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

  1. Assessment of long-term radiotoxicity after treatment with the low-dose-rate alpha-particle-emitting radioimmunoconjugate 227Th-rituximab

    International Nuclear Information System (INIS)

    Dahle, Jostein; Heyerdahl, Helen; Hjelmerud, Anne Kristine; Larsen, Roy H.; Jonasdottir, Thora J.; Nesland, Jahn M.; Borrebaek, Joergen

    2010-01-01

    The anti-CD20 antibody rituximab labelled with the α-particle-emitting radionuclide 227 Th is of interest as a radiotherapeutic agent for treatment of lymphoma. Complete regression of human lymphoma Raji xenografts in 60% of mice treated with 200 kBq/kg 227 Th-rituximab has been observed. To evaluate possible late side effects of 227 Th-rituximab, the long-term radiotoxicity of this potential radiopharmaceutical was investigated. BALB/c mice were injected with saline, cold rituximab or 50, 200 or 1,000 kBq/kg 227 Th-rituximab and followed for up to 1 year. In addition, nude mice with Raji xenografts treated with various doses of 227 Th-rituximab were also included in the study. Toxicity was evaluated by measurements of mouse body weight, white blood cell (WBC) and platelet counts, serum clinical chemistry parameters and histological examination of tissues. Only the 1,000 kBq/kg dosage resulted in decreased body weight of the BALB/c mice. There was a significant but temporary decrease in WBC and platelet count in mice treated with 400 and 1,000 kBq/kg 227 Th-rituximab. Therefore, the no-observed-adverse-effect level (NOAEL) was 200 kBq/kg. The maximum tolerated activity was between 600 and 1,000 kBq/kg. No significant signs of toxicity were observed in histological sections in any examined tissue. There were significantly (p 227 Th-rituximab or non-labelled antibody when compared with control mice. The maximum tolerated dose to bone marrow was between 2.1 and 3.5 Gy. Therapeutically relevant dose levels of 227 Th-rituximab were well tolerated in mice. Bone marrow suppression, as indicated by decrease in WBC count, was the dose-limiting radiotoxicity. These toxicity data together with anti-tumour activity data in a CD20-positive xenograft mouse model indicate that therapeutic effects could be obtained with relatively safe dosage levels of the radioimmunoconjugate. (orig.)

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. A pilot study of the treatment of patients with recurrent malignant gliomas with intratumoral yttrium-90 radioimmunoconjugates

    International Nuclear Information System (INIS)

    Hopkins, K.; Chandler, C.; Bullimore, J.; Sandeman, D.; Coakham, H.; Kemshead, J.T.

    1995-01-01

    A pilot study of the treatment of patients with relapsed malignant gliomas with direct intratumoral injections of yttrium-90 ( 90 Y) radioimmunoconjugates has been completed. Patients were recruited following maximal tumour resection, and received 1-3 injections of 90 Y conjugated to a monoclonal antibody designated ERIC-1, which binds the neural cell-adhesion molecule. Data were collected to establish clinical toxicity, pharmacokinetics and radiation doses to the cavity wall and critical body organs. Twenty-three injections were completed in 15 patients, with a mean injected activity of 675 MBq (range 399-921). Early toxicity manifested as cerebral oedema and was readily controlled with dexamethasone. Delayed myelosuppression was observed but no intervention was required. Pharmacokinetic analysis confirmed prolonged retention of isotope in the cavity with correspondingly low activity in the bloodstream. These data were translated into estimates of absorbed radiation dose using the Medical Internal Radiation Dosimetry (MIRD) scheme. Mean doses, and dose rates, to the wall of the cavity, i.e. 'tumour,' were very high in comparison to normal tissue doses, with a further advantage if targeting was achieved

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

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    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.

  8. Radio-immunoconjugated, Dox-loaded, surface-modified superparamagnetic iron oxide nanoparticles (SPIONs) as a bioprobe for breast cancer tumor theranostics

    International Nuclear Information System (INIS)

    Hamidreza Zolata; Hossein Afarideh; Fereydoun Abbasi-Davani

    2014-01-01

    In this research, we develop dual modality molecular imaging and also radio-immunotherapy (RIT) bioprobes, in the form of modified superparamagnetic iron oxide nanoparticles (SPIONs) conjugated to radiolabeled antibodies, for PET and MRI of HER2 expressing cancers as well as a PH sensitive drug carrier by embedded an anticancer agent for cancer therapeutic applications. The bioprobes were developed by conjugating 64 Cu labeled trastuzumab (herceptin) and rituximab (Anti CD-20) antibodies to modified SPIONs. The SPIONs were modified with carboxymethyl chitosan and functionalized with acrylic acid (AA). Also, with the purpose of identifying more effective bifunctional chelator (BFC), we compared the properties of novel BFC, p-NO 2 -Bn-PCTA with the commonly used DOTA-NHS for radio-immunoconjugate preparations. Moreover, a chemotherapy drug, doxorubicin, was then loaded onto engineered nanoparticles for targeted intracellular drug delivery and selective cancer cell killing. Resulting radio-immunoconjugated-SPIONs were evaluated for molecular imaging and effective targeting of the HER2+ receptors in SKBR3 cell lines and breast tumor bearing Balb/C mice. Therefore, our biocompatible SPIONs could serve as a promising multifunctional theranostics nanoplatform in dual modality imaging guided RIT of HER2 overexpressing cancer applicable to drug delivery and controlled drug release for trigger both intrinsic and extrinsic pathways of apoptosis. (author)

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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)

  14. 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

    ... supplements DOE's expression of its preferred alternatives identified in the Final TC & WM EIS in Section S.7...\\ Transuranic (TRU) waste is waste that contains alpha particle-emitting radionuclides with atomic numbers... nanocuries per gram of waste. ``Mixed waste'' is radioactive waste containing hazardous constituents...

  15. Preliminary Geothermal Evaluation of the Mokapu Peninsula on the Island of Oahu, Hawaii.

    Science.gov (United States)

    1982-06-01

    of the cone. Cinder and spatter cones are formed from explosions within the conduit that propel molten ejecta upwards; cinder and molten lava droplets...NWC TP 6358 GROUND RADON SURVEYS* Radon (Rn) is an alpha-particle emitting radioactive gas in the uranium and thorium decay series. Radon...Utah, Salt Lake City, UTr Department of Geology, Dr. J. A. Whelan (1) Earth Science Laboratory, H. P. Ross (1) Glogy & Geophysics Library (1) 1

  16. 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

  17. {alpha}-particle production in the scattering of {sup 6}He by {sup 208}Pb at energies around the Coulomb barrier

    Energy Technology Data Exchange (ETDEWEB)

    Escrig, D. [Instituto de Estructura de la Materia, CSIC, E-28006 Madrid (Spain); Sanchez-Benitez, A.M. [Departamento de Fisica Aplicada, Universidad de Huelva, E-21071 Huelva (Spain); Institut de Physique Nucleaire and Centre de Recherches du Cyclotron, Universite catholique de Louvain, B-1348 Louvain-la-Neuve (Belgium); Moro, A.M. [Departamento de Fisica Atomica, Molecular y Nuclear, Universidad de Sevilla, Apdo. 1065, E-41080 Sevilla (Spain)]. E-mail: moro@us.es (and others)

    2007-08-01

    New experimental data from the scattering of {sup 6}He + {sup 208}Pb at energies around and below the Coulomb barrier are presented. The yield of breakup products coming from projectile fragmentation is dominated by a strong group of {alpha} particles. The energy and angular distribution of this group have been analyzed and compared with theoretical calculations. This analysis indicates that the {alpha} particles emitted at backward angles in this reaction are mainly due to two-neutron transfer to weakly bound states of the final nucleus.

  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. Diagnostics proposal for T-15 fusion research by means of charged products and neutrons

    Science.gov (United States)

    Zaveryaev, V. S.; Maisyukov, V. D.; Khramenkov, A. V.; Popovichev, S. V.; Shevchenko, A. P.; Trusillo, S. V.

    1995-12-01

    A majority of the planned fusion product diagnostics for the T-15 tokamak are described. These include a few dozen silicon diodes to detect escaping charged fusion products with high energy resolution. They will resolve the charged particle fluxes in radial, pitch angle, energy and time dependences. In addition, measurements of DD neutron birth profiles are proposed to be carried out using two independent system-a bubble chamber and a `sandwich` radiometer that have not been used in tokamaks to date. A new method of plasma current profile measurement is suggested, based on the detection of `test` alpha particles emitted by radioactive sources at the vessel wall

  1. Different ways to improve the clinical effectiveness of radioimmunotherapy in solid tumors.

    Science.gov (United States)

    Chatal, Jean-Francois; Davodeau, Francois; Cherel, Michel; Barbet, Jacques

    2009-09-01

    Radioimmunotherapy (RIT) has been proven effective in the treatment of radiosensitive non-Hodgkin lymphoma but, for radioresistant solid tumors, new approaches are necessary to improve the clinical effectiveness. A real improvement has been the introduction of the pretargeting technology which appeared to be able to significantly increase tumor-to-normal organ uptake ratios.Another very promising approach consists in associating RIT with other treatment modalities. Finally the use of alpha particle-emitting radionuclides such as astatin-211 or bismuth-213 (alpha-RIT) should allow to efficiently eradicate disseminated microscopic clusters of tumor cells or isolated tumor cells which fit well with the short path length of alpha particles.

  2. 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

  3. 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.)

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

    Science.gov (United States)

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

    2015-06-01

    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 213Bi, 225Ac, 212Pb and 211At. Clinical safety has been documented and encouraging efficacy has been shown for some of them (213Bi and 211At). 211At has been the most studied and could be the most promising radionuclide but 225Ac and 212Pb 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.

  5. Improved radioimmunotherapy of hematologic malignancies. Progress report, 1988--1991

    Energy Technology Data Exchange (ETDEWEB)

    Press, O.W.; Barofsky, D.F.

    1991-12-31

    This progress report describes accomplishments under four headings, namely: The study of the relative rates of metabolic degradation of radiolabeled monoclonal antibodies (MAb) targeting tumor associated antigens; Effects of lysosomotropic amines, carboxylic ionophores, and thioamides on the retention of radiolabeled MAbs by tumor cells; Subcellular site of radioimmunoconjugate degradation and the sizes of fragments generated by intracellular metabolism of radiolabeled antibodies; and Patterns of metabolic degradation of radioimmunoconjugates made with different techniques and with different radionuclides.

  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. 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)

  8. 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.

  9. 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...

  10. 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)

  11. Peculiarities of semiconductor detector performance at low temperatures

    International Nuclear Information System (INIS)

    Afanas'eva, N.P.; Eremin, V.K.; Strokan, N.B.; Shamagdiev, A.Sh.

    1982-01-01

    Temperature dependence of Ge and Si detector signal amplitude is investigated in the temperature range of 180-4.2 K. Main processes conditioning temperature dependence of charging signal amplitude and semiconductor detector resolution are analyzed. Expressions for the evaluation of temperature values corresponding to the most considerable changes in the detector signals are obtained. Amplitude spectra of alpha particles emitted by 238 Pu (Esub(α)=5.495 MeV) recorded by optimazed Si detector at temperatures of 77 and 4.2 K are given. Analysis of the spectra obtained shows that the detector possesses good resolution equal to 29 keV at 77 K and 38 keV at helium temperature. It is concluded that spectrometric properties of Si detectors do not change at helium temperatures [ru

  12. 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

  13. 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

  14. A new technique for radon measurement based on a combination of a track-etch detector and activated charcoal

    Energy Technology Data Exchange (ETDEWEB)

    Sutej, T.; Krizman, M.; Ilic, R. (Institut Jozef Stefan, Ljubljana (Yugoslavia))

    1991-01-01

    A new technique for radon measurement in the natural environment was investigated. It is based on the use of activated charcoal and a track-etch detector. The charcoal acts as a radon collector from the air and the track-etch detector as a recorder of the alpha particles emitted by radon and its decay products. Our preliminary results show that the response of the new dosimeter to radon, using Deodorant activated charcoal (TOK, Yugoslavia) and a CR-39 track-etch detector, is 1.4 tracks cm{sup -2}/Bqm{sup -3}d, which is about eight times higher than that obtained with a standard track-etch dosimeter. (author).

  15. 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.

  16. Measurement of the Internal Magnetic Field of Plasmas using an Alpha Particle Source

    Energy Technology Data Exchange (ETDEWEB)

    S.J. Zweben; D.S. Darrow; P.W. Ross; J.L. Lowrance; G. Renda

    2004-05-13

    The internal magnetic fields of plasmas can be measured under certain conditions from the integrated v x B deflection of MeV alpha particles emitted by a small radioactive source. This alpha source and large-area alpha particle detector would be located inside the vacuum vessel but outside the plasma. Alphas with a typical energy of 5.5 MeV (241Am) can reach the center of almost all laboratory plasmas and magnetic fusion devices, so this method can potentially determine the q(r) profile of tokamaks or STs. Orbit calculations, background evaluations, and conceptual designs for such a vxB (or ''AVB'') detector are described.

  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. 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

  19. 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)

  20. Acrylic purification and coatings

    International Nuclear Information System (INIS)

    Kuzniak, Marcin

    2011-01-01

    Radon (Rn) and its decay daughters are a well-known source of background in direct WIMP detection experiments, as either a Rn decay daughter or an alpha particle emitted from a thin inner surface layer of a detector could produce a WIMP-like signal. Different surface treatment and cleaning techniques have been employed in the past to remove this type of contamination. A new method of dealing with the problem has been proposed and used for a prototype acrylic DEAP-1 detector. Inner surfaces of the detector were coated with a layer of ultra pure acrylic, meant to shield the active volume from alphas and recoiling nuclei. An acrylic purification technique and two coating techniques are described: a solvent-borne (tested on DEAP-1) and solvent-less (being developed for the full scale DEAP-3600 detector).

  1. Different ways to improve the clinical effectiveness of radioimmunotherapy in solid tumors

    Directory of Open Access Journals (Sweden)

    Chatal Jean-Francois

    2009-09-01

    Full Text Available Radioimmunotherapy (RIT has been proven effective in the treatment of radiosensitive non-Hodgkin lymphoma but, for radioresistant solid tumors, new approaches are necessary to improve the clinical effectiveness. A real improvement has been the introduction of the pretargeting technology which appeared to be able to significantly increase tumor-to-normal organ uptake ratios.Another very promising approach consists in associating RIT with other treatment modalities. Finally the use of alpha particle-emitting radionuclides such as astatin-211 or bismuth-213 (alpha-RIT should allow to efficiently eradicate disseminated microscopic clusters of tumor cells or isolated tumor cells which fit well with the short path length of alpha particles.

  2. Study of counter E.M.F. on external cathodes proportional counters

    International Nuclear Information System (INIS)

    Tobias, C.C.B.

    1990-01-01

    Results previously obtained in our laboratory with Geiger-Mueller counters with external cathodes (Maze type), led us to build a cylindrical proportional counter around a tube of soda glass, covered by a thin layer of acquadag. The characteristics of this proportional counter were studied for argon and argon-methane mixture at atmospheric pressure, under continuous flow. Using alpha particles, emitted by an Am-241 source, the results obtained shown that its pulse amplitude decreases slowly with an increase of the counting rate, due to the counter e.m.f. which appears between the internal counter surface and the external cathode. This small effect, does not influence either the pulse amplitude distribution or the resolution, due to the large time constant of the distributed charge. (author)

  3. 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.

  4. 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.

  5. Improved radioimmunotherapy of hematologic malignancies. Final technical report

    Energy Technology Data Exchange (ETDEWEB)

    Press, O.W.

    1996-08-15

    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.

  6. 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

  7. Development of a transmission alpha particle dosimetry technique using A549 cells and a Ra-223 source for targeted alpha therapy.

    Science.gov (United States)

    Al Darwish, R; Staudacher, A H; Li, Y; Brown, M P; Bezak, E

    2016-11-01

    In targeted radionuclide therapy, regional tumors are targeted with radionuclides delivering therapeutic radiation doses. Targeted alpha therapy (TAT) is of particular interest due to its ability to deliver alpha particles of high linear energy transfer within the confines of the tumor. However, there is a lack of data related to alpha particle distribution in TAT. These data are required to more accurately estimate the absorbed dose on a cellular level. As a result, there is a need for a dosimeter that can estimate, or better yet determine the absorbed dose deposited by alpha particles in cells. In this study, as an initial step, the authors present a transmission dosimetry design for alpha particles using A549 lung carcinoma cells, an external alpha particle emitting source (radium 223; Ra-223) and a Timepix pixelated semiconductor detector. The dose delivery to the A549 lung carcinoma cell line from a Ra-223 source, considered to be an attractive radionuclide for alpha therapy, was investigated in the current work. A549 cells were either unirradiated (control) or irradiated for 12, 1, 2, or 3 h with alpha particles emitted from a Ra-223 source positioned below a monolayer of A549 cells. The Timepix detector was used to determine the number of transmitted alpha particles passing through the A549 cells and DNA double strand breaks (DSBs) in the form of γ-H2AX foci were examined by fluorescence microscopy. The number of transmitted alpha particles was correlated with the observed DNA DSBs and the delivered radiation dose was estimated. Additionally, the dose deposited was calculated using Monte Carlo code SRIM. Approximately 20% of alpha particles were transmitted and detected by Timepix. The frequency and number of γ-H2AX foci increased significantly following alpha particle irradiation as compared to unirradiated controls. The equivalent dose delivered to A549 cells was estimated to be approximately 0.66, 1.32, 2.53, and 3.96 Gy after 12, 1, 2, and 3 h

  8. 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)

  9. 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.

  10. Measurements of 220Rn in air using a flow-through Lucas cell and multiple time analysis of recorded pulse events

    International Nuclear Information System (INIS)

    Falk, R.; Moere, H.; Nyblom, L.

    1992-01-01

    A multiple time analysis technique has successfully been applied for measurements of environmental levels of 220 Rn using a flow-through Lucas radon detector. The method is based on selective alpha counting of the short-lived nuclide 216 Pu. Owing to its short half-life (0.145 s), the alpha particle emitted at the decay of a 220 Rn atom will, within a fraction of a second, be followed by an alpha particle from the decay of 216 Po. By measuring the time interval between successive alpha counts followed by a multiple time analysis, the 216 Po activity and thereby the 220 Rn activity can be calculated. The method applied to a commercial instrument with a 160 ml Lucas cell as detector shows that a mean 220 Rn air concentration of less than 20 Bq.m -3 can easily be determined even if the 222 Rn air concentration is 10 times higher and varies. At lower 222 Rn levels a 220 Rn concentration less than 1 Bq.m -3 can be assessed using this technique. The method will be described together with some examples of its practical use. (author)

  11. 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).

  12. 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

  13. 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

  14. Cyclotron production of cesium radionuclides as analogues for francium-221 biodistribution

    International Nuclear Information System (INIS)

    Finn, R.; McDevitt, M.; Sheh, Y.; Lom, C.; Qiao, J.; Cai, S.; Burnazi, E.; Nacca, A.; Pillarsetty, N.; Jaggi, J.; Scheinberg, D.

    2005-01-01

    In our clinical investigations focussing on improved therapeutic treatment of specific tumors we have concentrated on a targeted therapy approach utilizing designed radiolabeled monoclonal antibodies as the cytotoxic reagent. The physical characteristics of the alpha particle emitting radionuclide bismuth-213 including the short half-life of 45.6 min, has shown promise for the treatment of specific cancers such as leukemias and lymphomas or micrometastatic carcinomas. In an effort to increase the cytocidal effect of the HuM195, a humanized monoclonal antibody carrier to the CD33 antigen expressed on leukemia cells, our focus is directed toward an 'internal' nano-generator composed of Ac-225 radionuclide, the parent of the bismuth-213. The actinium-225 radionuclide decays through several short-lived, alpha emitting daughters including francium-221, astatine-217 and bismuth-213. In order to study the biodistribution and the pharmacokinetics of the individual daughter nuclide, francium-221, the cyclotron production and separation of cesium radionuclides, specifically cesium-132, from a natural xenon gas target was undertaken. The choice of cesium as an analogue for francium was predicated upon both elements being in Group 1A alkali metals and cesium radionuclide possesses a sufficient half-life to allow biodistribution studies to be performed. The preliminary experimental results of this investigation are presented

  15. 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

  16. 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)

  17. 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

  18. 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)

  19. 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)

  20. 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.

  1. 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.

  2. 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.

  3. 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 ).

  4. 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)

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

    International Nuclear Information System (INIS)

    Peters, W. A.; Smith, M. S.; Pittman, S.; Thompson, S. J.; Clement, R. R. C.; Cizewski, J. A.; Pain, S. D.; Febbraro, M.; Chipps, K. A.; Burcher, S.; Manning, B.; Reingold, C.; Avetisyan, R.; Battaglia, A.; Chen, Y.; Long, A.; Lyons, S.; Marley, S. T.; Seymour, C.; Siegl, K. T.; Smith, M. K.; Strauss, S.; Talwar, R.; Bardayan, D. W.; Gyurjinyan, A.; Smith, K.; Thornsberry, C.; Thompson, P.; Madurga, M.; Stech, E.; Tan, W. P.; Wiescher, M.; Ilyushkin, S.; Tully, Z.; Grinder, M. M.

    2016-01-01

    Alpha particles emitted from the decay of uranium in a UF 6 matrix can interact with fluorine and generate neutrons via the 19 F(α,n) 22 Na reaction. These neutrons can be used to determine the uranium content in a UF 6 storage cylinder. The accuracy of this self-interrogating, non-destructive assay (NDA) technique is, however, limited by the uncertainty of the 19 F(α,n) 22 Na cross section. We have performed complementary measurements of the 19 F(α,n) 22 Na reaction with both 4 He and 19 F beams to improve the precision of the 19 F(α,n) 22 Na 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 19 F(α,n) 22 Na 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 UF 6 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.

  6. Radiation-induced systemic and local bone tumors: two types of late effects with possible different origins?

    Science.gov (United States)

    Müller, W A; Luz, A; Linzner, U

    1994-06-01

    Bone sarcomas may be induced throughout the skeleton (systemic) in mice by relatively low internal alpha-particle doses that are distributed over the whole skeleton. The induction of local (periosteal) bone sarcomas after paratibial deposition of insoluble radiocolloids required much higher doses, and in addition high energies of emitted particles. Paratibial deposition of alpha-particle-emitting radiocolloids of 227Th and 228Th resulted in formation of both local and systemic bone sarcomas. The latter were most probably induced by the released radium daughters of the thorium isotopes and were distributed about the skeleton. Paratibial injections with beta-particle emitters 144Ce+ 144Pr (29 kBq per mouse) showed an incidence of local bone sarcomas of more than 80%. An estimation of the local effective doses led to values of more than 1000 Gy for the beta-particle emitter 144Ce and around 150 Gy for the thorium isotopes. Thus induction of local bone sarcomas required doses considerably greater than those needed for systemic bone sarcomas. The local induction of bone sarcomas has been reported for high-energy beta particles using similar high doses of 144Ce+ 144Pr in rats and for external 90Sr+ 90Y irradiation in mice. We conclude that the processes involved in the induction of local and systemic bone sarcomas by radiation may be quite different.

  7. 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

  8. Deconvolution of alpha spectra from air filters applied for measurements of the short-lived radon progeny concentration

    Directory of Open Access Journals (Sweden)

    Skubacz Krystian

    2017-09-01

    Full Text Available The paper contains a description of a method for the analysis of the complex alpha spectra generated during the measurement of the activity of filters outside of a vacuum chamber under environmental conditions. The peaks corresponding to the energies of alpha particles emitted by the specific isotopes are particularly large on the low-energy side of the peak maximum, and the energy resolution strongly depended on the applied filters. The analysis was based on the non-linear regression to a function designed for four, six and eight parameters. Satisfactory results were obtained for each of these functions, and the best-fitting results were achieved for the eight-parameter function. In addition, the uncertainties related to the estimated parameters, as well as the signals corresponding to functions that describe the shape of the energy peak, have been evaluated. There are also examples of the implementation of the method with respect to short-lived radon progeny and thoron decay products.

  9. 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.

  10. A PLS-Based Weighted Artificial Neural Network Approach for Alpha Radioactivity Prediction inside Contaminated Pipes

    Directory of Open Access Journals (Sweden)

    Xianguo Tuo

    2014-01-01

    Full Text Available Long-range alpha detection (LRAD has been used to measure alpha particles emitting contamination inside decommissioned steel pipes. There exists a complex nonlinear relationship between input parameters and measuring results. The input parameters, for example, pipe diameter, pipe length, distance to radioactive source, radioactive source strength, wind speed, and flux, exhibit different contributions to the measuring results. To reflect these characteristics and estimate alpha radioactivity as exactly as possible, a hybrid partial least square back propagation (PLSBP neural network approach is presented in this paper. In this model, each node in the input layer is weighted, which indicates that different input nodes have different contributions on the system and this finding has been little reported. The weights are determined by the PLS. After this modification, a variety of normal three-layered BP networks are developed. The comparison of computational results of the proposed approach with traditional BP model and experiments confirms its clear advantage for dealing with this complex nonlinear estimation. Thus, an integrated picture of alpha particle activity inside contaminated pipes can be obtained.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. Cyclotron production of cesium radionuclides as analogues for francium-221 biodistribution

    Energy Technology Data Exchange (ETDEWEB)

    Finn, R. [Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021 (United States) and Cyclotron Core Facility, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021 (United States)]. E-mail: finnr@mskcc.org; McDevitt, M. [Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021 (United States); Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021 (United States); Sheh, Y. [Cyclotron Core Facility, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021 (United States); Lom, C. [Cyclotron Core Facility, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021 (United States); Qiao, J. [Cyclotron Core Facility, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021 (United States); Cai, S. [Cyclotron Core Facility, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021 (United States); Burnazi, E. [Cyclotron Core Facility, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021 (United States); Nacca, A. [Cyclotron Core Facility, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021 (United States); Pillarsetty, N. [Cyclotron Core Facility, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021 (United States); Jaggi, J. [Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021 (United States); Scheinberg, D. [Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021 (United States)

    2005-12-15

    In our clinical investigations focussing on improved therapeutic treatment of specific tumors we have concentrated on a targeted therapy approach utilizing designed radiolabeled monoclonal antibodies as the cytotoxic reagent. The physical characteristics of the alpha particle emitting radionuclide bismuth-213 including the short half-life of 45.6 min, has shown promise for the treatment of specific cancers such as leukemias and lymphomas or micrometastatic carcinomas. In an effort to increase the cytocidal effect of the HuM195, a humanized monoclonal antibody carrier to the CD33 antigen expressed on leukemia cells, our focus is directed toward an 'internal' nano-generator composed of Ac-225 radionuclide, the parent of the bismuth-213. The actinium-225 radionuclide decays through several short-lived, alpha emitting daughters including francium-221, astatine-217 and bismuth-213. In order to study the biodistribution and the pharmacokinetics of the individual daughter nuclide, francium-221, the cyclotron production and separation of cesium radionuclides, specifically cesium-132, from a natural xenon gas target was undertaken. The choice of cesium as an analogue for francium was predicated upon both elements being in Group 1A alkali metals and cesium radionuclide possesses a sufficient half-life to allow biodistribution studies to be performed. The preliminary experimental results of this investigation are presented.

  16. 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)

  17. 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

  18. 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

  19. 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)

  20. 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

  1. 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.

  2. 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.

  3. Calibration of the E Si detector in a DE-E telescope with a ^212Pb pin source

    Science.gov (United States)

    Chan, Ka Pang

    2012-10-01

    In nuclear physics experiments, telescopes composed of two or more large area silicon strip detectors are used to identify charged particles. To use the energy loss method for particle identification, a thin (˜0.065mm) silicon detector (DE) is mounted in front of a thicker E detector (˜1.5 mm). The DE Si detector can be calibrated with 8.785, 6.778, 6.288, 5.685 and 5.423 MeV alpha particles emitted from a ^228Th source. However, this method cannot be used to calibrate the E detector as the alpha particles cannot penetrate the front DE detector. We have developed a method to calibrate the E detector by inserting a small irradiated dowel pin between the two Si detectors. The pin source is electroplated with ^212Pb nuclei which emit alpha particles with 8.785 MeV, 6.090 and 6.051 MeV. Insertion of the dowel pin is designed and guided so that the head of the pin lies near the center of the detector at a distance of 2.72 mm away from the surface of the E detector. In addition to providing two strong alpha peaks for calibrations, the close distance and high pixilation of the E detector allows accurate determination of the front dead layer of the E Si strip detector. This technique has been implemented successfully in calibrating the E Si detectors in the NSCL High Resolution Array (HiRA) consisting of 20 closely pack DE-E-CsI telescopes.

  4. 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

  5. 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.)

  6. 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)

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

    International Nuclear Information System (INIS)

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

    2010-01-01

    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. (orig.)

  8. 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.)

  9. Compound and precompound emission in reactions of Zn isotopes with protons and alpha particles

    International Nuclear Information System (INIS)

    Lux, C.R.

    1975-01-01

    Targets of 64 Zn, 66 Zn, 68 Zn, and 70 Zn were bombarded by 12.5 MeV protons and 18.0 MeV alpha particles. Energy spectra and angular distributions of protons and alpha particles emitted in these reactions were measured. Integrated cross sections were determined from the experimental spectra. The assumption was made that emission in the backward direction was due to compound emission and that any ''excess'' cross section in the forward direction was due to precompound emission. Then an experimental percent precompound emission was calculated. It ranged from 2 to 95 percent. A constant temperature analysis was performed on all 150 0 and 30 0 spectra. The nuclear temperature of the 30 0 spectra was from 0.1 to 2.0 MeV higher, indicating more precompound emission in the 30 0 than in the 150 0 spectra. The ratios of (GAMMA/sub p//GAMMA/sub n/) and (GAMMA/sub α//GAMMA/sub n/) for 150 0 were adequately fit by evaporation theory indicating that a compound mechanism can account for the data. The spin-dependent statistical model was then used to fit the 150 0 spectra. Good fits were obtained using parameters that are in agreement with those calculated by Gilbert and Cameron. The spin-dependent statistical model was then combined with the precompound Quasi-Free Scattering Model and fits were made to the experimental data. Good fits were obtained and a calculated percent precompound emission wasobtained. This ranged from 1 to 95 percent and compared favorably with the percentages obtained experimentally

  10. Evaluation of internal alpha radiation exposure and subsequent infertility among a cohort of women formerly employed in the radium dial industry.

    Energy Technology Data Exchange (ETDEWEB)

    Schieve, L. A.; Davis, F.; Roeske, J.; Handler, A.; Freels, S.; Stinchcomb, T.; Keane, A.; Environmental Research; Univ. of Illinois at Chicago; Univ. of Chicago; DePaul Univ.

    1997-02-01

    This study examined the effect of internal exposure to {alpha}-particle radiation on subsequent fertility among women employed in the radium dial industry prior to 1930, when appreciable amounts of radium were often ingested through the practice of pointing the paint brush with the lips. The analysis was limited to women for whom a radium body burden measurement had been obtained and who were married prior to age 45 (n=603). Internal radiation dose to the ovary was calculated based on initial intakes of radium-226 and radium-228, average ovarian mass, number and energy of {alpha} particles emitted, fraction of energy absorbed with in the ovary, effective retention integrals and estimated photon irradiation. Time between marriage and pregnancy, number of pregnancies and number of live births served as surrogates for fertility. Radiation appeared to have no effect on fertility at estimated cumulative ovarian dose equivalents below 5 Sv; above this dose, however, statistically significant declines in both number of pregnancies and live births were observed. These trends persisted after multivariable adjustment for potential confounding variables and after exclusion of subjects contributing a potential classification or selection bias to the study. Additionally, the high-dose group experienced fewer live births than would have been expected based on population rates. There were no differences in time to first pregnancy between high- and low-dose groups. These results are consistent with earlier studies of {gamma}-ray exposures and suggest that exposure to high doses of radiation from internally deposited radium reduces fertility rather than inducing sterility.

  11. Alpha-particle fluence in radiobiological experiments.

    Science.gov (United States)

    Nikezic, Dragoslav; Yu, Kwan Ngok

    2017-03-01

    Two methods were proposed for determining alpha-particle fluence for radiobiological experiments. The first involved calculating the probabilities of hitting the target for alpha particles emitted from a source through Monte Carlo simulations, which when multiplied by the activity of the source gave the fluence at the target. The second relied on the number of chemically etched alpha-particle tracks developed on a solid-state nuclear track detector (SSNTD) that was irradiated by an alpha-particle source. The etching efficiencies (defined as percentages of latent tracks created by alpha particles from the source that could develop to become visible tracks upon chemical etching) were computed through Monte Carlo simulations, which when multiplied by the experimentally counted number of visible tracks would also give the fluence at the target. We studied alpha particles with an energy of 5.486 MeV emitted from an 241Am source, and considered the alpha-particle tracks developed on polyallyldiglycol carbonate film, which is a common SSNTD. Our results showed that the etching efficiencies were equal to one for source-film distances of from 0.6 to 3.5 cm for a circular film of radius of 1 cm, and for source-film distances of from 1 to 3 cm for circular film of radius of 2 cm. For circular film with a radius of 3 cm, the etching efficiencies never reached 1. On the other hand, the hit probability decreased monotonically with increase in the source-target distance, and fell to zero when the source-target distance was larger than the particle range in air. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

  12. Facilitated transport of uranium(VI) across supported liquid membranes containing T2EHDGA as the carrier extractant.

    Science.gov (United States)

    Panja, S; Mohapatra, P K; Tripathi, S C; Manchanda, V K

    2011-04-15

    Facilitated transport of uranyl ion from nitric acid feed solutions was investigated across PTFE supported liquid membranes using N,N,N',N'-tetra-2-ethylhexyl-3-pentane-diamide (T2EHDGA) in n-dodecane as the carrier extractant containing 30% iso-decanol as the phase modifier. Solvent extraction studies indicated extraction of species of the type, UO(2)(NO(3))(2)·T2EHDGA. The distribution coefficients increased in the presence of NaNO(3) as compared to equivalent concentration of HNO(3) which was exactly the opposite of what was reported for Am(III)-TODGA extraction system. Supported liquid membrane studies indicated about 11h were required for quantitative transport of U(VI) from a feed of 3M HNO(3) using 0.2M T2EHDGA in n-dodecane containing 30% iso-decanol as the carrier extractant. Effect of various parameters such as feed acidity, T2EHDGA concentration, and nature of the strippant on the transport rate was investigated. The transport was found to be diffusion controlled in the membrane phase and the permeability coefficient was calculated to be (3.20 ± 0.13)× 10(-4)cm/s for the feed composition of 3M HNO(3), receiver phase composition of 0.01 M HNO(3) and membrane carrier phase of 0.2M T2EHDGA in n-dodecane containing 30% iso-decanol. The present results may be useful for the separation of U from lean solutions or radioactive wastes considered hazardous due to the presence of alpha-particle emitting radionuclides. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Molecular characterization of plutonium-induced rat osteosarcomas

    Energy Technology Data Exchange (ETDEWEB)

    Daino, K.; Guilty, M.N.; Chevillard, S. [CEA Fontenay-aux-Roses, Dept. de Radiobiologie et de Radiopathologie (LCE/DRR/DSV), 92 (France); Roch-Lefevre, S. [CEA Fontenay-aux-Roses (LDB/SRBE/DRPH/IRSN), 92 (France)

    2006-07-01

    Osteosarcoma is a malignant tumor of bone. It is known that osteosarcomas occur from exposures to bone-seeking, alpha-particle-emitting radionuclides, such as plutonium (Pu). However, the specific genes and molecular mechanisms responsible for tumorigenesis of osteosarcoma by alpha-particle emitters remain poorly understood. In our previous study, gains and losses of genetic material were investigated in a series of sixteen Pu-induced rat osteosarcomas using the comparative genomic hybridization (CGH). The CGH analysis revealed recurrent gains/amplifications at chromosomal regions 7q22-32, 8g11-21, 9g11-21, and 12 q and losses at 1q, 5q22-33, 8q23-ter, 10q21-31, 15q and 18q. To identify the target genes for genomic gains and losses, in this study, we focused on several cell cycle-related genes located within the regions frequently (33-60%) gained or lost, and determined their expression levels by quantitative real-time reverse transcription-PCR (RT-PCR). Significant correlation was found between genomic gain and high-level expression of the CDK4 gene (located at 7q22). Overexpression of the CDK4 gene through genomic gain is likely to lead to aberrant cell cycle control. In addition, oligonucleotide micro-array analysis is currently in progress in order to analyze the global gene expression profiles of Pu-induced rat osteosarcomas. This study will provide further insight into whether here are the molecular specificities in radiation-induced tumors. (author)

  14. 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.

  15. 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

  16. 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

  17. 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).

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. Optimization of 90 Y-antiCD20 preparation for radioimmunotherapy

    Directory of Open Access Journals (Sweden)

    Nazila Gholipour

    2013-01-01

    Full Text Available Context: The advent of monoclonal antibodies such as Rituximab, in recent years, has brought about decisive progress in the treatment of aggressive and indolent non-Hodgkin′s lymphoma. Aims: A further tried and tested improvement to the unmodified antibody has been its coupling to the beta-emitters Y-90. The optimization of 90 Y-antiCD20 radioimmunoconjugate production and quality control methods for future clinical studies in the country was targeted in this work. Materials and Methods: The antibody was labeled with 90 Y-yttrium chloride (185 MBq after conjugation with freshly prepared ccDTPA. Y-90 chloride was obtained by thermal neutron flux (4 × 10 13 n/cm 2 /s of a natural Y 2 O 3 sample, dissolved in acidic media. Radiolabeling was completed in 24 h by the addition of DTPA-Rituximab conjugate at room temperature. Statistical Analysis Used: All values were expressed as mean ± standard deviation (mean ± SD, and the data were compared using Student′s t-test. Statistical significance was defined as P < 0.05. Results: Radiochemical purity of 96% was obtained by using ITLC method for the final radioimmunoconjugate (specific activity = 440-480 MBq/mg. The final isotonic 90 Y-Rituximab complex was checked by gel electrophoresis for protein integrity retention. Biodistribution studies in normal rats were carried out to determine the radioimmunoconjugate distribution up to 72 h. Conclusion: The results showed that 90 Y-DTPA-Rituximab could be considered for further evaluation in animals and possibly in humans as a radiopharmaceutical for use in radioimmunotherapy against non-Hodgkin′s lymphomas. Because of the importance of developing anti-lymphoma B agents in nuclear medicine for country use, an optimized radiolabeling method has been introduced.

  5. 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.

  6. 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

  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. 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

  9. 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

  10. Luminous phenomena and electromagnetic VHF wave emission originated from earthquake-related radon exhalation

    Science.gov (United States)

    Seki, A.; Tobo, I.; Omori, Y.; Muto, J.; Nagahama, H.

    2013-12-01

    Anomalous luminous phenomena and electromagnetic wave emission before or during earthquakes have been reported (e.g., the 1965 Matsushiro earthquake swarm). However, their mechanism is still unsolved, in spite of many models for these phenomena. Here, we propose a new model about luminous phenomena and electromagnetic wave emission during earthquake by focusing on atmospheric radon (Rn-222) and its daughter nuclides (Po-218 and Po-214). Rn-222, Po-218 and Po-214 are alpha emitters, and these alpha particles ionize atmospheric molecules. A light emission phenomenon, called 'the air luminescence', is caused by de-excitation of the ionized molecules of atmospheric nitrogen due to electron impact ionization from alpha particles. The de-excitation is from the second positive system of neutral nitrogen molecules and the first negative system of nitrogen molecule ion. Wavelengths of lights by these transitions include the visible light wavelength. So based on this mechanism, we proposed a new luminous phenomenon model before or during earthquake: 1. The concentration of atmospheric radon and its daughter nuclides increase anomalously before or during earthquakes, 2. Nitrogen molecules and their ions are excited by alpha particles emitted from Rn-222, Po-218 and Po-214, and air luminescence is generated by their de-excitation. Similarly, electromagnetic VHF wave emission can be explained by ionizing effect of radon and its daughter nuclides. Boyarchuk et al. (2005) proposed a model that electromagnetic VHF wave emission is originated when excited state of neutral clusters changes. Radon gas ionizes atmosphere and forms positively and negatively charged heavy particles. The process of ion hydration in ordinary air can be determined by the formation of complex chemically active structures of the various types of ion radicals. As a result of the association of such hydration radical ions, a neutral cluster, which is dipole quasi-molecules, is formed. A neutral cluster

  11. 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)

  12. 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)

  13. [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

  14. 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)

  15. 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

  16. 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

  17. Solid-tumor radionuclide therapy dosimetry: New paradigms in view of tumor microenvironment and angiogenesis

    Science.gov (United States)

    Zhu, Xuping; Palmer, Matthew R.; Makrigiorgos, G. Mike; Kassis, Amin I.

    2010-01-01

    Purpose: The objective of this study is to evaluate requirements for radionuclide-based solid tumor therapy by assessing the radial dose distribution of beta-particle-emitting and alpha-particle-emitting molecules localized either solely within endothelial cells of tumor vasculature or diffusing from the vasculature throughout the adjacent viable tumor cells. Methods: Tumor blood vessels were modeled as a group of microcylindrical layers comprising endothelial cells (one-cell thick, 10 μm diameter), viable tumor cells (25-cell thick, 250 μm radius), and necrotic tumor region (>250 μm from any blood vessel). Sources of radioactivity were assumed to distribute uniformly in either endothelial cells or in concentric cylindrical 10 μm shells within the viable tumor-cell region. The EGSnrc Monte Carlo simulation code system was used for beta particle dosimetry and a dose-point kernel method for alpha particle dosimetry. The radioactive decays required to deposit cytocidal doses (≥100 Gy) in the vascular endothelial cells (endothelial cell mean dose) or, alternatively, at the tumor edge [tumor-edge mean dose (TEMD)] of adjacent viable tumor cells were then determined for six beta (32P, 33P, 67Cu, 90Y, 131I, and 188Re) and two alpha (211At and 213Bi) particle emitters. Results: Contrary to previous modeling in targeted radionuclide therapy dosimetry of solid tumors, the present work restricts the region of tumor viability to 250 μm around tumor blood vessels for consistency with biological observations. For delivering ≥100 Gy at the viable tumor edge (TEMD) rather than throughout a solid tumor, energetic beta emitters 90Y, 32P, and 188Re can be effective even when the radionuclide is confined to the blood vessel (i.e., no diffusion into the tumor). Furthermore, the increase in tumor-edge dose consequent to beta emitter diffusion is dependent on the energy of the emitted beta particles, being much greater for lower-energy emitters 131I, 67Cu, and 33P relative to

  18. 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

  19. Development of anti-CD30 radioimmunoconstructs (RICs) for treatment of Hodgkin's lymphoma. Studies with cell lines and animal studies

    Energy Technology Data Exchange (ETDEWEB)

    Dietlein, M.; Boerner, S.M.; Fischer, T.; Zimmermanns, B.; Kobe, C.; Schicha, H.; Schomaecker, K. [Dept. of Nuclear Medicine, Univ. of Cologne (Germany); Hansen, H.; Schnell, R.; Tawadros, S.; Engert, A.; Staak, O.; Pogge von Strandmann, E. [Dept. of Internal Medicine I, Univ. of Cologne (Germany)

    2010-07-01

    Objectives: comparison of the binding affinity to a CD30-positive Hodgkin lymphoma (HL) cell line and biodistribution in HL bearing mice of new anti-CD30 radioimmunoconjugates (RICs) of varying structure and labelling nuclides. Methods: The antibodies Ki-4 and 5F11 were radioiodinated by the chloramine T method or labelled with {sup 111}In via p-NCS-Benzyl-DOTA. In addition, the Ki-4-dimer was investigated in the iodinated form. The RICs were analyzed for retained immunoreactivity by immunochromatography. In-vitro binding studies were performed on CD30-positive L540 cell lines. For in-vivo biodistribution studies, SCID mice bearing human HL xenografts were injected with the various radio-immunoconjugates. After 24 h, activities in the organs and tumour were measured for all 5 RICs. Tumour-free animals were studied in the same way with {sup 131}I-Ki-4 24 h p. i. The three RICs with the highest tumour/background ratios 24 h p.i. ({sup 131}I-Ki-4, {sup 131}I-5F11, {sup 111}In-bz-DOTA-Ki-4) were analysed further at 48 h and 72 h. Results: all the RICs were successfully labelled with high specific activities (28-47 TBq/mmol) and sufficient radiochemical yields (> 80%). Scatchard plot analysis proved high tumour affinity (K{sub D} = 20-220 nmol/l). In-vivo tumour accumulation in % of injected dose per g tissue (% ID/g) lay between 2.6 ({sup 131}I-5F11) and 12.3 % ID/g ({sup 131}I-Ki-4) with permanently high background in blood. Tumour/blood-ratios of all RICs were below one at all time points. Conclusions: in-vitro tumour cell affinities of all RICs were promising. However, in-vivo biokinetics tested in the mouse model did not meet expectations. This highlights the importance of developing and testing further new anti-CD30 conjugates. (orig.)

  20. 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

  1. 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

  2. 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.

  3. Myeloablative radioimmunotherapy in conditioning prior to haematological stem cell transplantation: closing the gap between benefit and toxicity?

    Energy Technology Data Exchange (ETDEWEB)

    Buchmann, Inga; Haberkorn, Uwe [University of Heidelberg, Department of Nuclear Medicine, Heidelberg (Germany); University of Luebeck, Luebeck (Germany); Meyer, Ralf G. [University of Mainz, Department of Medicine 3, Mainz (Germany); Mier, Walter [University of Heidelberg, Department of Nuclear Medicine, Heidelberg (Germany)

    2009-03-15

    High-dose radio-/chemotherapy in the context of autologous and allogeneic haematopoietic stem cell transplantation is a double-edged sword. The requirement for dose intensification is linked to an increase in toxicity to noninvolved organs. Particularly for older patients and patients with comorbidities, efficient but toxicity-reduced schemes are needed. Myeloablative radioimmunotherapy is a targeted, internal radiotherapy that uses radiolabelled monoclonal antibodies (mAb) with affinity to the bone marrow. It involves the administration of high radiation doses (up to 30 Gy) to the bone marrow and spleen but without exposing radiosensitive organs to doses higher than 1-7 Gy. Added to conventional or intensity-reduced conditioning, myeloablative radioimmunotherapy may achieve a pronounced antileukaemic effect with tolerable toxicities. A rational and individual design of the ideal nuclide-antibody combination optimizes therapy. The anti-CD33, anti-CD45 and anti-CD66 mAbs appear to be ideal tracers so far. The {beta}-emitter {sup 90}Y is coupled by DTPA and is the best nuclide for myeloablation. Approval trials for DTPA anti-CD66 mAb are underway in Europe, and in the near future these therapies may become applicable in practice. This review gives an overview of current myeloablative conditioning radioimmunotherapy. We discuss the selection of the optimal radioimmunoconjugate and discuss how radioimmunotherapy might be optimized in the future by individualization of therapy protocols. We also highlight the potential advantages of combination therapies. (orig.)

  4. A new bifunctional chelating agent conjugated with monoclonal antibody and labelled with technetium-99m for targeted scintigraphy: 6-(4-isothiocyanatobenzyl)-5,7-dioxo-1,11-(carboxymethyl)-1,4,8,11-tetraazacyclotridecane.

    Science.gov (United States)

    Mishra, Anil Kumar; Panwar, Puja; Hosono, Makoto; Chuttani, Krishna; Mishra, Pushpa; Sharma, Rakesh Kumar; Chatal, Jean-Francois

    2004-01-01

    The purpose of this study was to obtain the convenient, synthetically useful bifunctional chelating agent, 6-(4-isothiocyanatobenzyl)-5,7-dioxo-1,11-(carboxymethyl)-1,4,8,11-tetraazacyclotridecane, and to apply it to stable (99m)Tc-labelling of monoclonal antibodies (mAbs). The chelate was synthesised by reaction of nitrobenzyl malonate and triethylenetetramine followed by alkylation by reacting with bromoacetic acid at pH 10. The amino group was converted to isothiocyanato derivative by reacting with thiophosgene at pH 2.0. Conjugation with mAbs [(anti-carcinoembryonic antigen (CEA) and anti-epidermal growth factor receptor (EGFr)] was performed at pH 8.4 using trisodium phosphate solution by incubating at 37 degrees C for 1 h and subjected to purification on size exclusion chromatography. When radioimmunoconjugates were labelled with (99m)Tc, the specific activity of immunoconjugates was 20-30 mCi/mg of protein and their immunoreactivity exceeded 80%. The stability in serum indicated that the metal remained bound to antibodies. Biodistribution studies in athymic mice grafted with U-87 human glioblastoma multiforme and MDA-MB-468 human breast carcinoma tumours revealed significant localisation of (99m)Tc-labelled antibodies in tumours and reduced accumulation in normal organs. This bifunctional chelating agent is promising for immunoscintigraphy because of good tumour-to-normal organ contrast.

  5. 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).

  6. 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)

  7. 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

  8. Synthesis of polyglutamide-based metal-chelating polymers and their site-specific conjugation to trastuzumab for auger electron radioimmunotherapy.

    Science.gov (United States)

    Lu, Yijie; Ngo Ndjock Mbong, Ghislaine; Liu, Peng; Chan, Conrad; Cai, Zhongli; Weinrich, Dirk; Boyle, Amanda J; Reilly, Raymond M; Winnik, Mitchell A

    2014-06-09

    Three types of metal-chelating polymers (MCPs) with hydrazide end groups were synthesized. (1) The first set of polymers (the F-series) was synthesized with a furan end group, and all of the pendant groups along the chain carried only a diethylenetriaminepentaacetic acid (DTPA) metal-chelating functionality. The hydrazide was introduced via a Diels-Alder reaction between the furan and 3,3'-N-[ε-maleimidocaproic acid] hydrazide (EMCH). (2) The P-series polymers was designed to carry several copies of a nuclear-localization peptide sequence (NLS peptides, CGYGPKKKRKVGG, harboring the NLS from the simian virus 40 large T-antigen) in addition to the DTPA metal-chelating groups. (3) The third type of polymer (the P-Py series) was a variation of the P-series polymers but with the introduction of a small number of pyrene chromophores along the backbone to allow for UV measurement of the incorporation of the MCPs into trastuzumab (tmab). These hydrazide-terminated polymers were site-specifically conjugated to aldehyde groups generated by NaIO4 oxidation of the pendant glycan in the Fc domain of tmab. The immunoconjugates were radiolabeled with (111)In and analyzed by SE-HPLC to confirm the attachment of the polymer to the antibody. HER2 binding assays demonstrated that neither the MCPs nor the presence of the NLS peptides interfered with specific antigen recognition on SK-Br-3 cells, although nonspecific binding was increased by polymer conjugation. Our results suggest that MCPs can be site-specifically attached to antibodies via oxidized glycans in the Fc domain and labeled with (111)In to construct radioimmunoconjugates with preserved immunoreactivity.

  9. 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.

  10. 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)

  11. Validation of analytical method to calculate the concentration of conjugated monoclonal antibody

    International Nuclear Information System (INIS)

    Alcarde, Lais F.; Massicano, Adriana V.F.; Oliveira, Ricardo S.; Araujo, Elaine B. de

    2013-01-01

    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

  12. Radiolabeled antibody therapy in non-Hodgkins lymphoma: radiation protection, isotope comparisons and quality of life issues.

    Science.gov (United States)

    Silverman, Daniel H; Delpassand, Ebrahim S; Torabi, Farzad; Goy, Andre; McLaughlin, Peter; Murray, James L

    2004-04-01

    Anti-CD20 antibodies radiolabeled with I-131 tositumomab (Bexxar) or Y-90-Ibritumomab tiuxetan (Zevalin), are similarly efficacious in treating chemotherapy-refractory non-Hodgkin's lymphoma. The relative merits of both radioimmunoconjugates with respect to practical issues, including radiation exposure risk, the advantages and disadvantages of the respective isotopes and other parameters that could affect a patient's quality of life are also important. I-131-labeled antibody treatment often requires inpatient hospitalization due to the inherent risk of exposure from gamma emissions, and patients and families should follow detailed instructions to prevent undue exposure. Other issues relevant to patients and medical staff include: (1) the need for dosimetry to calculate effective therapeutic doses of I-131-labeled anti-B1 (Bexxar) compared with the lack of correlation of dosimetry with marrow toxicity for IDEC-Y2B8 (Zevalin), (2) determining the acute and long-term toxic effects of each agent, (3) time commitments for nuclear medicine staff and patients along with the relative ease of administration, and (4) cost considerations. A more challenging future issue will be to determine the optimal use of Bexxar and Zevalin alone and in combination in ways that will significantly affect patient outcome without compromising quality of life. The recent demonstration of significant response rates in patients having chemotherapy-refractory Non-Hodgkin's Lymphoma (NHL) using both on I-131- and Y-90-labeled anti-CD20 antibodies with minimal toxicity has stimulated comparison of I-131 tositumomab (Bexxar) and Ibritumomab tiuxetan (Zevalin) in terms of radiation safety requirements, the advantages and disadvantages of both radionuclides, and quality-of-life (QOL) issues. Therefore, in this review, we attempt to compare the relative merits of (Bexxar and Zevalin) and address important practical considerations that may influence patient and physician choices regarding treatment

  13. 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.)

  14. Reappraising the role of autologous transplantation for indolent B-cell lymphomas in the chemoimmunotherapy era: is it still relevant?

    Science.gov (United States)

    Hamadani, M

    2013-08-01

    The role of autologous hematopoietic cell transplantation (auto-HCT) in the management of indolent non-Hodgkin lymphomas (NHL) is shrouded in controversy. The outcomes of conventional therapies for many indolent lymphoma subtypes have dramatically improved over the last several years with the use of monoclonal antibodies, maintenance therapy programs and with the incorporation of radio-immunoconjugates. These significant advances in the armamentarium of lymphoma therapeutics warrant reappraisal of the current role of auto-HCT in the treatment algorithm of indolent NHL. Prospective randomized studies comparing contemporary chemoimmunotherapies against auto-HCT are lacking, leading to significant debate about the role and timing of auto-HCT for indolent NHL in the modern era. Although autografting for follicular lymphoma (FL) in first remission has been largely abandoned, it remains a useful modality for relapsed disease, especially for the subgroup of patients who are not candidates for allogeneic transplantation with a curative intent. Auto-HCT can provide durable disease control in chemosensitive transformed FL and mantle cell lymphoma (MCL) in first remission, with relatively low toxicity, and remains appropriate in chemoimmunotherapy era. Contemporary data are also reviewed to clarify the often underutilized role of autografting in relapsed MCL and other less frequent indolent NHL histologies. The biological basis of the increased risks of second malignancies with auto-HCT are reviewed to identify strategies designed to mitigate this risk by, for example, avoiding exposure to genotoxic agents, planning early stem cell collection/cryopreservation and minimizing the use of TBI with transplant conditioning, and so on. Genetic testing able to identify patients at high risk of therapy-related complications and novel post-transplant immune therapies with the potential of transforming autografting in indolent NHL from a remission-extending therapy to a curative

  15. 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.

  16. 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.

  17. Antibody conjugate radioimmunotherapy of superficial bladder cancer

    Directory of Open Access Journals (Sweden)

    Alan Perkins

    2002-09-01

    Full Text Available The administration of antibody conjugates for cancer therapy is now proving to be of clinical value. We are currently undertaking a programme of clinical studies using the monoclonal antibody C595 (IgG3 which reacts with the MUC1 glycoprotein antigen that is aberrantly expressed in a high proportion of bladder tumours. Radioimmunoconjugates of the C595 antibody have been produced with high radiolabelling efficiency and immunoreactivity using Tc-99m and In-111 for diagnostic imaging, and disease staging and the cytotoxic radionuclides Cu-67 and Re-188 for therapy of superficial bladder cancer. A Phase I/II therapeutic trail involving the intravesical administration of antibody directly into the bladder has now begun.A administração de anticorpos conjugados para o tratamento do câncer está agora provando ser de valor clínico. Nós estamos atualmente realizando um programa de estudos clínicos usando o anticorpo monoclonal C595 (IgG3 que reage com a glicoproteína MUC1 que está aberrantemente expressa numa alta proporção de tumores de bexiga. Tem sido produzidos radioimunoconjugados do anticorpo C595, com alta eficiência de radiomarcação e a imunoreatividade, usando-se o Tc-99m e In-111, para o diagnóstico por imagem e estagiamento de doenças. Tem sido produzidos, também, radionuclídeos citotóxicos (Cu-67 e Re-188 para o tratamento de cânceres superficiais de bexiga. A fase terapêutica I/II já se iniciou, envolvendo a administração intravesical do anticorpo diretamente na bexiga.

  18. Cancer radioimmunotherapy with alpha-emitting nuclides

    Energy Technology Data Exchange (ETDEWEB)

    Couturier, Olivier [INSERM U 601, Nantes (France); Place Alexis Ricordeau, Department of Nuclear Medicine, Nantes, Cedex (France); Supiot, Stephane; Degraef-Mougin, Marie; Faivre-Chauvet, Alain; Carlier, Thomas; Chatal, Jean-Francois; Davodeau, Francois; Cherel, Michel [INSERM U 601, Nantes (France)

    2005-04-01

    In lymphoid malignancies and in certain solid cancers such as medullary thyroid carcinoma, somewhat mixed success has been achieved when applying radioimmunotherapy (RIT) with {beta}-emitters for the treatment of refractory cases. The development of novel RIT with {alpha}-emitters has created new opportunities and theoretical advantages due to the high linear energy transfer (LET) and the short path length in biological tissue of {alpha}-particles. These physical properties offer the prospect of achieving selective tumoural cell killing. Thus, RIT with {alpha}-emitters appears particularly suited for the elimination of circulating single cells or cell clusters or for the treatment of micrometastases at an early stage. However, to avoid non-specific irradiation of healthy tissues, it is necessary to identify accessible tumoural targets easily and rapidly. For this purpose, a small number of {alpha}-emitters have been investigated, among which only a few have been used for in vivo preclinical studies. Another problem is the availability and cost of these radionuclides; for instance, the low cost and the development of a reliable actinium-225/bismuth-213 generator were probably determining elements in the choice of bismuth-213 in the only human trial of RIT with an {alpha}-emitter. This article reviews the literature concerning monoclonal antibodies radiolabelled with {alpha}-emitters that have been developed for possible RIT in cancer patients. The principal radio-immunoconjugates are considered, starting with physical and chemical properties of {alpha}-emitters, their mode of production, the possibilities and difficulties of labelling, in vitro studies and finally, when available, in vivo preclinical and clinical studies. (orig.)

  19. Cancer radioimmunotherapy with alpha-emitting nuclides.

    Science.gov (United States)

    Couturier, Olivier; Supiot, Stéphane; Degraef-Mougin, Marie; Faivre-Chauvet, Alain; Carlier, Thomas; Chatal, Jean-François; Davodeau, François; Cherel, Michel

    2005-05-01

    In lymphoid malignancies and in certain solid cancers such as medullary thyroid carcinoma, somewhat mixed success has been achieved when applying radioimmunotherapy (RIT) with beta-emitters for the treatment of refractory cases. The development of novel RIT with alpha-emitters has created new opportunities and theoretical advantages due to the high linear energy transfer (LET) and the short path length in biological tissue of alpha-particles. These physical properties offer the prospect of achieving selective tumoural cell killing. Thus, RIT with alpha-emitters appears particularly suited for the elimination of circulating single cells or cell clusters or for the treatment of micrometastases at an early stage. However, to avoid non-specific irradiation of healthy tissues, it is necessary to identify accessible tumoural targets easily and rapidly. For this purpose, a small number of alpha-emitters have been investigated, among which only a few have been used for in vivo preclinical studies. Another problem is the availability and cost of these radionuclides; for instance, the low cost and the development of a reliable actinium-225/bismuth-213 generator were probably determining elements in the choice of bismuth-213 in the only human trial of RIT with an alpha-emitter. This article reviews the literature concerning monoclonal antibodies radiolabelled with alpha-emitters that have been developed for possible RIT in cancer patients. The principal radio-immunoconjugates are considered, starting with physical and chemical properties of alpha-emitters, their mode of production, the possibilities and difficulties of labelling, in vitro studies and finally, when available, in vivo preclinical and clinical studies.

  20. Cancer radioimmunotherapy with alpha-emitting nuclides

    International Nuclear Information System (INIS)

    Couturier, Olivier; Supiot, Stephane; Degraef-Mougin, Marie; Faivre-Chauvet, Alain; Carlier, Thomas; Chatal, Jean-Francois; Davodeau, Francois; Cherel, Michel

    2005-01-01

    In lymphoid malignancies and in certain solid cancers such as medullary thyroid carcinoma, somewhat mixed success has been achieved when applying radioimmunotherapy (RIT) with β-emitters for the treatment of refractory cases. The development of novel RIT with α-emitters has created new opportunities and theoretical advantages due to the high linear energy transfer (LET) and the short path length in biological tissue of α-particles. These physical properties offer the prospect of achieving selective tumoural cell killing. Thus, RIT with α-emitters appears particularly suited for the elimination of circulating single cells or cell clusters or for the treatment of micrometastases at an early stage. However, to avoid non-specific irradiation of healthy tissues, it is necessary to identify accessible tumoural targets easily and rapidly. For this purpose, a small number of α-emitters have been investigated, among which only a few have been used for in vivo preclinical studies. Another problem is the availability and cost of these radionuclides; for instance, the low cost and the development of a reliable actinium-225/bismuth-213 generator were probably determining elements in the choice of bismuth-213 in the only human trial of RIT with an α-emitter. This article reviews the literature concerning monoclonal antibodies radiolabelled with α-emitters that have been developed for possible RIT in cancer patients. The principal radio-immunoconjugates are considered, starting with physical and chemical properties of α-emitters, their mode of production, the possibilities and difficulties of labelling, in vitro studies and finally, when available, in vivo preclinical and clinical studies. (orig.)

  1. 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.

  2. 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.)

  3. 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

  4. Alpha radioimmunotherapy of multiple myeloma: study of feasibility of ex vivo medullary purge; Radioimmunotherapie alpha du myelome multiple: etude de faisabilite de purge de moelle ex vivo

    Energy Technology Data Exchange (ETDEWEB)

    Couturier, O.; Filippovitch, I.V.; Sorokina, N.I.; Cherel, M.; Thedrez, P.; Faivre-Chauvet, A.; Chatal, J.F. [INSERM U463, Nantes (France)

    1997-12-31

    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 {mu}m). 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{sup 5} cells (0.4 {mu}Ci) to 29.6 kBq/10{sup 5} cells (0.8 {mu}Ci). The cellular mortality was total at 300 kBq/10{sup 5} cells (8 {mu}Ci). The cells in an apoptosis state were evidenced at rates up to 40% for a dose of 7.4 kBq/10{sup 5} cells (0.2 {mu} 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

  5. 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

  6. 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

  7. 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

  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

  9. Metal ion cage complexes as imaging agents for cancer cells

    International Nuclear Information System (INIS)

    Di Bartolo, N.; Smith, S.; Sargeson, A.

    2000-01-01

    , food intake and hunching). Radiotoxic effects were monitored at predetermined time points (2 days, 1, 2, 3, 4 weeks, 2, 3, 4, 5 and 6 months). Indicators for the endpoint of the study were body weight loss > 20 %, rapid weight loss of > 10 % overnight, ulceration of tumour, limitation of normal behaviour (e.g. ability to feed or drink) and tumour size > 10 x 10 mm (UK Cancer Council). A significant extension of mouse life was achieved with doses of greater than 20 MBq (from 25 to 46 days for 30 MBq) with no major radiotoxic effects. Complexation of copper by SarAr is extremely fast making the production of 64 Cu-SarArB-72.3 immunoconjugate attractive for kit formulation and applicable for use in Nuclear Medicine Departments. Biological studies show the radioimmunoconjugate is stable in vivo and able to induce a therapeutic effect in tumour bearing animals. The shorter half life of 64 Cu and the MIRDOSE calculations support the potential of 64 Cu for use in treatment on an outpatient basis