liver toxicity and in vivo instability of the immunoconjugate. Data suggest that for future trials in human patients, a more stable chelated immunoconjugate for yttrium is needed to achieve less liver uptake and a better correlation with the 111 In-labeled product than the 90 Y-labeled B72.3 GYK-DTPA used in this investigation. (Author)

  1. Gas-flow detector for uranium contamination on finned-can surface of a reactor fuel; Detecteur a courant gazeux pour deceler la contamination en uranium des nervures des gaines de combustible nucleaire; Gazopotochnyj detektor zagryazneniya uranom rebristoj poverkhnosti obolochki reaktornykh teplovydelyayushchikh ehlementov; Detector de flujo gaseoso para medir la contaminacion de uranio en la superficie de la vaina de aletas de los elementos combustibles para reactores

    Energy Technology Data Exchange (ETDEWEB)

    Miwa, H; Shiojiri, T; Maeda, Y [Kobe Kogyo Corporation, Okubo, Akashi, Hyogo (Japan)

    1962-04-15

    This gas-flow detector is a gridded proportional-counter specially designed for detecting uranium contamination on the finned-can surface of a reactor fuel. A conventional proportional-counter constructed only by a cathode and collector can hardly detect alpha particles emitted from uranium which is contaminated on rugged surfaces such as those of the fins of a reactor-fuel can because of the lack of uniformity of the electric field near the surface. This is the reason why we have constructed the gridded proportional-counter. This counter comprises the fuel, a grid, collectors and a cathode which are cylindrical in construction and arranged coaxially. The fuel is placed in the centre of the grid and negative voltage is applied. The space between the fuel and the grid serves as an ion-collecting space. The grid is made of fine parallel tungsten wires which are constructed cylindrically around the fuel and connected to ground potential. The collectors are 16 fine tungsten wires constructed similarly to the grid, but each wire is electrically insulated from the others. Through 50-k{Omega} resistors all collectors are connected together and to positive high voltage via a feeding resistor. The space between the grid, the collectors and the cathode serves as a gas-multiplication space just like a conventional proportional-counter. Each 50-k{Omega} resistor separates the stray capacity of the connected collector from the others. The detector output is coupled with a low input-impedance-current amplifier. The low inputimpedance also lessens the bad influence of the stray capacity of the input circuitry. These result in a good S/N ratio and allow the sensitive detection of alpha particles. Before measurement, the counter is first evacuated by a rotary pump and then PR gas (A: 90%, Methane: 10%) is admitted. By the use of this new equipment we have successfully detected alpha particles emitted from 1 x 10{sup -5} g natural-uranium contamination of the finned-can surface of a

  2. Design Techniques for Power-Aware Combinational Logic SER Mitigation

    Science.gov (United States)

    Mahatme, Nihaar N.

    The history of modern semiconductor devices and circuits suggests that technologists have been able to maintain scaling at the rate predicted by Moore's Law [Moor-65]. With improved performance, speed and lower area, technology scaling has also exacerbated reliability issues such as soft errors. Soft errors are transient errors that occur in microelectronic circuits due to ionizing radiation particle strikes on reverse biased semiconductor junctions. These radiation induced errors at the terrestrial-level are caused due to radiation particle strikes by (1) alpha particles emitted as decay products of packing material (2) cosmic rays that produce energetic protons and neutrons, and (3) thermal neutrons [Dodd-03], [Srou-88] and more recently muons and electrons [Ma-79] [Nara-08] [Siew-10] [King-10]. In the space environment radiation induced errors are a much bigger threat and are mainly caused by cosmic heavy-ions, protons etc. The effects of radiation exposure on circuits and measures to protect against them have been studied extensively for the past 40 years, especially for parts operating in space. Radiation particle strikes can affect memory as well as combinational logic. Typically when these particles strike semiconductor junctions of transistors that are part of feedback structures such as SRAM memory cells or flip-flops, it can lead to an inversion of the cell content. Such a failure is formally called a bit-flip or single-event upset (SEU). When such particles strike sensitive junctions part of combinational logic gates they produce transient voltage spikes or glitches called single-event transients (SETs) that could be latched by receiving flip-flops. As the circuits are clocked faster, there are more number of clocking edges which increases the likelihood of latching these transients. In older technology generations the probability of errors in flip-flops due to SETs being latched was much lower compared to direct strikes on flip-flops or SRAMs leading to

  3. Pursuing nuclear energy with no nuclear contamination - from neutron flux reactor to deuteron flux reactor

    International Nuclear Information System (INIS)

    Li, X. Z.; Wei, Q. M.; Liu, B.; Zhu, X. G.; Ren, S. L.

    2007-01-01

    follows: (1) Selective Resonant tunneling model has predicted 3-deuteron fusion which has been found in experiments [6, 7] as well. The reasonable inference is the neutrino emission from the metal hydrides. The feasibility of detection of this neutrino is discussed based on the information from the KamLAND neutrino detector in Japan. (2) Nano-meter technique should be used to increase the deuterium flux through the palladium surface. (3) Gas-discharge tube in combination with optical monochrometer would be the suitable experiment at the current funding level. (4) Negative feed-back should be used to solve the problem of the reproducibility; then, based on the deuteron flux a self-sustaining reactor would be feasible. References [1]. Xing Z. Li, Jian Tian, Ming Y. Mei and Chong X. Li, 'Sub-barrier Fusion and Selective Resonant Tunneling,' Phys. Rev., C 61, 024610 (2000) [2]. Xing Z. Li, Bin Liu, Si Chen, Qing Ming Wei, and Heinrich Hora, 'Fusion cross-sections for inertial fusion energy,' Laser and Particle Beam, 22,469 (2004) [3]. G. Fralick , et al., 'Results of an Attempt to Measure Increased Rates of the Reaction D +D--- 3 He + n in a Nonelectrochemical Cold Fusion Experiment,' NASA Technical Memorandum 102430 (1989) [4]. Xing Z. Li, et al., 'Correlation between abnormal deuterium flux and heat flow in a D/Pd system,' J. Phys. D: Appl. Phys. 36 3095-3097, (2003) [5]. Y. Iwamura, et al., 'Elemental Analysis of Pd Complexes: Effects of D 2 gas permeation, 'Jpn. J. Appl. Phys., 41 4642 (2002) [6]. J. Kasagi, et al., 'Energetic Protons and Alpha Particles Emitted in 150-keV Deuteron Bombardment on Deuterated Ti,' J. Phys. Soc. Japan, 64 (3), 778 (1995) [7]. A. Takahashi, et al., 'Anomalous enhancement of three-body deuteron fusion in titanium deuteride with low-energy D + beam implantation,' Fusion Technol., 34, 256 (1998)

  4. Nature of the bifunctional chelating agent used for radioimmunotherapy with yttrium-88 monoclonal antibodies: critical factors in determining in vivo survival and organ toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Kozak, R.W.; Raubitschek, A.; Mirzadeh, S.; Brechbiel, M.W.; Junghaus, R.; Gansow, O.A.; Waldmann, T.A. (Center for Biologics Evaluation and Research, FDA, Bethesda, MD (USA))

    1989-05-15

    One factor that is critical to the potential effectiveness of radioimmunotherapy is the design of radiometal-chelated antibodies that will be stable in vivo. Stability in vivo depends on the condition that both the chelate linkage and radiolabeling procedures not alter antibody specificity and biodistribution. In addition, synthesis and selection of the chelating agent is critical for each radiometal in order to prevent inappropriate release of the radiometal in vivo. In the present study, we compare the in vivo stability of seven radioimmunoconjugates that use different polyaminocarboxylate chelating agents to complex yttrium-88 to the mouse anti-human interleukin-2 receptor monoclonal antibody, anti-Tac. Chelate linkage and radiolabeling procedures did not alter the immunospecificity of anti-Tac. In order to assess whether yttrium was inappropriately released from the chelate-coupled antibody in vivo, iodine-131-labeled and yttrium-88 chelate-coupled antibodies were simultaneously administered to the same animals to correlate the decline in yttrium and radioiodinated antibody activity. The four stable yttrium-88 chelate-coupled antibodies studied displayed similar iodine-131 and yttrium-88 activity, indicating minimal elution of yttrium-88 from the complex. In contrast, the unstable yttrium-88 chelate-coupled antibodies had serum yttrium-88 activities that declined much more rapidly than their iodine-131 activities, suggesting loss of the radiolabel yttrium-88 from the chelate. Furthermore, high rates of yttrium-88 elution correlated with deposition in bone. Four chelating agents emerged as promising immunotherapeutic reagents: isothiocyanate benzyl DTPA and its derivatives 1B3M, MX, and 1M3B.

  5. Studies on the optimization of leukemia and non-Hodgkin lymphoma therapies using opioids, chemotherapy and radioimmunotherapy

    International Nuclear Information System (INIS)

    Roscher, Mareike

    2013-01-01

    Despite complex treatment schedules for cancer, the occurrence of resistances and relapses is a major concern in oncology. Hence, novel treatment options are needed. In this thesis, different approaches using radioimmunotherapy and the opioid D,L-methadone alone or in combination with doxorubicin were analyzed regarding their cytotoxic potential and the triggered signalling pathways in sensitive and resistant leukaemia and non-Hodgkin lymphoma (NHL). The radioimmunoconjugates [Bi-213]anti-CD33 and [Bi-213]anti-CD20 for treatment of acute myeloid leukaemia (AML) or NHL, respectively, were applied exemplary for the use of targeted alpha-therapies (TAT). Depending on the analyzed cell lines, the used activity concentrations and specific activities (MBq/μg antibody) apoptosis was induced abrogating radio- and chemo-cross-resistances specifically. The cell death was caspase-dependent activating the mitochondrial pathway and was executed by downregulation of the anti-apoptotic proteins XIAP and Bcl-xL. D,L-Methadone induces apoptosis in vitro and in vivo in opioid-receptor (OR) expressing cells depending on the OR density and the used concentrations. Resistances could be overcome and proliferation was inhibited. In combination with doxorubicin, a synergistic effect regarding cytotoxicity in ex vivo patient cells and cell lines was observed. This effect depends on the increase of doxorubicin uptake co-administering D,L-methadone whereas doxorubicin enhances OR expression. The activation of OR leads to the downregulation of cAMP playing a pivotal role in apoptosis induction. In vivo, the therapeutic potential of D,L-methadone alone or in combination with doxorubicin could be proven as mice transplanted with human T-ALL-cells could be identified as tumour free. In summary, these studies show that TAT using [Bi-213]anti-CD33 and [Bi-213]anti-CD20 as well as the opioid D,L-methadone harbour the potential to optimize conventional treatment modalities for leukaemia and NHL.

  6. Pharmacokinetics of chimeric L6 conjugated to indium-111- and yttrium-90-DOTA-peptide in tumor-bearing mice

    International Nuclear Information System (INIS)

    DeNardo, S.J.; Zhong, G.R.; Salako, Q.

    1995-01-01

    A bifunctional chelating agent, DOTA-Gly 3 -L-(p-isothiocyanato)-phenylalanine amide (DOTA-peptide-NCS), was studied in nude mice bearing human breast cancer xenografts (HBT 3477) to determine its potential for radioimmunoconjugate therapy. Indium-111 and yttrium-90 were attached to an anti-adenocarcinoma chimeric L6 (ChL6) monoclonal antibody (MAb) after pre-chelation to the DOTA-peptide-NCS and the desired neutral radiochelates were obtained by purification. The unique characteristic of the DOTA-peptide-NCS to form neutral complexes with trivalent metals was utilized to separate the resulting 111 In and 90 Y radiochelates from excess chelating agent and other anionic by-products resulting from metal impurities. The purified radiochelates were then conjugated to ChL6. The paramacokinetics of 111 In- and 90 Y-DOTA-peptide-ChL6 were obtained for 5 days after injection in nude mice bearing HBT 3477 xenographs. The results were compared with the pharmacokinetics of 125 I-ChL6 obtained in the same mouse model. The whole-body clearance of 125 I-ChL6, 90 Y-and 111 In-DOTA-peptide-ChL6 was monoexponential with biologic half-times of 92, 104 and 160 hr, respectively. Blood clearances of the three radiopharmaceuticals were biphasic. The radiometal immunoconjugates had greater tumor uptake and slower clearances. Indium-111- and 90 Y-DOTA-peptide-ChL6 can be produced at high specific activity with fewer than one chelate per MAb by using a pre-labeling method that permits radiochelate purification by charge selection. Studies in mouse xenografts indicate that tumor uptake in enhanced and a favorable therapeutic index is achieved using these agents. 29 refs., 7 figs., 2 tabs

  7. The inverse electron demand Diels-Alder click reaction in radiochemistry.

    Science.gov (United States)

    Reiner, Thomas; Zeglis, Brian M

    2014-04-01

    The inverse electron-demand Diels-Alder (IEDDA) cycloaddition between 1,2,4,5-tetrazines and strained alkene dienophiles is an emergent variety of catalyst-free 'click' chemistry that has the potential to have a transformational impact on the synthesis and development of radiopharmaceuticals. The ligation is selective, rapid, high-yielding, clean, and bioorthogonal and, since its advent in 2008, has been employed in a wide variety of chemical settings. In radiochemistry, the reaction has proven particularly useful with (18)  F and has already been utilized to create a number of (18)  F-labeled agents, including the PARP1-targeting small molecule (18)  F-AZD2281, the αv β3 integrin-targeting peptide (18)  F-RGD, and the GLP-1-targeting peptide (18)  F-exendin. The inherent flexibility of the ligation has also been applied to the construction of radiometal-based probes, specifically the development of a modular strategy for the synthesis of radioimmunoconjugates that effectively eliminates variability in the construction of these agents. Further, the exceptional speed and biorthogonality of the reaction have made it especially promising in the realm of in vivo pretargeted imaging and therapy, and pretargeted imaging strategies based on the isotopes (111) In, (18)  F, and (64) Cu have already proven capable of producing images with high tumor contrast and low levels of uptake in background, nontarget organs. Ultimately, the characteristics of inverse electron-demand Diels-Alder click chemistry make it almost uniquely well-suited for radiochemistry, and although the field is young, this ligation has the potential to make a tremendous impact on the synthesis, development, and study of novel radiopharmaceuticals. Copyright © 2013 John Wiley & Sons, Ltd.

  8. Beta-irradiation used for systemic radioimmunotherapy induces apoptosis and activates apoptosis pathways in leukaemia cells

    International Nuclear Information System (INIS)

    Friesen, Claudia; Lubatschofski, Annelie; Debatin, Klaus-Michael; Kotzerke, Joerg; Buchmann, Inga; Reske, Sven N.

    2003-01-01

    Beta-irradiation used for systemic radioimmunotherapy (RIT) is a promising treatment approach for high-risk leukaemia and lymphoma. In bone marrow-selective radioimmunotherapy, beta-irradiation is applied using iodine-131, yttrium-90 or rhenium-188 labelled radioimmunoconjugates. However, the mechanisms by which beta-irradiation induces cell death are not understood at the molecular level. Here, we report that beta-irradiation induced apoptosis and activated apoptosis pathways in leukaemia cells depending on doses, time points and dose rates. After beta-irradiation, upregulation of CD95 ligand and CD95 receptor was detected and activation of caspases resulting in apoptosis was found. These effects were completely blocked by the broad-range caspase inhibitor zVAD-fmk. In addition, irradiation-mediated mitochondrial damage resulted in perturbation of mitochondrial membrane potential, caspase-9 activation and cytochrome c release. Bax, a death-promoting protein, was upregulated and Bcl-x L , a death-inhibiting protein, was downregulated. We also found higher apoptosis rates and earlier activation of apoptosis pathways after gamma-irradiation in comparison to beta-irradiation at the same dose rate. Furthermore, irradiation-resistant cells were cross-resistant to CD95 and CD95-resistant cells were cross-resistant to irradiation, indicating that CD95 and irradiation used, at least in part, identical effector pathways. These findings demonstrate that beta-irradiation induces apoptosis and activates apoptosis pathways in leukaemia cells using both mitochondrial and death receptor pathways. Understanding the timing, sequence and molecular pathways of beta-irradiation-mediated apoptosis may allow rational adjustment of chemo- and radiotherapeutic strategies. (orig.)

  9. Alpha radioimmunotherapy of multiple myeloma: study of feasibility of ex vivo medullary purge

    International Nuclear Information System (INIS)

    Couturier, O.; Filippovitch, I.V.; Sorokina, N.I.; Cherel, M.; Thedrez, P.; Faivre-Chauvet, A.; Chatal, J.F.

    1997-01-01

    The efficiency of the radioimmunotherapy (RIT) using beta emitters has been clinically proved in treatments of refractory forms of lymphoma. The alpha-emitting radioelements of short half-life are also good potential candidates for RIT, applicable to tumor targets accessible rapidly to the molecules of the radio-immuno-conjugates of size compatible with the short range of alpha particles (50 to 80 μm). The goal of this study is to demonstrate the feasibility of such an approach on a model of myeloma multiply targeted by specific antibodies (B-B4) coupled to bismuth-213 with a chelating agent (benzyl-DTPA). The efficiency of the alpha RIT was evaluated in vitro by means of different techniques analyzing the cellular mortality (the method of limited dilution), the effects on DNA (the testing of micro-nuclei), the analysis of radio-induced apoptosis (the test with acridine orange) and finally the study of non-specific irradiation on population of cells of hematopoietic system un-recognized by the B-B4 benzyl-DTPA) immuno-conjugate. The first results have shown besides the technical feasibility of the project a strong dose dependent cellular mortality with a survival falling rapidly from 28% to around 1 o/oo for a single doubling of the dose from 14.8 kBq / 10 5 cells (0.4 μCi) to 29.6 kBq/10 5 cells (0.8 μCi). The cellular mortality was total at 300 kBq/10 5 cells (8 μCi). The cells in an apoptosis state were evidenced at rates up to 40% for a dose of 7.4 kBq/10 5 cells (0.2 μ Ci). New experiments will permit confirming these first results and determining the irradiation range having in view a utilization in protocols of purging of the myeloma cells on pockets obtained after plasmaphereses

  10. Preparation and in vivo evaluation of a novel stabilized linker for 211At labeling of protein

    International Nuclear Information System (INIS)

    Talanov, Vladimir S.; Garmestani, Kayhan; Regino, Celeste A.S.; Milenic, Diane E.; Plascjak, Paul S.; Waldmann, Thomas A.; Brechbiel, Martin W.

    2006-01-01

    Significant improvement of in vivo stability of 211 At-labeled radioimmunoconjugates achieved upon employment of a recently reported new linker, succinimidyl N-2-(4-[ 211 At]astatophenethyl)succinamate (SAPS), prompted additional studies of its chemistry. The 211 At radiolabeling of succinimidyl N-2-(4-tributylstannylphenethyl)succinamate (1) was noted to decline after storage at -15 o C for greater than 6 months. Compound 1 was found to degrade via a ring closure reaction with the formation of N-2-(4-tributylstannylphenethyl)succinimide (3), and a modified procedure for the preparation of 1 was developed. The N-methyl structural analog of 1, succinimidyl N-2-(4-tributylstannylphenethyl)-N-methyl succinamate (SPEMS), was synthesized to investigate the possibility of improving the stability of reagent-protein linkage chemistry. Radiolabeling of SPEMS with 211 At generates succinimidyl N-2-(4-[ 211 At]astatophenethyl)-N-methyl succinamate (Methyl-SAPS), with yields being consistent for greater than 1 year. Radiolabelings of 1 and SPEMS with 125 I generated succinimidyl N-2-(4-[ 125 I]iodophenethyl)succinamate (SIPS) and succinimidyl N-2-(4-[ 125 I]iodophenethyl)-N-methyl succinamate (Methyl-SIPS), respectively, and showed no decline in yields. Methyl-SAPS, SAPS, Methyl-SIPS and SIPS were conjugated to Herceptin for a comparative assessment in LS-174T xenograft-bearing mice. The conjugates of Herceptin with Methyl-SAPS or Methyl-SIPS demonstrated immunoreactivity equivalent to if not superior to the SAPS and SIPS paired analogs. The in vivo studies also revealed that the N-methyl modification resulted in a superior statinated product

  11. Preparation and quality control of radiometal-DOTARituximab

    International Nuclear Information System (INIS)

    Jalilian, A.R.; Kamali-dehghan, M.; Moradkhani, S.; Saddadi, F.; Mirsadeghi, L.

    2008-01-01

    In this work Rituximab has been labeled by Ga-67 using a new one-step method for in-situ preparation of macrocyclic bifunctional chelating agent, N-succinimidyl-1,4,7,10- tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTANHS). DOTA-NHS was prepared at 25 deg. C using DOTA, Nhydroxy succinimide (NHS) in CH Cl in one step. DOTA- 2 2 Rituximab was obtained by the addition of 1 ml of a Rituximab pharmaceutical solution (5 mg/ml, in phosphate buffer, pH=7.8) to a glass tube pre-coated with DOTA-NHS (0.01-0.1 mg) at 25 deg. C with continuous mild stirring for 15 hours. Radiolabeling was performed at 37 deg. C in 3 hrs using Ga-67 Chlorides or Cu-64 Acetate. Thin layer radiochromatography demonstrated an overall radiochemical purity of 90-95% at optimized conditions (specific activity =30 GBq/mg, labeling efficacy= 82%). The final isotonic radio-metal-DOTA-Rituximab complex was checked by gel electrophoresis for radiolysis. TLC was performed to ensure that only one species was present after filtration through a 0.22 μm filter. Preliminary bio-distribution studies of the Ga-67 immunoconjugate in normal rat model performed to determine complex distribution of the radioimmunoconjugate up to 28hrs by imaging and organ counting after sacrificing the rats. In this study a facile method for incorporation of metal chelating moiety into peptides and antibody structure is presented. (author)

  12. Validation of analytical method to calculate the concentration of conjugated monoclonal antibody; Validacao de metodo analitico para calculo de concentracao de anticorpo monoclonal conjugado

    Energy Technology Data Exchange (ETDEWEB)

    Alcarde, Lais F.; Massicano, Adriana V.F.; Oliveira, Ricardo S.; Araujo, Elaine B. de, E-mail: lais_alcarde@hotmail.com [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2013-07-01

    The objective of this study was to develop a quantitative analytical method using high performance liquid chromatography (HPLC) to determine the antibody concentration in conjunction with bifunctional chelator. Assays were performed using a high performance liquid chromatograph, and the following conditions were used: flow rate of 1 mL / min, 15 min run time, 0.2 M sodium phosphate buffer pH 7.0 as the mobile phase and column of molecular exclusion BioSep SEC S-3000 (300 x 7.8 mm, 5 μM - Phenomenex). The calibration curve was obtained with AcM diluted in 0.2 M sodium phosphate buffer pH 7.0 by serial dilution, yielding the concentrations: 400 μg/mL, 200 μg/mL, 100 μg/mL, 50 μg/mL, 25 μg/mL and 12.5 μg/mL. From the calibration curve calculated the equation of the line and with it the concentration of the immunoconjugate. To ensure the validity of the method accuracy and precision studies were conducted. The accuracy test consisted in the evaluation of 3 samples of known concentration, being this test performed with low concentrations (50 μg/mL), medium (100 μg/mL) and high (200 μg/mL). The precision test consisted of 3 consecutive measurements of one sample of known concentration, subject to the conditions set forth above for the other tests. The correlation coefficient of the standard curve was greater than 97%, the accuracy was satisfactory at low concentrations as well as accuracy. The method was validated by showing it for the accurate and precise determination of the concentration of the immunoconjugate. Furthermore, this assay was found to be extremely important, because using the correct mass of the protein, the radiochemical purity of the radioimmunoconjugate was above 95% in all studies.

  13. Pharmacokinetics and normal organ dosimetry following intraperitoneal rhenium-186-labeled monoclonal antibody

    International Nuclear Information System (INIS)

    Breitz, H.B.; Durham, J.S.; Fisher, D.R.

    1995-01-01

    Pharmacokinetics, biodistribution and radiation dose estimates following intraperitoneal administration of a 186 Re-labeled murine antibody, NR-LU-10, were assessed in 27 patients with advanced ovarian cancer. Quantitative gamma camera imaging and gamma counting of serum and intraperitoneal fluid radioactivity were used to obtain data for dosimetry estimation. The MIRD intraperitoneal model was used to estimate dose to normal organs from radioactivity within the peritoneal cavity. The absorbed dose to normal peritoneum was estimated in two ways: from the gamma camera activity and peritoneal fluid samples. Serum activity peaked at 44 hr and depended on the concentration of radioactivity in the peritoneal fluid. Mean cumulative urinary excretion of 186 Re was 50% by 140 hr. Estimates of radiation absorbed dose to normal organs in rad/mCi administered (mean ± s.d.) were whole body 0.7 ± 0.3; marrow 0.4 ±0.1; liver 1.9 ±0.9; lungs 1.3 ± 0.7; kidneys 0.2 ± 0.2; intestine 0.2 ±0.2. Peritoneal surface dose estimates varied depending on the volume of fluid infused and the method of dose determination. Using gamma camera data, the peritoneal dose ranged for 7 to 36 rad/mCi. Using peritoneal fluid sample data, the dose ranged from 2 to 25 rad/mCi. Significant myelosuppression was observed at marrow doses above 100 rad. Noninvasive methods of dose estimation for intraperitoneal administration of radioimmunoconjugates provide reasonable estimates when compared with previously described methods. 31 refs., 6 figs., 2 tabs

  14. Studies on the optimization of leukemia and non-Hodgkin lymphoma therapies using opioids, chemotherapy and radioimmunotherapy; Studien zur Optimierung von Leukaemie- und non-Hodgkin-Lymphom-Therapien durch den Einsatz von Opioiden, Chemotherapeutika und Radioimmuntherapien

    Energy Technology Data Exchange (ETDEWEB)

    Roscher, Mareike

    2013-05-24

    Despite complex treatment schedules for cancer, the occurrence of resistances and relapses is a major concern in oncology. Hence, novel treatment options are needed. In this thesis, different approaches using radioimmunotherapy and the opioid D,L-methadone alone or in combination with doxorubicin were analyzed regarding their cytotoxic potential and the triggered signalling pathways in sensitive and resistant leukaemia and non-Hodgkin lymphoma (NHL). The radioimmunoconjugates [Bi-213]anti-CD33 and [Bi-213]anti-CD20 for treatment of acute myeloid leukaemia (AML) or NHL, respectively, were applied exemplary for the use of targeted alpha-therapies (TAT). Depending on the analyzed cell lines, the used activity concentrations and specific activities (MBq/μg antibody) apoptosis was induced abrogating radio- and chemo-cross-resistances specifically. The cell death was caspase-dependent activating the mitochondrial pathway and was executed by downregulation of the anti-apoptotic proteins XIAP and Bcl-xL. D,L-Methadone induces apoptosis in vitro and in vivo in opioid-receptor (OR) expressing cells depending on the OR density and the used concentrations. Resistances could be overcome and proliferation was inhibited. In combination with doxorubicin, a synergistic effect regarding cytotoxicity in ex vivo patient cells and cell lines was observed. This effect depends on the increase of doxorubicin uptake co-administering D,L-methadone whereas doxorubicin enhances OR expression. The activation of OR leads to the downregulation of cAMP playing a pivotal role in apoptosis induction. In vivo, the therapeutic potential of D,L-methadone alone or in combination with doxorubicin could be proven as mice transplanted with human T-ALL-cells could be identified as tumour free. In summary, these studies show that TAT using [Bi-213]anti-CD33 and [Bi-213]anti-CD20 as well as the opioid D,L-methadone harbour the potential to optimize conventional treatment modalities for leukaemia and NHL.

  15. Characterisation of chemically-modified proteins by electrospray ionisation mass spectrometry

    International Nuclear Information System (INIS)

    Bennett, K.L.

    1996-09-01

    Electrospray mass spectrometry (ESI-MS) has been used to examine a range of intact monoclonal antibodies (MAbs), antibody fragments such as F(ab') 2 , F ab and F c , chemically-modified fragments and a range of other chemically-modified peptides and proteins as part of a broader study aimed at establishing ESI-MS as a method for the characterisation of radioimmunoconjugates (radiolabelled monoclonal antibodies). For example, the addition of up to 10 biotin molecules to the 'papain-sensitive' 50 kDa F ab fragment can be easily detected in ESI mass spectra. For intact MAbs, however, it is only possible to detect average shifts in the mass of intact antibodies following modification. Successful ESI-MS analysis of complexes formed between chelators and other small molecules conjugated to synthetic peptides, hen egg-white Iysozyme (HEL) (M r 14 306) and horse heart myoglobin (M r 16 951) has been demonstrated. ESI-MS offers considerable advantages compared with existing methods for the characterisation of chemically-conjugated proteins including speed and sensitivity of analysis and the capability for obtaining specific structural information. The conditions for ESI-MS of intact MAbs and MAb fragments have been examined in detail and it was found that 150 kDa MAbs generally required lower sample concentration and higher skimmer potentials compared with the 50 kDa F ab fragment and other lower molecular weight proteins. In addition, the m/z range over which ions from MAbs were observed was higher (m/z ∼2000-4500) than for smaller proteins. ESI-MS was also found to be useful for probing the action of the protease papain, that is used to generate MAb fragments (F(ab) '2, F ab and F c ). Further, different sensitivities to papain for different MAb preparations was demonstrated. Finally, the tandem mass spectra of a range of peptides modified by iodine and biotin were examined. In the case of biotinylated peptides, a characteristic fragment ion was identified that could

  16. Myeloablative radioimmunotherapies in the conditioning of patients with AML, MDS and multiple myeloma prior to stem cell transplantation

    International Nuclear Information System (INIS)

    Buchmann, I.

    2008-01-01

    Aggressive consolidation chemotherapy and hematopoietic stem cell transplantation have improved the prognosis of patients with acute myeloid leukemia (AML), myelodyplastic syndrome (MDS) and multiple myeloma. Nevertheless, only a minor fraction of patients achieve long-term disease-free survival after stem cell transplantation with disease recurrence being the most common cause of treatment failure. In addition, therapy-related effects such as toxicity of chemotherapy and complications of stem cell transplantation increase mortality rates significantly. Myeloablative radioimmunotherapy uses radiolabeled monoclonal antibodies (mAb) with affinity for the hematopoietic marrow. It applies high radiation doses in the bone marrow but spares normal organs. Adding myeloablative radioimmunotherapy to the conditioning schemes of AML, MDS and multiple myeloma before stem cell transplantation allows for the achievement of a pronounced antileukemic/antimyeloma effect for the reduction of relapse rates without significant increase of acute organ toxicity and therapy-related mortality. In order to optimise therapy, a rational design of the nuclide-antibody combination is necessary. 90 Y, 188 Re and 131 I are the most frequently used β - -particles. Of these, 90 Y is the most qualified nuclide for myeloablation. Backbone stabilised DTPA are ideal chelators to stably conjugate 90 Y to antibodies so far. For myeloablative conditioning, anti-CD66-, -45- and -33-mAb are used. The anti-CD66-antibody BW250/183 binds to normal hematopoietic cells but not to leukemic blasts and myeloma cells. The 90 Y-2B3M-DTPA-BW250/183 is the most suited radioimmunoconjugate for patients with an infiltration grade of leukemic blasts in the bone marrow 90 Y-anti-CD45-mAb YAML568 are 6.4 ± 1.2 (bone marrow), 3.9 ± 1.4 (liver) and 1.1 ± 0.4 (kidneys). CD45 is expressed also on the extramedullar clonogenic myeloma progenitor cell that circulates in the peripheral blood. Thus, the conditioning of

  17. Radiolabeling of rituximab with 188Re and 99mTc using the tricarbonyl technology

    International Nuclear Information System (INIS)

    Dias, Carla Roberta; Jeger, Simone; Osso, Joao Alberto; Mueller, Cristina; De Pasquale, Christine; Hohn, Alexander; Waibel, Robert; Schibli, Roger

    2011-01-01

    Introduction: The most successful clinical studies of immunotherapy in patients with non-Hodgkin's lymphoma (NHL) use the antibody rituximab (RTX) targeting CD20 + B-cell tumors. Rituximab radiolabeled with β - emitters could potentiate the therapeutic efficacy of the antibody by virtue of the particle radiation. Here, we report on a direct radiolabeling approach of rituximab with the 99m Tc- and 188 Re-tricarbonyl core (IsoLink technology). Methods: The native format of the antibody (RTX wt ) as well as a reduced form (RTX red ) was labeled with 99m Tc/ 188 Re(CO) 3 . The partial reduction of the disulfide bonds to produce free sulfhydryl groups (-SH) was achieved with 2-mercaptoethanol. Radiolabeling efficiency, in vitro human plasma stability as well as transchelation toward cysteine and histidine was investigated. The immunoreactivity and binding affinity were determined on Ramos and/or Raji cells expressing CD20. Biodistribution was performed in mice bearing subcutaneous Ramos lymphoma xenografts. Results: The radiolabeling efficiency and kinetics of RTX red were superior to that of RTX wt ( 99m Tc: 98% after 3 h for RTX red vs. 70% after 24 h for RTX wt ). 99m Tc(CO) 3 -RTX red was used without purification for in vitro and in vivo studies whereas 188 Re(CO) 3 -RTX red was purified to eliminate free 188 Re-precursor. Both radioimmunoconjugates were stable in human plasma for 24 h at 37 o C. In contrast, displacement experiments with excess cysteine/histidine showed significant transchelation in the case of 99m Tc(CO) 3 -RTX red but not with pre-purified 188 Re(CO) 3 -RTX red . Both conjugates revealed high binding affinity to the CD20 antigen (K d =5-6 nM). Tumor uptake of 188 Re(CO) 3 -RTX red was 2.5 %ID/g and 0.8 %ID/g for 99m Tc(CO) 3 -RTX red 48 h after injection. The values for other organs and tissues were similar for both compounds, for example the tumor-to-blood and tumor-to-liver ratios were 0.4 and 0.3 for 99m Tc(CO) 3 -RTX red and for 188 Re

  18. Targeted bone marrow irradiation in the conditioning of high-risk leukaemia prior to stem cell transplantation

    International Nuclear Information System (INIS)

    Reske, S.N.; Buchmann, I.; Seitz, U.; Glatting, G.; Neumaier, B.; Kotzerke, J.; Buck, A.; Martin, H.; Bergmann, L.

    2001-01-01

    Disease recurrence following stem cell transplantation (SCT) remains a major problem. Despite the sensitivity of leukaemias to chemotherapy and irradiation, conventional conditioning before SCT is limited by significant organ toxicity. Targeted irradiation of bone marrow and spleen by radioimmunotherapy may provide considerable dose escalation, with limited toxicity to non-target organs. In this study, 27 patients with high-risk or relapsing leukaemia were treated with rhenium-188-labelled CD66a,b,c,e radioimmunoconjugates ( 188 Re-mAb) specific for normal bone marrow in addition to conventional conditioning with high-dose chemotherapy and 12 Gy total body irradiation prior to SCT. A mean activity of 10.2±2.1 (range 6.9-15.8) GBq 188 Re-mAb was administered intravenously. Acute side-effects were assessed according to the CTC classification and patient outcome was determined. Mean radiation doses (Gy; range in parentheses) to relevant organs and whole body were as follows: 13.1 (6.5-22) to bone marrow, 11.6 (1.7-31.1) to spleen, 5.0 (2.0-11.7) to liver, 7.0 (2.3-11.6) to kidneys, 0.7 (0.3-1.3) to lungs and 1.4 (0.8-2.1) to the whole body. Stem cells engrafted in all patients within 9-18 days post SCT. Acute organ toxicity of grade II or less was observed. During follow-up for 25.4±5.3 (range 18-34) months, 4/27 (15%) patients died from relapse, and 9/27 (33%) from transplantation-related complications. Fourteen patients (52%) are still alive and in ongoing complete clinical remission. Radioimmunotherapy with the bone marrow-seeking 188 Re-labelled CD66 mAb can double the dose to bone marrow and spleen without undue extramedullary acute organ toxicity, when given in addition to high-dose chemotherapy and 12 Gy TBI before allogeneic SCT. This intensified conditioning regimen may reduce the relapse rate of high-risk leukaemia. (orig.)

  19. Anti-L1CAM radioimmunotherapy is more effective with the radiolanthanide terbium-161 compared to lutetium-177 in an ovarian cancer model

    International Nuclear Information System (INIS)

    Gruenberg, Juergen; Lindenblatt, Dennis; Cohrs, Susan; Fischer, Eliane; Dorrer, Holger; Zhernosekov, Konstantin; Koester, Ulli; Tuerler, Andreas; Schibli, Roger

    2014-01-01

    The L1 cell adhesion molecule (L1CAM) is considered a valuable target for therapeutic intervention in different types of cancer. Recent studies have shown that anti-L1CAM radioimmunotherapy (RIT) with 67 Cu- and 177 Lu-labelled internalising monoclonal antibody (mAb) chCE7 was effective in the treatment of human ovarian cancer xenografts. In this study, we directly compared the therapeutic efficacy of anti-L1CAM RIT against human ovarian cancer under equitoxic conditions with the radiolanthanide 177 Lu and the potential alternative 161 Tb in an ovarian cancer therapy model. Tb was produced by neutron bombardment of enriched 160 Gd targets. 161 Tb and 177 Lu were used for radiolabelling of DOTA-conjugated antibodies. The in vivo behaviour of the radioimmunoconjugates (RICs) was assessed in IGROV1 tumour-bearing nude mice using biodistribution experiments and SPECT/CT imaging. After ascertaining the maximal tolerated doses (MTD) the therapeutic impact of 50 % MTD of 177 Lu- and 161 Tb-DOTA-chCE7 was evaluated in groups of ten mice by monitoring the tumour size of subcutaneous IGROV1 tumours. The average number of DOTA ligands per antibody was 2.5 and maximum specific activities of 600 MBq/mg were achieved under identical radiolabelling conditions. RICs were stable in human plasma for at least 48 h. 177 Lu- and 161 Tb-DOTA-chCE7 showed high tumour uptake (37.8-39.0 %IA/g, 144 h p.i.) with low levels in off-target organs. SPECT/CT images confirmed the biodistribution data. 161 Tb-labelled chCE7 revealed a higher radiotoxicity in nude mice (MTD: 10 MBq) than the 177 Lu-labelled counterpart (MTD: 12 MBq). In a comparative therapy study with equitoxic doses, tumour growth inhibition was better by 82.6 % for the 161 Tb-DOTA-chCE7 than the 177 Lu-DOTA-chCE7 RIT. Our study is the first to show that anti-L1CAM 161 Tb RIT is more effective compared to 177 Lu RIT in ovarian cancer xenografts. These results suggest that 161 Tb is a promising candidate for future clinical

  20. ¹¹¹In-Bn-DTPA-nimotuzumab with/without modification with nuclear translocation sequence (NLS) peptides: an Auger electron-emitting radioimmunotherapeutic agent for EGFR-positive and trastuzumab (Herceptin)-resistant breast cancer.

    Science.gov (United States)

    Fasih, Aisha; Fonge, Humphrey; Cai, Zhongli; Leyton, Jeffrey V; Tikhomirov, Ilia; Done, Susan J; Reilly, Raymond M

    2012-08-01

    Increased expression of epidermal growth factor receptors (EGFR) in breast cancer (BC) is often associated with trastuzumab (Herceptin)-resistant forms of the disease and represents an attractive target for novel therapies. Nimotuzumab is a humanized IgG(1) monoclonal antibody that is in clinical trials for treatment of EGFR-overexpressing malignancies. We show here that nimotuzumab derivatized with benzylisothiocyanate diethylenetriaminepentaacetic acid for labelling with the subcellular range Auger electron-emitter, (111)In and modified with nuclear translocation sequence (NLS) peptides ((111)In-NLS-Bn-DTPA-nimotuzumab) was bound, internalized and transported to the nucleus of EGFR-positive BC cells. Emission of Auger electrons in close proximity to the nucleus caused multiple DNA double-strand breaks which diminished the clonogenic survival (CS) of MDA-MB-468 cells that have high EGFR density (2.4 × 10(6) receptors/cell) to less than 3 %. (111)In-Bn-DTPA-nimotuzumab without NLS peptide modification was sevenfold less effective for killing MDA-MB-468 cells. (111)In-Bn-DTPA-nimotuzumab with/without NLS peptide modification were equivalently cytotoxic to MDA-MB-231 and TrR1 BC cells that have moderate EGFR density (5.4 × 10(5) or 4.2 × 10(5) receptors/cell, respectively) reducing their CS by twofold. MDA-MB-231 cells have intrinsic trastuzumab resistance due to low HER2 density, whereas TrR1 cells have acquired resistance despite HER2 overexpression. Biodistribution and microSPECT/CT imaging revealed that (111)In-NLS-Bn-DTPA-nimotuzumab exhibited more rapid elimination from the blood and lower tumour uptake than (111)In-Bn-DTPA-nimotuzumab. Tumour uptake of the radioimmunoconjugates in mice with MDA-MB-468 xenografts was high (8-16 % injected dose/g) and was blocked by administration of an excess of unlabelled nimotuzumab, demonstrating EGFR specificity. We conclude that (111)In-Bn-DTPA-nimotuzumab with/without NLS peptide modification are promising Auger

  1. Optimization of a Pretargeted Strategy for the PET Imaging of Colorectal Carcinoma via the Modulation of Radioligand Pharmacokinetics.

    Science.gov (United States)

    Zeglis, Brian M; Brand, Christian; Abdel-Atti, Dalya; Carnazza, Kathryn E; Cook, Brendon E; Carlin, Sean; Reiner, Thomas; Lewis, Jason S

    2015-10-05

    increases in tumor-to-blood activity concentration ratios. This new strategy offers dosimetric benefits as well, yielding a total effective dose of 0.041 rem/mCi, far below the doses produced by directly labeled (64)Cu-NOTA-huA33 (0.133 rem/mCi) and (89)Zr-DFO-huA33 (1.54 rem/mCi). Ultimately, this pretargeted PET imaging strategy boasts a dramatically improved pharmacokinetic profile compared to our first generation system and is capable of clearly delineating tumor tissue with high image contrast at only a fraction of the radiation dose created by directly labeled radioimmunoconjugates.

  2. Anti-L1CAM radioimmunotherapy is more effective with the radiolanthanide terbium-161 compared to lutetium-177 in an ovarian cancer model

    Energy Technology Data Exchange (ETDEWEB)

    Gruenberg, Juergen; Lindenblatt, Dennis; Cohrs, Susan; Fischer, Eliane [Paul Scherrer Institute, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Villigen (Switzerland); Dorrer, Holger [Paul Scherrer Institute, Laboratory of Radiochemistry and Environmental Chemistry, Villigen (Switzerland); Zhernosekov, Konstantin [ITG Isotope Technologies Garching GmbH, Garching (Germany); Koester, Ulli [Institut Laue-Langevin, Grenoble (France); Tuerler, Andreas [Paul Scherrer Institute, Laboratory of Radiochemistry and Environmental Chemistry, Villigen (Switzerland); University of Bern, Department of Chemistry and Biochemistry, Berne (Switzerland); Schibli, Roger [Paul Scherrer Institute, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Villigen (Switzerland); ETH Zurich, Department of Chemistry and Applied Biosciences, Zurich (Switzerland)

    2014-10-15

    The L1 cell adhesion molecule (L1CAM) is considered a valuable target for therapeutic intervention in different types of cancer. Recent studies have shown that anti-L1CAM radioimmunotherapy (RIT) with {sup 67}Cu- and {sup 177}Lu-labelled internalising monoclonal antibody (mAb) chCE7 was effective in the treatment of human ovarian cancer xenografts. In this study, we directly compared the therapeutic efficacy of anti-L1CAM RIT against human ovarian cancer under equitoxic conditions with the radiolanthanide {sup 177}Lu and the potential alternative {sup 161}Tb in an ovarian cancer therapy model. Tb was produced by neutron bombardment of enriched {sup 160}Gd targets. {sup 161}Tb and {sup 177}Lu were used for radiolabelling of DOTA-conjugated antibodies. The in vivo behaviour of the radioimmunoconjugates (RICs) was assessed in IGROV1 tumour-bearing nude mice using biodistribution experiments and SPECT/CT imaging. After ascertaining the maximal tolerated doses (MTD) the therapeutic impact of 50 % MTD of {sup 177}Lu- and {sup 161}Tb-DOTA-chCE7 was evaluated in groups of ten mice by monitoring the tumour size of subcutaneous IGROV1 tumours. The average number of DOTA ligands per antibody was 2.5 and maximum specific activities of 600 MBq/mg were achieved under identical radiolabelling conditions. RICs were stable in human plasma for at least 48 h. {sup 177}Lu- and {sup 161}Tb-DOTA-chCE7 showed high tumour uptake (37.8-39.0 %IA/g, 144 h p.i.) with low levels in off-target organs. SPECT/CT images confirmed the biodistribution data. {sup 161}Tb-labelled chCE7 revealed a higher radiotoxicity in nude mice (MTD: 10 MBq) than the {sup 177}Lu-labelled counterpart (MTD: 12 MBq). In a comparative therapy study with equitoxic doses, tumour growth inhibition was better by 82.6 % for the {sup 161}Tb-DOTA-chCE7 than the {sup 177}Lu-DOTA-chCE7 RIT. Our study is the first to show that anti-L1CAM {sup 161}Tb RIT is more effective compared to {sup 177}Lu RIT in ovarian cancer xenografts

  3. Dosimetric analysis of 177Lu-DOTA-rituximab in patients with relapsed/refractory non-Hodgkin's lymphoma.

    Science.gov (United States)

    Yadav, Madhav P; Singla, Suhas; Thakral, Parul; Ballal, Sanjana; Bal, Chandrasekhar

    2016-07-01

    Radioimmunotherapy targeting CD20 receptors in lymphoma using radiolabeled chimeric antibodies may lead to better therapeutic responses than cold anti-CD20 antibodies. This study aimed to assess the biodistribution and present reasonable estimates of normal organ doses, including red marrow using Lu-DOTA-rituximab. Patients with relapsed/refractory CD20+ B-cell non-Hodgkin's lymphoma were recruited into this prospective study. In-house labeling of Lu-DOTA-rituximab was performed and administered after quality assurance. Rituximab (375 mg/m), followed by 50 mCi (1850 MBq) of Lu-DOTA-rituximab was administered as a slow intravenous infusion and emission images were acquired. Regions of interest were drawn for kidney, liver, heart, bladder, spleen, and tumor lesions on both anterior and posterior images. Internal dose estimation was performed using OLINDA v1.0 software. The mean age of the 10 patients (eight men and two women) was 52±13 years. The uptake of radiolabeled antibody was visualized within 30 min of administration in the liver, kidneys, heart, spleen, and bladder. The coefficient of determination (R) was greater than 0.95 for organs and the whole body in all patients. The effective half-life of radioimmunoconjugate was 100±28 h (42-126 h). The critical organ in our study was the red marrow. The average total body dose, effective dose, and effective dose equivalent calculated in all 10 patients were 0.13±0.02, 0.15±0.03, and 0.22±0.04 mGy/MBq, respectively. There may be considerable interindividual differences in absorbed doses of organs and generalization or extrapolation of doses in the clinical setting at present is not feasible with Lu-DOTA-rituximab in non-Hodgkin's lymphoma patients. Patient-specific dosimetry is thus recommended to eliminate the variations and reduce the possibility of dose-limiting toxicity.

  4. Fractionated therapy of HER2-expressing breast and ovarian cancer xenografts in mice with targeted alpha emitting 227Th-DOTA-p-benzyl-trastuzumab.

    Directory of Open Access Journals (Sweden)

    Helen Heyerdahl

    Full Text Available BACKGROUND: The aim of this study was to investigate therapeutic efficacy and normal tissue toxicity of single dosage and fractionated targeted alpha therapy (TAT in mice with HER2-expressing breast and ovarian cancer xenografts using the low dose rate radioimmunoconjugate (227Th-DOTA-p-benzyl-trastuzumab. METHODOLOGY/PRINCIPAL FINDINGS: Nude mice carrying HER2-overexpressing subcutaneous SKOV-3 or SKBR-3 xenografts were treated with 1000 kBq/kg (227Th-trastuzumab as single injection or four injections of 250 kBq/kg with intervals of 4-5 days, 2 weeks, or 4 weeks. Control animals were treated with normal saline or unlabeled trastuzumab. In SKOV-3 xenografts tumor growth to 10-fold size was delayed (p<0.01 and survival with tumor diameter less than 16 mm was prolonged (p<0.05 in all TAT groups compared to the control groups. No statistically significant differences were seen among the treated groups. In SKBR-3 xenografts tumor growth to 10-fold size was delayed in the single injection and 4-5 days interval groups (p<0.001 and all except the 4 weeks interval TAT group showed improved survival to the control groups (p<0.05. Toxicity was assessed by blood cell counts, clinical chemistry measurements and body weight. Transient reduction in white blood cells was seen for the single injection and 4-5 days interval groups (p<0.05. No significant changes were seen in red blood cells, platelets or clinical chemistry parameters. Survival without life threatening loss of body weight was significantly prolonged in 4 weeks interval group compared to single injection group (p<0.05 for SKOV-3 animals and in 2 weeks interval group compared with the 4-5 days interval groups (p<0.05 for SKBR-3 animals. CONCLUSIONS/SIGNIFICANCE: The same concentration of radioactivity split into several fractions may improve toxicity of (227Th-radioimmunotherapy while the therapeutic effect is maintained. Thus, it might be possible to increase the cumulative absorbed radiation dose

  5. Radiolabeling of rituximab with {sup 188}Re and {sup 99m}Tc using the tricarbonyl technology

    Energy Technology Data Exchange (ETDEWEB)

    Dias, Carla Roberta [Instituto de Pesquisas Energeticas e Nucleares, Av. Professor Lineu Prestes 2242, 05508-000 Sao Paulo (Brazil); Jeger, Simone [Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232 Villigen-PSI (Switzerland); Osso, Joao Alberto [Instituto de Pesquisas Energeticas e Nucleares, Av. Professor Lineu Prestes 2242, 05508-000 Sao Paulo (Brazil); Mueller, Cristina; De Pasquale, Christine; Hohn, Alexander; Waibel, Robert [Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232 Villigen-PSI (Switzerland); Schibli, Roger, E-mail: roger.schibli@psi.c [Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232 Villigen-PSI (Switzerland); Department of Chemistry and Applied Biosciences of the ETH, 8093 Zurich (Switzerland)

    2011-01-15

    Introduction: The most successful clinical studies of immunotherapy in patients with non-Hodgkin's lymphoma (NHL) use the antibody rituximab (RTX) targeting CD20{sup +} B-cell tumors. Rituximab radiolabeled with {beta}{sup -} emitters could potentiate the therapeutic efficacy of the antibody by virtue of the particle radiation. Here, we report on a direct radiolabeling approach of rituximab with the {sup 99m}Tc- and {sup 188}Re-tricarbonyl core (IsoLink technology). Methods: The native format of the antibody (RTX{sub wt}) as well as a reduced form (RTX{sub red}) was labeled with {sup 99m}Tc/{sup 188}Re(CO){sub 3}. The partial reduction of the disulfide bonds to produce free sulfhydryl groups (-SH) was achieved with 2-mercaptoethanol. Radiolabeling efficiency, in vitro human plasma stability as well as transchelation toward cysteine and histidine was investigated. The immunoreactivity and binding affinity were determined on Ramos and/or Raji cells expressing CD20. Biodistribution was performed in mice bearing subcutaneous Ramos lymphoma xenografts. Results: The radiolabeling efficiency and kinetics of RTX{sub red} were superior to that of RTX{sub wt} ({sup 99m}Tc: 98% after 3 h for RTX{sub red} vs. 70% after 24 h for RTX{sub wt}). {sup 99m}Tc(CO){sub 3}-RTX{sub red} was used without purification for in vitro and in vivo studies whereas {sup 188}Re(CO){sub 3}-RTX{sub red} was purified to eliminate free {sup 188}Re-precursor. Both radioimmunoconjugates were stable in human plasma for 24 h at 37{sup o}C. In contrast, displacement experiments with excess cysteine/histidine showed significant transchelation in the case of {sup 99m}Tc(CO){sub 3}-RTX{sub red} but not with pre-purified {sup 188}Re(CO){sub 3}-RTX{sub red}. Both conjugates revealed high binding affinity to the CD20 antigen (K{sub d}=5-6 nM). Tumor uptake of {sup 188}Re(CO){sub 3}-RTX{sub red} was 2.5 %ID/g and 0.8 %ID/g for {sup 99m}Tc(CO){sub 3}-RTX{sub red} 48 h after injection. The values for other

  6. In vivo monitoring of intranuclear p27{sup kip1} protein expression in breast cancer cells during trastuzumab (Herceptin) therapy

    Energy Technology Data Exchange (ETDEWEB)

    Cornelissen, Bart [Division of Nuclear Medicine, University Health Network, Toronto, ON, Canada M5S 3E2 (Canada); Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, M5S 3M2 (Canada); MRC/CRUK Gray Institute for Radiation Oncology and Biology, Oxford University, OX3 7LJ Oxford (United Kingdom)], E-mail: bart.cornelissen@rob.ox.ac.uk; Kersemans, Veerle; McLarty, Kristin [Division of Nuclear Medicine, University Health Network, Toronto, ON, M5S 3E2 (Canada); Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Tran, Lara [Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Vallis, Katherine A. [MRC/CRUK Gray Institute for Radiation Oncology and Biology, Oxford University, OX3 7LJ Oxford (United Kingdom); Reilly, Raymond M. [Division of Nuclear Medicine, University Health Network, Toronto, ON, M5S 3E2 (Canada); Department of Medical Imaging, University of Toronto, Toronto, ON, M5S 3E2 (Canada); Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, M5S 3M2 (Canada)

    2009-10-15

    Introduction: Trastuzumab, a humanized antibody directed against the Her2 receptor, induces the expression of p27{sup kip1}, an intranuclear cyclin-dependent kinase inhibitor in some breast cancer cells. The aim of this study was to develop a radioimmunoconjugate (RIC) to monitor trastuzumab-induced p27{sup kip1} protein up-regulation in vivo. Materials and Methods: Anti-p27{sup kip1} IgG was purified, and conjugated to diethylenetriaminopentaacetate, to allow radiolabeling with {sup 111}In for in vivo detection. Then tat peptide (GRKKRRQRRRPPQGYG), containing a nuclear localization sequence (underlined), was conjugated to the Fc-domain of IgG, using NaIO{sub 4} oxidation of carbohydrates and the resulting Schiff base stabilized with NaCNBH{sub 3}. The conjugate was radiolabeled with {sup 111}In, yielding [{sup 111}In]-anti-p27{sup kip1}-tat. {sup 111}In labeling efficiency, purity and p27{sup kip1} binding were measured. Trastuzumab-induced p27{sup kip1} up-regulation was assessed in a panel of breast cancer cell lines by Western blot analysis. Uptake and retention of [{sup 111}In]-anti-p27{sup kip1}-tat were measured in MDA-MB-361 and SKBr3 cells after exposure to trastuzumab. Uptake of [{sup 111}In]-anti-p27{sup kip1}-tat was determined at 72 h postintravenous injection in MDA-MB-361 xenografts in athymic mice treated with trastuzumab or saline. Results: [{sup 111}In]-anti-p27{sup kip1}-tat was synthesized to 97% purity. The RIC was able to bind to p27{sup kip1} protein and internalized in the cells and was transported to the nuclei of MDA-MB-361 cells. The level of p27{sup kip1} protein in MDA-MB-361 cells was increased after exposure to clinically relevant doses of trastuzumab for 3 days. Trastuzumab-mediated induction of p27{sup kip1} was not associated with increased cellular uptake or nuclear localization of [{sup 111}In]-anti-p27{sup kip1}-tat (6.53{+-}0.61% vs. 6.98{+-}1.36% internalized into trastuzumab-treated vs. control cells, respectively). However

  7. Monoclonal antibodies in the treatment of non-Hodgkin's lymphoma.

    Science.gov (United States)

    Fanale, Michelle A; Younes, Anas

    2007-01-01

    Antibody-based therapeutic approaches have had a significant impact in the treatment of non-Hodgkin's lymphoma (NHL). Rituximab's development as an anti-CD20 antibody heralded a new era in treatment approaches for NHL. While rituximab was first shown to be effective in the treatment of relapsed follicular lymphoma, it is now standard monotherapy for front-line treatment of follicular lymphoma, and is also used in conjunction with chemotherapy for other indolent, intermediate and aggressive B-cell lymphomas. The development of rituximab has led to intense interest in this type of therapeutic approach and to development and approval of the radioimmunoconjugates of rituximab, (90)Y-ibritumomab tiuxetan and (131)I-tositumomab, which have added to the repertoire of treatments for relapsed follicular lymphoma and increased interest in developing other conjugated antibodies. Since rituximab is a chimeric antibody, there is a need to develop fully humanised antibodies, such as IMMU-106 (hA20), in order to minimise infusion reactions and eliminate the development of human antibodies against the drug. Further clinical evaluation of antibodies has been based largely on our knowledge of antigen expression on the surface of lymphoma cells and has led to the development of antibodies against CD22 (unconjugated epratuzumab and calicheamicin conjugated CMC-544 [inotuzumab ozogamicin]), CD80 (galiximab), CD52 (alemtuzumab), CD2 (MEDI-507 [siplizumab]), CD30 (SGN-30 and MDX-060 [iratumumab]), and CD40 (SGN-40). Furthermore, the VEGF (vascular endothelial growth factor) inhibitor bevacizumab, which was first approved for the treatment of colon cancer is currently under investigation in NHL, and agonists rather than antibodies to TRAIL (tumour necrosis factor-related apoptosis-inducing ligand) [rApo2L/TRAIL, HGS-ETR1{mapatumumab}, HGS-ETR2] are currently being investigated as treatments for both advanced solid tumours and NHL. Knowledge of the ability of cancer cells to become

  8. Myeloablative radioimmunotherapies in the conditioning of patients with AML, MDS and multiple myeloma prior to stem cell transplantation; Myeloablative Radioimmuntherapien zur Konditionierung bei Patienten mit AML, MDS und multiplem Myelom vor Stammzelltransplantation

    Energy Technology Data Exchange (ETDEWEB)

    Buchmann, I. [Abt. fuer Nuklearmedizin, Universitaetsklinik Heidelberg (Germany)

    2008-06-15

    Aggressive consolidation chemotherapy and hematopoietic stem cell transplantation have improved the prognosis of patients with acute myeloid leukemia (AML), myelodyplastic syndrome (MDS) and multiple myeloma. Nevertheless, only a minor fraction of patients achieve long-term disease-free survival after stem cell transplantation with disease recurrence being the most common cause of treatment failure. In addition, therapy-related effects such as toxicity of chemotherapy and complications of stem cell transplantation increase mortality rates significantly. Myeloablative radioimmunotherapy uses radiolabeled monoclonal antibodies (mAb) with affinity for the hematopoietic marrow. It applies high radiation doses in the bone marrow but spares normal organs. Adding myeloablative radioimmunotherapy to the conditioning schemes of AML, MDS and multiple myeloma before stem cell transplantation allows for the achievement of a pronounced antileukemic/antimyeloma effect for the reduction of relapse rates without significant increase of acute organ toxicity and therapy-related mortality. In order to optimise therapy, a rational design of the nuclide-antibody combination is necessary. {sup 90}Y, {sup 188}Re and {sup 131}I are the most frequently used {beta}{sup -}-particles. Of these, {sup 90}Y is the most qualified nuclide for myeloablation. Backbone stabilised DTPA are ideal chelators to stably conjugate {sup 90}Y to antibodies so far. For myeloablative conditioning, anti-CD66-, -45- and -33-mAb are used. The anti-CD66-antibody BW250/183 binds to normal hematopoietic cells but not to leukemic blasts and myeloma cells. The {sup 90}Y-2B3M-DTPA-BW250/183 is the most suited radioimmunoconjugate for patients with an infiltration grade of leukemic blasts in the bone marrow < 25%. The specific doses (Gy/GBq) are 10.2 {+-} 1.8 (bone marrow), 2.7 {+-} 2 (liver) and < 1 (kidneys). In contrast, radiolabeled anti-CD33- and anti-CD45-antibodies bind to both, most of white blood cells and