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Sample records for 90y ibritumomab tiuxetan

  1. External Beam Radiotherapy Followed by {sup 90}Y Ibritumomab Tiuxetan in Relapsed or Refractory Bulky Follicular Lymphoma

    SciTech Connect

    Burdick, Michael J.; Neumann, Donald; Pohlman, Brad; Reddy, Chandana A.; Tendulkar, Rahul D.; Macklis, Roger

    2011-03-15

    Purpose: We combined external beam radiotherapy (EBRT) with yttrium-90 ibritumomab tiuxetan ({sup 90}Y-IT) in an attempt to improve therapeutic response in patients with relapsed or refractory bulky follicular lymphoma (RRBFL). Methods and Materials: Between February 2006 and September 2007, 11 patients with RRBFL were treated with EBRT followed by {sup 90}Y-IT. Bulky disease (BD) was defined as >5 cm. EBRT was delivered to BD as 2,400 cGy in eight fractions using computed tomography (CT)-based planning. BD was contoured as the gross tumor volume. A planning margin of 1 to 2 cm was added depending on anatomical location. After recovery of complete blood counts (CBC), {sup 90}Y-IT was administered at a dose of 0.3 or 0.4 mCi/kg depending on platelet counts. Hematologic toxicity was monitored through weekly CBC. Response was measured by positron emission tomography/CT or CT 3-4 months after {sup 90}Y-IT. Results: Only 2 patients required prolonged breaks between EBRT and {sup 90}Y-IT. The median time after {sup 90}Y-IT for platelets to recover to >100,000/ml was 55 days (range, 41-128 days). Platelet counts for 1 patient, who had received 4 previous chemotherapy regimens, never reached 100,000/ml. The complete and overall responses to combined therapy as measured 3-4 months after {sup 90}Y-IT were 64%. No patients relapsed within the EBRT field. With a median follow-up of 36.1 months, 6 patients have relapsed, 2 of whom have died. Median progression-free survival was 17.5 months. Conclusions: In contrast to prior failure analysis data for RRBFL patients treated with {sup 90}Y-IT alone, a brief course of EBRT prevented relapse in sites of BD. EBRT used to pretreat bulky sites may improve clinical outcomes and potentially extend survival when combined with {sup 90}Y-IT.

  2. First-line treatment with rituximab-hyperCVAD alternating with rituximab-methotrexate-cytarabine and followed by consolidation with 90Y-ibritumomab-tiuxetan in patients with mantle cell lymphoma. Results of a multicenter, phase 2 pilot trial from the GELTAMO group

    PubMed Central

    Arranz, Reyes; García-Noblejas, Ana; Grande, Carlos; Cannata-Ortiz, Jimena; Sánchez, José J.; García-Marco, José-Antonio; Aláez, Concepción; Pérez-Calvo, Javier; Martínez-Sánchez, Pilar; Sánchez-González, Blanca; Canales, Miguel-Angel; Conde, Eulogio; Martín, Alejandro; Arranz, Eva; Terol, María-José; Salar, Antonio; Caballero, Dolores

    2013-01-01

    The prognosis for fit patients with mantle cell lymphoma has improved with intensive strategies. Currently, the role of maintenance/consolidation approaches is being tested as relapses continue to appear. In this trial we evaluated the feasibility, safety and efficacy of rituximab-hyperCVAD alternating with rituximab-methotrexate-cytarabine followed by consolidation with 90Y-ibritumomab tiuxetan. Patients received six cycles followed by a single dose of 90Y-ibritumomab tiuxetan. Thirty patients were enrolled; their median age was 59 years. Twenty-four patients finished the induction treatment, 23 achieved complete remission (77%, 95% confidence interval 60–93) and one patient had progressive disease (3%). Eighteen patients (60%), all in complete remission, received consolidation therapy. In the intent-to-treat population, failure-free, progression-free and overall survival rates at 4 years were 40% (95% confidence interval 20.4–59.6), 52% (95% confidence interval 32.4–71.6) and 81% (95% confidence interval 67.28–94.72), respectively. For patients who received consolidation, failure-free and overall survival rates were 55% (95% confidence interval 31.48–78.52) and 87% (95% confidence interval 70–100), respectively. Hematologic toxicity was significant during induction and responsible for one death (3.3%). After consolidation, grade 3–4 neutropenia and thrombocytopenia were observed in 72% and 83% of patients, with a median duration of 5 and 12 weeks, respectively. Six (20%) patients died, three due to secondary malignancies (myelodysplastic syndrome and bladder and rectum carcinomas). In conclusion, in our experience, rituximab-hyperCVAD alternated with rituximab-methotrexate-cytarabine and followed by consolidation with 90Y-ibritumomab tiuxetan was efficacious although less feasible than expected. The unacceptable toxicity observed, especially secondary malignancies, advise against the use of this strategy. Trial registration: clinical.gov identifier

  3. Logistics of therapy with the ibritumomab tiuxetan regimen

    SciTech Connect

    Meredith, Ruby F. . E-mail: rmeredith@uabmc.edu

    2006-10-01

    Radioimmunotherapy is an important new modality for treating patients with B-cell non-Hodgkin's lymphoma (NHL). Clinical trials have shown the safety and efficacy of agents that deliver radiation directly to malignant cells by attaching the {sup 131}I or {sup 9}Y radionuclide to monoclonal antibodies against CD20. In clinical trials, {sup 9}Y ibritumomab tiuxetan has produced rates of response as high as 83% in patients with relapsed or refractory CD20+ NHL. The ibritumomab tiuxetan regimen is conveniently given in an outpatient setting over the course of 7-9 days. This article describes the logistics for initiating treatment, coordinating a multidisciplinary team, identifying eligible patients, and delivering the imaging and therapeutic doses of ibritumomab tiuxetan. The standard radiation safety procedures to protect family members and healthcare professionals involved in the care of patients treated with {sup 9}Y ibritumomab tiuxetan are also reviewed. Treatment with the ibritumomab tiuxetan regimen involves only standard precautions needed to minimize radiation exposure to other persons.

  4. Zevalin(®) (ibritumomab tiuxetan): After more than a decade of treatment experience, what have we learned?

    PubMed

    Rizzieri, David

    2016-09-01

    Non-Hodgkin's lymphoma (NHL) comprises a clinically and biologically heterogeneous group of lymphoproliferative disorders originating in B lymphocytes, T lymphocytes, or natural killer (NK) cells. The disease course may range from indolent to aggressive. Zevalin(®) (ibritumomab tiuxetan) is a radioactive drug product, which is the combination of a β-emitting isotope, (90)Y, linked to the anti-CD20 monoclonal antibody (mAb), rituximab. It has demonstrated therapeutic efficacy with durable responses and allows delivery of ionizing radiation directly to the tumor site, while minimizing toxicity to normal tissue. Ibritumomab tiuxetan is indicated for treatment of patients with relapsed or refractory low-grade, follicular NHL, including patients who are refractory to rituximab, and as consolidation therapy in previously untreated follicular NHL in patients who achieve a partial or complete response to first-line chemotherapy. Despite the efficacy and acceptable safety profile of ibritumomab tiuxetan, utilization has not been broadly adopted in practice due to a number of factors. This manuscript will review the literature available for ibritumomab tiuxetan, including several new trials that are currently being studied, and discuss the rationale for use of ibritumomab tiuxetan in NHL. PMID:27497027

  5. Salvage therapy for primary central nervous system lymphoma with (90)Y-Ibritumomab and Temozolomide.

    PubMed

    Pitini, Vincenzo; Baldari, Sergio; Altavilla, Giuseppe; Arrigo, Carmela; Naro, Claudia; Perniciaro, Francesca

    2007-07-01

    Aggressive initial treatment of Primary Central Nervous System Lymphoma (PCNSL) has achieved prolonged survival and occasional cures. However, some patients do not respond to initial therapy and others relapse after an initial remission. The optimal salvage regimen is not known and many different strategies have been proposed. In this report we describe the efficacy of a combination of (90)Y-Ibritumomab Tiuxetan (Zevalin) and Temozolamide as a maintenance therapy for recurrent PCNS Lymphoma in two patients that are both alive and in complete remission after 9 and 10 months respectively. This combination merits further study and provides a reasonable therapeutic alternative for older patients with progressive PCNSL.

  6. Upfront consolidation combining yttrium-90 ibritumomab tiuxetan and high-dose therapy with stem cell transplantation in poor-risk patients with diffuse large B cell lymphoma.

    PubMed

    Fruchart, Christophe; Tilly, Hervé; Morschhauser, Franck; Ghesquières, Hervé; Bouteloup, Marie; Fermé, Christophe; Van Den Neste, Eric; Bordessoule, Dominique; Bouabdallah, Reda; Delmer, Alain; Casasnovas, René Olivier; Ysebaert, Loïc; Ciappuccini, Renaud; Briere, Josette; Gisselbrecht, Christian

    2014-12-01

    We evaluated the safety and efficacy of standard-dose yttrium-90 (Y(90)) ibritumomab tiuxetan combined with high-dose BEAM (carmustine, etoposide, cytarabine, and melphalan) after first-line induction treatment in young patients with poor prognoses diffuse large B cell lymphoma (DLBCL) (clinicaltrials.gov: NCT00689169). Seventy-five high-risk (≥2 International Prognostic Index [IPI] factors) consecutive DLBCL patients (≤65 years old) in complete remission (CR) or partial remission (PR) after rituximab chemotherapy were treated with Y(90) ibritumomab tiuxetan and BEAM regimen followed by autologous stem cell transplantation (ASCT). The median follow-up was 34 months. Of the 75 patients, 71 underwent ASCT and were eligible for analysis. Median time to reach a neutrophil count of >500/μL and platelet count of >20,000/μL was 11 days. Mucositis ≥3 (51%) occurred in most patients. Other adverse events were similar to those seen with BEAM alone. The overall response rate was 86%; 59 patients (83%) achieved a CR or unconfirmed CR. The 2-year event-free survival (EFS), overall survival (OS), and disease-free survival were 79%, 83%, and 91%, respectively. Disease status (CR/PR) and positron emission tomography (PET) findings before transplantation did not predict treatment failure. The IPI (2 versus >2) and maximum tumor diameter of ≥10 cm at diagnosis appeared to be prognosis factors for OS but not for EFS. Adding Y(90) ibritumomab tiuxetan to BEAM is safe and does not increase transplantation-related toxicity. First-line consolidation with Y(90) ibritumomab tiuxetan and high-dose chemotherapy induced high rates of EFS and OS in poor-prognosis patients with DLBCL, regardless of PET status after induction treatment and warrants a randomized study. PMID:25072780

  7. Bulky Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma Treated with Yttrium-90 Ibritumomab Tiuxetan

    PubMed Central

    Tamura, Shinobu; Ikeda, Tokuji; Kurihara, Toshio; Kakuno, Yoshiteru; Nasu, Hideki; Nakano, Yoshio; Oshima, Koichi; Fujimoto, Tokuzo

    2013-01-01

    An 84-year-old woman was admitted to our hospital with nonproductive cough and dyspnea on exertion. Computed tomography (CT) scan revealed extensive consolidation in the right lung. She was diagnosed with pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma using CT-guided lung biopsy. Her pulmonary images and respiratory symptoms did not improve two months after receiving 4 cycles of rituximab weekly; therefore, yttrium-90 ibritumomab tiuxetan was chosen as salvage therapy. The abnormal shadow on her pulmonary images was significantly reduced two months later, and she had no symptoms without nonhematological toxicities. She has had no progression for 18 months. Furthermore, radiation pneumonitis has not also been observed. We herein reported bulky pulmonary MALT lymphoma treated with yttrium-90 ibritumomab tiuxetan. PMID:24371530

  8. p53-Based Strategy for Protection of Bone Marrow From Y-90 Ibritumomab Tiuxetan

    SciTech Connect

    Su, Hang; Ganapathy, Suthakar; Li, Xiaolei; Yuan, Zhi-Min; Ha, Chul S.

    2015-08-01

    Purpose: The main drawbacks of radioimmunotherapy have been severe hematological toxicity and potential development of myelodysplastic syndrome and secondary leukemia. Activation of p53 follows a major pathway by which normal tissues respond to DNA-damaging agents, such as chemotherapy and radiation therapy, that result in injuries and pathological consequences. This pathway is separate from the tumor suppressor pathway of p53. We have previously reported that use of low-dose arsenic (LDA) temporarily and reversibly suppresses p53 activation, thereby ameliorating normal tissue toxicity from exposure to 5-fluorouracil and X rays. We have also demonstrated that LDA-mediated protection requires functional p53 and thus is selective to normal tissues, as essentially every cancer cell has dysfunctional p53. Here we tested the protective efficacy of LDA for bone marrow tissue against radioimmunotherapy through animal experiments. Methods and Materials: Mice were subjected to LDA pretreatment for 3 days, followed by treatment with Y-90 ibritumomab tiuxetan. Both dose course (10, 25, 50, 100, and 200 μCi) and time course (6, 24, and 72 hours and 1 and 2 weeks) experiments were performed. The response of bone marrow cells to LDA was determined by examining the expression of NFκB, Glut1, and Glut3. Staining with hematoxylin and eosin, γ-H2AX, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used to examine morphology, DNA damage response, and apoptotic cell populations. Results: Elevated levels of NFκB, Glut1, and Glut3 were observed in bone marrow cells after LDA treatment. Bone marrow damage levels induced by Y-90 ibritumomab tiuxetan were greatly reduced by LDA pretreatment. Consistent with this observation, significantly less DNA damage and fewer apoptotic cells were accumulated after Y-90 ibritumomab tiuxetan treatment in LDA-pretreated mice. Furthermore, in the mouse xenograft model implanted with human Karpas-422 lymphoma cells, LDA

  9. Administration guidelines for radioimmunotherapy of non-Hodgkin's lymphoma with (90)Y-labeled anti-CD20 monoclonal antibody.

    PubMed

    Wagner, Henry N; Wiseman, Gregory A; Marcus, Carol S; Nabi, Hani A; Nagle, Conrad E; Fink-Bennett, Darlene M; Lamonica, Dominick M; Conti, Peter S

    2002-02-01

    90Y-ibritumomab tiuxetan is a novel radioimmunotherapeutic agent recently approved for the treatment of relapsed or refractory low-grade, follicular, or CD20+ transformed non-Hodgkin's lymphoma (NHL). (90)Y-ibritumomab tiuxetan consists of a murine monoclonal antibody covalently attached to a metal chelator, which stably chelates (111)In for imaging and (90)Y for therapy. Both health care workers and patients receiving this therapy need to become familiar with how it differs from conventional chemotherapy and what, if any, safety precautions are necessary. Because (90)Y is a pure beta-emitter, the requisite safety precautions are not overly burdensome for health care workers or for patients and their families. (90)Y-ibritumomab tiuxetan is dosed on the basis of the patient's body weight and baseline platelet count; dosimetry is not required for determining the therapeutic dose in patients meeting eligibility criteria similar to those used in clinical trials, such as <25% lymphomatous involvement of the bone marrow. (111)In- and (90)Y-ibritumomab tiuxetan are labeled at commercial radiopharmacies and delivered for on-site dose preparation and administration. Plastic and acrylic materials are appropriate for shielding during dose preparation and administration; primary lead shielding should be avoided because of the potential exposure risk from bremsstrahlung. Because there are no penetrating gamma-emissions associated with the therapy, (90)Y-ibritumomab tiuxetan is routinely administered on an outpatient basis. Furthermore, the risk of radiation exposure to patients' family members has been shown to be in the range of background radiation, even without restrictions on contact. There is therefore no need to determine activity limits or dose rate limits before patients who have been treated with (90)Y radioimmunotherapy are released, as is necessary with patients who have been treated with radiopharmaceuticals that contain (131)I. Standard universal precautions for

  10. Late Occurrence of PML in a Patient Treated for Lymphoma with Immunomodulatory Chemotherapies, Bendamustine, Rituximab, and Ibritumomab Tiuxetan

    PubMed Central

    Lane, Michael A.; Renga, Vijay; Pachner, Andrew R.; Cohen, Jeffrey A.

    2015-01-01

    PML caused by John Cunningham (JC) virus is a rare but an increasingly recognized entity. With the advent of newer immunomodulatory therapies with monoclonal antibodies, there is an increasing incidence of PML. Initially concern was restricted to patients treated for multiple sclerosis with natalizumab but more case reports are being reported during treatment for other conditions like Crohn's disease and lymphoma with agents such as rituximab. We report the case of a 66-year-old woman who developed PML a year after completion of therapy with rituximab, ibritumomab, and bendamustine. PMID:25705531

  11. Consolidation treatment with Yttrium-90 ibritumomab tiuxetan after new induction regimen in patients with intermediate- and high-risk follicular lymphoma according to the follicular lymphoma international prognostic index: a multicenter, prospective phase II trial of the Spanish Lymphoma Oncology Group.

    PubMed

    Provencio, Mariano; Cruz Mora, Miguel Á; Gómez-Codina, José; Quero Blanco, Cristina; Llanos, Marta; García-Arroyo, Francisco R; de la Cruz, Luis; Gumá Padró, Josep; Delgado Pérez, Juan R; Sánchez, Antonio; Alvarez Cabellos, Ruth; Rueda, Antonio

    2014-01-01

    Relapse is the main cause of therapeutic failure in follicular lymphoma (FL). We set out to evaluate the role of consolidation with Yttrium-90 ibritumomab tiuxetan in patients with intermediate- and high-risk FL after four cycles of CHOP-R (cyclophosphamide, doxorubicin, vincristine, prednisone, rituximab) and two cycles of CHOP. Thirty patients were included. The overall response rate after consolidation therapy was 93%. Of the 18 patients who presented with a partial response after induction treatment, 11 had a complete response after consolidation treatment. The complete clinical response rate was 76.6%. The most important grade 3-4 toxicity was hematological, with 46% thrombopenia and 56% neutropenia. With a median follow-up of 26 months, the means for progression-free survival and overall survival were not reached. Our data support consolidation with Yttrium-90 ibritumomab tiuxetan as an effective treatment, which provides long progression-free and overall survival, in first line after a response to induction treatment in patients with intermediate- and high-risk FL. PMID:23573825

  12. Relative Biologic Effects of Low-Dose-Rate {alpha}-Emitting {sup 227}Th-Rituximab and {beta}-Emitting {sup 90}Y-Tiuexetan-Ibritumomab Versus External Beam X-Radiation

    SciTech Connect

    Dahle, Jostein Bruland, Oyvind S.; Larsen, Roy H.

    2008-09-01

    Purpose: To determine the relative biologic effects (RBE) of {alpha}-particle radiation from {sup 227}Th-rituximab and of {beta}-radiation from {sup 90}Y-tiuexetan-ibritumomab (Zevalin) compared with external beam X-radiation in the Raji lymphoma xenograft model. Methods and Materials: Radioimmunoconjugates were administered intravenously in nude mice with Raji lymphoma xenografts at different levels of activity. Absorbed dose to tumor was estimated by separate biodistribution experiments for {sup 227}Th-rituximab and Zevalin. Tumor growth was measured two to three times per week after injection or X-radiation. Treatment-induced increase in growth delay to reach tumor volumes of 500 and 1,000 mm{sup 3}, respectively, was used as an end point. Results: The absorbed radiation dose-rate in tumor was slightly more than 0.1 Gy/d for the first week following injection of {sup 227}Th-rituximab, and thereafter gradually decreased to 0.03 Gy/d at 21 days after injection. For treatment with Zevalin the maximum dose-rate in tumor was achieved already 6 h after injection (0.2 Gy/d), and thereafter decreased to 0.01 Gy/d after 7 days. The relative biologic effect was between 2.5 and 7.2 for {sup 227}Th-rituximab and between 1 and 1.3 for Zevalin. Conclusions: Both at low doses and low-dose-rates, the {sup 227}Th-rituximab treatment was more effective per absorbed radiation dose unit than the two other treatments. The considerable effect at low doses suggests that the best way to administer low-dose-rates, {alpha}-emitting radioimmunoconjugates is via multiple injections.

  13. Ibritumomab Injection

    MedlinePlus

    ... is in a class of medications called monoclonal antibodies with radioisotopes. It works by attaching to cancer ... you receive ibritumomab injection, your body may develop antibodies (substances in the blood that help the immune ...

  14. Evaluation of quantitative 90Y SPECT based on experimental phantom studies

    NASA Astrophysics Data System (ADS)

    Minarik, D.; Sjögreen Gleisner, K.; Ljungberg, M.

    2008-10-01

    In SPECT imaging of pure beta emitters, such as 90Y, the acquired spectrum is very complex, which increases the demands on the imaging protocol and the reconstruction. In this work, we have evaluated the quantitative accuracy of bremsstrahlung SPECT with focus on the reconstruction algorithm including model-based attenuation, scatter and collimator-detector response (CDR) compensations. The scatter and CDR compensation methods require pre-calculated point-spread functions, which were generated with the SIMIND MC program. The SIMIND program is dedicated for simulation of scintillation camera imaging and only handles photons. The aim of this work was therefore twofold. The first aim was to implement simulation of bremsstrahlung imaging into the SIMIND code and to validate simulations against experimental measurements. The second was to investigate the quality of bremsstrahlung SPECT imaging and to evaluate the possibility of quantifying the activity in differently shaped sources. In addition, a feasibility test was performed on a patient that underwent treatment with 90Y-Ibritumomab tiuxetan (Zevalin®). The MCNPX MC program was used to generate bremsstrahlung photon spectra which were used as source input in the SIMIND program. The obtained bremsstrahlung spectra were separately validated by experimental measurement using a HPGe detector. Validation of the SIMIND generated images was done by a comparison to gamma camera measurements of a syringe containing 90Y. Results showed a slight deviation between simulations and measurements in image regions outside the source, but the agreement was sufficient for the purpose of generating scatter and CDR kernels. For the bremsstrahlung SPECT experiment, the RSD torso phantom with 90Y in the liver insert was measured with and without background activities. Projection data were obtained using a GE VH/Hawkeye system. Image reconstruction was performed by using the OSEM algorithm with and without different combinations of model

  15. Therapeutic Potential of 90Y- and 131I-Labeled Anti-CD20 Monoclonal Antibody in Treating Non-Hodgkin's Lymphoma with Pulmonary Involvement: A Monte Carlo–Based Dosimetric Analysis

    PubMed Central

    Song, Hong; Du, Yong; Sgouros, George; Prideaux, Andrew; Frey, Eric; Wahl, Richard L.

    2010-01-01

    Pulmonary involvement is common in patients with non-Hodgkin's lymphoma (NHL). 90Y- and 131I-anti-CD20 antibodies (ibritumomab tiuxetan and tositumomab, respectively) have been approved for the treatment of refractory low-grade follicular NHL. In this work, we used Monte Carlo–based dosimetry to compare the potential of 90Y and 131I, based purely on their emission properties, in targeted therapy for NHL lung metastases of various nodule sizes and tumor burdens. Methods Lung metastases were simulated as spheres, with radii ranging from 0.2 to 5.0 cm, which were randomly distributed in a voxelized adult male lung phantom. Total tumor burden was varied from 0.2 to 1,641 g. Tumor uptake and retention kinetics of the 2 radionuclides were assumed equivalent; a uniform distribution of activity within tumors was assumed. Absorbed dose to tumors and lung parenchyma per unit activity in lung tumors was calculated by a Monte Carlo–based system using the MCNP4B package. Therapeutic efficacy was defined as the ratio of mean absorbed dose in the tumor to that in normal lung. Dosimetric analysis was also performed for a lung-surface distribution of tumor nodules mimicking pleural metastatic disease. Results The therapeutic efficacy of both 90Y and 131I declined with increasing tumor burden. In treating tumors with radii less than 2.0 cm, 131I targeting was more efficacious than 90Y targeting. 90Y yielded a broader distribution of tumor absorbed doses, with the minimum 54.1% lower than the average dose; for 131I, the minimum absorbed dose was 33.3% lower than the average. The absorbed dose to normal lungs was reduced when the tumors were distributed on the lung surface. For surface tumors, the reductions in normal-lung absorbed dose were greater for 90Y than for 131I, but 131I continued to provide a greater therapeutic ratio across different tumor burdens and sizes. Conclusion Monte Carlo–based dosimetry was performed to compare the therapeutic potential of 90Y and 131I

  16. Ibritumomab consolidation after 3 cycles of CHOP plus radiotherapy in high-risk limited-stage aggressive B-cell lymphoma: SWOG S0313

    PubMed Central

    Miller, Thomas P.; Unger, Joseph M.; Spier, Catherine M.; Puvvada, Soham; Stea, B. Dino; Press, Oliver W.; Constine, Louis S.; Barton, Kevin P.; Friedberg, Jonathan W.; LeBlanc, Michael; Fisher, Richard I.

    2015-01-01

    In the S0313 trial, we evaluated the impact of adding ibritumomab tiuxetan consolidation to 3 cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy plus involved field radiotherapy (IFRT) in patients with limited-stage aggressive B-cell non-Hodgkin lymphoma (LD-NHL). Patients with at least 1 stage-modified adverse risk factor (nonbulky stage II, age >60 years, elevated lactate dehydrogenase, or World Health Organization performance status of 2) were treated with CHOP on days 1, 22, and 43, followed 3 weeks later by 40 to 50 Gy of IFRT. An ibritumomab tiuxetan regimen was initiated 3 to 6 weeks following IFRT. Forty-six patients were registered and eligible, with median follow-up of 7.3 years. The progression-free survival estimate is 89% at 2 years, 82% at 5 years, and 75% at 7 years. The overall survival estimate is 91% at 2 years, 87% at 5 years, and 82% at 7 years. Grade 4 adverse events occurring more than once included neutropenia (8), leukopenia (5), and lymphopenia (2). Febrile neutropenia was observed in 4 patients. No cases of treatment-related myeloid neoplasms were noted. In conclusion, patients with high-risk LD-NHL treated with 3 cycles of CHOP plus IFRT followed by ibritumomab tiuxetan consolidation had outcomes that compare favorably to our historical experience. The clinical trial was registered at www.clinicaltrials.gov as #NCT00070018. PMID:25395425

  17. Rituximab With or Without Yttrium Y-90 Ibritumomab Tiuxetan in Treating Patients With Untreated Follicular Lymphoma

    ClinicalTrials.gov

    2016-06-15

    Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage II Grade 1 Contiguous Follicular Lymphoma; Stage II Grade 1 Non-Contiguous Follicular Lymphoma; Stage II Grade 2 Contiguous Follicular Lymphoma; Stage II Grade 2 Non-Contiguous Follicular Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma

  18. Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab in Treating Patients With Post-Transplant Lymphoproliferative Disorder

    ClinicalTrials.gov

    2013-01-24

    Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Waldenström Macroglobulinemia

  19. Rituximab, Combination Chemotherapy, and 90-Yttrium Ibritumomab Tiuxetan for Patients With Stage I or II Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2015-02-17

    Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

  20. Agatolimod Sodium, Rituximab, and Yttrium Y 90 Ibritumomab Tiuxetan in Treating Patients With Recurrent or Refractory Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-01-04

    Adult Non-Hodgkin Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Nodal Marginal Zone Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

  1. 90Y labeled phosphorodiamidate morpholino oligomer for pretargeting radiotherapy.

    PubMed

    Liu, Guozheng; Dou, Shuping; Liu, Yuxia; Wang, Yuzhen; Rusckowski, Mary; Hnatowich, Donald J

    2011-12-21

    While (188)Re has been used successfully in mice for tumor radiotherapy by MORF/cMORF pretargeting, previous radiolabeling of the amine-derivatized cMORF with (90)Y, a longer physical half-life nuclide, was not very successful. After developing a method involving a prepurification heating step during conjugation that increases labeling efficiency and label stability, the biodistribution of (90)Y-DOTA-Bn-SCN-cMORF ((90)Y-DOTA-cMORF) was measured in normal mice and in MORF-CC49 pretargeted mice that bear LS174T tumors. Absorbed radiation doses were then estimated and compared to those estimated for (188)Re. The pharmacokinetics of the (90)Y-DOTA-cMORF in normal mice and in the pretargeted nude mice was similar to that observed previously with (99m)Tc- and (188)Re-MAG(3)-cMORFs. While the (90)Y-DOTA-cMORF cleared rapidly from normal tissues, tumor clearance was very slow and tumor radioactivity accumulation was constant for at least 7 days such that the tumor/blood (T/B) ratio increased linearly from 6 to 25 over this period. Therefore, by extrapolation, normal tissue toxicities following administration of therapeutic doses of (90)Y may be comparable to that observed for (188)Re in which the T/B increased from 5 to 20. In conclusion, radiolabeling of DOTA-cMORF with (90)Y was improved by introducing a prepurification heating step during conjugation. The (90)Y-DOTA-cMORF provided a similar T/B ratio and biodistribution to that of (188)Re-MAG(3)-cMORF and was retained well in the tumor pretargeted with MORF-CC49. Because of the longer physical half-life, the T/NT absorbed radiation dose ratios were improved in most organs and especially in blood. PMID:21985267

  2. Monte Carlo dosimetry of a new 90Y brachytherapy source

    PubMed Central

    Junxiang, Wu; Shihu, You; Jing, Huang; Fengxiang, Long; Chengkai, Wang; Zhangwen, Wu; Qing, Hou

    2015-01-01

    Purpose In this study, we attempted to obtain full dosimetric data for a new 90Y brachytherapy source developed by the College of Chemistry (Sichuan University) for use in high-dose-rate after-loading systems. Material and methods The dosimetric data for this new source were used as required by the dose calculation formalisms proposed by the AAPM Task Group 60 and Task Group 149. The active core length of the new 90Y source was increased to 4.7 mm compared to the value of 2.5 mm for the old 90Sr/90Y source. The Monte Carlo simulation toolkit Geant4 was used to calculate these parameters. The source was located in a 30-cm-radius theoretical sphere water phantom. Results The dosimetric data included the reference absorbed dose rate, the radial dose function in the range of 1.0 to 8.0 mm in the longitudinal axis, and the anisotropy function with a θ in the range of 0° to 90° at 5° intervals and an r in the range of 1.0 to 8.0 mm in 0.2-mm intervals. The reference absorbed dose rate for the new 90Y source was determined to be equal to 1.6608 ± 0.0008 cGy s–1 mCi–1, compared to the values of 0.9063 ± 0.0005 cGy s–1 mCi–1 that were calculated for the old 90Sr/90Y source. A polynomial function was also obtained for the radial dose function by curve fitting. Conclusions Dosimetric data are provided for the new 90Y brachytherapy source. These data are meant to be used commercially in after-loading system. PMID:26622247

  3. Preparation & in vitro evaluation of 90Y-DOTA-rituximab

    PubMed Central

    Kameswaran, Mythili; Pandey, Usha; Dash, Ashutosh; Samuel, Grace; Venkatesh, Meera

    2016-01-01

    Background & objectives: Radioimmunotherapy is extensively being used for the treatment of non-Hodgkin's lymphoma (NHL). Use of rituximab, a chimeric anti-CD20 antibody directed against the CD20 antigen in combination with suitable beta emitters is expected to result in good treatment response by its cross-fire and bystander effects. The present work involves the conjugation of p-isothiocyanatobenzyl DOTA (p-SCN-Bn-DOTA) to rituximab, its radiolabelling with 90Y and in vitro and in vivo evaluation to determine its potential as a radioimmunotherapeutic agent. Methods: Rituximab was conjugated with p-SCN-Bn-DOTA at 1:1 antibody: DOTA molar ratio. The number of DOTA molecules linked to one molecule of rituximab was determined by radioassay and spectroscopic assay. Radiolabelling of rituximab with 90Y was carried out and its in vitro stability was evaluated. In vitro cell binding studies were carried out in Raji cells expressing CD20 antigen. Biodistribution studies were carried out in normal Swiss mice. Results: Using both radioassay and spectroscopic method, it was determined that about five molecules of DOTA were linked to rituximab. Radiolabelling of the rituximab conjugate with 90Y and subsequent purification on PD-10 column gave a product with radiochemical purity (RCP) > 98 per cent which was retained at > 90 per cent up to 72 h when stored at 37°C. In vitro cell binding experiments of 90Y-DOTA-rituximab with Raji cells exhibited specific binding of 20.7 ± 0.1 per cent with 90Y-DOTA-rituximab which reduced to 15.5 ± 0.2 per cent when incubated with cold rituximab. The equilibrium constant Kd for 90Y-DOTA-Rituximab was determined to be 3.38 nM. Radiolabelled antibody showed clearance via hepatobiliary and renal routes and activity in tibia was found to be quite low indicating in vivo stability of 90Y-DOTA-rituximab. Interpretation & conclusions: p-SCN-Bn-DOTA was conjugated with rituximab and radiolabelling with 90Y was carried out. In vitro studies carried

  4. Resin {sup 90}Y microsphere activity measurements for liver brachytherapy

    SciTech Connect

    Dezarn, William A.; Kennedy, Andrew S.

    2007-06-15

    The measurement of the radioactivity administered to the patient is one of the major components of {sup 90}Y microsphere liver brachytherapy. The activity of {sup 90}Y microspheres in a glass delivery vial was measured in a dose calibrator. The calibration value to use for {sup 90}Y in the dose calibrator was verified using an activity calibration standard provided by the microsphere manufacturer. This method allowed for the determination of a consistent, reproducible local activity standard. Additional measurements were made to determine some of the factors that could affect activity measurement. The axial response of the dose calibrator was determined by the ratio of activity measurements at the bottom and center of the dose calibrator. The axial response was 0.964 for a glass shipping vial, 1.001 for a glass V-vial, and 0.988 for a polycarbonate V-vial. Comparisons between activity measurements in the dose calibrator and those using a radiation survey meter were found to agree within 10%. It was determined that the dose calibrator method was superior to the survey meter method because the former allowed better defined measurement geometry and traceability of the activity standard back to the manufacturer. Part of the preparation of resin {sup 90}Y microspheres for patient delivery is to draw out a predetermined activity from a shipping vial and place it into a V-vial for delivery to the patient. If the drawn activity was placed in a glass V-vial, the activity measured in the dose calibrator with a glass V-vial was 4% higher than the drawn activity from the shipping vial standard. If the drawn activity was placed in a polycarbonate V-vial, the activity measured in the dose calibrator with a polycarbonate V-vial activity was 20% higher than the drawn activity from the shipping vial standard. Careful characterization of the local activity measurement standard is recommended instead of simply accepting the calibration value of the dose calibrator manufacturer.

  5. Yttrium Y 90 Ibritumomab Tiuxetan, Fludarabine, Radiation Therapy, and Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2016-03-21

    B-cell Chronic Lymphocytic Leukemia; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  6. High-Dose Y-90-Ibritumomab Tiuxetan Added to Reduced-Intensity Allogeneic Stem Cell Transplant Regimen for Relapsed or Refractory Aggressive B-Cell Lymphoma

    ClinicalTrials.gov

    2016-07-08

    Post-Transplant Lymphoproliferative Disorder; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma

  7. Hanford isotope project strategic business analysis yttrium-90 (Y-90)

    SciTech Connect

    1995-10-01

    The purpose of this analysis is to address the short-term direction for the Hanford yttrium-90 (Y-90) project. Hanford is the sole DOE producer of Y-90, and is the largest repository for its source in this country. The production of Y-90 is part of the DOE Isotope Production and Distribution (IP and D) mission. The Y-90 is ``milked`` from strontium-90 (Sr-90), a byproduct of the previous Hanford missions. The use of Sr-90 to produce Y-90 could help reduce the amount of waste material processed and the related costs incurred by the clean-up mission, while providing medical and economic benefits. The cost of producing Y-90 is being subsidized by DOE-IP and D due to its use for research, and resultant low production level. It is possible that the sales of Y-90 could produce full cost recovery within two to three years, at two curies per week. Preliminary projections place the demand at between 20,000 and 50,000 curies per year within the next ten years, assuming FDA approval of one or more of the current therapies now in clinical trials. This level of production would incentivize private firms to commercialize the operation, and allow the government to recover some of its sunk costs. There are a number of potential barriers to the success of the Y-90 project, outside the control of the Hanford Site. The key issues include: efficacy, Food and Drug Administration (FDA) approval and medical community acceptance. There are at least three other sources for Y-90 available to the US users, but they appear to have limited resources to produce the isotope. Several companies have communicated interest in entering into agreements with Hanford for the processing and distribution of Y-90, including some of the major pharmaceutical firms in this country.

  8. Survival after somatostatin based radiopeptide therapy with 90Y-DOTATOC vs. 90Y-DOTATOC plus 177Lu-DOTATOC in metastasized gastrinoma

    PubMed Central

    Dumont, Rebecca A; Seiler, Daniela; Marincek, Nicolas; Brunner, Philippe; Radojewski, Piotr; Rochlitz, Christoph; Müller-Brand, Jan; Maecke, Helmut R; Briel, Matthias; Walter, Martin A

    2015-01-01

    We aimed to explore the effects of 90Y-DOTATOC and 90Y-DOTATOC plus 177Lu-DOTATOC on survival of patients with metastasized gastrinoma. Patients with progressive metastasized gastrinoma were treated with repeated cycles of 90Y-DOTATOC or with cycles alternating between 90Y-DOTATOC and 177Lu-DOTATOC until tumor progression or permanent toxicity. Multivariable Cox regression analyses were used to study predictors of survival. A total of 36 patients were enrolled; 30 patients received 90Y-DOTATOC (median activity per patient 11.8GBq; range: 6.1-62.2GBq) and 6 patients received 90Y-DOTATOC plus 177Lu-DOTATOC (median activity per patient: 14.8GBq; range: 7.4-14.8GBq). Response was found in 26 patients (72.2%), including morphological (n=12, 33.3%), biochemical (n=14, 38.9%) and/or clinical response (n=6, 16.2%). A total of 21 patients (58.3%) experienced hematotoxicity grade 1/2, while 1 patient (2.8%) experienced hematotoxicity grade 3; no grade 4 hematotoxicity occurred. Furthermore, 2 patients (5.6%) developed grade 4 renal toxicity; no grade 5 renal toxicity occurred. Responders had a significantly longer median survival from time of enrollment than non-responders (45.1 months, range: 37.1-53.1 months vs. 12.6 months, range: 11.0-14.2, hazard ratio: 0.12 (0.027-0.52), p=0.005). Additionally, there was a trend towards longer median survival with 90Y-DOTATOC plus 177Lu-DOTATOC as compared to 90Y-DOTATOC alone (60.2 months, range: 19.8-100.6 months vs. 27.0 months, range: 4.0-50.0, hazard ratio: 0.21 (0.01-3.98), p=0.16). Response to 90Y-DOTATOC and 90Y-DOTATOC plus 177Lu-DOTATOC therapy is associated with a longer survival in patients with metastasized gastrinoma. Both treatment regimens are promising tools for management of progressive gastrinoma. PMID:25625026

  9. Monte Carlo simulation of PET and SPECT imaging of {sup 90}Y

    SciTech Connect

    Takahashi, Akihiko Sasaki, Masayuki; Himuro, Kazuhiko; Yamashita, Yasuo; Komiya, Isao; Baba, Shingo

    2015-04-15

    Purpose: Yittrium-90 ({sup 90}Y) is traditionally thought of as a pure beta emitter, and is used in targeted radionuclide therapy, with imaging performed using bremsstrahlung single-photon emission computed tomography (SPECT). However, because {sup 90}Y also emits positrons through internal pair production with a very small branching ratio, positron emission tomography (PET) imaging is also available. Because of the insufficient image quality of {sup 90}Y bremsstrahlung SPECT, PET imaging has been suggested as an alternative. In this paper, the authors present the Monte Carlo-based simulation–reconstruction framework for {sup 90}Y to comprehensively analyze the PET and SPECT imaging techniques and to quantitatively consider the disadvantages associated with them. Methods: Our PET and SPECT simulation modules were developed using Monte Carlo simulation of Electrons and Photons (MCEP), developed by Dr. S. Uehara. PET code (MCEP-PET) generates a sinogram, and reconstructs the tomography image using a time-of-flight ordered subset expectation maximization (TOF-OSEM) algorithm with attenuation compensation. To evaluate MCEP-PET, simulated results of {sup 18}F PET imaging were compared with the experimental results. The results confirmed that MCEP-PET can simulate the experimental results very well. The SPECT code (MCEP-SPECT) models the collimator and NaI detector system, and generates the projection images and projection data. To save the computational time, the authors adopt the prerecorded {sup 90}Y bremsstrahlung photon data calculated by MCEP. The projection data are also reconstructed using the OSEM algorithm. The authors simulated PET and SPECT images of a water phantom containing six hot spheres filled with different concentrations of {sup 90}Y without background activity. The amount of activity was 163 MBq, with an acquisition time of 40 min. Results: The simulated {sup 90}Y-PET image accurately simulated the experimental results. PET image is visually

  10. Administered activity and outcomes of glass versus resin 90Y microsphere radioembolization in patients with colorectal liver metastases

    PubMed Central

    Nasr, Elie C.; Kunam, Vamsi K.; Bullen, Jennifer A.; Purysko, Andrei S.

    2016-01-01

    Background Given the differences in size, specific activity, and dosing methods for glass yttrium-90 microspheres (90Y-glass) and resin 90Y microspheres (90Y-resin), these therapies may expose the liver to different amounts of radiation, thereby affecting their efficacy and tolerability. We aimed to compare the prescribed activity of 90Y-glass and 90Y-resin for real-world patients undergoing selective internal radiation therapy (SIRT) for liver-dominant metastatic colorectal cancer (mCRC) and to assess efficacy and safety outcomes in these patients. Methods We examined the records of 28 consecutive patients with unresectable colorectal liver metastases treated with SIRT between June 2008 and May 2011 at our institution. Using baseline CT and MR images, we calculated a projected activity as if we had used the other product and compared it to the actual prescribed activity of 90Y-glass and 90Y-resin for each SIRT treatment per manufacturer guidelines. Progression and adverse events were evaluated at follow up visits. Survival was analyzed by the Kaplan-Meier method. Results For 90Y-glass treatments with a mean prescribed 90Y activity of 1.77 GBq, the mean projected 90Y-resin activity was 0.84 GBq. For 90Y-resin treatments with a mean prescribed 90Y activity of 1.05 GBq, the mean projected 90Y-glass activity was 2.48 GBq. The median survival was 9.3 months versus 18.2 months for 90Y-glass and 90Y-resin, respectively (P=0.292). During the second year after SIRT, the hazard ratio of death for patients treated with 90Y-glass versus 90Y-resin was 4.0 (95% CI: 1.3, 12.3; P=0.017). No significant difference in progression, adverse events or liver toxicity was observed. Conclusions Using manufacturer recommended guidelines, 90Y-resin delivers significantly less activity than 90Y-glass to patients with liver-dominant mCRC undergoing SIRT with no significant difference in adverse events and a trend toward improved survival. PMID:27563442

  11. MO-G-17A-06: Kernel Based Dosimetry for 90Y Microsphere Liver Therapy Using 90Y Bremsstrahlung SPECT/CT

    SciTech Connect

    Mikell, J; Siman, W; Kappadath, S; Mahvash, A; Mourtada, F

    2014-06-15

    Purpose: 90Y microsphere therapy in liver presents a situation where beta transport is dominant and the tissue is relatively homogenous. We compare voxel-based absorbed doses from a 90Y kernel to Monte Carlo (MC) using quantitative 90Y bremsstrahlung SPECT/CT as source distribution. Methods: Liver, normal liver, and tumors were delineated by an interventional radiologist using contrast-enhanced CT registered with 90Y SPECT/CT scans for 14 therapies. Right lung was segmented via region growing. The kernel was generated with 1.04 g/cc soft tissue for 4.8 mm voxel matching the SPECT. MC simulation materials included air, lung, soft tissue, and bone with varying densities. We report percent difference between kernel and MC (%Δ(K,MC)) for mean absorbed dose, D70, and V20Gy in total liver, normal liver, tumors, and right lung. We also report %Δ(K,MC) for heterogeneity metrics: coefficient of variation (COV) and D10/D90. The impact of spatial resolution (0, 10, 20 mm FWHM) and lung shunt fraction (LSF) (1,5,10,20%) on the accuracy of MC and kernel doses near the liver-lung interface was modeled in 1D. We report the distance from the interface where errors become <10% of unblurred MC as d10(side of interface, dose calculation, FWHM blurring, LSF). Results: The %Δ(K,MC) for mean, D70, and V20Gy in tumor and liver was <7% while right lung differences varied from 60–90%. The %Δ(K,MC) for COV was <4.8% for tumor and liver and <54% for the right lung. The %Δ(K,MC) for D10/D90 was <5% for 22/23 tumors. d10(liver,MC,10,1–20) awere <9mm and d10(liver,MC,20,1–20) awere <15mm; both agreed within 3mm to the kernel. d10(lung,MC,10,20), d10(lung,MC,10,1), d10(lung,MC,20,20), and d10(lung,MC,20,1) awere 6, 25, 15, and 34mm, respectively. Kernel calculations on blurred distributions in lung had errors > 10%. Conclusions: Liver and tumor voxel doses with 90Y kernel and MC agree within 7%. Large differences exist between the two methods in right lung. Research reported in this

  12. A pioneer experience in Malaysia on In-house Radio-labelling of (131)I-rituximab in the treatment of Non-Hodgkin's Lymphoma and a case report of high dose (131)I-rituximab-BEAM conditioning autologous transplant.

    PubMed

    Kuan, Jew Win; Law, Chiong Soon; Wong, Xiang Qi; Ko, Ching Tiong; Awang, Zool Hilmi; Chew, Lee Ping; Chang, Kian Meng

    2016-10-01

    Radioimmunotherapy is an established treatment modality in Non-Hodgkin's lymphoma. The only two commercially available radioimmunotherapies - (90)Y-ibritumomab tiuxetan is expensive and (131)I-tositumomab has been discontinued from commercial production. In resource limited environment, self-labelling (131)I-rituximab might be the only viable practical option. We reported our pioneer experience in Malaysia on self-labelling (131)I-rituximab, substituting autologous haematopoietic stem cell transplantation (HSCT) and a patient, the first reported case, received high dose (131)I-rituximab (6000MBq/163mCi) combined with BEAM conditioning for autologous HSCT.

  13. A pioneer experience in Malaysia on In-house Radio-labelling of (131)I-rituximab in the treatment of Non-Hodgkin's Lymphoma and a case report of high dose (131)I-rituximab-BEAM conditioning autologous transplant.

    PubMed

    Kuan, Jew Win; Law, Chiong Soon; Wong, Xiang Qi; Ko, Ching Tiong; Awang, Zool Hilmi; Chew, Lee Ping; Chang, Kian Meng

    2016-10-01

    Radioimmunotherapy is an established treatment modality in Non-Hodgkin's lymphoma. The only two commercially available radioimmunotherapies - (90)Y-ibritumomab tiuxetan is expensive and (131)I-tositumomab has been discontinued from commercial production. In resource limited environment, self-labelling (131)I-rituximab might be the only viable practical option. We reported our pioneer experience in Malaysia on self-labelling (131)I-rituximab, substituting autologous haematopoietic stem cell transplantation (HSCT) and a patient, the first reported case, received high dose (131)I-rituximab (6000MBq/163mCi) combined with BEAM conditioning for autologous HSCT. PMID:27472826

  14. Comparison of (90)Y activity measurements in nuclear medicine in Germany.

    PubMed

    Kossert, Karsten; Bokeloh, Karen; Ehlers, Marion; Nähle, Ole; Scheibe, Olaf; Schwarz, Uwe; Thieme, Klaus

    2016-03-01

    In 2014, PTB and the company Eckert & Ziegler organized a national comparison exercise to determine the activity of a (90)Y solution. One aim of the comparison was to assess the measurement capability of hospitals and medical practices in Germany. P6-type vials were filled with aliquots of a radioactive (90)Y solution and then sent to 19 participants who were asked to measure the activity in the ampoules as well as in their own standard geometry using syringes. Most of the submitted results have a deviation of less than ±10% from the PTB reference activity when measured in the P6-type vials. The spread is somewhat larger when measured in a syringe geometry. The comparison revealed that some participants have difficulties in applying decay corrections and only a few participants were capable of estimating realistic measurement uncertainties. PMID:26597654

  15. Disproof of solar influence on the decay rates of 90Sr/90 Y

    NASA Astrophysics Data System (ADS)

    Kossert, Karsten; Nähle, Ole J.

    2015-09-01

    A custom-built liquid scintillation counter was used for long-term measurements of 90Sr/90 Y sources. The detector system is equipped with an automated sample changer and three photomultiplier tubes, which makes the application of the triple-to-double coincidence ratio (TDCR) method possible. After decay correction, the measured decay rates were found to be stable and no annual oscillation could be observed. Thus, the findings of this work are in strong contradiction to those of Parkhomov (2011) who reported on annual oscillations when measuring 90Sr/90 Y with a Geiger-Müller counter. Sturrock et al. (2012) carried out a more detailed analysis of the experimental data from Parkhomov and claimed to have found correlations between the decay rates and processes inside the Sun. These findings are questionable, since they are based on inappropriate experimental data as is demonstrated in this work. A frequency analysis of our activity data does not show any significant periodicity.

  16. (90) Y/(177) Lu-labelled Cetuximab immunoconjugates: radiochemistry optimization to clinical dose formulation.

    PubMed

    Chakravarty, Rubel; Chakraborty, Sudipta; Sarma, Haladhar Dev; Nair, K V Vimalnath; Rajeswari, Ardhi; Dash, Ashutosh

    2016-07-01

    Radiolabelled monoclonal antibodies (mAbs) are increasingly being utilized in cancer theranostics, which is a significant move toward tailored treatment for individual patients. Cetuximab is a recombinant, human-mouse chimeric IgG1 mAb that binds to the epidermal growth factor receptor with high affinity. We have optimized a protocol for formulation of clinically relevant doses (~2.22 GBq) of (90) Y-labelled Cetuximab and (177) Lu-labelled Cetuximab by conjugation of the mAb with a suitable bifunctional chelator, N-[(R)-2-amino-3-(paraisothiocyanato-phenyl)propyl]-trans-(S,S)-cyclohexane-1,2-diamine-N,N,N',N″,N″-pentaacetic acid (CHX-A″-DTPA). The radioimmunoconjugates demonstrated reasonably high specific activity (1.26 ± 0.27 GBq/mg for (90) Y-CHX-A″-DTPA-Cetuximab and 1.14 ± 0.15 GBq/mg for (177) Lu-CHX-A″-DTPA-Cetuximab), high radiochemical purity (>95%) and appreciable in vitro stability under physiological conditions. Preliminary biodistribution studies with both (90) Y-CHX-A″-DTPA-Cetuximab and (177) Lu-CHX-A″-DTPA-Cetuximab in Swiss mice bearing fibrosarcoma tumours demonstrated significant tumour uptake at 24-h post-injection (p.i.) (~16%ID/g) with good tumour-to-background contrast. The results of the biodistribution studies were further corroborated by ex vivo Cerenkov luminescence imaging after administration of (90) Y-CHX-A″-DTPA-Cetuximab in tumour-bearing mice. The tumour uptake at 24 h p.i. was significantly reduced with excess unlabelled Cetuximab, suggesting that the uptake was receptor mediated. The results of this study hold promise, and this strategy should be further explored for clinical translation. PMID:27264196

  17. Reducing renal uptake of 90Y- and 177Lu-labeled alpha-melanocyte stimulating hormone peptide analogues

    SciTech Connect

    Miao, Yubin; Fisher, Darrell R.; Quinn, Thomas P.

    2006-06-15

    The purpose of this study was to improve the tumor-to-kidney uptake ratios of 90Y- and 177Lu-[1,2,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Re-Cys,D-Phe,Arg]alpha-melanocyte stimulating hormone (DOTA-RE(Arg)CCMSH), through coupling a negatively charged glutamic acid (Glu) to the peptide sequence. A new peptide of DOTA-Re(Glu,Arg)CCMSH was designed, synthesized and labeled with 90Y and 177Lu. Pharmacokinetics of 90Y- and 177Lu-DOTA-RE(Glu,Arg)CCNSH were determined in B16/F1 murine melanoma-bearing C57 mice. Both exhibited significantly less renal uptake than 90Y- and 177Lu-DOTA-Re(Arg)CCMSH at 30 min and at 2, 3, and 24 h after dose administration. The renal uptake values of 90Y- and 177Lu-DOTA-Re(Glu,Arg)CCMSH were 28.16% and 28.81% of those of 90Y- and 177Lu-DOTA-RE(Arg)CCMSH, respectively, at 4 hr post-injection. We also showed higher tumor-to-kidney uptake ratios 2.28 and 1.69 times that of 90Y- and 177Lu-DOTA-Re(Arg)CCMSH, respectively, at 4 h post-injection. The90Y- and 177Lu-DOTA-Re(Glu,Arg)CCMSH activity accumulation was low in normal organs except for kidneys. Coupling a negatively charged amino acid (Glu) to the CCMSH peptide sequence dramatically reduced the renal uptake values and increased the tumor-to-kidney uptake ratios of 90Y- and 177Lu-DOTA-Re(Glu,Arg)CCMSH, facilitating their potential applications as radiopharmaceuticals for targeted radionuclide therapy of melanoma.

  18. Treatment of cystic craniopharyngioma with 90Y-Colloid. Four clinical cases.

    PubMed

    Sabaté-Llobera, A; Rojas-Camacho, J G; Mora Salvadó, J; Acebes Martín, J J; Rodríguez-Gasén, A; Ramal Leiva, D; Martín-Comín, J

    2013-01-01

    Craniopharyngioma is a histologically benign and frequently cystic intracranial tumor. It may present aggressive behavior due to compression from nearby structures. Its therapeutic management is complicated because although surgery is the usual treatment of choice, it is not exempt of high morbidity and mortality and frequent tumor recurrence. In craniopharyngiomas with a significant cystic component,internal irradiation with radioactive isotopes is a therapeutic alternative to conventional treatments. We present the cases of four patients with cystic craniopharyngiomas who were treated with intracystic administration of 90Y-colloid, and their evolution after the treatment.

  19. A Sr-90/Y-90 field calibrator for performance testing of beta-gamma survey instruments

    SciTech Connect

    Olsher, R.H.; Haynie, J.S.

    1988-01-01

    ANSI and regulatory agency guidelines prescribe periodic performance tests for radiation protection instrumentation. Reference readings should be obtained for one point on each scale or decade normally used. A small and lightweight calibrator has been developed that facilitates field testing of beta-gamma survey instruments. The calibrator uses a 45 microcurie Sr-90/Y-90 beta source with a filter wheel to generate variable dose rates in the range from 4 to 400 mrad/hr. Thus, several ranges may be checked by dialing in appropriate filters. The design, use, and typical applications of the calibrator are described.

  20. PET optimization for improved assessment and accurate quantification of {sup 90}Y-microsphere biodistribution after radioembolization

    SciTech Connect

    Martí-Climent, Josep M. Prieto, Elena; Elosúa, César; Rodríguez-Fraile, Macarena; Domínguez-Prado, Inés; Vigil, Carmen; García-Velloso, María J.; Arbizu, Javier; Peñuelas, Iván; Richter, José A.

    2014-09-15

    Purpose: {sup 90}Y-microspheres are widely used for the radioembolization of metastatic liver cancer or hepatocellular carcinoma and there is a growing interest for imaging {sup 90}Y-microspheres with PET. The aim of this study is to evaluate the performance of a current generation PET/CT scanner for {sup 90}Y imaging and to optimize the PET protocol to improve the assessment and the quantification of {sup 90}Y-microsphere biodistribution after radioembolization. Methods: Data were acquired on a Biograph mCT-TrueV scanner with time of flight (TOF) and point spread function (PSF) modeling. Spatial resolution was measured with a{sup 90}Y point source. Sensitivity was evaluated using the NEMA 70 cm line source filled with {sup 90}Y. To evaluate the count rate performance, {sup 90}Y vials with activity ranging from 3.64 to 0.035 GBq were measured in the center of the field of view (CFOV). The energy spectrum was evaluated. Image quality with different reconstructions was studied using the Jaszczak phantom containing six hollow spheres (diameters: 31.3, 28.1, 21.8, 16.1, 13.3, and 10.5 mm), filled with a 207 kBq/ml {sup 90}Y concentration and a 5:1 sphere-to-background ratio. Acquisition time was adjusted to simulate the quality of a realistic clinical PET acquisition of a patient treated with SIR-Spheres{sup ®}. The developed methodology was applied to ten patients after SIR-Spheres{sup ®} treatment acquiring a 10 min per bed PET. Results: The energy spectrum showed the{sup 90}Y bremsstrahlung radiation. The {sup 90}Y transverse resolution, with filtered backprojection reconstruction, was 4.5 mm in the CFOV and degraded to 5.0 mm at 10 cm off-axis. {sup 90}Y absolute sensitivity was 0.40 kcps/MBq in the center of the field of view. Tendency of true and random rates as a function of the {sup 90}Y activity could be accurately described using linear and quadratic models, respectively. Phantom studies demonstrated that, due to low count statistics in {sup 90}Y PET

  1. Time optimization of (90)Sr measurements: Sequential measurement of multiple samples during ingrowth of (90)Y.

    PubMed

    Holmgren, Stina; Tovedal, Annika; Björnham, Oscar; Ramebäck, Henrik

    2016-04-01

    The aim of this paper is to contribute to a more rapid determination of a series of samples containing (90)Sr by making the Cherenkov measurement of the daughter nuclide (90)Y more time efficient. There are many instances when an optimization of the measurement method might be favorable, such as; situations requiring rapid results in order to make urgent decisions or, on the other hand, to maximize the throughput of samples in a limited available time span. In order to minimize the total analysis time, a mathematical model was developed which calculates the time of ingrowth as well as individual measurement times for n samples in a series. This work is focused on the measurement of (90)Y during ingrowth, after an initial chemical separation of strontium, in which it is assumed that no other radioactive strontium isotopes are present. By using a fixed minimum detectable activity (MDA) and iterating the measurement time for each consecutive sample the total analysis time will be less, compared to using the same measurement time for all samples. It was found that by optimization, the total analysis time for 10 samples can be decreased greatly, from 21h to 6.5h, when assuming a MDA of 1Bq/L and at a background count rate of approximately 0.8cpm.

  2. [Determination of 90 Sr in milk by solvent extraction of 90Y (author's transl)].

    PubMed

    Mitsuhashi, T; Sakanoue, M

    1977-10-01

    In order to replace the conventional method using violent fuming nitric acid, a new method for the determination of 90 Sr in milk has been developed by using the solvent extraction with bis (2-ethylhexyl) phosphoric acid (HDEHP). The daughter nuclide 90Y in a radiochemical equilibrium with its parent 90Sr was extracted with 2:1 HDEHP-toluene from the acid solution (1M HCL) of milk ash sample prepared by dry-ashing. After stripping with 8M HCL, 90Y, together with stable yttrium added as carrier, was precipated as oxalate to prepare beta-counting source. The radiochemical purity was confirmed by decay curve. The decontamination of strontium was checked by applying non-dispersive fluorescence X-ray analysis using 133Ba as irradiating source. Bone samples of cow were also analyzed by the same method and the results were compared with those obtained by other methods. The duplicate crosschecking analyses of finely ground bone samples were carried out to examine the effectiveness of this method. This simple new method was found to be very effective for the routine analysis of 90Sr in these samples. PMID:579456

  3. Synthesis and comparative biological evaluation of bifunctional ligands for radiotherapy applications of (90)Y and (177)Lu.

    PubMed

    Chong, Hyun-Soon; Sun, Xiang; Chen, Yunwei; Sin, Inseok; Kang, Chi Soo; Lewis, Michael R; Liu, Dijie; Ruthengael, Varyanna C; Zhong, Yongliang; Wu, Ningjie; Song, Hyun A

    2015-03-01

    Zevalin® is an antibody-drug conjugate radiolabeled with a cytotoxic radioisotope ((90)Y) that was approved for radioimmunotherapy (RIT) of B-cell non-Hodgkin's lymphoma. A bifunctional ligand that displays favorable complexation kinetics and in vivo stability is required for effective RIT. New bifunctional ligands 3p-C-DE4TA and 3p-C-NE3TA for potential use in RIT were efficiently prepared by the synthetic route based on regiospecific ring opening of aziridinium ions with prealkylated triaza- or tetraaza-backboned macrocycles. The new bifunctional ligands 3p-C-DE4TA and 3p-C-NE3TA along with the known bimodal ligands 3p-C-NETA and 3p-C-DEPA were comparatively evaluated for potential use in targeted radiotherapy using β-emitting radionuclides (90)Y and (177)Lu. The bifunctional ligands were evaluated for radiolabeling kinetics with (90)Y and (177)Lu, and the corresponding (90)Y or (177)Lu-radiolabeled complexes were studied for in vitro stability in human serum and in vivo biodistribution in mice. The results of the comparative complexation kinetic and stability studies indicate that size of macrocyclic cavity, ligand denticity, and bimodality of donor groups have a substantial impact on complexation of the bifunctional ligands with the radiolanthanides. The new promising bifunctional chelates in the DE4TA and NE3TA series were rapid in binding (90)Y and (177)Lu, and the corresponding (90)Y- and (177)Lu-radiolabeled complexes remained inert in human serum or in mice. The in vitro and in vivo data show that 3p-C-DE4TA and 3p-C-NE3TA are promising bifunctional ligands for targeted radiotherapy applications of (90)Y and (177)Lu.

  4. External bremsstrahlung of 90Sr-90Y, 147Pm and 204Tl in detector compounds

    NASA Astrophysics Data System (ADS)

    Manjunatha, H. C.; Rudraswamy, B.

    2013-04-01

    External Bremsstrahlung spectra produced by the complete absorption of beta particles from 90Sr to 90Y, 147Pm and 204Tl in nuclear radiation detection compounds like Cesium iodide (CsI) and Sodium Iodide (NaI) has been measured using 0.038 m×0.038 m NaI(Tl) crystal and is compared with Tseng-Pratt theory. The Bremsstrahlung yields are calculated using the unfolded spectra. This paper also describes a new procedure for the calculation of effective absorption coefficient of Bremsstrahlung from the Bremsstrahlung spectra. The measured spectra show fairly good agreement at low energy end of spectrum and some deviation at higher energy end of spectrum with the theory. The measured Bremsstrahlung yields may be useful to apply corrections, whenever beta particle passes through CsI and NaI detectors.

  5. Comparative efficacy of 177Lu and 90Y for Anti-CD20 Pretargeted Radioimmunotherapy in Murine Lymphoma Xenograft Models

    DOE PAGES

    Frost, Sofia H. L.; Frayo, Shani L.; Miller, Brian W.; Orozco, Johnnie J.; Booth, Garrett C.; Hylarides, Mark D.; Lin, Yukang; Green, Damian J.; Gopal, Ajay K.; Pagel, John M.; et al

    2015-03-18

    Purpose Pretargeted radioimmunotherapy (PRIT) is a multi-step method of selectively delivering high doses of radiotherapy to tumor cells while minimizing exposure to surrounding tissues. Yttrium-90 (90Y) and lutetium-177 (177Lu) are two of the most promising beta-particle emitting radionuclides used for radioimmunotherapy, which despite having similar chemistries differ distinctly in terms of radiophysical features. These differences may have important consequences for the absorbed dose to tumors and normal organs. Whereas 90Y has been successfully applied in a number of preclinical and clinical radioimmunotherapy settings, there have been few published pretargeting studies with 177Lu. We therefore compared the therapeutic potential of targetingmore » either 90Y or 177Lu to human B-cell lymphoma xenografts in mice. Methods Parallel experiments evaluating the biodistribution, imaging, dosimetry, therapeutic efficacy, and toxicity were performed in female athymic nude mice bearing either Ramos (Burkitt lymphoma) or Granta (mantle cell lymphoma) xenografts, utilizing an anti-CD20 antibodystreptavidin conjugate (1F5-SA) and an 90Y- or 177Lu-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-biotin second step reagent. Results The two radionuclides displayed comparable biodistributions in tumors and normal organs; however, the absorbed radiation dose delivered to tumor was more than twice as high for 90Y (1.3 Gy/MBq) as for 177Lu (0.6 Gy/MBq). More importantly, therapy with 90Y-DOTAbiotin was dramatically more effective than with 177Lu-DOTA-biotin, with 100% of Ramos xenograft-bearing mice cured with 37 MBq 90Y, whereas 0% were cured using identical amounts of 177Lu-DOTA-biotin. Similar results were observed in mice bearing Granta xenografts, with 80% of the mice cured with 90Y-PRIT and 0% cured with 177Lu-PRIT. Toxicities were comparable with both isotopes. Conclusion 90Y was therapeutically superior to 177Lu for streptavidin-biotin PRIT

  6. Comparative Efficacy of 177Lu and 90Y for Anti-CD20 Pretargeted Radioimmunotherapy in Murine Lymphoma Xenograft Models

    PubMed Central

    Frost, Sofia H. L.; Frayo, Shani L.; Miller, Brian W.; Orozco, Johnnie J.; Booth, Garrett C.; Hylarides, Mark D.; Lin, Yukang; Green, Damian J.; Gopal, Ajay K.; Pagel, John M.; Bäck, Tom A.; Fisher, Darrell R.; Press, Oliver W.

    2015-01-01

    Purpose Pretargeted radioimmunotherapy (PRIT) is a multi-step method of selectively delivering high doses of radiotherapy to tumor cells while minimizing exposure to surrounding tissues. Yttrium-90 (90Y) and lutetium-177 (177Lu) are two of the most promising beta-particle emitting radionuclides used for radioimmunotherapy, which despite having similar chemistries differ distinctly in terms of radiophysical features. These differences may have important consequences for the absorbed dose to tumors and normal organs. Whereas 90Y has been successfully applied in a number of preclinical and clinical radioimmunotherapy settings, there have been few published pretargeting studies with 177Lu. We therefore compared the therapeutic potential of targeting either 90Y or 177Lu to human B-cell lymphoma xenografts in mice. Methods Parallel experiments evaluating the biodistribution, imaging, dosimetry, therapeutic efficacy, and toxicity were performed in female athymic nude mice bearing either Ramos (Burkitt lymphoma) or Granta (mantle cell lymphoma) xenografts, utilizing an anti-CD20 antibody-streptavidin conjugate (1F5-SA) and an 90Y- or 177Lu-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-biotin second step reagent. Results The two radionuclides displayed comparable biodistributions in tumors and normal organs; however, the absorbed radiation dose delivered to tumor was more than twice as high for 90Y (1.3 Gy/MBq) as for 177Lu (0.6 Gy/MBq). More importantly, therapy with 90Y-DOTA-biotin was dramatically more effective than with 177Lu-DOTA-biotin, with 100% of Ramos xenograft-bearing mice cured with 37 MBq 90Y, whereas 0% were cured using identical amounts of 177Lu-DOTA-biotin. Similar results were observed in mice bearing Granta xenografts, with 80% of the mice cured with 90Y-PRIT and 0% cured with 177Lu-PRIT. Toxicities were comparable with both isotopes. Conclusion 90Y was therapeutically superior to 177Lu for streptavidin-biotin PRIT approaches in

  7. Comparative Efficacy of 177Lu and 90Y for Anti-CD20 Pretargeted Radioimmunotherapy in Murine Lymphoma Xenograft Models

    SciTech Connect

    Frost, Sophia; Frayo, Shani; Miller, Brian W.; Orozco, Johnnie J.; Booth, Garrett C.; Hylarides, Mark; Lin, Yukang; Green, Damian J.; Gopal, Ajay K.; Pagel, John M.; Back, Tom; Fisher, Darrell R.; Press, Oliver W.

    2015-03-01

    Pretargeted radioimmunotherapy (PRIT) is a multi-step method of selectively delivering high doses of radiotherapy to tumor cells while minimizing exposure to surrounding tissues. Yttrium-90 (90Y) and lutetium-177 (177Lu) are two of the most promising beta-particle emitting radionuclides used for radioimmunotherapy, which despite having similar chemistries differ distinctly in terms of radiophysical features. These differences may have important consequences for the absorbed dose to tumors and normal organs. Whereas 90Y has been successfully applied in a number of preclinical and clinical radioimmunotherapy settings, there have been few published pretargeting studies with 177Lu. We therefore compared the therapeutic potential of targeting either 90Y or 177Lu to human B-cell lymphoma xenografts in mice.

  8. Three dosimetry models of lipoma arborescens treated by {sup 90}Y synovectomy

    SciTech Connect

    O’Doherty, Jim; Clauss, Ralf; Scuffham, James; Khan, Aman; Petitguillaume, Alice; Desbrée, Aurélie

    2014-05-15

    Purpose: Lipoma arborescens (LA) is a benign intra-articular lipomatous proliferation of the synovial membrane. This extremely rare condition has previously been treated by intra-articular{sup 90}Y radiosynoviorthesis but dosimetry literature on this form of radionuclide therapy is nonexistent. The authors detail methodology for successful treatment of LA and provide for the first time estimates of radiation dosimetry. The authors also analyze the biodistribution of the radiopharmaceutical over the course of the patient's treatment through sequential imaging. Methods: A patient with bilateral LA underwent intracavity injection of{sup 90}Y citrate colloid to the right and left knee joint spaces (181 and 198 MBq, respectively). SPECT/CT datasets were acquired over 9 days to quantify the biodistribution and kinetics of the radiopharmaceutical. Radiation dosimetry was performed using the MIRD schema (through OLINDA software), a custom voxel-based method, and a direct Monte Carlo calculation (OEDIPE). Results: Follow-up MRI showed marked reduction in LA size in both knees. Mean absorbed doses to the LA were 21.2 ± 0.8 and 42.9 ± 2.3 Gy using OLINDA, 8.1 ± 0.3 and 16.7 ± 0.5 Gy using voxel based methodology, and 8.2 ± 0.3 and 15.7 ± 0.5 Gy for OEDIPE in the right and left LA, respectively. Distribution of the radiopharmaceutical within the joint space alters over the imaging period, with less than 1% of the remaining activity having moved posteriorly in the knee cavity. No uptake was detected outside of the joint space after assessment with whole-body scintigraphy. Conclusions: An activity of approximately 185 MBq successfully relieved clinical symptoms of LA. There was good correlation between direct Monte Carlo and voxel based techniques, but OLINDA was shown to overestimate the absorbed dose to the tumor. Accurate dosimetry may help select an activity more tailored to the specific size and location of the LA.

  9. Gold nanorod-mediated hyperthermia enhances the efficacy of HPMA copolymer - 90Y conjugates in treatment of prostate tumors

    PubMed Central

    Buckway, Brandon; Frazier, Nick; Gormley, Adam J.; Ray, Abhijit; Ghandehari, Hamidreza

    2014-01-01

    Introduction The treatment of prostate cancer using a radiotherapeutic 90Y labeled N-(2-hydroxypropyl)methacrylamide (HPMA)copolymer can be enhanced with localized tumor hyperthermia. An 111In labeled HPMA copolymer system for single photon emission computerized tomography (SPECT) was developed to observe the biodistribution changes associated with hyperthermia. Efficacy studies were conducted in prostate tumor bearing mice using the 90Y HPMA copolymer with hyperthermia. Methods HPMA copolymers containing 1, 4, 7, 10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) were synthesized by reversible addition-fragmentation transfer (RAFT) copolymerization and subsequently labeled with either 111In for imaging or 90Y for efficacy studies. Radiolabel stability was characterized in vitro with mouse serum. Imaging and efficacy studies were conducted in DU145 prostate tumor bearing mice. Imaging was performed using single photon emission computerized tomography (SPECT). Localized mild tumor hyperthermia was achieved by plasmonic photothermal therapy using gold nanorods. Results HPMA copolymer-DOTA conjugates demonstrated efficient labeling and stability for both radionuclides. Imaging analysis showed a marked increase of radiolabeled copolymer within the hyperthermia treated prostate tumors, with no significant accumulation in non-targeted tissues. The greatest reduction in tumor growth was observed in the hyperthermia treated tumors with 90Y HPMA copolymer conjugates. Histological analysis confirmed treatment efficacy and safety. Conclusion HPMA copolymer-DOTA conjugates radiolabeled with both the imaging and treatment radioisotopes, when combined with hyperthermia can serve as an image guided approach for efficacious treatment of prostate tumors. PMID:24461626

  10. Dosimetric comparison of {sup 90}Y, {sup 32}P, and {sup 186}Re radiocolloids in craniopharyngioma treatments

    SciTech Connect

    Sadeghi, Mahdi; Karimi, Elham; Hosseini, S. Hamed

    2009-11-15

    Purpose: In the radionuclide treatment of some forms of brain tumors such as craniopharyngiomas, the selection of the appropriate radionuclide for therapy is a key element in treatment planning. The aim was to study the influence by considering the beta-emitter radionuclide dose rate in an intracranial cyst. Methods: Dosimetry was performed using the MCNP4C radiation transport code. Analytical dosimetry was additionally performed using the Loevinger and the Berger formulas in the MATLAB software. Each result was compared under identical conditions. The advantages and disadvantages of using {sup 90}Y versus {sup 32}P and {sup 186}Re were investigated. Results: The dose rate at the inner surface of the cyst wall was estimated to be 400 mGy/h for a 1 MBq/ml concentration of {sup 90}Y. Under identical conditions of treatment, the corresponding dose rates were 300 mGy/h for {sup 32}P and 160 mGy/h for {sup 186}Re. For a well-defined cyst radius and identical wall thickness, higher dose rates resulted for {sup 90}Y. Conclusions: To achieve the same radiological burden, the required amount of physical activity of injectable solution is lower for {sup 32}P. This is found to be a consequence of both the radionuclide physical half-life and the pattern of energy deposition from the emitted radiation. According to the half-life and dose-rate results, {sup 90}Y would be a good substitute for {sup 32}P.

  11. (90)Y microspheres prepared by sol-gel method, promising medical material for radioembolization of liver malignancies.

    PubMed

    Łada, Wiesława; Iller, Edward; Wawszczak, Danuta; Konior, Marcin; Dziel, Tomasz

    2016-10-01

    A new technology for the production of radiopharmaceutical (90)Y microspheres in the form of spherical yttrium oxide grains obtained by sol-gel method has been described. The authors present and discuss the results of investigations performed in the development of new production technology of yttrium microspheres and determination of their physic-chemical properties. The final product has the structure of spherical yttrium oxide grains with a diameter 25-100μm, is stable and free from contaminants. Irradiation of 20mg samples of grains with diameter of 20-50μm in the thermal neutron flux of 1.7×10(14)cm(-2)s(-1) at the core of MARIA research nuclear reactor allowed to obtain microspheres labelled with the (90)Y isotope on the way of the nuclear reaction (89)Y(n, ɤ)(90)Y. Specific activity of irradiated microspheres has been determined by application of absolute triple to double coincidence ratio method (TDCR) and has been evaluated at 190MBq/mg Y. (90)Y microspheres prepared by the proposed technique can be regarded as a promising medical material for radioembolization of liver malignancies.

  12. (90)Y microspheres prepared by sol-gel method, promising medical material for radioembolization of liver malignancies.

    PubMed

    Łada, Wiesława; Iller, Edward; Wawszczak, Danuta; Konior, Marcin; Dziel, Tomasz

    2016-10-01

    A new technology for the production of radiopharmaceutical (90)Y microspheres in the form of spherical yttrium oxide grains obtained by sol-gel method has been described. The authors present and discuss the results of investigations performed in the development of new production technology of yttrium microspheres and determination of their physic-chemical properties. The final product has the structure of spherical yttrium oxide grains with a diameter 25-100μm, is stable and free from contaminants. Irradiation of 20mg samples of grains with diameter of 20-50μm in the thermal neutron flux of 1.7×10(14)cm(-2)s(-1) at the core of MARIA research nuclear reactor allowed to obtain microspheres labelled with the (90)Y isotope on the way of the nuclear reaction (89)Y(n, ɤ)(90)Y. Specific activity of irradiated microspheres has been determined by application of absolute triple to double coincidence ratio method (TDCR) and has been evaluated at 190MBq/mg Y. (90)Y microspheres prepared by the proposed technique can be regarded as a promising medical material for radioembolization of liver malignancies. PMID:27287162

  13. Performance of thin CaSO4:Dy pellets for calibration of a Sr90+Y90 source

    NASA Astrophysics Data System (ADS)

    Oliveira, M. L.; Caldas, L. V. E.

    2007-09-01

    Because of the radionuclide long half-life, Sr90+Y90, plane or concave sources, utilized in brachytherapy, have to be calibrated initially by the manufacturer and then routinely while they are utilized. Plane applicators can be calibrated against a conventional extrapolation chamber, but concave sources, because of their geometry, should be calibrated using relative dosimeters, as thermoluminescent (TL) materials. Thin CaSO4:Dy pellets are produced at IPEN specially for beta radiation detection. Previous works showed the feasibility of this material in the dosimetry of Sr90+Y90 sources in a wide range of absorbed dose in air. The aim of this work was to study the usefulness of these pellets for the calibration of a Sr90+Y90 concave applicator. To reach this objective, a special phantom was designed and manufactured in PTFE with semi spherical geometry. Because of the dependence of the TL response on the mass of the pellet, the response of each pellet was normalized by its mass in order to reduce the dispersion on TL response. Important characteristics of this material were obtained in reference of a standard Sr90+Y90 source, and the pellets were calibrated against a plane applicator; then they were utilized to calibrate the concave applicator.

  14. 90Y-Labeled Anti-ROBO1 Monoclonal Antibody Exhibits Antitumor Activity against Small Cell Lung Cancer Xenografts

    PubMed Central

    Fujiwara, Kentaro; Koyama, Keitaro; Suga, Kosuke; Ikemura, Masako; Saito, Yasutaka; Hino, Akihiro; Iwanari, Hiroko; Kusano-Arai, Osamu; Mitsui, Kenichi; Kasahara, Hiroyuki; Fukayama, Masashi; Kodama, Tatsuhiko; Hamakubo, Takao; Momose, Toshimitsu

    2015-01-01

    Introduction ROBO1 is a membrane protein that contributes to tumor metastasis and angiogenesis. We previously reported that 90Y-labeled anti-ROBO1 monoclonal antibody (90Y-anti-ROBO1 IgG) showed an antitumor effect against ROBO1-positive tumors. In this study, we performed a biodistribution study and radioimmunotherapy (RIT) against ROBO1-positive small cell lung cancer (SCLC) models. Methods For the biodistribution study, 111In-labeled anti-ROBO1 monoclonal antibody (111In-anti-ROBO1 IgG) was injected into ROBO1-positive SCLC xenograft mice via the tail vein. To evaluate antitumor effects, an RIT study was performed, and SCLC xenograft mice were treated with 90Y-anti-ROBO1 IgG. Tumor volume and body weight were periodically measured throughout the experiments. The tumors and organs of mice were then collected, and a pathological analysis was carried out. Results As a result of the biodistribution study, we observed tumor uptake of 111In-anti-ROBO1 IgG. The liver, kidney, spleen, and lung showed comparably high accumulation of 111In-labeled anti-ROBO1. In the RIT study, 90Y-anti-ROBO1 IgG significantly reduced tumor volume compared with baseline. Pathological analyses of tumors revealed coagulation necrosis and fatal degeneration of tumor cells, significant reduction in the number of Ki-67-positive cells, and an increase in the number of apoptotic cells. A transient reduction of hematopoietic cells was observed in the spleen, sternum, and femur. Conclusions These results suggest that RIT with 90Y-anti-ROBO1 IgG is a promising treatment for ROBO1-positive SCLC. PMID:26017283

  15. Safety of {sup 90}Y Radioembolization in Patients Who Have Undergone Previous External Beam Radiation Therapy

    SciTech Connect

    Lam, Marnix G.E.H.; Abdelmaksoud, Mohamed H.K.; Chang, Daniel T.; Eclov, Neville C.; Chung, Melody P.; Koong, Albert C.; Louie, John D.; Sze, Daniel Y.

    2013-10-01

    Purpose: Previous external beam radiation therapy (EBRT) is theoretically contraindicated for yttrium-90 ({sup 90}Y) radioembolization (RE) because the liver has a lifetime tolerance to radiation before becoming vulnerable to radiation-induced liver disease. We analyzed the safety of RE as salvage treatment in patients who had previously undergone EBRT. Methods and Materials: Between June 2004 and December 2010, a total of 31 patients who had previously undergone EBRT were treated with RE. Three-dimensional treatment planning with dose–volume histogram (DVH) analysis of the liver was used to calculate the EBRT liver dose. Liver-related toxicities including RE-induced liver disease (REILD) were reviewed and classified according to Common Terminology Criteria for Adverse Events version 4.02. Results: The mean EBRT and RE liver doses were 4.40 Gy (range, 0-23.13 Gy) and 57.9 Gy (range, 27.0-125.9 Gy), respectively. Patients who experienced hepatotoxicity (≥grade2; n=12) had higher EBRT mean liver doses (7.96 ± 8.55 Gy vs 1.62 ± 3.39 Gy; P=.037), the only independent predictor in multivariate analysis. DVH analysis showed that the fraction of liver exposed to ≥30 Gy (V30) was the strongest predictor of hepatotoxicity (10.14% ± 12.75% vs 0.84% ± 3.24%; P=.006). All patients with V30 >13% experienced hepatotoxicity. Fatal REILD (n=2) occurred at the 2 highest EBRT mean liver doses (20.9 Gy and 23.1 Gy) but also at the highest cumulative liver doses (91.8 Gy and 149 Gy). Conclusions: Prior exposure of the liver to EBRT may lead to increased liver toxicity after RE treatment, depending on fractional liver exposure and dose level. The V30 was the strongest predictor of toxicity. RE appears to be safe for the treatment of hepatic malignancies only in patients who have had limited hepatic exposure to prior EBRT.

  16. Role of neutron and proton system in spin cut off parameter and entropy of 89,90Y

    NASA Astrophysics Data System (ADS)

    Rahmatinejad, A.; Razavi, R.; Kakavand, T.

    2015-09-01

    The nuclear level densities, entropies and spin cut off parameters have been determined in 89,90Y nuclei using the BCS model with inclusion of pairing interaction. The results have a good agreement with the recent experimental data on the level densities measured by the Oslo group. In addition, the entropy excess of 90Y compared to 89Y as a function of temperature has been extracted. Also, the role of neutron and proton systems in the entropy excess as well as the spin cut off excess have been investigated using the entropy excess ratio and spin cut off excess ratio introduced in our previous publication. The role of the neutron system at low temperatures, the temperatures below critical temperature, in the semi-magic nucleus 89Y is similar compared to the closed shell proton system in the tin isotopes.

  17. A review of 3D image-based dosimetry, technical considerations and emerging perspectives in 90Y microsphere therapy

    PubMed Central

    O’ Doherty, Jim

    2016-01-01

    Yttrium-90 radioembolization (90Y-RE) is a well-established therapy for the treatment of hepatocellular carcinoma (HCC) and also of metastatic liver deposits from other malignancies. Nuclear Medicine and Cath Lab diagnostic imaging takes a pivotal role in the success of the treatment, and in order to fully exploit the efficacy of the technique and provide reliable quantitative dosimetry that are related to clinical endpoints in the era of personalized medicine, technical challenges in imaging need to be overcome. In this paper, the extensive literature of current 90Y-RE techniques and challenges facing it in terms of quantification and dosimetry are reviewed, with a focus on the current generation of 3D dosimetry techniques. Finally, new emerging techniques are reviewed which seek to overcome these challenges, such as high-resolution imaging, novel surgical procedures and the use of other radiopharmaceuticals for therapy and pre-therapeutic planning. PMID:27182449

  18. Pathologic response and microdosimetry of {sup 90}Y microspheres in man: Review of four explanted whole livers

    SciTech Connect

    Kennedy, Andrew S. . E-mail: akennedy@wakerad.com; Nutting, Charles; Coldwell, Douglas; Gaiser, James; Drachenberg, Cinthia

    2004-12-01

    Introduction: Radioactive microsphere {sup 90}Y therapy is increasingly used for primary and metastatic solid tumors in the liver. We present an analysis of 4 explanted livers previously treated with {sup 90}Y microsphere agents (glass or resin). One tumor nodule was analyzed with submillimeter three-dimensional microdosimetry. Methods and materials: Four patients received hepatic artery delivery of {sup 90}Y microspheres for unresectable hepatocellular and colon cancers. Whole livers were explanted as part of lifesaving cadaveric transplant in 2 patients with hepatoma. These patients had received glass microspheres as a procedural bridge to transplant. Autopsy was performed on 2 patients with colon cancer who died of progressive metastatic disease and who had been treated with resin microspheres. Complete pathologic review was performed on each whole liver, including estimation of the response of the tumor to therapy, distribution of microspheres in the tumor and normal liver tissues, and normal-tissue radiation response. A biopsy taken from the edge of a tumor nodule was sectioned serially for three-dimensional radiation dosimetry analyses. Three-dimensional microsphere coordinates within the biopsy specimen were used to calculate dosage using a three-dimensional dose kernel. Isodose coverage of tumor and normal liver areas and total dose delivered were determined. Results: Preferential and heterogeneous deposition of microspheres was noted at the edge of tumor nodules compared with the center portion of the tumor or normal liver parenchyma. Both glass and resin microspheres delivered high cumulative doses to the tumor, which varied from 100 Gy to more than 3000 Gy. No veno-occlusive disease or widespread radiation hepatitis was seen. Conclusion: Microsphere ({sup 90}Y) therapy delivers high numbers of spheres with resulting high total doses of radiation, preferentially in the periphery of tumors. Normal liver parenchyma showed little radiation effect away from

  19. Development of anthropomorphic hand phantoms for personal dosimetry in 90Y-Zevalin preparation and patient delivering.

    PubMed

    Ciolini, R; d'Errico, F; Traino, A C; Paternostro, E; Laganà, A; Romei, C; Pazzagli, F; Del Gratta, A

    2014-01-01

    Anthropomorphic tissue-equivalent hand phantoms were achieved to measure the extremity dose involved in Zevalin (90)Y-labelling and patient delivering procedure for radioimmunotherapy treatment of non-Hodgkin lymphoma. The extremity doses to hands and wrists of operators were measured by using thermoluminescent detectors mounted on the developed phantoms. Measurements of chest- and lens-equivalent doses performed on a Rando phantom are also reported.

  20. Magnetically directed poly(lactic acid) [sup 90]Y-microspheres: Novel agents for targeted intracavitary radiotherapy

    SciTech Connect

    Haefeli, U.O.; Sweeney, S.M.; Beresford, B.A.; Sim, E.H.; Macklis, R.M. . Joint Center for Radiation Therapy)

    1994-08-01

    High energy [beta]-emitting radioisotopes like Yttrium-90 have a radiotoxic range of about one centimeter. For cancer treatment they must be brought near the tumor cells and kept there for as long as they are radioactive. The authors developed as carriers for the ionic form of [sup 90]Y a matrix-type polymeric drug delivery system, poly(lactic acid) (PLA) microspheres. This radiopharmaceutical could be selectively delivered to the target site after incorporating 10% Fe[sub 3]O[sub 4] which made the magnetic microspheres (MMS) responsive to an external magnetic field. Furthermore, MMS are biodegradable and slowly hydrolyze into physiologic lactic acid after the radioactivity is completely decayed. Previously prepared 10--40 [mu]m MMS were radiochemically loaded to high specific activity with [sup 90]Y at a pH of 5.7. Stability studies showed that approximately 95% of added [sup 90]Y is retained within the PLA matrix after 28 days (> 10 half-lives) at 37 C in serum, and electron microscopy showed that the microspheres retained their characteristic morphologic appearance for the same time period. Cytotoxicity studies with SK-N-SH neuroblastoma cells growing in monolayer showed that the radiocytotoxicity of the microspheres could be directed magnetically to either kill or spare specific cell populations, thus making them of great interest for targeted intracavitary tumor therapy. The authors are currently optimizing this system for use in the treatment of neoplastic meningitis.

  1. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-06-01

    (+)-Dapoxetine hydrochloride; Abatacept, Adalimumab, Agalsidase beta, Alemtuzumab, Alglucosidase alfa, Aliskiren fumarate, Ambrisentan, Amlodipine, Aripiprazole, Atrasentan, Azacitidine, Azelnidipine; Belotecan hydrochloride, Bevacizumab, Bilastine, Biphasic insulin aspart, Bortezomib, Bosentan; Caspofungin acetate, CG-100649, Cinacalcet hydrochloride, Clindamycin phosphate/ benzoyl peroxide; Dasatinib, Denosumab, Duloxetine hydrochloride, Dutasteride, Dutasteride/tamsulosin; Ecogramostim, Eculizumab, Eltrombopag olamine, EndoTAG-1, Erlotinib hydrochloride, Everolimus, Exenatide, Ezetimibe; FAHF-2, Fondaparinux sodium; Gefitinib, Golimumab; HEV-239, HSV-TK; Imatinib mesylate, Indium 111 ((111)In) ibritumomab tiuxetan, Influenza vaccine(surface antigen, inactivated, prepared in cell culture), Insulin glargine; Kisspeptin-54; Lidocaine/prilocaine, Lomitapide; Maraviroc, Mirodenafil hydrochloride, MK-8141, MVA-Ag85A; Nilotinib hydrochloride monohydrate; Olmesartan medoxomil; Paclitaxel-eluting stent, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pitavastatin calcium, Prasugrel; Recombinant human relaxin H2, RHAMM R3 peptide, Rivaroxaban, Rosuvastatin calcium, RRz2; Sagopilone, Salinosporamide A, SB-509, Serlopitant, Sirolimus-eluting stent, Sorafenib, Sunitinib malate; Tadalafil, Temsirolimus, Teriparatide, TG-4010, Tositumomab/iodine (I131) tositumomab; Velusetrag Hydrochloride; Ximelagatran; Yttrium 90 (90Y) ibritumomab tiuxetan. PMID:19649342

  2. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2003-10-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 3,4-DAP; Adefovir dipivoxil, ADL-10-0101, alefacept, alemtuzumab, alosetron hydrochloride, ALT-711, aprepitant, atazanavir sulfate, atlizumab, atvogen; Bortezomib; CETP vaccine, clevudine, crofelemer; DAC:GLP-1, darbepoetin alfa, decitabine, drotrecogin alfa (activated), DX-9065a; E-7010, edodekin alfa, emivirine, emtricitabine, entecavir, erlosamide, erlotinib hydrochloride, everolimus, exenatide; Fondaparinux sodium, frovatriptan, fulvestrant; Gemtuzumab ozogamicin, gestodene; Homoharringtonine, human insulin; Imatinib mesylate, indiplon, indium 111 (111In) ibritumomab tiuxetan, inhaled insulin, insulin detemir, insulin glargine, ivabradine hydrochloride; Lanthanum carbonate, lapatinib, LAS-34475, levetiracetam, liraglutide, lumiracoxib; Maxacalcitol, melagatran, micafungin sodium; Natalizumab, NSC-640488; Oblimersen sodium; Parecoxib sodium, PEG-filgrastim, peginterferon alfa-2(a), peginterferon alfa-2b, pexelizumab, pimecrolimus, pleconaril, pramlintide acetate, pregabalin, prucalopride; rAHF-PFM, Ranelic acid distrontium salt, ranolazine, rDNA insulin, recombinant human soluble thrombomodulin, rhGM-CSF, roxifiban acetate, RSD-1235, rubitecan, ruboxistaurin mesilate hydrate; SC-51, squalamine; Tegaserod maleate, telbivudine, tesaglitazar, testosterone gel, tezosentan disodium, tipranavir; Vatalanib succinate; Ximelagatran; Yttrium 90 (90Y) ibritumomab tiuxetan; Zoledronic acid monohydrate. PMID:14671684

  3. Automated radioanalytical system for the determination of 90Sr in environmental water samples by 90Y Cherenkov radiation counting.

    PubMed

    O'Hara, Matthew J; Burge, Scott R; Grate, Jay W

    2009-02-01

    Strontium-90 is an environmental contaminant at several U.S. Department of Energy sites, including the Hanford site, Washington. Due to its high biological toxicity and moderately long half-life of approximately 29 years, groundwater and surface water contamination plumes containing 90Sr must be closely monitored. The highly energetic beta radiation from the short-lived 90Y daughter of 90Sr generates Cherenkov photons in aqueous media that can be detected by photomultiplier tubes with good sensitivity, without the use of scintillation cocktails. A laboratory-based automated fluid handling system coupled to a Cherenkov radiation detector for measuring 90Sr via the high-energy beta decay of its daughter, 90Y, has been assembled and tested using standards prepared in Hanford groundwater. A SuperLig 620 column in the system enables preconcentration and separation of 90Sr from matrix and radiological interferences and, by removing the 90Y present in the sample, creates a pure 90Sr source from which subsequent 90Y ingrowth can be measured. This 90Y is fluidically transferred from the column to the Cherenkov detection flow cell for quantification and calculation of the original 90Sr concentration. Preconcentrating 0.35 L sample volumes by this approach, we have demonstrated a detection limit of 0.057 Bq/L using a 5 mL volume Cherenkov flow cell, which is below the drinking water limit of 0.30 Bq/L. This method does not require that the sample be at secular equilibrium prior to measurement. The system can also deliver water samples directly to the counting cell for analysis without preconcentration or separation, assuming that the sample is in secular equilibrium, with a detection limit of 7 Bq/L. The performance of the analysis method using a preconcentrating separation column is characterized in detail and compared with direct counting. This method is proposed as the basis for an automated fluidic monitor for 90Sr for unattended at-site operation.

  4. Anti-CD45 Radioimmunotherapy with 90Y but Not 177Lu Is Effective Treatment in a Syngeneic Murine Leukemia Model

    PubMed Central

    Orozco, Johnnie J.; Balkin, Ethan R.; Gooley, Ted A.; Kenoyer, Aimee; Hamlin, Donald K.; Wilbur, D. Scott; Fisher, Darrell R.; Hylarides, Mark D.; Shadman, Mazyar; Green, Damian J.; Gopal, Ajay K.; Press, Oliver W.; Pagel, John M.

    2014-01-01

    Radioimmunotherapy (RIT) for treatment of hematologic malignancies has primarily employed monoclonal antibodies (Ab) labeled with 131I or 90Y which have limitations, and alternative radionuclides are needed to facilitate wider adoption of RIT. We therefore compared the relative therapeutic efficacy and toxicity of anti-CD45 RIT employing 90Y and 177Lu in a syngeneic, disseminated murine myeloid leukemia (B6SJLF1/J) model. Biodistribution studies showed that both 90Y- and 177Lu-anti-murine CD45 Ab conjugates (DOTA-30F11) targeted hematologic tissues, as at 24 hours 48.8±21.2 and 156±14.6% injected dose per gram of tissue (% ID/g) of 90Y-DOTA-30F11 and 54.2±9.5 and 199±11.7% ID/g of 177Lu-DOTA-30F11 accumulated in bone marrow (BM) and spleen, respectively. However, 90Y-DOTA-30F11 RIT demonstrated a dose-dependent survival benefit: 60% of mice treated with 300 µCi 90Y-DOTA-30F11 lived over 180 days after therapy, and mice treated with 100 µCi 90Y-DOTA-30F11 had a median survival 66 days. 90Y-anti-CD45 RIT was associated with transient, mild myelotoxicity without hepatic or renal toxicity. Conversely, 177Lu- anti-CD45 RIT yielded no long-term survivors. Thus, 90Y was more effective than 177Lu for anti-CD45 RIT of AML in this murine leukemia model. PMID:25460570

  5. Radiometals as payloads for radioimmunotherapy for lymphoma.

    PubMed

    DeNardo, Gerald L; Kennel, Stephen J; Siegel, Jeffry A; Denardo, Sally J

    2004-10-01

    Because of their remarkable effectiveness in radioimmunotherapy (RIT), 2 anti-CD20 monoclonal antibody (MAb) drugs, one labeled with indium 111 for imaging or yttrium 90 for therapy, and another labeled with iodine I 131 for imaging and therapy, have been approved for use in patients with non-Hodgkin's lymphoma (NHL). Successful RIT for lymphomas is due in large part to the rapid and efficient binding of the targeted MAb to lymphoma cells. Carcinomas are more difficult to access, necessitating novel strategies matched with radionuclides with specific physical properties. Because there are many radionuclides from which to choose, a systematic approach is required to select those preferred for a specific application. Thus far, radionuclides with g emissions for imaging and particulate emissions for therapy have been investigated. Radionuclides of iodine were the first to be used for RIT. Many conventionally radioiodinated MAbs are degraded after endocytosis by target cells, releasing radioiodinated peptides and amino acids. In contrast, radiometals have been shown to have residualizing properties, advantageous when the MAb is localized in malignant tissue. b-emitting lanthanides like those of 90Y, lutetium 177, etc. have attractive combinations of biologic, physical, radiochemical, production, economic, and radiation safety characteristics. Other radiometals, such as copper-67 and copper-64, are also of interest. a-emitters, including actinium-225 and bismuth-213, have been used for therapy in selected applications. Evidence for the impact of the radionuclide is provided by data from the randomized pivotal phase III trial of 90Y ibritumomab tiuxetan (Zevalin) in patients with NHL; responses were about 2 times greater in the 90Y ibritumomab tiuxetan arm than in the rituximab arm. It is clear that RIT has emerged as a safe and efficient method for treatment of NHL, especially in specific settings. PMID:15498149

  6. Hepatic Toxicity After Radioembolization of the Liver Using {sup 90}Y-Microspheres: Sequential Lobar Versus Whole Liver Approach

    SciTech Connect

    Seidensticker, Ricarda; Seidensticker, Max; Damm, Robert; Mohnike, Konrad; Schuette, Kerstin; Malfertheiner, Peter; Buskirk, Mark Van; Pech, Maciej; Amthauer, Holger; Ricke, Jens

    2012-10-15

    Purpose: {sup 90}Y-radioembolization (RE) is a promising technique for delivering high doses of radiation to liver tumors but may result in compromise of liver function. To gain further perspective, we evaluated the toxicity rates of sequential lobar versus 'whole liver' {sup 90}Y-radioembolization. Methods: Thirty-four patients with liver malignancy in noncirrhotic livers were included; {sup 90}Y-radioembolization was performed as either whole liver or sequential lobar treatment in 17 patients each. Standard clinical and liver specific laboratory parameters as well as MR imaging before treatment and at follow-up (6 and 12 weeks) after radioembolization were evaluated for toxicity using the Common Terminology Criteria for Adverse Events (CTCAE). Volumetry of the liver, tumor, and spleen and measurement of portal vein diameter also were performed. Results: Three months after whole liver RE, 14 liver-related grade 3/4 events were recorded versus 2 events after sequential lobar treatment (P < 0.05). Three patients treated with whole liver RE suffered from radioembolization-induced liver disease (REILD). Pathological increases in bilirubin at 3 months were observed for the whole liver group only (52.3 vs. 18.7 {mu}mol/l, P = 0.012). Total liver volume did not change significantly in either group, but shrinkage of the initially treated hepatic lobe with compensatory hypertrophy of the subsequently treated lobe was observed in the sequential lobar group (P < 0.05). Portal vein diameter increased significantly in whole liver-treated patients only (+17% vs. +6.6%, P = 0.043). Conclusions: Noncirrhotic patients undergoing sequential lobar radioembolization had less hepatic toxicity compared to whole liver embolization. The sequential approach should be the preferred strategy.

  7. Inhibiting the effect of 90Sr-90Y ophthalmic applicators on rat corneal neovascularization induced by sutures

    PubMed Central

    Zhou, Hong-Yan; Wang, Shuang; Zhang, Hong; Wang, Ling; Zhang, Wen-Song

    2016-01-01

    AIM To investigate a practical technique used to inhibit corneal angiogenesis with a 90Sr-90Y ophthalmic applicator. METHODS A 90Sr-90Y ophthalmic applicator was detected with a radioactive nuclide application treatment healthy protection standard. The applicator used was produced through medical dosimetry research; it had a concave applicator add measured the applicator temperature, serviceable humidity range, applicator appearance status, applicator radiation homogeneity, radioautography, and radiological safety of the original applicator surface. A vessel model was established using newborn rats, with sutures around the corneal limbus. Corneal neovascularization (CNV) were observed with a slit lamp. The new vessel length and response area were measured. RESULTS Low-dose radiation can inhibit CNV after corneal sutures. The absorbed dose of the applicator (0.046 Gy/s) was safe for the treatment of it. The lengths of new vessels and the areas of new vessels were lower than the new born vessel rat group (P<0.01). CONCLUSION The optimal radiation dose emitting from the applicator can be safe and potentially used in humans.

  8. Inhibiting the effect of 90Sr-90Y ophthalmic applicators on rat corneal neovascularization induced by sutures

    PubMed Central

    Zhou, Hong-Yan; Wang, Shuang; Zhang, Hong; Wang, Ling; Zhang, Wen-Song

    2016-01-01

    AIM To investigate a practical technique used to inhibit corneal angiogenesis with a 90Sr-90Y ophthalmic applicator. METHODS A 90Sr-90Y ophthalmic applicator was detected with a radioactive nuclide application treatment healthy protection standard. The applicator used was produced through medical dosimetry research; it had a concave applicator add measured the applicator temperature, serviceable humidity range, applicator appearance status, applicator radiation homogeneity, radioautography, and radiological safety of the original applicator surface. A vessel model was established using newborn rats, with sutures around the corneal limbus. Corneal neovascularization (CNV) were observed with a slit lamp. The new vessel length and response area were measured. RESULTS Low-dose radiation can inhibit CNV after corneal sutures. The absorbed dose of the applicator (0.046 Gy/s) was safe for the treatment of it. The lengths of new vessels and the areas of new vessels were lower than the new born vessel rat group (P<0.01). CONCLUSION The optimal radiation dose emitting from the applicator can be safe and potentially used in humans. PMID:27672586

  9. A new approach for dose calculation in targeted radionuclide therapy (TRT) based on collapsed cone superposition: validation with 90Y

    NASA Astrophysics Data System (ADS)

    Sanchez-Garcia, Manuel; Gardin, Isabelle; Lebtahi, Rachida; Dieudonné, Arnaud

    2014-09-01

    To speed-up the absorbed dose (AD) computation while accounting for tissue heterogeneities, a Collapsed Cone (CC) superposition algorithm was developed and validated for 90Y. The superposition was implemented with an Energy Deposition Kernel scaled with the radiological distance, along with CC acceleration. The validation relative to Monte Carlo simulations was performed on 6 phantoms involving soft tissue, lung and bone, a radioembolisation treatment and a simulated bone metastasis treatment. As a figure of merit, the relative AD difference (ΔAD) in low gradient regions (LGR), distance to agreement (DTA) in high gradient regions and the γ(1%,1 mm) criterion were used for the phantoms. Mean organ doses and γ(3%,3 mm) were used for the patient data. For the semi-infinite sources, ΔAD in LGR was below 1%. DTA was below 0.6 mm. All profiles verified the γ(1%,1 mm) criterion. For both clinical cases, mean doses differed by less than 1% for the considered organs and all profiles verified the γ(3%,3 mm). The calculation time was below 4 min on a single processor for CC superposition and 40 h on a 40 nodes cluster for MCNP (108 histories). Our results show that the CC superposition is a very promising alternative to MC for 90Y dosimetry, while significantly reducing computation time.

  10. A new approach for dose calculation in targeted radionuclide therapy (TRT) based on collapsed cone superposition: validation with (90)Y.

    PubMed

    Sanchez-Garcia, Manuel; Gardin, Isabelle; Lebtahi, Rachida; Dieudonné, Arnaud

    2014-09-01

    To speed-up the absorbed dose (AD) computation while accounting for tissue heterogeneities, a Collapsed Cone (CC) superposition algorithm was developed and validated for (90)Y. The superposition was implemented with an Energy Deposition Kernel scaled with the radiological distance, along with CC acceleration. The validation relative to Monte Carlo simulations was performed on 6 phantoms involving soft tissue, lung and bone, a radioembolisation treatment and a simulated bone metastasis treatment. As a figure of merit, the relative AD difference (ΔAD) in low gradient regions (LGR), distance to agreement (DTA) in high gradient regions and the γ(1%,1 mm) criterion were used for the phantoms. Mean organ doses and γ(3%,3 mm) were used for the patient data. For the semi-infinite sources, ΔAD in LGR was below 1%. DTA was below 0.6 mm. All profiles verified the γ(1%,1 mm) criterion. For both clinical cases, mean doses differed by less than 1% for the considered organs and all profiles verified the γ(3%,3 mm). The calculation time was below 4 min on a single processor for CC superposition and 40 h on a 40 nodes cluster for MCNP (10(8) histories). Our results show that the CC superposition is a very promising alternative to MC for (90)Y dosimetry, while significantly reducing computation time. PMID:25097006

  11. Organ doses from hepatic radioembolization with 90Y, 153Sm, 166Ho and 177Lu: A Monte Carlo simulation study using Geant4

    NASA Astrophysics Data System (ADS)

    Hashikin, N. A. A.; Yeong, C. H.; Guatelli, S.; Abdullah, B. J. J.; Ng, K. H.; Malaroda, A.; Rosenfeld, A. B.; Perkins, A. C.

    2016-03-01

    90Y-radioembolization is a palliative treatment for liver cancer. 90Y decays via beta emission, making imaging difficult due to absence of gamma radiation. Since post-procedure imaging is crucial, several theranostic radionuclides have been explored as alternatives. However, exposures to gamma radiation throughout the treatment caused concern for the organs near the liver. Geant4 Monte Carlo simulation using MIRD Pamphlet 5 reference phantom was carried out. A spherical tumour with 4.3cm radius was modelled within the liver. 1.82GBq of 90Y sources were isotropically distributed within the tumour, with no extrahepatic shunting. The simulation was repeated with 153Sm, 166Ho and 177Lu. The estimated tumour doses for all radionuclides were 262.9Gy. Tumour dose equivalent to 1.82GBq 90Y can be achieved with 8.32, 5.83, and 4.44GBq for 153Sm, 166Ho and 177Lu, respectively. Normal liver doses by the other radionuclides were lower than 90Y, hence beneficial for normal tissue sparing. The organ doses from 153Sm and 177Lu were relatively higher due to higher gamma energy, but were still well below 1Gy. 166Ho, 177Lu and 153Sm offer useful gamma emission for post-procedure imaging. They show potential as 90Y substitutes, delivering comparable tumour doses, lower normal liver doses and other organs doses far below the tolerance limit.

  12. A computational tool for patient specific dosimetry and radiobiological modeling of selective internal radiation therapy with (90)Y microspheres.

    PubMed

    Kalantzis, Georgios; Leventouri, Theodora; Apte, Aditiya; Shang, Charles

    2015-11-01

    In recent years we have witnessed tremendous progress in selective internal radiation therapy. In clinical practice, quite often, radionuclide therapy is planned using simple models based on standard activity values or activity administered per unit body weight or surface area in spite of the admission that radiation-dose methods provide more accurate dosimetric results. To address that issue, the authors developed a Matlab-based computational software, named Patient Specific Yttrium-90 Dosimetry Toolkit (PSYDT). PSYDT was designed for patient specific voxel-based dosimetric calculations and radiobiological modeling of selective internal radiation therapy with (90)Y microspheres. The developed toolkit is composed of three dimensional dose calculations for both bremsstrahlung and beta emissions. Subsequently, radiobiological modeling is performed on a per-voxel basis and cumulative dose volume histograms (DVHs) are generated. In this report we describe the functionality and visualization features of PSYDT. PMID:26296058

  13. Experimental determination of the radial dose function of {sup 90}Sr/{sup 90}Y IVBT sources

    SciTech Connect

    Holmes, Shannon M.; DeWerd, Larry A.; Micka, John A.

    2006-09-15

    A series of measurements were undertaken using both high sensitivity radiochromic film and new lithium fluoride thermoluminescent dosimeters in a liquid water medium to define the radial dose function of {sup 90}Sr/{sup 90}Y beta emitting intravascular brachytherapy sources more accurately. These measurements of a single 5 French source pellet served to verify current Monte Carlo transport models and extrapolation chamber measurements of the radial dose function, thus providing the recommended independent published measurements for g(r) of these sources. A slight deviation in the published radial dose function at depth leads the authors to recommend that treatment planning be performed using updated g(r) values from current Monte Carlo transport models verified by measurements such as those shown in this investigation.

  14. Radioimmunotherapy of breast cancer metastases with alpha-particle emitter 225Ac: comparing efficacy with 213Bi and 90Y.

    PubMed

    Song, Hong; Hobbs, Robert F; Vajravelu, Ravy; Huso, David L; Esaias, Caroline; Apostolidis, Christos; Morgenstern, Alfred; Sgouros, George

    2009-12-01

    alpha-Particles are suitable to treat cancer micrometastases because of their short range and very high linear energy transfer. alpha-Particle emitter (213)Bi-based radioimmunotherapy has shown efficacy in a variety of metastatic animal cancer models, such as breast, ovarian, and prostate cancers. Its clinical implementation, however, is challenging due to the limited supply of (225)Ac, high technical requirement to prepare radioimmunoconjugate with very short half-life (T(1/2) = 45.6 min) on site, and prohibitive cost. In this study, we investigated the efficacy of the alpha-particle emitter (225)Ac, parent of (213)Bi, in a mouse model of breast cancer metastases. A single administration of (225)Ac (400 nCi)-labeled anti-rat HER-2/neu monoclonal antibody (7.16.4) completely eradicated breast cancer lung micrometastases in approximately 67% of HER-2/neu transgenic mice and led to long-term survival of these mice for up to 1 year. Treatment with (225)Ac-7.16.4 is significantly more effective than (213)Bi-7.16.4 (120 microCi; median survival, 61 days; P = 0.001) and (90)Y-7.16.4 (120 microCi; median survival, 50 days; P < 0.001) as well as untreated control (median survival, 41 days; P < 0.0001). Dosimetric analysis showed that (225)Ac-treated metastases received a total dose of 9.6 Gy, significantly higher than 2.0 Gy from (213)Bi and 2.4 Gy from (90)Y. Biodistribution studies revealed that (225)Ac daughters, (221)Fr and (213)Bi, accumulated in kidneys and probably contributed to the long-term renal toxicity observed in surviving mice. These data suggest (225)Ac-labeled anti-HER-2/neu monoclonal antibody could significantly prolong survival in HER-2/neu-positive metastatic breast cancer patients.

  15. Radioimmunotherapy of breast cancer metastases with alpha-particle emitter 225Ac: comparing efficacy with 213Bi and 90Y.

    PubMed

    Song, Hong; Hobbs, Robert F; Vajravelu, Ravy; Huso, David L; Esaias, Caroline; Apostolidis, Christos; Morgenstern, Alfred; Sgouros, George

    2009-12-01

    alpha-Particles are suitable to treat cancer micrometastases because of their short range and very high linear energy transfer. alpha-Particle emitter (213)Bi-based radioimmunotherapy has shown efficacy in a variety of metastatic animal cancer models, such as breast, ovarian, and prostate cancers. Its clinical implementation, however, is challenging due to the limited supply of (225)Ac, high technical requirement to prepare radioimmunoconjugate with very short half-life (T(1/2) = 45.6 min) on site, and prohibitive cost. In this study, we investigated the efficacy of the alpha-particle emitter (225)Ac, parent of (213)Bi, in a mouse model of breast cancer metastases. A single administration of (225)Ac (400 nCi)-labeled anti-rat HER-2/neu monoclonal antibody (7.16.4) completely eradicated breast cancer lung micrometastases in approximately 67% of HER-2/neu transgenic mice and led to long-term survival of these mice for up to 1 year. Treatment with (225)Ac-7.16.4 is significantly more effective than (213)Bi-7.16.4 (120 microCi; median survival, 61 days; P = 0.001) and (90)Y-7.16.4 (120 microCi; median survival, 50 days; P < 0.001) as well as untreated control (median survival, 41 days; P < 0.0001). Dosimetric analysis showed that (225)Ac-treated metastases received a total dose of 9.6 Gy, significantly higher than 2.0 Gy from (213)Bi and 2.4 Gy from (90)Y. Biodistribution studies revealed that (225)Ac daughters, (221)Fr and (213)Bi, accumulated in kidneys and probably contributed to the long-term renal toxicity observed in surviving mice. These data suggest (225)Ac-labeled anti-HER-2/neu monoclonal antibody could significantly prolong survival in HER-2/neu-positive metastatic breast cancer patients. PMID:19920193

  16. Radioimmunotherapy: A Specific Treatment Protocol for Cancer by Cytotoxic Radioisotopes Conjugated to Antibodies

    PubMed Central

    Kawashima, Hidekazu

    2014-01-01

    Radioimmunotherapy (RIT) represents a selective internal radiation therapy, that is, the use of radionuclides conjugated to tumor-directed monoclonal antibodies (including those fragments) or peptides. In a clinical field, two successful examples of this treatment protocol are currently extended by 90Y-ibritumomab tiuxetan (Zevalin) and 131I-tositumomab (Bexxar), both of which are anti-CD20 monoclonal antibodies coupled to cytotoxic radioisotopes and are approved for the treatment of non-Hodgkin lymphoma patients. In addition, some beneficial observations are obtained in preclinical studies targeting solid tumors. To date, in order to reduce the unnecessary exposure and to enhance the therapeutic efficacy, various biological, chemical, and treatment procedural improvements have been investigated in RIT. This review outlines the fundamentals of RIT and current knowledge of the preclinical/clinical trials for cancer treatment. PMID:25379535

  17. Radioimmunotherapy: a specific treatment protocol for cancer by cytotoxic radioisotopes conjugated to antibodies.

    PubMed

    Kawashima, Hidekazu

    2014-01-01

    Radioimmunotherapy (RIT) represents a selective internal radiation therapy, that is, the use of radionuclides conjugated to tumor-directed monoclonal antibodies (including those fragments) or peptides. In a clinical field, two successful examples of this treatment protocol are currently extended by (90)Y-ibritumomab tiuxetan (Zevalin) and (131)I-tositumomab (Bexxar), both of which are anti-CD20 monoclonal antibodies coupled to cytotoxic radioisotopes and are approved for the treatment of non-Hodgkin lymphoma patients. In addition, some beneficial observations are obtained in preclinical studies targeting solid tumors. To date, in order to reduce the unnecessary exposure and to enhance the therapeutic efficacy, various biological, chemical, and treatment procedural improvements have been investigated in RIT. This review outlines the fundamentals of RIT and current knowledge of the preclinical/clinical trials for cancer treatment.

  18. Optimizing safety of selective internal radiation therapy (SIRT) of hepatic tumors with 90Y resin microspheres: a systematic approach to preparation and radiometric procedures.

    PubMed

    Schleipman, A Robert; Gallagher, Patrick W; Gerbaudo, Victor H

    2009-02-01

    Arterial administration of 90Y microspheres is used for salvage therapy in patients with primary or metastasized tumors within the liver. The clinical use of high-yield beta emitters presents unique calibration, dosage measurement, and exposure monitoring tasks. This report illustrates the following issues: determination of container and volume-specific correction factors in a standard dose calibrator for various receipt and dispensing vial geometries using a U.S. National Institute of Standards and Technology-traceable 90Y standard solution; documentation of delivery and localization of the radionuclide; statistically-verified ion chamber measurements of residual (non infused) radioactivity; and measurement of occupational radiation exposures.

  19. Radionuclide Therapy of Unresectable Tumors with AvidinOX and (90)Y-biotinDOTA: Tongue Cancer Paradigm.

    PubMed

    Albertoni, Claudio; Leoni, Barbara; Rosi, Antonio; D'Alessio, Valeria; Carollo, Valeria; Spagnoli, Luigi Giusto; van Echteld, Cees; De Santis, Rita

    2015-09-01

    Local treatment of unresectable tumors is challenging, particularly with radioactivity. Current practice relies on external beam irradiation or on a variety of medical devices for brachytherapy. Both approaches proved useful in controlling tumor growth, but are characterized by poor compliance of the patient, significant side-effects, high costs, and technological complexity, which hamper widespread use. The authors recently described a novel form of radionuclide therapy based on the oxidized form of avidin that, chemically reacting with tissue proteins, can secure radioactive biotin within the injected tissue, either when precomplexed or when taken from the blood stream after intravenous administration. AvidinOX-pretargeted (177)Lu-biotinDOTA ((177)Lu-ST2210) is currently under clinical investigation for the treatment of liver oligometastases from colorectal cancer (clinicaltrials.gov/NCT02053324). In the present work, the authors show that injected AvidinOX can link tissues of various natures such as prostate, kidney, breast, or brain and can react by contact with scraped tissues such as skin or urinary bladder. AvidinOX injected into human OSC19 tongue cancer masses orthotopically transplanted in nude mice takes up intravenously administered (90)Y-ST2210, which exerts significant antitumor activity, while preserving the integrity and functionality of the tongue. Present data confirm that AvidinOX-based radionuclide therapy is an innovative and promising approach for the local treatment of inoperable tumors.

  20. Comparison of yttrium and indium complexes of DOTA-BA and DOTA-MBA: models for (90)Y- and (111)In-labeled DOTA-biomolecule conjugates.

    PubMed

    Liu, Shuang; Pietryka, John; Ellars, Charles E; Edwards, D Scott

    2002-01-01

    Yttrium and indium complexes of 1,4,7,10-tetraaza-4,7,10-tris(carboxymethyl)-1-cyclododecylacetylbenzylamine (DOTA-BA) and 1,4,7,10-tetraaza-4,7,10-tris(carboxymethyl)-1-cyclododecylacetyl-R-(+)-alpha-methylbenzylamine (DOTA-MBA) were prepared in order to study solution structures of (90)Y- and (111)In-labeled DOTA-biomolecule conjugates. (90)Y and (111)In complexes M(L) (M = (90)Y and (111)In; L = DOTA-BA and DOTA-MBA) were prepared from the reaction of MCl(3) with DOTA-BA and DOTA-MBA, respectively, in ammonium acetate buffer. A reverse phase HPLC method revealed that both (90)Y and (111)In complexes show only one radiometric peak in their radio-HPLC chromatograms. It was also found that (111)In(DOTA-BA) and (111)In(DOTA-MBA) are more hydrophilic than their corresponding (90)Y analogues, suggesting different coordination spheres in (111)In and (90)Y complexes of the same DOTA conjugate. Complexes M(L) (M = Y and In; L = DOTA-BA and DOTA-MBA) were prepared and characterized by HPLC, LC-MS, and NMR ((1)H and (13)C) methods. The HPLC concordance experiments for (90)Y(DOTA-MBA)/Y(DOTA-MBA) and (111)In(DOTA-MBA)/In(DOTA-MBA) show that the same complex is prepared at both tracer and macroscopic levels. The NMR data ((1)H and (13)C) clearly demonstrates that Y(DOTA-BA) and Y(DOTA-MBA) exist in solution as one predominant isomer. VT NMR data ((1)H and (13)C) show that In(DOTA-BA) and In(DOTA-MBA) are fluxional at room temperature while Y(DOTA-BA) and Y(DOTA-MBA) become fluxional only at elevated temperatures. The fluxionality of these complexes is due to rapid rotation of acetate/acetamide chelating arms and inversion of ethylenic groups of the macrocyclic ring.

  1. Evaluation of EGS4/PRESTA multiple-scattering algorithms for 90Sr/90Y intravascular brachytherapy dosimetry.

    PubMed

    Wang, R; Li, X A; Yu, C X

    2000-08-01

    The purpose of this work is to evaluate the EGS4/PRESTA electron multiple-scattering (MS) algorithms for dose calculation in intravascular brachytherapy (IVBT) using a 90Sr/90Y source. The small source size and the small volume of interest in IVBT require very fine spatial resolution, which may break down the constraints of Molière's MS theory as implemented in EGS4. The theory is accurate only when the electron step sizes are large enough to allow the number of collisions omega0 to be much greater than e = 2.7183. When step sizes are too small to allow at least 2.7183 collisions, as may be necessitated by the fine geometry, the algorithm may switch off MS, producing dosimetric artefacts. This study showed that switching off MS could produce a dose deviation of up to 6% when the half-thickness (d/2) of the dose scoring region is comparable with the Moliere minimum step size (t(min) = 2.7183). The effect of switching off MS is negligible if d/2 > t(min) For the case of omega0 > e, if the electron step sizes are chosen to allow five to 40 collisions, with increasing step size, the doses surrounding the source increase and the error decreases. On the other hand, when larger step sizes are chosen, the dose calculation voxel size must also be increased in order for the calculations to converge. A good compromise between accuracy and applicability for IVBT simulation can be made, if the thickness of the scoring region is 0.1 mm and the electron step sizes are in the range allowing 10 to 30 collisions.

  2. Optimization of energy window for {sup 90}Y bremsstrahlung SPECT imaging for detection tasks using the ideal observer with model-mismatch

    SciTech Connect

    Rong Xing; Ghaly, Michael; Frey, Eric C.

    2013-06-15

    Purpose: In yttrium-90 ({sup 90}Y) microsphere brachytherapy (radioembolization) of unresectable liver cancer, posttherapy {sup 90}Y bremsstrahlung single photon emission computed tomography (SPECT) has been used to document the distribution of microspheres in the patient and to help predict potential side effects. The energy window used during projection acquisition can have a significant effect on image quality. Thus, using an optimal energy window is desirable. However, there has been great variability in the choice of energy window due to the continuous and broad energy distribution of {sup 90}Y bremsstrahlung photons. The area under the receiver operating characteristic curve (AUC) for the ideal observer (IO) is a widely used figure of merit (FOM) for optimizing the imaging system for detection tasks. The IO implicitly assumes a perfect model of the image formation process. However, for {sup 90}Y bremsstrahlung SPECT there can be substantial model-mismatch (i.e., difference between the actual image formation process and the model of it assumed in reconstruction), and the amount of the model-mismatch depends on the energy window. It is thus important to account for the degradation of the observer performance due to model-mismatch in the optimization of the energy window. The purpose of this paper is to optimize the energy window for {sup 90}Y bremsstrahlung SPECT for a detection task while taking into account the effects of the model-mismatch. Methods: An observer, termed the ideal observer with model-mismatch (IO-MM), has been proposed previously to account for the effects of the model-mismatch on IO performance. In this work, the AUC for the IO-MM was used as the FOM for the optimization. To provide a clinically realistic object model and imaging simulation, the authors used a background-known-statistically and signal-known-statistically task. The background was modeled as multiple compartments in the liver with activity parameters independently following a

  3. 90Y-daclizumab, an anti-CD25 monoclonal antibody, provided responses in 50% of patients with relapsed Hodgkin’s lymphoma

    PubMed Central

    Janik, John E.; Morris, John C.; O’Mahony, Deirdre; Pittaluga, Stefania; Jaffe, Elaine S.; Redon, Christophe E.; Bonner, William M.; Brechbiel, Martin W.; Paik, Chang H.; Whatley, Millie; Chen, Clara; Lee, Jae-Ho; Fleisher, Thomas A.; Brown, Maggie; White, Jeffrey D.; Stewart, Donn M.; Fioravanti, Suzanne; Lee, Cathryn C.; Goldman, Carolyn K.; Bryant, Bonita R.; Junghans, Richard P.; Carrasquillo, Jorge A.; Worthy, Tat’Yana; Corcoran, Erin; Conlon, Kevin C.; Waldmann, Thomas A.

    2015-01-01

    Despite significant advances in the treatment of Hodgkin’s lymphoma (HL), a significant proportion of patients will not respond or will subsequently relapse. We identified CD25, the IL-2 receptor alpha subunit, as a favorable target for systemic radioimmunotherapy of HL. The scientific basis for the clinical trial was that, although most normal cells with exception of Treg cells do not express CD25, it is expressed by a minority of Reed–Sternberg cells and by most polyclonal T cells rosetting around Reed–Sternberg cells. Forty-six patients with refractory and relapsed HL were evaluated with up to seven i.v. infusions of the radiolabeled anti-CD25 antibody 90Y-daclizumab. 90Y provides strong β emissions that kill tumor cells at a distance by a crossfire effect. In 46 evaluable HL patients treated with 90Y-daclizumab there were 14 complete responses and nine partial responses; 14 patients had stable disease, and nine progressed. Responses were observed both in patients whose Reed–Sternberg cells expressed CD25 and in those whose neoplastic cells were CD25− provided that associated rosetting T cells expressed CD25. As assessed using phosphorylated H2AX (γ-H2AX) as a bioindicator of the effects of radiation exposure, predominantly nonmalignant cells in the tumor microenvironment manifested DNA damage, as reflected by increased expression of γ-H2AX. Toxicities were transient bone-marrow suppression and myelodysplastic syndrome in six patients who had not been evaluated with bone-marrow karyotype analyses before therapy. In conclusion, repeated 90Y-daclizumab infusions directed predominantly toward nonmalignant T cells rosetting around Reed–Sternberg cells provided meaningful therapy for select HL patients. PMID:26438866

  4. Distribution of intraperitoneally injected microspheres labeled with the alpha-emitter astatine (211At) compared with phosphorus (32P) and yttrium (90Y) colloids in mice.

    PubMed

    Vergote, I; Larsen, R H; De Vos, L; Winderen, M; Ellingsen, T; Bjørgum, J; Hoff, P; Aas, M; Tropé, C; Nustad, K

    1992-12-01

    The alpha-emitter 211At was bound to polymer microspheres with a diameter of 1.8 microns. The distributions in mice of intraperitoneally injected 211At microspheres, 90Y silicate colloid, and 32P chromic phosphate colloid were compared. The microspheres with 211At spread rapidly in the peritoneal cavity and remained mainly on the intraperitoneal surfaces. Intraperitoneal injection of 90Y colloid resulted in high levels in intraperitoneal fat and the diaphragm, but 1 day after injection 8.5% of the injected dose per gram was found in blood and after 6 days 2.5% was observed in bone. The highest accumulation of 32P was found in liver and spleen. The injection of additional nonradioactive chromic phosphate colloid resulted in an even higher accumulation of 32P in spleen and liver. The same phenomenon was not observed with 211At microspheres. It is suggested that it is not only the particle size which is important in the distribution of intraperitoneally injected colloid, but the amount of colloid, the type of colloid, the addition or presence of other substances such as ascites, and the animal species might also influence the distribution. In conclusion, the intraperitoneal distribution of 211At-labeled microspheres in mice was favorable compared with 90Y and 32P colloid. These data must be viewed cautiously since the distribution might be different in other animal species or humans.

  5. Carcinoid crisis induced by receptor radionuclide therapy with 90Y-DOTATOC in a case of liver metastases from bronchial neuroendocrine tumor (atypical carcinoid).

    PubMed

    Davì, M V; Bodei, L; Francia, G; Bartolomei, M; Oliani, C; Scilanga, L; Reghellin, D; Falconi, M; Paganelli, G; Lo Cascio, V; Ferdeghini, M

    2006-06-01

    SS receptors are overexpressed in many tumors, mainly of neuroendocrine origin, thus enabling the treatment with SS analogs. The clinical experience of receptor radionuclide therapy with the new analog [90Y-DOTA0-Tyr3 ]-octreotide [90Y-DOTATOC] has been developed over the last decade and is gaining a pivotal role in the therapeutic workout of these tumors. It is well known that some procedures performed in diagnostic and therapeutic management of endocrine tumors, such as agobiopsy and hepatic chemoembolization, can be associated with the occurrence of symptoms related to the release of vasoactive amines and/or hormonal peptides from tumor cell lysis. This is the first report of a severe carcinoid crisis developed after receptor radionuclide therapy with 90Y-DOTATOC administered in a patient affected by liver metastases from bronchial neuroendocrine tumor (atypical carcinoid). Despite protection with H1 receptor antagonists, octreotide and corticosteroids, few days after the therapy the patient complained of persistent flushing of the face and upper trunk, severe labial and periocular oedema, diarrhoea and loss of appetite. These symptoms increased and required new hospitalisation. The patient received iv infusion of octreotide associated with H1 and H2 receptor antagonists and corticosteroid therapy, which induced symptom remission within few days. The case here reported confirms that radionuclide therapy is highly effective in determining early rupture of metastatic tissue and also suggests that pre-medication should be implemented before the radiopeptide administration associated with a close monitoring of the patient in the following days.

  6. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-12-01

    hydrochloride; Sertindole, Sivelestat sodium hydrate, Sorafenib, Sumatriptan succinate/naproxen sodium, Sunitinib malate; Tafluprost, Telithromycin, Temsirolimus, Tenofovir disoproxil fumavate, Tenofovir disoproxil fumarate/emtricitabine, Teriparatide, Ticagrelor, Tigecycline, Tipranavir, Tirapazamine, Trimetrexate; Ulipristal acetate; Valganciclovir hydrochloride, Vicriviroc, Vorinostat; Yttrium 90 (90Y) ibritumomab tiuxetan. PMID:21225012

  7. Evaluation of Beta-Absorbed Fractions in a Mouse Model for 90Y, 188Re, 166Ho, 149Pm, 64Cu, and 177Lu Radionuclides

    SciTech Connect

    Miller, William H.; Hartmann-Siantar, Christine; Fisher, Darrell R.; Descalle, Marie-Anne; Daly, Tom; Lehmann, Joerg; Lewis, Michael R.; Hoffman, Timothy J.; Smith, Jeff; Situ, Peter D.; Volkert, Wynn A.

    2005-08-01

    Several short-lived, high-energy beta emitters are being proposed as the radionuclide components for molecular-targeted potential cancer therapeutic agents. The laboratory mice used to determine the efficacy of these new agents have organs that are relatively small compared to the ranges of these high-energy particles. The dosimetry model developed by Hui et al. was extended to provide realistic beta-dose estimates for organs in mice that received therapeutic radiopharmaceuticals containing 90Y, 188Re, 166Ho, 149Pm, 64Cu, and 177 Lu. Major organs in this model included the liver, spleen, kidneys, lungs, heart, stomach, small and large bowel, thyroid, pancreas, bone, marrow, carcass, and a 0.025-g tumor. The study as reported in this paper verifies their results for 90Y and extends them by using their organ geometry factors combined with newly calculated organ self-absorbed fractions from PEREGRINE and MCNP. PEREGRINE and MCNP agree to within 8% for the worst-case organ with average differences (averaged over all organs) decreasing from 5% for 90Y to 1% for 177Lu. When used with typical biodistribution data, the three different models predict doses that are in agreement to within 5% for the worst-case organ. The beta-absorbed fractions and cross-organ-deposited energy provided in this paper can be used by researchers to predict mouse-organ doses and should contribute to an improved understanding of the relationship between dose and radiation toxicity in mouse models where use of these isotopes is favorable.

  8. Evaluation of beta-absorbed fractions in a mouse model for 90Y, 188Re, 166Ho, 149Pm, 64Cu, and 177Lu radionuclides.

    PubMed

    Miller, William H; Hartmann-Siantar, Christine; Fisher, Darrell; Descalle, Marie-Anne; Daly, Tom; Lehmann, Joerg; Lewis, Michael R; Hoffman, Timothy; Smith, Jeff; Situ, Peter D; Volkert, Wynn A

    2005-08-01

    Several short-lived, high-energy beta emitters are being proposed as the radionuclide components for molecular- targeted potential cancer therapeutic agents. The laboratory mice used to determine the efficacy of these new agents have organs that are relatively small compared to the ranges of these high-energy particles. The dosimetry model developed by Hui et al. was extended to provide realistic beta-dose estimates for organs in mice that received therapeutic radiopharmaceuticals containing (90)Y, (188)Re, (166)Ho, (149)Pm, (64)Cu, and (177)Lu. Major organs in this model included the liver, spleen, kidneys, lungs, heart, stomach, small and large bowel, thyroid, pancreas, bone, marrow, carcass, and a 0.025-g tumor. The study as reported in this paper verifies their results for (90)Y and extends them by using their organ geometry factors combined with newly calculated organ self-absorbed fractions from PEREGRINE and MCNP. PEREGRINE and MCNP agree to within 8% for the worst-case organ with average differences (averaged over all organs) decreasing from 5% for (90)Y to 1% for (177)Lu. When used with typical biodistribution data, the three different models predict doses that are in agreement to within 5% for the worst-case organ. The beta-absorbed fractions and cross-organ-deposited energy provided in this paper can be used by researchers to predict mouse-organ doses and should contribute to an improved understanding of the relationship between dose and radiation toxicity in mouse models where use of these isotopes is favorable.

  9. Growth hormone-secreting macroadenoma of the pituitary gland successfully treated with the radiolabeled somatostatin analog (90)Y-DOTATATE: case report.

    PubMed

    Waligórska-Stachura, Joanna; Gut, Paweł; Sawicka-Gutaj, Nadia; Liebert, Włodzimierz; Gryczyńska, Maria; Baszko-Błaszyk, Daria; Blanco-Gangoo, Al Ricardo; Ruchała, Marek

    2016-08-01

    Pituitary tumors causing acromegaly are usually macroadenomas at the time of diagnosis, and they can grow aggressively, infiltrating surrounding tissues. Difficulty in achieving complete tumor removal at surgery can lead toward a strong tendency for recurrence, making it necessary to consider a means of treatment other than those currently used such as somatostatin analogs (SSAs), growth hormone (GH) receptor antagonist, surgical removal, and radiotherapy. The purpose of this paper is to describe a patient diagnosed with an aggressive, giant GH-secreting tumor refractory to medical therapy but ultimately treated with the radiolabeled somatostatin analog (90)Y-DOTATATE. A 26-year-old male with an invasive macroadenoma of the pituitary gland (5.6 × 2.5 × 3.6 cm) and biochemically confirmed acromegaly underwent 2 partial tumor resections: the first used the transsphenoidal approach and the second used the transcranial method. The patient received SSAs pre- and postoperatively. Because of the progression in pituitary tumor size, he underwent classic irradiation of the tumor (50 Gy). One and a half years later, the patient presented with clinically and biochemically active disease, and the tumor size was still 52 mm in diameter (height). Two neurosurgeons disqualified him from further surgical procedures. After confirming the presence of somatostatin receptors in the pituitary tumor by using (68)Ga-DOTATATE PET/CT, we treated the patient 4 times with an SSA bound with (90)Y-DOTATATE. After this treatment, the patient attained partial biochemical remission and a reduction in the tumor mass for the first time. Treatment with an SSA bound with (90)Y-DOTATATE may be a promising option for some aggressive GH-secreting pituitary adenomas when other methods have failed. PMID:26636388

  10. Pyclen Tri-n-butylphosphonate Ester as Potential Chelator for Targeted Radiotherapy: From Yttrium(III) Complexation to (90)Y Radiolabeling.

    PubMed

    Le Fur, Mariane; Beyler, Maryline; Lepareur, Nicolas; Fougère, Olivier; Platas-Iglesias, Carlos; Rousseaux, Olivier; Tripier, Raphaël

    2016-08-15

    The Y(3+) complex of PCTMB, the tri-n-butyl phosphonate ester of pyclen (3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene), was synthesized as well as its Ho(3+) and Lu(3+) analogues. X-ray diffraction analyses revealed isomorphous dimeric M2(PCTMB)2·9H2O (M = Y, Ho, Lu) structures that crystallize in the centrosymmetric P1̅ triclinic space group. (1)H NMR and UV studies in aqueous solutions indicated that Y(3+) complexation is fast, being quantitative in 167 min at pH 3.8 and in 13 min at pH 5.5 (25 °C, acetate buffer, I = 0.150 M, [Y(3+)] = [PCTMB] = 0.2 mM). (1)H NMR DOSY and photon correlation spectroscopy experiments evidenced the formation of aggregates in chloroform with a bimodal distribution that changes slightly with concentration (11-24 and 240-258 nm). The behavior of the acid-assisted dissociation of the complex of Y(3+) with PCTMB was studied under pseudo-first-order conditions, and the half-life of the [Y(PCTMB)] complex in 0.5 M HCl at 25 °C was found to be 37 min, a value that decreases to 2.6 min in 5 M HCl. The Y(3+) complex of PCTMB is thermodynamically very stable, with a stability constant of log KY-PCTMB = 19.49 and pY = 16.7 measured by potentiometry. (90)Y complexation studies revealed fast radiolabeling kinetics; optimal radiolabeling conditions were obtained for (90)Y in acetate medium, PCTMB at 10(-4) to 10(-2) M in acetate buffer pH = 4.75, 15 min at 45-60 °C. In vitro stability studies in human serum showed that [(90)Y(PCTMB)] is quite stable, with about 90% of the activity still in the form of the radiotracer at 24 h and 80% from 48 h to 72 h. A comparison with other ligands such as PCTA, DOTA, and DTPA already used for in vivo application shows that [(90)Y(PCTMB)] is an interesting lipophilic and neutral analogue of these reference chelates for therapeutic applications in aqueous and nonaqueous media.

  11. Pyclen Tri-n-butylphosphonate Ester as Potential Chelator for Targeted Radiotherapy: From Yttrium(III) Complexation to (90)Y Radiolabeling.

    PubMed

    Le Fur, Mariane; Beyler, Maryline; Lepareur, Nicolas; Fougère, Olivier; Platas-Iglesias, Carlos; Rousseaux, Olivier; Tripier, Raphaël

    2016-08-15

    The Y(3+) complex of PCTMB, the tri-n-butyl phosphonate ester of pyclen (3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene), was synthesized as well as its Ho(3+) and Lu(3+) analogues. X-ray diffraction analyses revealed isomorphous dimeric M2(PCTMB)2·9H2O (M = Y, Ho, Lu) structures that crystallize in the centrosymmetric P1̅ triclinic space group. (1)H NMR and UV studies in aqueous solutions indicated that Y(3+) complexation is fast, being quantitative in 167 min at pH 3.8 and in 13 min at pH 5.5 (25 °C, acetate buffer, I = 0.150 M, [Y(3+)] = [PCTMB] = 0.2 mM). (1)H NMR DOSY and photon correlation spectroscopy experiments evidenced the formation of aggregates in chloroform with a bimodal distribution that changes slightly with concentration (11-24 and 240-258 nm). The behavior of the acid-assisted dissociation of the complex of Y(3+) with PCTMB was studied under pseudo-first-order conditions, and the half-life of the [Y(PCTMB)] complex in 0.5 M HCl at 25 °C was found to be 37 min, a value that decreases to 2.6 min in 5 M HCl. The Y(3+) complex of PCTMB is thermodynamically very stable, with a stability constant of log KY-PCTMB = 19.49 and pY = 16.7 measured by potentiometry. (90)Y complexation studies revealed fast radiolabeling kinetics; optimal radiolabeling conditions were obtained for (90)Y in acetate medium, PCTMB at 10(-4) to 10(-2) M in acetate buffer pH = 4.75, 15 min at 45-60 °C. In vitro stability studies in human serum showed that [(90)Y(PCTMB)] is quite stable, with about 90% of the activity still in the form of the radiotracer at 24 h and 80% from 48 h to 72 h. A comparison with other ligands such as PCTA, DOTA, and DTPA already used for in vivo application shows that [(90)Y(PCTMB)] is an interesting lipophilic and neutral analogue of these reference chelates for therapeutic applications in aqueous and nonaqueous media. PMID:27486673

  12. Treatment Parameters and Outcome in 680 Treatments of Internal Radiation With Resin {sup 90}Y-Microspheres for Unresectable Hepatic Tumors

    SciTech Connect

    Kennedy, Andrew S. McNeillie, Patrick M.S.; Dezarn, William A.; Nutting, Charles; Sangro, Bruno; Wertman, Dan; Garafalo, Michael; Liu, David; Coldwell, Douglas; Savin, Michael; Jakobs, Tobias; Rose, Steven; Warner, Richard; Carter, Dennis; Sapareto, Stephen; Nag, Subir; Gulec, Seza; Calkins, Allison; Gates, Vanessa L.; Salem, Riad

    2009-08-01

    Purpose: Radioembolization (RE) using {sup 90}Y-microspheres is an effective and safe treatment for patients with unresectable liver malignancies. Radiation-induced liver disease (RILD) is rare after RE; however, greater understanding of radiation-related factors leading to serious liver toxicity is needed. Methods and Materials: Retrospective review of radiation parameters was performed. All data pertaining to demographics, tumor, radiation, and outcomes were analyzed for significance and dependencies to develop a predictive model for RILD. Toxicity was scored using the National Cancer Institute Common Toxicity Criteria Adverse Events Version 3.0 scale. Results: A total of 515 patients (287 men; 228 women) from 14 US and 2 EU centers underwent 680 separate RE treatments with resin {sup 90}Y-microspheres in 2003-2006. Multifactorial analyses identified factors related to toxicity, including activity (GBq) Selective Internal Radiation Therapy delivered (p < 0.0001), prescribed (GBq) activity (p < 0.0001), percentage of empiric activity (GBq) delivered (p < 0.0001), number of prior liver treatments (p < 0.0008), and medical center (p < 0.0001). The RILD was diagnosed in 28 of 680 treatments (4%), with 21 of 28 cases (75%) from one center, which used the empiric method. Conclusions: There was an association between the empiric method, percentage of calculated activity delivered to the patient, and the most severe toxicity, RILD. A predictive model for RILD is not yet possible given the large variance in these data.

  13. (Depth-dose curves of the beta reference fields (147)Pm, (85)Kr and (90)Sr/(90)Y produced by the beta secondary standard BSS2.

    PubMed

    Brunzendorf, Jens

    2012-08-01

    The most common reference fields in beta dosimetry are the ISO 6980 series 1 radiation fields produced by the beta secondary standard BSS2 and its predecessor BSS. These reference fields require sealed beta radiation sources ((147)Pm, (85)Kr or (90)Sr/(90)Y) in combination with a source-specific beam-flattening filter, and are defined only at a given distance from the source. Every radiation sources shipped with the BSS2 is sold with a calibration certificate of the Physikalisch-Technische Bundesanstalt. The calibration workflow also comprises regular depth-dose measurements. This work publishes complete depth-dose curves of the series 1 sources (147)Pm, (85)Kr and (90)Sr/(90)Y in ICRU tissue up to a depth of 11 mm,when all electrons are stopped. For this purpose, the individual depth-dose curves of all BSS2 sources calibrated so far have been determined, i.e. the complete datasets of all BSS2 beta sources have been re-evaluated. It includes 191 depth-dose curves of 116 different sources comprising more than 2200 data points in total. Appropriate analytical representations of the nuclide-specific depth-dose curves are provided for the first time.

  14. Human dose assessment for the radionuclides {sup 90}Sr and {sup 90}Y at TA-35 SWMU 35-003 (r) and Ten Site Canyon

    SciTech Connect

    Jarmer, D.; Lyman, J.

    1997-07-01

    This report gives an estimate of the radiological dose to an individual living on or working at a site contaminated with strontium-90 ({sup 90}Sr) and yttrium-90 ({sup 90}Y). The site consists of a small receiving canyon that drains into Ten-Site Canyon at the eastern end of Los Alamos National Laboratory`s technical area 35 (TA-35). Between 1951 and 1963 a wastewater treatment facility located at TA-35 discharged water containing {sup 90}Sr and {sup 90}Y to this receiving canyon. The authors used the RESRAD computer code to calculate the dose to an on-site individual, based on two exposure scenarios: (1) a person working at the site for eight hours a day, five days a week, for twenty-five years and (2) a farmer living at the site twenty four hours a day, seven days a week, for thirty years. The exposure pathways considered were direct exposure to external radiation; inhalation of contaminated dusts; and ingestion of plants, water, and soil. The authors found that the maximum estimated dose rates were 1 and 21 mrem y{sup {minus}1} for the worker and farmer scenarios respectively. The authors have concluded that the value for the worker scenario is well below the DOE dose limit of 100 mrem y{sup {minus}1} but the farmer is overexposed.

  15. Yield constants of external Bremsstrahlung excited by 90Sr- 90Y, 147Pm and 204Tl in CdO and lead compounds

    NASA Astrophysics Data System (ADS)

    Manjunatha, H. C.; Rudraswamy, B.

    2011-03-01

    Bremsstrahlung yield of 90Sr- 90Y, 147Pm and 204Tl in CdO, PbF 2, Pb(NO 3) 2 and PbCl 2 has been measured using 3.8 cm×3.8 cm NaI(Tl) crystal and is compared with Tseng and Pratt theory. The Z dependence of external Bremsstrahlung (EB) is also measured and compared with the theory. The Bremsstrahlung photon yield and energy yield constants ( K' and K) are evaluated from the measured and theoretical yields. These values decrease with the increase in Emax of beta. The evaluated K' and K may be useful to calculate the photon yield and the energy yield, when these beta particles interact with the compounds of modified atomic number ranging from 42 to 73.

  16. In vivo Localization of 90Y- and 177Lu-Radioimmunoconjugates Using Cerenkov Luminescence Imaging in a Disseminated Murine Leukemia Model

    PubMed Central

    Balkin, Ethan R.; Kenoyer, Aimee; Orozco, Johnnie J.; Hernandez, Alexandra; Shadman, Mazyar; Fisher, Darrell R.; Green, Damian J.; Hylarides, Mark D.; Press, Oliver W.; Wilbur, D. Scott; Pagel, John M.

    2014-01-01

    Cerenkov radiation generated by positron-emitting radionuclides can be exploited for a molecular imaging technique known as Cerenkov Luminescence Imaging (CLI). Data have been limited, however, on the use of medium-to-high energy β-emitting radionuclides of interest for cancer imaging and treatment. We assessed the use of CLI as an adjunct to determine localization of radioimmunoconjugates to hematolymphoid tissues. Radiolabeled 177Lu- or 90Y-anti-CD45 antibody (Ab; DOTA-30F11) was administered by tail vein injection to athymic mice bearing disseminated murine myeloid leukemia with CLI images acquired at times afterward. Gamma counting of individual organs showed preferential uptake in CD45+ tissues with significant retention of radiolabeled Ab in sites of leukemia (spleen and bone marrow). This result was confirmed in CLI images with 1.35 × 105 ± 2.2 × 104 p/sec/cm2/sr and 3.45 × 103 ± 7.0 × 102 p/sec/cm2/sr for 90Y-DOTA-30F11 and 177Lu-DOTA-30F11, respectively, compared to undetectable signal for both radionuclides using the non-binding control Ab. Results showed that CLI allows for in vivo visualization of localized β-emissions. Pixel intensity variability resulted from differences in absorbed doses of the associated energies of the β-emitting radionuclide. Overall, our findings offer a preclinical proof of concept for the use of CLI techniques in tandem with currently available clinical diagnostic tools. PMID:25261237

  17. PET/CT-Based Dosimetry in 90Y-Microsphere Selective Internal Radiation Therapy: Single Cohort Comparison With Pretreatment Planning on 99mTc-MAA Imaging and Correlation With Treatment Efficacy

    PubMed Central

    Song, Yoo Sung; Paeng, Jin Chul; Kim, Hyo-Cheol; Chung, Jin Wook; Cheon, Gi Jeong; Chung, June-Key; Lee, Dong Soo; Kang, Keon Wook

    2015-01-01

    Abstract 90Y PET/CT can be acquired after 90Y-microsphere selective radiation internal therapy (SIRT) to describe radioactivity distribution. We performed dosimetry using 90Y-microsphere PET/CT data to evaluate treatment efficacy and appropriateness of activity planning from 99mTc-MAA scan and SPECT/CT. Twenty-three patients with liver malignancy were included in the study. 99mTc-MAA was injected during planning angiography and whole body 99mTc-MAA scan and liver SPECT/CT were acquired. After SIRT using 90Y-resin microsphere, 90Y-microsphere PET/CT was acquired. A partition model (PM) using 4 compartments (tumor, intarget normal liver, out-target normal liver, and lung) was adopted, and absorbed dose to each compartment was calculated based on measurements from 99mTc-MAA SPECT/CT and 90Y-microsphere PET/CT, respectively, to be compared with each other. Progression-free survival (PFS) was evaluated in terms of tumor absorbed doses calculated by 99mTc-MAA SPECT/CT and 90Y-microsphere PET/CT results. Lung shunt fraction was overestimated on 99mTc-MAA scan compared with 90Y-microsphere PET/CT (0.060 ± 0.037 vs. 0.018 ± 0.026, P < 0.01). Tumor absorbed dose exhibited a close correlation between the results from 99mTc-MAA SPECT/CT and 90Y-microsphere PET/CT (r = 0.64, P < 0.01), although the result from 99mTc-MAA SPECT/CT was significantly lower than that from 90Y-microsphere PET/CT (135.4 ± 64.2 Gy vs. 185.0 ± 87.8 Gy, P < 0.01). Absorbed dose to in-target normal liver was overestimated on 99mTc-MAA SPECT/CT compared with PET/CT (62.6 ± 38.2 Gy vs. 45.2 ± 32.0 Gy, P = 0.02). Absorbed dose to out-target normal liver did not differ between 99mTc-MAA SPECT/CT and 90Y-microsphere PET/CT (P = 0.49). Patients with tumor absorbed dose >200 Gy on 90Y-microsphere PET/CT had longer PFS than those with tumor absorbed dose ≤200 Gy (286 ± 56 days vs. 92 ± 20 days, P = 0.046). Tumor absorbed dose calculated by 99m

  18. 3D inpatient dose reconstruction from the PET-CT imaging of {sup 90}Y microspheres for metastatic cancer to the liver: Feasibility study

    SciTech Connect

    Fourkal, E.; Veltchev, I.; Lin, M.; Meyer, J.; Koren, S.; Doss, M.; Yu, J. Q.

    2013-08-15

    Purpose: The introduction of radioembolization with microspheres represents a significant step forward in the treatment of patients with metastatic disease to the liver. This technique uses semiempirical formulae based on body surface area or liver and target volumes to calculate the required total activity for a given patient. However, this treatment modality lacks extremely important information, which is the three-dimensional (3D) dose delivered by microspheres to different organs after their administration. The absence of this information dramatically limits the clinical efficacy of this modality, specifically the predictive power of the treatment. Therefore, the aim of this study is to develop a 3D dose calculation technique that is based on the PET imaging of the infused microspheres.Methods: The Fluka Monte Carlo code was used to calculate the voxel dose kernel for {sup 90}Y source with voxel size equal to that of the PET scan. The measured PET activity distribution was converted to total activity distribution for the subsequent convolution with the voxel dose kernel to obtain the 3D dose distribution. In addition, dose-volume histograms were generated to analyze the dose to the tumor and critical structures.Results: The 3D inpatient dose distribution can be reconstructed from the PET data of a patient scanned after the infusion of microspheres. A total of seven patients have been analyzed so far using the proposed reconstruction method. Four patients underwent treatment with SIR-Spheres for liver metastases from colorectal cancer and three patients were treated with Therasphere for hepatocellular cancer. A total of 14 target tumors were contoured on post-treatment PET-CT scans for dosimetric evaluation. Mean prescription activity was 1.7 GBq (range: 0.58–3.8 GBq). The resulting mean maximum measured dose to targets was 167 Gy (range: 71–311 Gy). Mean minimum dose to 70% of target (D70) was 68 Gy (range: 25–155 Gy). Mean minimum dose to 90% of target

  19. Antibody mass escalation study in patients with castration resistant prostate cancer using 111I-J591: Lesion detectability and dosimetric projections for 90Y radioimmunotherapy

    PubMed Central

    Pandit-Taskar, Neeta; O’Donoghue, Joseph A.; Morris, Michael J; Wills, Eze A.; Schwartz, Lawrence H.; Gonen, Mithat; Scher, Howard I.; Larson, Steven M.; Divgi, Chaitanya R.

    2009-01-01

    Background J591, a monoclonal antibody that targets the external domain of the prostate specific membrane antigen (PSMA), has potential as an agent for radioimmunotherapy. A pilot trial was carried out in patients with prostate cancer using repetitive administrations of escalating masses of J591. An analysis was carried out to assess (1) lesion detectability by 111InJ591 gamma camera imaging compared to standard imaging methods and (2) the effect of increasing antibody mass on lesion detectability, biodistribution and dosimetry. Methods Fourteen patients with metastatic prostate cancer received escalating amounts (10, 25, 50 and 100 mg) of J591 in a series of administrations each separated by 3 weeks. All antibody administrations included a fixed amount of radiolabeled antibody 111In-DOTA-J591 (2mg of J591 labeled with 185MBq (5 mCi) of 111In via the chelating agent DOTA). Three whole body gamma camera scans with at least one SPECT scan together with multiple whole body count-rate measurements and serum activity concentration measurements were obtained in all patients. Images were analyzed for distribution and lesion targeting. Estimates of clearance rates and liver and lesion uptake were made for each treatment cycle. These estimates were used to generate dosimetric projections for radioimmunotherapy with 90Y-labeled J591. Results A total of 80 lesions in 14 patients were detected. Both skeletal and soft tissue disease was targeted by the antibody as seen on 111In-J591 scans. Antibody localized to 93.7% of skeletal lesions detected by conventional imaging. Clearance of radioactivity from whole body, serum and liver was dependent on antibody mass. Normalized average values of the ratio of residence times between lesion and liver for 10, 25, 50 and 100mg of antibody were 1.0, 1.9, 3.2 and 4.0 respectively. Dosimetric projections for radioimmunotherapy with 90Y-labeled J591 suggested similar absorbed doses to lesions, for treatment at the maximally tolerated activity

  20. Monte Carlo Calculation of Radioimmunotherapy with 90Y-, 177Lu-, 131I-, 124I-, and 188Re-Nanoobjects: Choice of the Best Radionuclide for Solid Tumour Treatment by Using TCP and NTCP Concepts

    PubMed Central

    Lucas, S.; Feron, O.; Gallez, B.; Masereel, B.; Michiels, C.; Vander Borght, T.

    2015-01-01

    Radioimmunotherapy has shown that the use of monoclonal antibodies combined with a radioisotope like 131I or 90Y still remains ineffective for solid and radioresistant tumour treatment. Previous simulations have revealed that an increase in the number of 90Y labelled to each antibody or nanoobject could be a solution to improve treatment output. It now seems important to assess the treatment output and toxicity when radionuclides such as 90Y, 177Lu, 131I, 124I, and 188Re are used. Tumour control probability (TCP) and normal tissue complication probability (NTCP) curves versus the number of radionuclides per nanoobject were computed with MCNPX to evaluate treatment efficacy for solid tumours and to predict the incidence of surrounding side effects. Analyses were carried out for two solid tumour sizes of 0.5 and 1.0 cm radius and for nanoobject (i.e., a radiolabelled antibody) distributed uniformly or nonuniformly throughout a solid tumour (e.g., Non-small-cell-lung cancer (NSCLC)). 90Y and 188Re are the best candidates for solid tumour treatment when only one radionuclide is coupled to one carrier. Furthermore, regardless of the radionuclide properties, high values of TCP can be reached without toxicity if the number of radionuclides per nanoobject increases. PMID:26136812

  1. Monte Carlo Calculation of Radioimmunotherapy with (90)Y-, (177)Lu-, (131)I-, (124)I-, and (188)Re-Nanoobjects: Choice of the Best Radionuclide for Solid Tumour Treatment by Using TCP and NTCP Concepts.

    PubMed

    Lucas, S; Feron, O; Gallez, B; Masereel, B; Michiels, C; Vander Borght, T

    2015-01-01

    Radioimmunotherapy has shown that the use of monoclonal antibodies combined with a radioisotope like (131)I or (90)Y still remains ineffective for solid and radioresistant tumour treatment. Previous simulations have revealed that an increase in the number of (90)Y labelled to each antibody or nanoobject could be a solution to improve treatment output. It now seems important to assess the treatment output and toxicity when radionuclides such as (90)Y, (177)Lu, (131)I, (124)I, and (188)Re are used. Tumour control probability (TCP) and normal tissue complication probability (NTCP) curves versus the number of radionuclides per nanoobject were computed with MCNPX to evaluate treatment efficacy for solid tumours and to predict the incidence of surrounding side effects. Analyses were carried out for two solid tumour sizes of 0.5 and 1.0 cm radius and for nanoobject (i.e., a radiolabelled antibody) distributed uniformly or nonuniformly throughout a solid tumour (e.g., Non-small-cell-lung cancer (NSCLC)). (90)Y and (188)Re are the best candidates for solid tumour treatment when only one radionuclide is coupled to one carrier. Furthermore, regardless of the radionuclide properties, high values of TCP can be reached without toxicity if the number of radionuclides per nanoobject increases. PMID:26136812

  2. Monte Carlo Calculation of Radioimmunotherapy with (90)Y-, (177)Lu-, (131)I-, (124)I-, and (188)Re-Nanoobjects: Choice of the Best Radionuclide for Solid Tumour Treatment by Using TCP and NTCP Concepts.

    PubMed

    Lucas, S; Feron, O; Gallez, B; Masereel, B; Michiels, C; Vander Borght, T

    2015-01-01

    Radioimmunotherapy has shown that the use of monoclonal antibodies combined with a radioisotope like (131)I or (90)Y still remains ineffective for solid and radioresistant tumour treatment. Previous simulations have revealed that an increase in the number of (90)Y labelled to each antibody or nanoobject could be a solution to improve treatment output. It now seems important to assess the treatment output and toxicity when radionuclides such as (90)Y, (177)Lu, (131)I, (124)I, and (188)Re are used. Tumour control probability (TCP) and normal tissue complication probability (NTCP) curves versus the number of radionuclides per nanoobject were computed with MCNPX to evaluate treatment efficacy for solid tumours and to predict the incidence of surrounding side effects. Analyses were carried out for two solid tumour sizes of 0.5 and 1.0 cm radius and for nanoobject (i.e., a radiolabelled antibody) distributed uniformly or nonuniformly throughout a solid tumour (e.g., Non-small-cell-lung cancer (NSCLC)). (90)Y and (188)Re are the best candidates for solid tumour treatment when only one radionuclide is coupled to one carrier. Furthermore, regardless of the radionuclide properties, high values of TCP can be reached without toxicity if the number of radionuclides per nanoobject increases.

  3. Influence of cations on the complexation yield of DOTATATE with yttrium and lutetium: a perspective study for enhancing the 90Y and 177Lu labeling conditions.

    PubMed

    Asti, Mattia; Tegoni, Matteo; Farioli, Daniela; Iori, Michele; Guidotti, Claudio; Cutler, Cathy S; Mayer, Pat; Versari, Annibale; Salvo, Diana

    2012-05-01

    The DOTA macrocyclic ligand can form stable complexes with many cations besides yttrium and lutetium. For this reason, the presence of competing cationic metals in yttrium-90 and lutetium-177 chloride solutions can dramatically influence the radiolabeling yield. The aim of this study was to evaluate the coordination yield of yttrium- and lutetium-DOTATATE complexes when the reaction is performed in the presence of varying amounts of competing cationic impurities. In the first set of experiments, the preparation of the samples was performed by using natural yttrium and lutetium (20.4 nmol). The molar ratio between DOTATATE and these metals was 1 to 1. Metal competitors (Pb(2+), Zn(2+), Cu(2+), Fe(3+), Al(3+), Ni(2+), Co(2+), Cr(3+)) were added separately to obtain samples with varying molar ratio with respect to yttrium or lutetium (0.1, 0.5, 1, 2 and 10). The final solutions were analyzed through ultra high-performance liquid chromatography with an UV detector. In the second set of experiments, an amount of (90)Y or (177)Lu chloride (6 MBq corresponding to 3.3 and 45 pmol, respectively) was added to the samples, and a radio-thin layer chromatography analysis was carried out. The coordination of Y(3+) and Lu(3+) was dramatically influenced by low levels of Zn(2+), Cu(2+) and Co(2+). Pb(2+) and Ni(2+) were also shown to be strong competitors at higher concentrations. Fe(3+) was expected to be a strong competitor, but the effect on the incorporation was only partly dependent on its concentration. Al(3+) and Cr(3+) did not compete with Y(3+) and Lu(3+) in the formation of DOTATATE complexes.

  4. Investigation of a {sup 90}Sr/{sup 90}Y source for intra-ocular treatment of wet age-related macular degeneration

    SciTech Connect

    Holmes, Shannon M.; Micka, John A.; DeWerd, Larry A.

    2009-10-15

    Purpose: The purpose of this study is to perform an extensive investigation of an approximately 2.5 mm long {sup 90}Sr/{sup 90}Y source designed for treating wet age-related macular degeneration. Methods: As part of this investigation, a NIST-traceable absorbed dose to water calibration technique was established, and a source deployment verification test was developed. The influence of treatment cannula construction tolerance on the measurements as well as the dose delivered to the patient was investigated using the Monte Carlo code MCNP5. Variation between production cannulae was quantified experimentally using a well-type ionization chamber, and additional measurements along with Monte Carlo calculations of the collimating insert used for source deployment verification were performed to validate the model. Results: Maximum variation in the integrated target dose was seen when the source was shifted laterally within the treatment cannula. For the well chamber measurements, the observed standard deviation in ionization current for a single source placed in different reference cannulae was {+-}0.3%, with a maximum observed range of less than {+-}0.5%. Clinical cannulae in the collimating insert showed an average of 17.8%{+-}0.4% of the reference signal when sources were fully deployed compared to 18.5% predicted by Monte Carlo calculations. This discrepancy has been attributed primarily to construction of the collimator since the collimation gap was observed to be approximately 0.025-0.075 mm smaller than specified. Construction tolerance of the well chamber insert as well as position tolerance of the cannula tip were both investigated, and their influence on the predicted signal was quantified. Additional measurements along with Monte Carlo based calculations of the collimating insert with polyethylene spacers added to the setup were performed to validate the Monte Carlo model. The shimmed Monte Carlo and measured data agree to within 1%, which is a magnitude

  5. Tumour control probability derived from dose distribution in homogeneous and heterogeneous models: assuming similar pharmacokinetics, 125Sn-177Lu is superior to 90Y-177Lu in peptide receptor radiotherapy

    NASA Astrophysics Data System (ADS)

    Walrand, Stephan; Hanin, François-Xavier; Pauwels, Stanislas; Jamar, François

    2012-07-01

    Clinical trials on 177Lu-90Y therapy used empirical activity ratios. Radionuclides (RN) with larger beta maximal range could favourably replace 90Y. Our aim is to provide RN dose-deposition kernels and to compare the tumour control probability (TCP) of RN combinations. Dose kernels were derived by integration of the mono-energetic beta-ray dose distributions (computed using Monte Carlo) weighted by their respective beta spectrum. Nine homogeneous spherical tumours (1-25 mm in diameter) and four spherical tumours including a lattice of cold, but alive, spheres (1, 3, 5, 7 mm in diameter) were modelled. The TCP for 93Y, 90Y and 125Sn in combination with 177Lu in variable proportions (that kept constant the renal cortex biological effective dose) were derived by 3D dose kernel convolution. For a mean tumour-absorbed dose of 180 Gy, 2 mm homogeneous tumours and tumours including 3 mm diameter cold alive spheres were both well controlled (TCP > 0.9) using a 75-25% combination of 177Lu and 90Y activity. However, 125Sn-177Lu achieved a significantly better result by controlling 1 mm-homogeneous tumour simultaneously with tumours including 5 mm diameter cold alive spheres. Clinical trials using RN combinations should use RN proportions tuned to the patient dosimetry. 125Sn production and its coupling to somatostatin analogue appear feasible. Assuming similar pharmacokinetics 125Sn is the best RN for combination with 177Lu in peptide receptor radiotherapy justifying pharmacokinetics studies in rodent of 125Sn-labelled somatostatin analogues.

  6. Nuclear oncology, a fast growing field of nuclear medicine

    NASA Astrophysics Data System (ADS)

    Olivier, Pierre

    2004-07-01

    Nuclear Medicine in oncology has been for a long time synonymous with bone scintigraphy, the first ever whole body imaging modality, and with treatment of thyroid cancer with iodine-131. More recently, somatostatin receptor scintigraphy (SRS) using peptides such as 111In-labelled octreotide became a reference imaging method in the detection and staging of neuroendocrine tumors while 131I- and 123I-MIBG remain the tracers of reference for pheochromocytomas and neuroblastomas. Lymphoscintigraphic imaging based on peritumoral injection of 99mTc-labelled colloids supports, in combination with per operative detection, the procedure of sentinel node identification in breast cancers and melanomas. Positron Emission Tomography (PET) is currently experiencing a considerable growth in oncology based on the use of 18F-FDG (fluorodeoxyglucose), a very sensitive, although non-specific, tumor tracer. Development of instrumentation is crucial in this expansion of PET imaging with new crystals being more sensitive and hybrid imagers that permit to reduce the acquisition time and offer fused PET-CT images. Current developments in therapy can be classified into three categories. Radioimmunotherapy (RIT) based on monoclonal antibodies (or fragments) labelled with beta-emitters. This technique has recently made its entrance in clinical practice with a 90Y-labelled anti-CD20 antibody ( 90Y-ibritumomab tiuxetan (Zevalin ®)) approved in US for the treatment of some subtypes of non-Hodgkin's lymphoma. Radionuclide-bone pain palliation has experienced developments with 153Sm-EDTMP, 186Re-HEDP or 89Sr, efficient in patients with widespread disease. Last, the same peptides, as those used in SRS, are being developed for therapy, labelled with 90Y, 111In or 177Lu in patients who failed to respond to other treatments. Overall, nuclear oncology is currently a fast growing field thanks to the combined developments of radiopharmaceuticals and instrumentation.

  7. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-11-01

    disoproxil fumarate, Tenofovir disoproxil fumarate/emtricitabine, Tenofovir disoproxil fumarate/emtricitabine/efavirenz, Ticlopidine hydrochloride, Tigecycline, TST-10088, Tularemia vaccine, Valsartan/amlodipine besylate, Vandetanib, Vardenafil hydrochloride hydrate, Vincristine, Vorinostat, Yttrium 90 (90Y) ibritumomab tiuxetan. PMID:20094643

  8. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2006-04-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: ABT-510, adalimumab, alefacept, alemtuzumab, AMG-531, anakinra, armodafinil, asenapine maleate, atazanavir sulfate, atorvastatin; Bortezomib, bosentan; CEB-1555, cetuximab, ciclesonide, clodronate, CT-011; Darifenacin hydrobromide, desloratadine; E-7010, ecallantide, eculizumab, efalizumab, eltrombopag, erlotinib hydrochloride, eslicarbazepine acetate, eszopiclone, ezetimibe; Febuxostat, fosamprenavir calcium, fulvestrant; Gefitinib, genistein; Haemophilus influenzae B vaccine, human papillomavirus vaccine; Imatinib mesylate, insulin glargine; Lenalidomide, liposomal cisplatin; MAb G250, mapatumumab, midostaurin, MP4, mycophenolic acid sodium salt; Natalizumab, neridronic acid, NSC-330507; Oblimersen sodium, ofatumumab, omalizumab, oral insulin, oregovomab; Paliperidone, parathyroid hormone (human recombinant), peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pegylated arginine deiminase 20000, pemetrexed disodium, pimecrolimus, pitavastatin, pneumococcal 7-valent conjugate vaccine, prasterone, pregabalin, pumosetrag hydrochloride; Recombinant malaria vaccine, retigabine, rivaroxaban, Ro-26-9228, romidepsin, rosuvastatin calcium, rotavirus vaccine; SGN-30, sitaxsentan sodium, solifenacin succinate, sorafenib, sunitinib malate; Tadalafil, tegaserod maleate, temsirolimus, TER-199, tifacogin, tiludronic acid, tiotropium bromide; Vildagliptin, VNP-40101M, vorinostat; YM-150, yttrium 90 (90Y) ibritumomab tiuxetan; Zanolimumab, zoledronic acid monohydrate. PMID:16810345

  9. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2006-01-01

    , sirolimus-eluting stent, solifenacin succinate, sunitinib malate; Tadalafil, talampanel, tasidotin hydrochloride, Taxus, tegaserod maleate, telavancin hydrochloride, tenofovir disoproxil fumarate, tiotropium bromide, tocilizumab, tositumomab, treprostinil sodium, tridolgosir hydrochloride, TTS-CD3; Ularitide; Valdecoxib, Val-Tyr sardine peptidase, vardenafil hydrochloride hydrate, voriconazole; Yttrium (90Y) edotreotide, Yttrium 90 (90Y) ibritumomab tiuxetan; Zileuton, zucapsaicin. PMID:16894408

  10. Comparison of two different types of LiF:Mg,Cu,P thermoluminescent dosimeters for detection of beta rays (beta-TLDs) from 90Sr/90Y, 85Kr and 147Pm sources.

    PubMed

    Grassi, Elisa; Sghedoni, Roberto; Piccagli, Vando; Fioroni, Federica; Borasi, Giovanni; Iori, Mauro

    2011-05-01

    Targeted radionuclide therapies in nuclear medicine departments increasingly depend on using unsealed beta radiation sources in the labeling of peptides and antibodies. Monitoring doses received by the fingers and hands during these procedures is best accomplished with TLD dosimeters that can be located at the fingertips. The present study examines the response of two TLD dosimeters (MCP-Ns and GR200A) to 90Sr/90Y, 85Kr, and 147Pm. The dosimeters were supplied by two different services, and all irradiations were performed at the PTB Institute in Germany. Each dosimetry service evaluated the dosimeters without knowledge that they had been purposefully irradiated. The accuracy and precision of the dosimeters were evaluated as a function of delivered dose, energy of beta particles and angular incidence. The results are compared to performance measures recommended by the IEC. Both dosimeter types displayed significant energy dependence. Angular dependence was moderate. Accuracy and precision as a function of dose (linearity) differed between the two systems, with the MCP-Ns being noticeably better than the GR200A. The superior precision makes the MCP-Ns much more useful for extremity dose measurements. The differences between these two dosimeter systems reinforce the need to evaluate a dosimeter carefully before using it in the daily work routine.

  11. Radioimmunotherapy for non-Hodgkin's lymphoma: A review for radiation oncologists

    SciTech Connect

    Macklis, Roger M. . E-mail: macklir@ccf.org; Pohlman, Brad

    2006-11-01

    Purpose: The aim of this study was to review advances in radioimmunotherapy (RIT) for non-Hodgkin's lymphoma (NHL) and to discuss the role of Radiation oncologist in administering this important new form of biologically targeted radiotherapy. Methods and Materials: A review of articles and abstracts on the clinical efficacy, safety, and radiation safety of yttrium Y 90 ({sup 9}Y) ibritumomab tiuxetan (Zevalin) and iodine I 131 tositumomab (Bexxar) was performed. Results: The clinical efficacy of RIT in NHL has been shown in numerous clinical trials of {sup 9}Y ibritumomab tiuxetan and {sup 131}I tositumomab. Both agents have produced significant responses in patients with low-grade, follicular, or transformed NHL, including patients with disease that had not responded or had responded poorly to previous chemotherapy or immunotherapy. Reversible toxicities such as neutropenia, thrombocytopenia, and anemia are the most common adverse events with both agents. Conclusions: Radioimmunotherapy is safe and effective in many patients with B-cell NHL. {sup 9}Y ibritumomab tiuxetan and {sup 131}I tositumomab can produce clinically meaningful and durable responses even in patients in whom chemotherapy has failed. Treatment with RIT requires a multispecialty approach and close communication between Radiation oncologist and other members of the treatment team. Radiation oncologist plays an important role in treating patients with RIT and monitoring them for responses and adverse events after treatment.

  12. Evaluation of S-values and dose distributions for {sup 90}Y, {sup 131}I, {sup 166}Ho, and {sup 188}Re in seven lobes of the rat liver

    SciTech Connect

    Xie Tianwu; Liu Qian; Zaidi, Habib

    2012-03-15

    Purpose: Rats have been widely used in radionuclide therapy research for the treatment of hepatocellular carcinoma (HCC). This has created the need to assess rat liver absorbed radiation dose. In most dose estimation studies, the rat liver is considered as a homogeneous integrated target organ with a tissue composition assumed to be similar to that of human liver tissue. However, the rat liver is composed of several lobes having different anatomical and chemical characteristics. To assess the overall impact on rat liver dose calculation, the authors use a new voxel-based rat model with identified suborgan regions of the liver. Methods: The liver in the original cryosectional color images was manually segmented into seven individual lobes and subsequently integrated into a voxel-based computational rat model. Photon and electron particle transport was simulated using the MCNPX Monte Carlo code to calculate absorbed fractions and S-values for {sup 90}Y, {sup 131}I, {sup 166}Ho, and {sup 188}Re for the seven liver lobes. The effect of chemical composition on organ-specific absorbed dose was investigated by changing the chemical composition of the voxel filling liver material. Radionuclide-specific absorbed doses at the voxel level were further assessed for a small spherical hepatic tumor. Results: The self-absorbed dose for different liver lobes varied depending on their respective masses. A maximum difference of 3.5% was observed for the liver self-absorbed fraction between rat and human tissues for photon energies below 100 keV. {sup 166}Ho and {sup 188}Re produce a uniformly distributed high dose in the tumor and relatively low absorbed dose for surrounding tissues. Conclusions: The authors evaluated rat liver radiation doses from various radionuclides used in HCC treatments using a realistic computational rat model. This work contributes to a better understanding of all aspects influencing radiation transport in organ-specific radiation dose evaluation for

  13. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2007-10-01

    , Solifenacin succinate, Sunitinib malate; Tadalafil, Talnetant, Tanespimycin, Taxus, Tegaserod maleate, Telmisartan/hydrochlorothiazide, Tenofovir disoproxil fumarate/emtricitabine, Teriparatide, tgAAC-94, Tiotropium bromide, Tocilizumab, Tolvaptan, Trimethoprim; Vardenafil hydrochloride hydrate, Vatalanib succinate, Vinflunine, Voriconazole, VX-680; XL-880; Yttrium 90 (90Y) ibritumomab tiuxetan. PMID:18040531

  14. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-10-01

    , travoprost; UCN-01; Vardenafil hydrochloride hydrate; XB-947; Yttrium 90 (90Y) ibritumomab tiuxetan.

  15. [Cancer therapy using unsealed radioisotopes-the present and future].

    PubMed

    Karasawa, Katsuyuki

    2014-12-01

    Iodine-131 (I-131) has been used for the ablation of residual thyroid remnants and cancer cells in well-differentiated thyroid cancers. It has also been used for metastatic well-differentiated thyroid cancers, especially lung and bone metastases. For small lung metastases, I-131 treatment has curative potential, particularly in young patients. Suppression of the thyroid stimulating hormone is also important for prolonging the survival of thyroid cancer patients. Strontium-89 (Sr-89) chloride has a mechanism similar to calcium, and it has been used for the treatment of bone metastases, especially osteoblastic metastases. It has been reported to have analgesic effects in an average of 76% of cases, and it is more effective if used in the early bone metastatic phase. Ibritumomab tiuxetan (Zevalin) is an anti-CD20 mouse monoclonal antibody labeled with Yttrium-90 (Y-90). It is used for treatment-resistant low grade or follicular B-cell non-Hodgkin's lymphomas and mantle lymphomas. Recently, radium-223 (Ra-223) has been used for bone metastases from castration resistant prostate cancers, and in a phase III trial, it has been proven to prolong survival of these patients. Cancer therapy using unsealed radioisotopes has been thought to be promising because it exhibits more targeted therapy than external beam irradiation. Therefore, if many more ideal targeting agents are developed in the future, this treatment might be used more commonly. As many agents such as I-131, Sr-89, and Ra-223 are available for treating bone metastasis, the combined use of other treatments such as high precision radiotherapy, bisphosphonates, hormonal agents, and molecular targeted agents should be investigated.

  16. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-04-01

    , Rosuvastatin calcium, RWJ-676070; SAR-109659, Sitagliptin phosphate monohydrate, Sorafenib, Stavudine/Lamivudine/Nevirapine, Sunitinib malate; Tadalafil, Telaprevir, Telbivudine, Tenofovir disoproxil fumarate, Tenofovir disoproxil fumarate/emtricitabine, Tenofovir disoproxil fumarate/emtricitabine/efavirenz, Teriparatide, Tigecycline, Tiotropium bromide, Tipifarnib, Tipranavir, Tocilizumab, Trifluridine/TPI; UP-780; Vandetanib, Vardenafil hydrochloride hydrate, Vatalanib succinate, Vitespen, Vorinostat; Yttrium 90 (90Y) ibritumomab tiuxetan; Zoledronic acid monohydrate. PMID:19536362

  17. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-10-01

    , travoprost; UCN-01; Vardenafil hydrochloride hydrate; XB-947; Yttrium 90 (90Y) ibritumomab tiuxetan. PMID:15605126

  18. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-11-01

    fumarate, Tocilizumab, Tositumomab/iodine (I131) tositumomab, Trabectedin, TransVax™ hepatitis C vaccine; Ustekinumab; V-260, Valspodar, Varenicline tartrate, VCL-IPT1, Vildagliptin, VRC-HIVADV014-00-VP, VRC-HIVDNA009-00-VP, VRC-HIVDNA016-00-VP; Yttrium 90 (90Y) ibritumomab tiuxetan, Yttrium Y90 Epratuzumab; Zibotentan, Zotarolimus-eluting stent. PMID:21225019

  19. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2006-09-01

    , Pseudostat; R24, rasburicase, RHAMM R3 peptide, rilonacept, rosuvastatin calcium, rotavirus vaccine, rufinamide; Sabarubicin hydrochloride, SHL-749, sirolimus-eluting stent, SLx-2101, sodium butyrate, sorafenib, SU-6668; TachoSil, tadalafil, taxus, tegaserod maleate, telbivudine, tenofovir disoproxil fumarate, teriparatide, tetramethylpyrazine, teverelix, tiotropium bromide, tipifarnib, tirapazamine, tolvaptan, TransvaxTM hepatitis C vaccine, treprostinil sodium; Valganciclovir hydrochloride, valsartan/amlodipine, vandetanib, vardenafil hydrochloride hydrate, vatalanib succinate, veglin, voriconazole; Yttrium 90 (90Y) ibritumomab tiuxetan; Zileuton, zotarolimus, zotarolimus-eluting stent. PMID:17003851

  20. Gateways to clinical trials.

    PubMed

    Moral, M A; Tomillero, A

    2008-03-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 131-I-Chlorotoxin, 423557; Abatacept, Ad.Egr.TNF.11D, Adalimumab, AE-941, Ambrisentan, AMR-001, Anacetrapib, Anakinra, Aripiprazole, Atazanavir sulfate; BAY-639044, Bazedoxifene acetate, Belimumab, Bevacizumab, Bortezomib, Botulinum toxin type B, Brivaracetam, Bucindolol hydrochloride; Carfilzomib, Carisbamate, CCX-282, CD20Bi, Ceftobiprole, Certolizumab pegol, CF-101, Cinacalcet hydrochloride, Cypher; Darifenacin hydrobromide, Degarelix acetate, Denosumab, Desvenlafaxine succinate, Dexlansoprazole, Dexverapamil, Drotrecogin alfa (activated), Duloxetine hydrochloride, Dutasteride; Efalizumab, EPs-7630, Escitalopram oxalate, Etoricoxib; Fluticasone furoate, Fondaparinux sodium, Fospropofol disodium; Hexadecyloxypropyl-cidofovir, HIV gp120/NefTat/AS02A, HPV-6/11/16/18; INCB-18424, Incyclinide, Inhalable human insulin, Insulin detemir; KNS-760704, KW-0761; Lacosamide, Lenalidomide, Levetiracetam, Licofelone, Lidocaine/prilocaine; mAb 216, MEDI-528, Men ACWY, Meningococcal C-CRM197 vaccine, Methylnaltrexone bromide; Nemifitide ditriflutate, Nicotine conjugate vaccine, Nilotinib hydrochloride monohydrate; Octaparin; Parathyroid hormone (human recombinant), Pegaptanib octasodium, Pitrakinra, Prasterone, Pregabalin; Ranelic acid distrontium salt, Rasagiline mesilate, Retigabine, Rimonabant, RTS,S/AS02D; Sarcosine, Sitaxentan sodium, Solifenacin succinate, Sunitinib malate; Taranabant, Taxus, Teduglutide, Teriparatide, Ticagrelor, Travoprost, TRU-015; USlipristal acetate, Urocortin 2; Vardenafil hydrochloride hydrate; YM-155, Yttrium 90 (90Y) ibritumomab tiuxetan; Zanolimumab, Zoledronic acid monohydrate, Zotarolimus

  1. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2005-06-01

    , vildagliptin, vincristine sulfate, voriconazole, VRX-496, VX-385; Warfarin sodium; Ximelagatran; Yttrium 90 (90Y) ibritumomab tiuxetan; Zanolimumab, zidovudine. PMID:16082422

  2. Use of Monte Carlo simulations with a realistic rat phantom for examining the correlation between hematopoietic system response and red marrow absorbed dose in Brown Norway rats undergoing radionuclide therapy with {sup 177}Lu- and {sup 90}Y-BR96 mAbs

    SciTech Connect

    Larsson, Erik; Ljungberg, Michael; Martensson, Linda; Nilsson, Rune; Tennvall, Jan; Strand, Sven-Erik; Joensson, Bo-Anders

    2012-07-15

    Purpose: Biokinetic and dosimetry studies in laboratory animals often precede clinical radionuclide therapies in humans. A reliable evaluation of therapeutic efficacy is essential and should be based on accurate dosimetry data from a realistic dosimetry model. The aim of this study was to develop an anatomically realistic dosimetry model for Brown Norway rats to calculate S factors for use in evaluating correlations between absorbed dose and biological effects in a preclinical therapy study. Methods: A realistic rat phantom (Roby) was used, which has some flexibility that allows for a redefinition of organ sizes. The phantom was modified to represent the anatomic geometry of a Brown Norway rat, which was used for Monte Carlo calculations of S factors. Kinetic data for radiolabeled BR96 monoclonal antibodies were used to calculate the absorbed dose. Biological data were gathered from an activity escalation study with {sup 90}Y- and {sup 177}Lu-labeled BR96 monoclonal antibodies, in which blood cell counts and bodyweight were examined up to 2 months follow-up after injection. Reductions in white blood cell and platelet counts and declines in bodyweight were quantified by four methods and compared to the calculated absorbed dose to the bone marrow or the total body. Results: A red marrow absorbed dose-dependent effect on hematological parameters was observed, which could be evaluated by a decrease in blood cell counts. The absorbed dose to the bone marrow, corresponding to the maximal tolerable activity that could safely be administered, was determined to 8.3 Gy for {sup 177}Lu and 12.5 Gy for {sup 90}Y. Conclusions: There was a clear correlation between the hematological effects, quantified with some of the studied parameters, and the calculated red marrow absorbed doses. The decline in body weight was stronger correlated to the total body absorbed dose, rather than the red marrow absorbed dose. Finally, when considering a constant activity concentration, the phantom

  3. Radioembolization with {sup 90}Y Microspheres: Angiographic and Technical Considerations

    SciTech Connect

    Lewandowski, Robert J.; Sato, Kent T.; Atassi, Bassel; Ryu, Robert K.; Nemcek, Albert A.; Kulik, Laura; Geschwind, Jean-Francois; Murthy, Ravi; Rilling, William; Liu, David; Bilbao, Jose Ignacio; Kennedy, Andrew S.; Omary, Reed A.; Salem, Riad

    2007-07-15

    The anatomy of the mesenteric system and the hepatic arterial bed has been demonstrated to have a high degree of variation. This is important when considering pre-surgical planning, catheterization, and trans-arterial hepatic therapies. Although anatomical variants have been well described, the characterization and understanding of regional hepatic perfusion in the context of radioembolization have not been studied with great depth. The purpose of this review is to provide a thorough discussion and detailed presentation of the angiographic and technical aspects of radioembolization. Normal vascular anatomy, commonly encountered variants, and factors involved in changes to regional perfusion in the presence of liver tumors are discussed. Furthermore, the principles described here apply to all liver-directed transarterial therapies.

  4. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2006-10-01

    -globulin, ivabradine hydrochloride, ixabepilone; LA-419, lacosamide, landiolol, lanthanum carbonate, lidocaine/prilocaine, liposomal cisplatin, lutropin alfa; Matuzumab, MBP(82-98), mecasermin, MGCD-0103, MMR-V, morphine hydrochloride, mycophenolic acid sodium salt; Natalizumab, NCX-4016, neridronic acid, nesiritide, nilotinib, NSC-330507; O6-benzylguanine, olanzapine/fluoxetine hydrochloride, omalizumab; Panitumumab, parathyroid hormone (human recombinant), parecoxib sodium, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, pegvisomant, pemetrexed disodium, perospirone hydrochloride, pexelizumab, phorbol 12-myristate 13-acetate, pneumococcal 7-valent conjugate vaccine, posaconazole, pramiconazole, prasugrel, pregabalin, prilocaine; rAAV-GAD65, raclopride, rasagiline mesilate, retapamulin, rosuvastatin calcium, rotigotine, rufinamide; SarCNU, SB-743921, SHL-749, sirolimus-eluting stent, sitaxsentan sodium, sorafenib; TachoSil, tadalafil, talampanel, Taxus, tegaserod maleate, telithromycin, telmisartan/hydrochlorothiazide, temsirolimus, tenatoprazole, teriflunomide, tetrathiomolybdate, ticilimumab, timcodar dimesilate, tipifarnib, tirapazamine, TPI, tramiprosate, trifluridine/TPI, trimethoprim; Ularitide, Urocortin 2; Valdecoxib, valganciclovir hydrochloride, valproate magnesium, valspodar, vardenafil hydrochloride hydrate, vitespen, vofopitant hydrochloride, volociximab, vorinostat; Yttrium 90 (90Y) ibritumomab tiuxetan; Ziprasidone hydrochloride, zotarolimus, zotarolimus-eluting stent. PMID:17136234

  5. Experiments in Radiochemistry: Paper Electrophorectic Separation of Superscript 90 Sr and Superscript 90 Y.

    ERIC Educational Resources Information Center

    Miekely, N.; Roldao, L. A.

    1982-01-01

    Using different supporting electrolytes, the influence of complex-forming equilibria on migration velocities of strontium-90 and yttrium-90 can be demonstrated in this experiment. Includes procedures and materials needed. (SK)

  6. Radioembolization and the Dynamic Role of 90Y PET/CT

    PubMed Central

    Pasciak, Alexander S.; Bourgeois, Austin C.; McKinney, J. Mark; Chang, Ted T.; Osborne, Dustin R.; Acuff, Shelley N.; Bradley, Yong C.

    2014-01-01

    Before the advent of tomographic imaging, it was postulated that decay of 90 Y to the 0+ excited state of 90Zr may result in emission of a positron–electron pair. While the branching ratio for pair-production is small (~32 × 10−6), PET has been successfully used to image 90 Y in numerous recent patients and phantom studies. 90 Y PET imaging has been performed on a variety of PET/CT systems, with and without time-of-flight (TOF) and/or resolution recovery capabilities as well as on both bismuth-germanate and lutetium yttrium orthosilicate (LYSO)-based scanners. On all systems, resolution and contrast superior to bremsstrahlung SPECT has been reported. The intrinsic radioactivity present in LYSO-based PET scanners is a potential limitation associated with accurate quantification of 90 Y. However, intrinsic radioactivity has been shown to have a negligible effect at the high activity concentrations common in 90 Y radioembolization. Accurate quantification is possible on a variety of PET scanner models, with or without TOF, although TOF improves accuracy at lower activity concentrations. Quantitative 90 Y PET images can be transformed into 3-dimensional (3D) maps of absorbed dose based on the premise that the 90 Y activity distribution does not change after infusion. This transformation has been accomplished in several ways, although the most common is with the use of 3D dose-point-kernel convolution. From a clinical standpoint, 90 Y PET provides a superior post-infusion evaluation of treatment technical success owing to its improved resolution. Absorbed dose maps generated from quantitative PET data can be used to predict treatment efficacy and manage patient follow-up. For patients who receive multiple treatments, this information can also be used to provide patient-specific treatment-planning for successive therapies, potentially improving response. The broad utilization of 90 Y PET has the potential to provide a wealth of dose–response information, which may lead to development of improved radioembolization treatment-planning models in the future. PMID:24579065

  7. Radioembolization using 90Y-resin microspheres for patients with advanced hepatocellular carcinoma

    SciTech Connect

    Sangro, Bruno . E-mail: bsangro@unav.es; Bilbao, Jose I.; Boan, Jose; Martinez-Cuesta, Antonio; Benito, Alberto; Rodriguez, Javier; Panizo, Angel; Gil, Belen; Inarrairaegui, Mercedes; Herrero, Ignacio; Quiroga, Jorge; Prieto, Jesus

    2006-11-01

    Purpose: To investigate the antitumor effect of resin microspheres loaded with 90-yttrium against hepatocellular carcinoma and their safety in the setting of liver cirrhosis. Patients and Methods: Data from 24 consecutive patients with hepatocellular carcinoma (HCC) treated by radioembolization in the period from September 2003 to February 2005 were reviewed. Patients received no further antineoplastic therapy. A comprehensive evaluation was performed to prevent the risk of damage due to microsphere misplacing. Patients were discharged the day after microspheres injection. Results: Serious liver toxicity observed among cirrhotic patients in a first period was subsequently prevented by modifying the selection criteria and the method for calculating the activity to be administered. Among 21 patients evaluable for response using Response Evaluation Criteria in Solid Tumors (RECIST) criteria, a reduction in size of target lesions was observed in all but 1 patient. When considering only target lesions, disease control rate and response rate were 100% and 23.8%, respectively. However, 43% of patients progressed in the liver in the form of new lesions appearing a median time of 3 months after radioembolization. Conclusion: Our experience in these series of patients indicates that radioembolization using resin microspheres has a significant antitumor effect against HCC and that using stringent selection criteria and conservative models for calculating Radiation activity to be administered, radioembolization can be performed safely even in cirrhotic patients.

  8. Imaging enhancement by reduction of mask topography induced phase aberrations for horizontal 1D spaces under D90Y illumination

    NASA Astrophysics Data System (ADS)

    Last, T.; de Winter, L.; Finders, J.

    2015-10-01

    EUV reticles need to be considered as complex optical elements in the beam path with considerable impact on lithography. Here we present a work flow for absorber optimization by applying a complementary approach of investigating lithographic metrics and mask-topography induced phase aberrations. In the first part this complementary approach is applied to find an optimum thickness of a typical Ta-based absorber for imaging horizontal spaces through pitch. And although an absorber thickness of around 70 nm is found to be preferable for this particular application, the thickness choice leads to conflicting results for the general printability of 10 nm technology node features. Hence we show that a moderate reduction of the absorber thickness can be allowed when the mask bias of these features is optimized appropriately. The moderate thickness reduction already allows for the mitigation of some of the conflicting imaging aspects. In the second part we expand the workflow by analyzing phase aberrations in n & k material space. This phase-based optical property screening shows that an alternative absorber based on materials such as Ni with k higher than Ta show superior best focus and contrast metrics. These alternative absorber embodiments would allow the overall reduction of M3D effects and adverse application dependencies of current Ta-based absorbers due to a combination of thickness reduction and enhancement of absorption.

  9. PET/CT and Bremsstrahlung Imaging After 90Y DOTANOC Therapy for Rectal Net With Liver Metastases.

    PubMed

    Abdülrezzak, Ümmühan; Kula, Mustafa; Tutuş, Ahmet; Buyukkaya, Fikret; Karaca, Halit

    2015-10-01

    Peptide receptor radionuclide therapy with Lu or Y is promising with successful results in somatostatin receptor-positive tumors. In all radiation therapies, knowledge of the radiation dose received by the target, and other organs in the body is essential to evaluate the risks and benefits of any procedure. We report a case of liver metastases from a rectal neuroendocrine tumor, which was treated with Y DOTANOC. Posttreatment whole-body planar images were acquired through Bremsstrahlung radiations of Y on a γ-camera, and thoracolumbar PET/CT images were acquired on PET. PMID:26204211

  10. Radioimmunoconjugates for the treatment of cancer.

    PubMed

    Kraeber-Bodéré, Françoise; Bodet-Milin, Caroline; Rousseau, Caroline; Eugène, Thomas; Pallardy, Amandine; Frampas, Eric; Carlier, Thomas; Ferrer, Ludovic; Gaschet, Joëlle; Davodeau, François; Gestin, Jean-François; Faivre-Chauvet, Alain; Barbet, Jacques; Chérel, Michel

    2014-10-01

    Radioimmunotherapy (RIT) has been developed for more than 30 years. Two products targeting the CD20 antigen are approved in the treatment of non-Hodgkin B-cell lymphoma (NHBL): iodine 131-tositumomab and yttrium 90-ibritumomab tiuxetan. RIT can be integrated in clinical practice for the treatment of patients with relapsed or refractory follicular lymphoma (FL) or as consolidation after induction chemotherapy. High-dose treatment, RIT in first-line treatment, fractionated RIT, and use of new humanized monoclonal antibodies (MAbs), in particular targeting CD22, showed promising results in NHBL. In other hemopathies, such as multiple myeloma, efficacy has been demonstrated in preclinical studies. In solid tumors, more resistant to radiation and less accessible to large molecules such as MAbs, clinical efficacy remains limited. However, pretargeting methods have shown clinical efficacy. Finally, new beta emitters such as lutetium 177, with better physical properties will further improve the safety of RIT and alpha emitters, such as bismuth 213 or astatine 211, offer the theoretical possibility to eradicate the last microscopic clusters of tumor cells, in the consolidation setting. Personalized treatments, based on quantitative positron emission tomography (PET), pre-therapeutic imaging, and dosimetry procedures, also could be applied to adapt injected activity to each patient. PMID:25440606

  11. Current Status of Allogeneic transplantation for Aggressive Non-Hodgkin lymphoma

    PubMed Central

    van Besien, Koen

    2016-01-01

    Purpose To provide a succinct update on the role of allogeneic stem cell transplantation in the management of patients with aggressive lymphomas. To clarify the indications for allogeneic transplantation vis-à-vis autologous transplant and to discuss the rational and potential benefits of reduced intensity conditioning(RIC), non-myeloablative (NMA) transplant, T-cell depletion and variations in GVHD prophylaxis. Recent findings Considerable effort has been spent in developing transplant regimens with reduced toxicity and reduced GVHD. The role of allogeneic transplantation has also been redefined in light of advances in lymphoma classification, diagnostic methods, particularly PET scan and advances in transplant technology. Haplo and UCB SCT allow identification of a donor for nearly all patients. Summary RIC and NMA conditioning have reduced early toxicity but are associated with increased risk for disease recurrence. Promising data have been reported from a novel conditioning regimen combining NMAwith ibritumomab tiuxetan. T-cell depletion reduces cGVHD but has some increase in rate of recurrence. Rapamycin may be associated with reduction in risk for disease recurrence. In diffuse large B cell lymphoma, the outcome of allo SCT depends on patient characteristics and chemosensitivity. It is seful after failure of autoSCT and in partial responses to salvage therapy. Allo SCT may be the treatment of choice for advanced T-cell and NK cell lymphoma and for ATLL. Prophylactic or preemptive DLI may be useful, but requires controlled studies. PMID:21946246

  12. Clinical development of radioimmunotherapy for B-cell non-Hodgkin's lymphoma

    SciTech Connect

    Meredith, Ruby F. . E-mail: rmeredith@uabmc.edu; Knox, Susan J.

    2006-10-01

    Over the past several decades, several biomolecules have been investigated for their ability to deliver radiation to cancer cells, but antibodies have been the carriers of choice in systemic targeted radionuclide therapy (STaRT). Two radioimmunotherapy agents that target the CD20 antigen, {sup 131}I-tositumomab and {sup 9}Y-ibritumomab tiuxetan, have been approved by the U.S. Food and Drug Administration for the treatment of patients with relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL), and clinical trials have shown that they are effective as monotherapies in the salvage setting, producing response rates that are often higher and durations of response that are often longer than those with chemotherapy. Escalated doses of these agents can be supported with stem cell transplantation and can produce high rates of complete response and greater survival in patients with relapsed NHL. The quality and duration of responses are greater with radioimmunotherapy when it is used earlier in the course of treatment.

  13. A review of human anti-globulin antibody (HAGA, HAMA, HACA, HAHA) responses to monoclonal antibodies. Not four letter words.

    PubMed

    Mirick, G R; Bradt, B M; Denardo, S J; Denardo, G L

    2004-12-01

    The United States Food and Drug Administration (FDA) has approved unconjugated monoclonal antibodies (MAbs) for immunotherapy (IT) of B-cell lymphoma, breast cancer and acute myeloid leukemia. More recently, approval has been given for conjugated ZevalinTM ((90)yttrium ibritumomab tiuxetan, IDEC-Y2B8, Biogen Idec, Cambridge, MA) and BexxarTM ((131)I-tositumomab, Corixa, Corp., Seattle, WA and GlaxoSmithKline, Philadelphia, PA) anti-CD20 MAbs for use in radioimmunotherapy (RIT) of non-Hodgkin's lymphoma (NHL), thus redefining the standard care of cancer patients. Because of, and despite a lack of basis for concern about allergic reactions due to human antibody responses to these foreign proteins, assays were developed to determine HAGA (human anti-globulin antibody) levels that developed in patient sera following treatment with MAbs. Strategies were also devised to ''humanize'' MAbs and to temporarily block patient immune function with drugs in order to decrease the seroconversion rates, with considerable success. On the other hand, a survival advantage has been observed in some patients who developed a HAGA following treatment. This correlates with development of an anti-idiotype antibody cascade directed toward the MAbs used to treat these patients. What follows is a selective review of HAGA and its effect on cancer treatment over the past 2 decades.

  14. Semi-automatic 3D-volumetry of liver metastases from neuroendocrine tumors to improve combination therapy with 177Lu-DOTATOC and 90Y-DOTATOC

    PubMed Central

    Cieciera, Matthaeus; Kratochwil, Clemens; Moltz, Jan; Kauczor, Hans-Ulrich; Holland-Letz, Tim; Choyke, Peter; Mier, Walter; Haberkorn, Uwe; Giesel, Frederik L.

    2016-01-01

    PURPOSE Patients with neuroendocrine tumors (NET) often present with disseminated liver metastases and can be treated with a number of different nuclides or nuclide combinations in peptide receptor radionuclide therapy (PRRT) depending on tumor load and lesion diameter. For quantification of disseminated liver lesions, semi-automatic lesion detection is helpful to determine tumor burden and tumor diameter in a time efficient manner. Here, we aimed to evaluate semi-automated measurement of total metastatic burden for therapy stratification. METHODS Nineteen patients with liver metastasized NET underwent contrast-enhanced 1.5 T MRI using gadolinium-ethoxybenzyl diethylenetriaminepentaacetic acid. Liver metastases (n=1537) were segmented using Fraunhofer MEVIS Software for three-dimensional (3D) segmentation. All lesions were stratified according to longest 3D diameter >20 mm or ≤20 mm and relative contribution to tumor load was used for therapy stratification. RESULTS Mean count of lesions ≤20 mm was 67.5 and mean count of lesions >20 mm was 13.4. However, mean contribution to total tumor volume of lesions ≤20 mm was 24%, while contribution of lesions >20 mm was 76%. CONCLUSION Semi-automatic lesion analysis provides useful information about lesion distribution in predominantly liver metastasized NET patients prior to PRRT. As conventional manual lesion measurements are laborious, our study shows this new approach is more efficient and less operator-dependent and may prove to be useful in the decision making process selecting the best combination PRRT in each patient. PMID:27015320

  15. Recommendations of the American Association of Physicists in Medicine on dosimetry, imaging, and quality assurance procedures for {sup 90}Y microsphere brachytherapy in the treatment of hepatic malignancies

    SciTech Connect

    Dezarn, William A.; Cessna, Jeffery T.; DeWerd, Larry A.; and others

    2011-08-15

    Yttrium-90 microsphere brachytherapy of the liver exploits the distinctive features of the liver anatomy to treat liver malignancies with beta radiation and is gaining more wide spread clinical use. This report provides a general overview of microsphere liver brachytherapy and assists the treatment team in creating local treatment practices to provide safe and efficient patient treatment. Suggestions for future improvements are incorporated with the basic rationale for the therapy and currently used procedures. Imaging modalities utilized and their respective quality assurance are discussed. General as well as vendor specific delivery procedures are reviewed. The current dosimetry models are reviewed and suggestions for dosimetry advancement are made. Beta activity standards are reviewed and vendor implementation strategies are discussed. Radioactive material licensing and radiation safety are discussed given the unique requirements of microsphere brachytherapy. A general, team-based quality assurance program is reviewed to provide guidance for the creation of the local procedures. Finally, recommendations are given on how to deliver the current state of the art treatments and directions for future improvements in the therapy.

  16. Changes in Normal Liver and Spleen Volume after Radioembolization with {sup 90}Y-Resin Microspheres in Metastatic Breast Cancer Patients: Findings and Clinical Significance

    SciTech Connect

    Paprottka, Philipp M. Schmidt, G. P.; Trumm, C. G.; Hoffmann, R. T.; Reiser, M. F.; Jakobs, T. F.

    2011-10-15

    Purpose: In clinical trials with yttrium-90-resin-microspheres for the management of colorectal cancer liver metastases, it was observed that radioembolization might result in splenomegaly and an increase in portal vein size. Subclinical hepatitis in normal liver tissue as well as the effects of radioembolization and prior chemotherapy are suspected to be responsible for this phenomenon. The purpose of this study was to quantify the changes in liver and spleen volume and portal vein diameter after radioembolization. Methods: Twenty-seven patients with liver-dominant metastatic disease from breast cancer who had not responded to chemotherapy or had to abandon chemotherapy because of its toxic effects were evaluated. Changes in liver and spleen volume and portal vein diameter as well as liver tumor volume and diameter were quantified using computed tomography scans. Results: Radioembolization was associated with a significant mean decrease in the whole liver volume of 10.2% (median 16.7%; P = 0.0024), mainly caused by a reduction in the right lobe volume (mean 16.0%; P < 0.0001). These changes were accompanied by a significant increase in the diameter of the main portal vein (mean 6.8%; P < 0.0001) as well as splenic volume (mean 50.4%; P < 0.0001). Liver-tumor volume and diameter decreased by a median of 24 and 39.7%. Conclusions: Radioembolization is an effective treatment for tumor size reduction in patients with breast cancer liver metastases. Treatment is associated with changes of hepatic parenchymal volume, splenic volume, and portal vein size that appear not to represent clinically important sequelae in this patient cohort.

  17. A Phase II Trial of R-CHOP Followed by Radioimmunotherapy for Early Stage (Stages I/II) Diffuse Large B-Cell Non-Hodgkin Lymphoma: ECOG3402

    PubMed Central

    Witzig, Thomas E.; Hong, Fangxin; Micallef, Ivana N.; Gascoyne, Randy D.; Dogan, Ahmet; Wagner, Henry; Kahl, Brad S.; Advani, Ranjana H.; Horning, Sandra J.

    2015-01-01

    Summary Patients with early stage diffuse large B-cell lymphoma (DLBCL) receive RCHOP alone or with involved field radiotherapy (IFRT). Anti-CD20 radioimmunotherapy (RIT) delivers radiation to microscopic sites outside of known disease. This phase II study aimed to achieve a functional CR rate of ≥75% to RCHOP and 90Yttrium-ibritumomab tiuxetan RIT. Patients with stages I/II DLBCL received 4–6 cycles of RCHOP followed by RIT (0.4 mCi/kg); patients with PET positive sites of disease after RCHOP/RIT received 30Gy IFRT. Of the 62 patients enrolled; 53 were eligible. 42% (22/53) had stage I/IE; 58% (31/53) stage II/IIE. After RCHOP, 79% (42/53) were in CR/CRu. Forty–eight patients proceeded to RIT and one patient in PR after RIT received IFRT and achieved a CR. The best response after RCHOP+RIT in all 53 patients was a functional CR rate of 89% (47/53; 95% CI:77–96%). With a median follow-up of 5.9 years, 7 (13%) patients have progressed and 4 (8%) have died (2 with DLBCL). At 5 years, 78% of patients remain in remission and 94% are alive. Chemoimmunotherapy and RIT is an active regimen for early stage DLBCL patients. Eighty-nine% of patients achieved functional CR without the requirement of IFRT. This regimen is worthy of further study for early stage DLBCL in a phase III trial. PMID:25974212

  18. Evaluation of quantitative imaging methods for organ activity and residence time estimation using a population of phantoms having realistic variations in anatomy and uptake

    SciTech Connect

    He Bin; Du Yong; Segars, W. Paul; Wahl, Richard L.; Sgouros, George; Jacene, Heather; Frey, Eric C.

    2009-02-15

    Estimating organ residence times is an essential part of patient-specific dosimetry for radioimmunotherapy (RIT). Quantitative imaging methods for RIT are often evaluated using a single physical or simulated phantom but are intended to be applied clinically where there is variability in patient anatomy, biodistribution, and biokinetics. To provide a more relevant evaluation, the authors have thus developed a population of phantoms with realistic variations in these factors and applied it to the evaluation of quantitative imaging methods both to find the best method and to demonstrate the effects of these variations. Using whole body scans and SPECT/CT images, organ shapes and time-activity curves of 111In ibritumomab tiuxetan were measured in dosimetrically important organs in seven patients undergoing a high dose therapy regimen. Based on these measurements, we created a 3D NURBS-based cardiac-torso (NCAT)-based phantom population. SPECT and planar data at realistic count levels were then simulated using previously validated Monte Carlo simulation tools. The projections from the population were used to evaluate the accuracy and variation in accuracy of residence time estimation methods that used a time series of SPECT and planar scans. Quantitative SPECT (QSPECT) reconstruction methods were used that compensated for attenuation, scatter, and the collimator-detector response. Planar images were processed with a conventional (CPlanar) method that used geometric mean attenuation and triple-energy window scatter compensation and a quantitative planar (QPlanar) processing method that used model-based compensation for image degrading effects. Residence times were estimated from activity estimates made at each of five time points. The authors also evaluated hybrid methods that used CPlanar or QPlanar time-activity curves rescaled to the activity estimated from a single QSPECT image. The methods were evaluated in terms of mean relative error and standard deviation of the

  19. The impact of 3D volume of interest definition on accuracy and precision of activity estimation in quantitative SPECT and planar processing methods

    NASA Astrophysics Data System (ADS)

    He, Bin; Frey, Eric C.

    2010-06-01

    Accurate and precise estimation of organ activities is essential for treatment planning in targeted radionuclide therapy. We have previously evaluated the impact of processing methodology, statistical noise and variability in activity distribution and anatomy on the accuracy and precision of organ activity estimates obtained with quantitative SPECT (QSPECT) and planar (QPlanar) processing. Another important factor impacting the accuracy and precision of organ activity estimates is accuracy of and variability in the definition of organ regions of interest (ROI) or volumes of interest (VOI). The goal of this work was thus to systematically study the effects of VOI definition on the reliability of activity estimates. To this end, we performed Monte Carlo simulation studies using randomly perturbed and shifted VOIs to assess the impact on organ activity estimates. The 3D NCAT phantom was used with activities that modeled clinically observed 111In ibritumomab tiuxetan distributions. In order to study the errors resulting from misdefinitions due to manual segmentation errors, VOIs of the liver and left kidney were first manually defined. Each control point was then randomly perturbed to one of the nearest or next-nearest voxels in three ways: with no, inward or outward directional bias, resulting in random perturbation, erosion or dilation, respectively, of the VOIs. In order to study the errors resulting from the misregistration of VOIs, as would happen, e.g. in the case where the VOIs were defined using a misregistered anatomical image, the reconstructed SPECT images or projections were shifted by amounts ranging from -1 to 1 voxels in increments of with 0.1 voxels in both the transaxial and axial directions. The activity estimates from the shifted reconstructions or projections were compared to those from the originals, and average errors were computed for the QSPECT and QPlanar methods, respectively. For misregistration, errors in organ activity estimations were

  20. The impact of 3D volume of interest definition on accuracy and precision of activity estimation in quantitative SPECT and planar processing methods.

    PubMed

    He, Bin; Frey, Eric C

    2010-06-21

    Accurate and precise estimation of organ activities is essential for treatment planning in targeted radionuclide therapy. We have previously evaluated the impact of processing methodology, statistical noise and variability in activity distribution and anatomy on the accuracy and precision of organ activity estimates obtained with quantitative SPECT (QSPECT) and planar (QPlanar) processing. Another important factor impacting the accuracy and precision of organ activity estimates is accuracy of and variability in the definition of organ regions of interest (ROI) or volumes of interest (VOI). The goal of this work was thus to systematically study the effects of VOI definition on the reliability of activity estimates. To this end, we performed Monte Carlo simulation studies using randomly perturbed and shifted VOIs to assess the impact on organ activity estimates. The 3D NCAT phantom was used with activities that modeled clinically observed (111)In ibritumomab tiuxetan distributions. In order to study the errors resulting from misdefinitions due to manual segmentation errors, VOIs of the liver and left kidney were first manually defined. Each control point was then randomly perturbed to one of the nearest or next-nearest voxels in three ways: with no, inward or outward directional bias, resulting in random perturbation, erosion or dilation, respectively, of the VOIs. In order to study the errors resulting from the misregistration of VOIs, as would happen, e.g. in the case where the VOIs were defined using a misregistered anatomical image, the reconstructed SPECT images or projections were shifted by amounts ranging from -1 to 1 voxels in increments of with 0.1 voxels in both the transaxial and axial directions. The activity estimates from the shifted reconstructions or projections were compared to those from the originals, and average errors were computed for the QSPECT and QPlanar methods, respectively. For misregistration, errors in organ activity estimations were

  1. Effect of antilymphoma antibody, 131I-Lym-1, on peripheral blood lymphocytes in patients with non-Hodgkin's lymphoma.

    PubMed

    Schillaci, Orazio; DeNardo, Gerald L; DeNardo, Sally J; Goldstein, Desiree S; Kroger, Linda A; O'Donnell, Robert T; Lamborn, Kathleen R

    2007-08-01

    Anti-CD20 monoclonal antibodies (mAbs), unlabeled rituximab (Rituxan, Biogen Idec Inc., Cambridge, MA; and Genentech Inc., South San Francisco, CA) or radiolabeled 90Y-ibritumomab (Zevalin, Biogen Idec Inc., Cambridge, MA) and 131I-tositumomab (Bexxar; Glaxo Smith Kline, Research Triangle Park, NC), have proven to be effective therapy for non-Hodgkin's lymphoma (NHL), but also induce immediate and persistent decreases in normal peripheral blood lymphocytes (PBLs). Lym-1, a mAb that selectively targets malignant lymphocytes, also has induced therapeutic responses and prolonged survival in patients with NHL when labeled with iodine-131 (131I). We have retrospectively examined its effect on PBLs in 41 NHL patients that had received 131I-Lym-1 therapy. Absolute lymphocyte counts (ALCs) were evaluated before and after the first and last 131I-Lym-1 infusion. Modest decreases in PBLs were observed in most of the patients. Using strict criteria to define recovery, time to recovery was determined for 19 patients, with the remainder censored because of insufficient follow-up (median follow up for censored patients: 22 days). Using Kaplan-Meier estimates, it would be predicted that 31% of patients would recover by 28 days and that median time to recovery would be 44 days after the last 131I-Lym-1 infusion. No predictors were found for time to recovery, considering such factors as the administered Lym-1 or 131I dose, spleen volume, or radiation doses to the body, marrow, or spleen. The data suggest that the effect of 131I-Lym-1 on ALC is the result of a nonspecific radiation effect, rather than a specific Lym-1 mAb effect. The shorter time required for ALC recovery after 131I-Lym-1 when compared to that reported for anti-CD20 mAbs, whether radiolabeled or otherwise, is probably related to differing mechanisms for lymphocytotoxicity and lesser Lym-1 antigenic density on normal B-lymphocytes.

  2. Theranostic Imaging of Yttrium-90

    PubMed Central

    Wright, Chadwick L.; Zhang, Jun; Tweedle, Michael F.; Knopp, Michael V.; Hall, Nathan C.

    2015-01-01

    This paper overviews Yttrium-90 (90Y) as a theranostic and nuclear medicine imaging of 90Y radioactivity with bremsstrahlung imaging and positron emission tomography. In addition, detection and optical imaging of 90Y radioactivity using Cerenkov luminescence will also be reviewed. Methods and approaches for qualitative and quantitative 90Y imaging will be briefly discussed. Although challenges remain for 90Y imaging, continued clinical demand for predictive imaging response assessment and target/nontarget dosimetry will drive research and technical innovation to provide greater clinical utility of 90Y as a theranostic agent. PMID:26106608

  3. Yttrium-90 internal pair production imaging using first generation PET/CT provides high-resolution images for qualitative diagnostic purposes.

    PubMed

    Kao, Y H; Tan, E H; Lim, K Y; Ng, C E; Goh, S W

    2012-07-01

    Yttrium-90 ((90)Y) internal pair production can be imaged by positron emission tomography (PET)/CT and is superior to bremsstrahlung single-photon emission CT/CT for evaluating hepatic (90)Y microsphere biodistribution. We illustrate a case of (90)Y imaging using first generation PET/CT technology, producing high-quality images for qualitative diagnostic purposes.

  4. Method for rapid screening analysis of Sr-90 in edible plant samples collected near Fukushima, Japan.

    PubMed

    Amano, Hikaru; Sakamoto, Hideaki; Shiga, Norikatsu; Suzuki, Kaori

    2016-06-01

    A screening method for measuring (90)Sr in edible plant samples by focusing on (90)Y in equilibrium with (90)Sr is reported. (90)Y was extracted from samples with acid, co-precipitated with iron hydroxide, and precipitated with oxalic acid. The dissolved oxalate precipitate was loaded on an extraction chromatography resin, and the (90)Y-enriched eluate was analyzed by Cherenkov counting with a TDCR liquid scintillation counter. (90)Sr ((90)Y) concentration was determined in plant samples collected near the damaged Fukushima Daiichi Nuclear Power Plants with this method. PMID:27043171

  5. Microvascular injury in persistent gastric ulcers after yttrium-90 microsphere radioembolization for liver malignancies.

    PubMed

    Sun, Belinda; Lapetino, Shawn R; Diffalha, Sameer A L; Yong, Sherri; Gaba, Ron C; Bui, James T; Koppe, Sean; Garzon, Steven; Guzman, Grace

    2016-04-01

    Yttrium-90 microsphere radioembolization ((90)Y MRE) is a therapy for liver malignancies by permanently implanting (90)Y-containing microspheres into tumors via hepatic artery. The etiology of persistent gastric ulcerations in patients presenting months after treatment remains unclear. Three patients who presented with gastric ulceration 4 to 13 months after (90)Y MRE were examined by esophagogastroduodenoscopy and biopsies. Pathological examinations showed multiple (90)Y microspheres scattered within the lamina propria and submucosa. Most of the microspheres were distributed in a linear fashion, consistent with an intravascular location; however, the vascular lumen and endothelial cells were not present. The microspheres were surrounded by fibrotic tissue infiltrated by chronic inflammatory cells and rare neutrophils. Epithelial granulation without pititis and miniaturized glands with intervening fibrosis were noted, compatible with chronic ischemic changes. These findings suggest that the persistent gastric ulceration is a result of localized ischemic injury in response to (90)Y MRE-induced vascular damage.

  6. Radiopharmaceuticals for radiation synovectomy: Evaluation of two yttrium-90 particulate agents

    SciTech Connect

    Davis, M.A.; Chinol, M.

    1989-06-01

    Radiation synovectomy, a noninvasive therapeutic alternative to surgical synovectomy, has not gained widespread acceptance in the United States because of the lack of a suitable radiopharmaceutical. Two new radioactive particles, (/sup 90/Y)Ca oxalate and (/sup 90/Y)ferric hydroxide macroaggregates (FHMA), were developed in our laboratory and evaluated for size, stability, and joint leakage. More than 90% of the (/sup 90/Y)Ca oxalate particles were in the optimal size range of 1-10 microns, and the unbound activity in serum and synovial fluid was 3.7% to 5.0%. Following injection in rabbit knees, leakage of (/sup 90/Y)Ca oxalate was 5 +/- 2%, with localization primarily in the bone and virtually no uptake by the lymph nodes or liver. Yttrium-90 FHMA particles were larger (95% greater than 10 microns), and at least on a microscopic level, appeared to distribute homogeneously over the articular surface. Leakage of (/sup 90/Y)FHMA was initially less but eventually slightly exceeded that of (/sup 90/Y)Ca oxalate. Nevertheless, both radiopharmaceuticals can provide a satisfactory therapeutic dose to the knee with less than half the leakage and a marked reduction in absorbed dose to nontarget tissues compared to previously tested agents. Ease of preparation, physical characteristics of the /sup 90/Y beta ray, and apparent lack of substantial leakage from the joint make these agents extremely attractive for clinical evaluation in rheumatoid arthritis patients who are unresponsive to medical therapy.

  7. Chemoradiation of Hepatic Malignancies: Prospective, Phase 1 Study of Full-Dose Capecitabine With Escalating Doses of Yttrium-90 Radioembolization

    SciTech Connect

    Hickey, Ryan; Mulcahy, Mary F.; Lewandowski, Robert J.; Gates, Vanessa L.; Vouche, Michael; Habib, Ali; Kircher, Sheetal; Newman, Steven; Nimeiri, Halla; Benson, Al B.; Salem, Riad

    2014-04-01

    Purpose: Radiosensitizing chemotherapy improves the outcomes in comparison with radiation alone for gastrointestinal cancers. The delivery of radiation therapy with yttrium90 ({sup 90}Y) radioembolization, in combination with the radiosensitizing chemotherapeutic agent capecitabine, provides the opportunity to enhance the effects of radiation on hepatic malignancies. This phase 1 study sought to determine the maximum tolerated dose (MTD) of {sup 90}Y plus capecitabine in patients with cholangiocarcinoma or liver metastases confined to the liver. Methods and Materials: Patients were given initial treatment at full-dose capecitabine during days 1 to 14 of a 21-day cycle. At days 1 to 7 of the second cycle, whole-liver {sup 90}Y was given at the test dose, after which time capecitabine was continued. Dose-limiting toxicity (DLT) was determined 6 weeks after {sup 90}Y infusion. If a DLT was not observed, the {sup 90}Y dose was escalated. The planned dose cohorts were 110, 130, 150, and 170 Gy. The primary endpoint was to determine the MTD of {sup 90}Y with full-dose capecitabine. Results: Sixteen patients were treated according to the study protocol. Two patients experienced DLTs. Nine patients required capecitabine dose reduction as a result of toxicities attributable to capecitabine alone. The criteria for establishing {sup 90}Y MTD were not met, indicating an MTD of >170 Gy. Conclusion: The MTD of {sup 90}Y delivered in conjunction with capecitabine in the setting of intrahepatic cholangiocarcinoma or metastatic disease confined to the liver exceeds 170 Gy. This is the highest {sup 90}Y dose reported to date and has important implications on combined therapy with the radiosensitizing oral chemotherapeutic capecitabine. Further studies are under way.

  8. Decrease of survivin, p53 and Bcl-2 expression in chemorefractory colorectal liver metastases may be predictive of radiosensivity after radioembolization with yttrium-90 resin microspheres

    PubMed Central

    2013-01-01

    In a prospective multicenter phase II trial of radioembolization with yttrium-90 (90Y-RE) in chemorefractory liver-dominant metastatic colorectal cancer (mCRC), we showed that median survival was 12.6 months (95% CI 7.0–18.3) with 48% of 50 patients achieving disease control. In this extension retrospective study, we analyzed whether a panel of biomarkers, known to be associated to an adverse clinical outcome, underwent variations in CRC liver metastases pre and post 90Y-RE. Of the 50 patients included in the study, 29 pre-90Y-RE therapy and 15 post-90Y-RE had liver biopsy specimens available. In these series we investigated survivin, p53, Bcl-2 and Ki-67 expression pre- and post-90Y-RE by immuhistochemistry (IHC). Our findings evidenced a decrease of survivin (77% vs 33%), p53 (93% vs 73%), Bcl-2 (37% vs 26%) expression as well as of Ki-67 proliferation index (62.5% vs 40%) on liver biopsies collected post-90Y-RE as compared to pre-90Y-RE. In the subset of 13 matched liver metastases we further confirmed the reduction of survivin (92.3% vs 53.8%; p = 0.06), p53 (100% vs 69.2%; p = 0.05) and Bcl-2 (69.2% vs 53.8%; p = 0.05) expression post-90Y-RE. This biomarker modulation was accompanied by morphological changes as steatohepatitis, hepatocyte necrosis, collagen deposition, proliferating and/or bile duct ectasia, focal sinusoidal dilatation and fibrosis. Although our analysis was conducted in a very limited number cases, these changes appear strictly related to the response to 90Y-RE therapy and may deserve further investigation on a larger series of patients. PMID:23497522

  9. Treatment modification of yttrium-90 radioembolization based on quantitative positron emission tomography/CT imaging.

    PubMed

    Chang, Ted T; Bourgeois, Austin C; Balius, Anastasia M; Pasciak, Alexander S

    2013-03-01

    Treatment activity for yttrium-90 ((90)Y) radioembolization when calculated by using the manufacturer-recommended technique is only partially patient-specific and may result in a subtumoricidal dose in some patients. The authors describe the use of quantitative (90)Y positron emission tomography/computed tomography as a tool to provide patient-specific optimization of treatment activity and evaluate this new method in a patient who previously received traditional (90)Y radioembolization. The modified treatment resulted in a 40-Gy increase in absorbed dose to tumor and complete resolution of disease in the treated area within 3 months.

  10. Process for the separation and purification of yttrium-90 for medical applications

    DOEpatents

    Horwitz, P.E.; Dietz, M.L.

    1994-11-29

    An extraction chromatographic method for the preparation of [sup 90]Y of high chemical and radiochemical purity is disclosed. After an initial purification of a [sup 90]Sr stock solution and a suitable period of [sup 90]Y ingrowth, the solution is passed through a series of strontium-selective chromatographic columns, each of which lowers the [sup 90]Sr content of the mixture by a factor of about 10[sup 3]. The [sup 90]Y remaining is freed from any residual [sup 90]Sr, from its [sup 90]Zr daughter, and from any remaining impurities by passing the sample through a final column designed to selectively retain yttrium. 5 figures.

  11. A process for the separation and purification of yttrium-90 for medical applications

    DOEpatents

    Horwitz, P.E.; Dietz, M.L.

    1993-01-01

    An extraction chromatographic method for the preparation of {sup 90}Y of high chemical and radiochemical purity is disclosed. After an initial purification of a {sup 90}Sr stock solution and a suitable period of {sup 90}Y ingrowth, the solution is passed through a series of strontium-selective chromatographic columns, each of which lowers the {sup 90}Sr content of the mixture by a factor of about 10{sup 3}. The {sup 90}Y remaining is freed from any residual {sup 90}Sr, from its {sup 90}Zr daughter, and from any remaining impurities by passing the sample through a final column designed to selectively retain yttrium.

  12. Process for the separation and purification of yttrium-90 for medical applications

    DOEpatents

    Horwitz, Philip E.; Dietz, Mark L.

    1994-01-01

    An extraction chromatographic method for the preparation of .sup.90 Y of high chemical and radiochemical purity is disclosed. After an initial purification of a .sup.90 Sr stock solution and a suitable period of .sup.90 Y ingrowth, the solution is passed through a series of strontium-selective chromatographic columns, each of which lowers the .sup.90 Sr content of the mixture by a factor of about 10.sup.3. The .sup.90 Y remaining is freed from any residual .sup.90 Sr, from its .sup.90 Zr daughter, and from any remaining impurities by passing the sample through a final column designed to selectively retain yttrium.

  13. Collimator and energy window optimization for ⁹⁰Y bremsstrahlung SPECT imaging: A SIMIND Monte Carlo study.

    PubMed

    Roshan, Hoda Rezaei; Mahmoudian, Babak; Gharepapagh, Esmaeil; Azarm, Ahmadreza; Islamian, Jalil Pirayesh

    2016-02-01

    Treatment efficacy of radioembolization using Yttrium-90 ((90)Y) microspheres is assessed by the (90)Y bremsstrahlung single photon emission computed tomography (SPECT) imaging following radioembolization. The radioisotopic image has the potential of providing reliable activity map of (90)Y microspheres distribution. One of the main reasons of the poor image quality in (90)Y bremsstrahlung SPECT imaging is the continuous and broad energy spectrum of the related bremsstrahlung photons. Furthermore, collimator geometry plays an impressive role in the spatial resolution, sensitivity and image contrast. Due to the relatively poor quality of the (90)Y bremsstrahlung SPECT images, we intend to optimize the medium-energy (ME) parallel-hole collimator and energy window. The Siemens e.cam gamma camera equipped with a ME collimator and a voxelized phantom was simulated by the SImulating Medical Imaging Nuclear Detectors (SIMIND) program. We used the SIMIND Monte Carlo program to generate the (90)Y bremsstrahlung SPECT projection of the digital Jaszczak phantom. The phantom consist of the six hot spheres ranging from 9.5 to 31.8mm in diameter, which are used to evaluate the image contrast. In order to assess the effect of the energy window on the image contrast, three energy windows ranging from 60 to 160 KeV, 160 to 400 KeV, and 60 to 400 KeV were set on a (90)Y bremsstrahlung spectrum. As well, the effect of the hole diameter of a ME collimator on the image contrast and bremsstrahlung spectrum were investigated. For the fixed collimator and septa thickness values (3.28 cm and 1.14 mm, respectively), a hole diameter range (2.35-3.3mm) was chosen based on the appropriate balance between the spatial resolution and sensitivity. The optimal energy window for (90)Y bremsstrahlung SPECT imaging was extended energy window from 60 to 400 KeV. Besides, The optimal value of the hole diameter of ME collimator was obtained 3.3mm. Geometry of the ME parallel-hole collimator and energy

  14. Chemoembolic Hepatopulmonary Shunt Reduction to Allow Safe Yttrium-90 Radioembolization Lobectomy of Hepatocellular Carcinoma

    SciTech Connect

    Gaba, Ron C.; VanMiddlesworth, Kyle A.

    2012-12-15

    Yttrium-90 ({sup 90}Y) radioembolization represents an emerging transcatheter treatment option for the management of hepatocellular carcinoma (HCC). Elevation of the hepatopulmonary shunt fraction risks nontarget radiation to the lungs and may limit the use of {sup 90}Y therapy in patients with locally advanced disease with vascular invasion, who often demonstrate increased shunting. We present two cases in which patients with HCC and portal vein invasion resulting in elevated hepatopulmonary shunt fractions underwent chemoembolic shunt closure to allow safe {sup 90}Y radioembolization. Both patients demonstrated excellent tumor response and patient survival. On this basis, we propose a role for chemoembolic reduction of the lung shunt fraction before {sup 90}Y radioembolization in patients with extensive tumor-related hepatopulmonary shunting.

  15. Non-Target Activity Detection by Post-Radioembolization Yttrium-90 PET/CT: Image Assessment Technique and Case Examples.

    PubMed

    Kao, Yung Hsiang; Tan, Andrew E H; Lo, Richard H G; Tay, Kiang Hiong; Tan, Bien Soo; Chow, Pierce K H; Ng, David C E; Goh, Anthony S W

    2014-01-01

    High resolution yttrium-90 ((90)Y) imaging of post-radioembolization microsphere biodistribution may be achieved by conventional positron emission tomography with integrated computed tomography (PET/CT) scanners that have time-of-flight capability. However, reconstructed (90)Y PET/CT images have high background noise, making non-target activity detection technically challenging. This educational article describes our image assessment technique for non-target activity detection by (90)Y PET/CT, which qualitatively overcomes the problem of background noise. We present selected case examples of non-target activity in untargeted liver, stomach, gallbladder, chest wall, and kidney, supported by angiography and (90)Y bremsstrahlung single-photon emission computed tomography with integrated computed tomography (SPECT/CT) or technetium-99m macroaggregated albumin SPECT/CT.

  16. Advances in SPECT for Optimizing the Liver Tumors Radioembolization Using Yttrium-90 Microspheres

    PubMed Central

    Roshan, Hoda Rezaei; Azarm, Ahmadreza; Mahmoudian, Babak; Islamian, Jalil Pirayesh

    2015-01-01

    Radioembolization (RE) with Yttrium-90 (90Y) microspheres is an effective treatment for unresectable liver tumors. The activity of the microspheres to be administered should be calculated based on the type of microspheres. Technetium-99m macroaggregated albumin (99mTc-MAA) single photon emission computed tomography/computed tomography (SPECT/CT) is a reliable assessment before RE to ensure the safe delivery of microspheres into the target. 90Y bremsstrahlung SPECT imaging as a posttherapeutic assessment approach enables the reliable determination of absorbed dose, which is indispensable for the verification of treatment efficacy. This article intends to provide a review of the methods of optimizing 90Y bremsstrahlung SPECT imaging to improve the treatment efficacy of liver tumor RE using 90Y microspheres. PMID:26097416

  17. Yttrium-90 Radioembolization of Hepatocellular Carcinoma-Performance, Technical Advances, and Future Concepts.

    PubMed

    Molvar, Christopher; Lewandowski, Robert

    2015-12-01

    Hepatocellular carcinoma (HCC) is a lethal tumor, claiming over half a million lives per year. Treatment of HCC is commonly performed without curative intent, and palliative options dominate, including catheter-based therapies, namely, transarterial chemoembolization and yttrium-90 ((90)Y) radioembolization. This review will showcase the performance of (90)Y radioembolization for the treatment of HCC, focusing on recent seminal data and technical advances. In particular, novel radioembolization treatment concepts are discussed and compared with conventional HCC therapy.

  18. Technical Solutions to Ensure Safe Yttrium-90 Radioembolization in Patients With Initial Extrahepatic Deposition of {sup 99m}Technetium-Albumin Macroaggregates

    SciTech Connect

    Barentsz, M. W.; Vente, M. A. D.; Lam, M. G. E. H.; Smits, M. L. J.; Nijsen, J. F. W.; Seinstra, B. A.; Rosenbaum, C. E. N. M.; Verkooijen, H. M.; Zonnenberg, B. A.; Van den Bosch, M. A. A. J.

    2011-10-15

    Purpose: To evaluate the incidence of extrahepatic deposition of technetium-99m-labeled albumin macroaggregates ({sup 99m}Tc-MAA) after pretreatment angiography, before yttrium-90 radioembolizaton ({sup 90}Y-RE), and to report on technical solutions that can be used to ensure safe delivery of {sup 90}Y-microspheres in patients with initial extrahepatic deposition. Materials and Methods: A retrospective analysis of 26 patients with primary and secondary liver malignancies, who were scheduled for treatment with {sup 90}Y-RE in our institution in 2009, was performed. The angiograms and single-photon emission computed tomography images of all patients were reviewed by an interventional radiologist and a nuclear medicine physician, respectively, to identify and localize extrahepatic deposition of {sup 99m}Tc-MAA when present. Subsequently, the technical solutions were used to successfully perform {sup 90}Y-RE in these patients were evaluated and described. Results: Extrahepatic deposition of {sup 99m}Tc-MAA was observed in 8 of 26 patients (31%). In 7 of 8 patients, a second pretreatment angiography was performed to detect the cause of extrahepatic deposition. The technical solutions to enable safe {sup 90}Y microspheres delivery included more distal placement of the microcatheter in the proper/right hepatic artery in 4 of 7 (57%) patients; (super)selective catheterization of multiple segmental branches in 2 of 7 (29%); and additional coiling of a newly detected branch in the remaining patient (14%). This was confirmed by a second MAA procedure. {sup 90}Y-RE was eventually performed in 25 of 26 (96%) patients. No procedure-related complications (<30 days) were observed. Conclusion: Extrahepatic deposition of {sup 99m}Tc-MAA after pretreatment angiography did occur in 8 of 26 (31%) patients. The technical solutions as presented allowed safe {sup 90}Y-RE delivery in 25 of 26 (96%) patients.

  19. Method of separation of yttrium-90 from strontium-90

    DOEpatents

    Bray, Lane A.; Wester, Dennis W.

    1996-01-01

    A method for purifying Y-90 from a Sr-90/Y-90 "cow" wherein raw Sr-90/Y-90 source containing impurities is obtained from nuclear material reprocessing. Raw Sr-90/Y-90 source is purified to a fresh Sr-90/Y-90 source "cow" by removing impurities by addition of sodium hydroxide and by removing Cs-137 by further addition of sodium carbonate. The "cow" is set aside to allow ingrowth. An HDEHP organic extractant is obtained from a commercial supplier and further purified by saturation with Cu(II), precipitation with acetone, and washing with nitric acid. The "cow" is then dissolved in nitric acid and the purified HDEHP is washed with nitric acid and scrubbed with either nitric or hydrochloric acid. The dissolved "cow" and scrubbed HDEHP are combined in an organic extraction, separating Y-90 from Sr-90, resulting in a Sr-90/Y-90 concentration ratio of not more than 10(E-7), and a metal impurity concentration of not more than 10 ppm per curie of Y-90. The separated Y-90 may then be prepared for delivery.

  20. Method of separation of yttrium-90 from strontium-90

    DOEpatents

    Bray, L.A.; Wester, D.W.

    1996-04-30

    A method is described for purifying Y-90 from a Sr-90/Y-90 ``cow`` wherein raw Sr-90/Y-90 source containing impurities is obtained from nuclear material reprocessing. Raw Sr-90/Y-90 source is purified to a fresh Sr-90/Y-90 source ``cow`` by removing impurities by addition of sodium hydroxide and by removing Cs-137 by further addition of sodium carbonate. The ``cow`` is set aside to allow ingrowth. An HDEHP organic extractant is obtained from a commercial supplier and further purified by saturation with Cu(II), precipitation with acetone, and washing with nitric acid. The ``cow`` is then dissolved in nitric acid and the purified HDEHP is washed with nitric acid and scrubbed with either nitric or hydrochloric acid. The dissolved ``cow`` and scrubbed HDEHP are combined in an organic extraction, separating Y-90 from Sr-90, resulting in a Sr-90/Y-90 concentration ratio of not more than 10(E-7), and a metal impurity concentration of not more than 10 ppm per curie of Y-90. The separated Y-90 may then be prepared for delivery. 1 fig.

  1. Patient Selection and Activity Planning Guide for Selective Internal Radiotherapy With Yttrium-90 Resin Microspheres

    SciTech Connect

    Lau, Wan-Yee; Kennedy, Andrew S.; Kim, Yun Hwan; Lai, Hee Kit; Lee, Rheun-Chuan; Leung, Thomas W.T.; Liu, Ching-Sheng; Salem, Riad; Sangro, Bruno; Shuter, Borys; Wang, Shih-Chang

    2012-01-01

    Purpose: Selective internal radiotherapy (SIRT) with yttrium-90 ({sup 90}Y) resin microspheres can improve the clinical outcomes for selected patients with inoperable liver cancer. This technique involves intra-arterial delivery of {beta}-emitting microspheres into hepatocellular carcinomas or liver metastases while sparing uninvolved structures. Its unique mode of action, including both {sup 90}Y brachytherapy and embolization of neoplastic microvasculature, necessitates activity planning methods specific to SIRT. Methods and Materials: A panel of clinicians experienced in {sup 90}Y resin microsphere SIRT was convened to integrate clinical experience with the published data to propose an activity planning pathway for radioembolization. Results: Accurate planning is essential to minimize potentially fatal sequelae such as radiation-induced liver disease while delivering tumoricidal {sup 90}Y activity. Planning methods have included empiric dosing according to degree of tumor involvement, empiric dosing adjusted for the body surface area, and partition model calculations using Medical Internal Radiation Dose principles. It has been recommended that at least two of these methods be compared when calculating the microsphere activity for each patient. Conclusions: Many factors inform {sup 90}Y resin microsphere SIRT activity planning, including the therapeutic intent, tissue and vasculature imaging, tumor and uninvolved liver characteristics, previous therapies, and localization of the microsphere infusion. The influence of each of these factors has been discussed.

  2. [Studies of biologic activation associated with molecular receptor increase and tumor response in ChL6/L6 protocol patients; Studies in phantoms; Quantitative SPECT; Preclinical studies; and Clinical studies]. DOE annual report, 1994--95

    SciTech Connect

    DeNardo, S.J.

    1995-12-31

    The authors describe results which have not yet been published from their associated studies listed in the title. For the first, they discuss Lym-1 single chain genetically engineered molecules, analysis of molecular genetic coded messages to enhance tumor response, and human dosimetry and therapeutic human use radiopharmaceuticals. Studies in phantoms includes a discussion of planar image quantitation, counts coincidence correction, organ studies, tumor studies, and {sup 90}Y quantitation with Bremsstrahlung imaging. The study on SPECT discusses attenuation correction and scatter correction. Preclinical studies investigated uptake of {sup 90}Y-BrE-3 in mice using autoradiography. Clinical studies discuss image quantitation verses counts from biopsy samples, S factors for radiation dose calculation, {sup 67}Cu imaging studies for lymphoma cancer, and {sup 111}In MoAb imaging studies for breast cancer to predict {sup 90}Y MoAb therapy.

  3. Biodistribution of Yttrium-90-Labeled Anti-CD45 Antibody in a Nonhuman Primate Model

    SciTech Connect

    Nemecek, Eneida; Hamlin, Donald K.; Fisher, Darrell R.; Krohn, Kenneth A.; Pagel, John M.; Applebaum, F. R.; Press, Oliver W.; Matthews, Dana C.

    2005-01-15

    Radioimmunotherapy may improve the outcome of hematopoietic cell transplantation for hematologic malignancies by delivering targeted radiation to hematopoietic organs while relatively sparing nontarget organs. We evaluated the organ localization of yttrium-90-labeled anti-CD45 (90Y-anti-CD45) antibody in macaques, a model that had previously predicted iodine-131-labeled anti-CD-45 (131I-anti-CD45) antibody biodistribution in humans. Experimental Design: Twelve Macaca nemestrina primates received anti-CD45 antibody labeled with 1 to 2 mCi of 90Y followed by serial blood sampling and marrow and lymph node biopsies, and necropsy. The content of 90Y per gram of tissue was determined by liquid scintillation spectrometry. Time-activity curves were constructed using average isotope concentrations in each tissue at measured time points to yield the fractional residence time and estimate radiation absorbed doses for each organ per unit of administered activity. The biodistribution of 90Y-anti-CD45 antibody was then compared with that previously obtained with 131I-anti-CD45 antibody in macaques. Results: The spleen received 2,120, marrow 1,060, and lymph nodes 315 cGy/mCi of 90Y injected. The liver and lungs were the nontarget organs receiving the highest radiation absorbed doses (440 and 285 cGy/mCi, respectively). Ytrrium-90-labeled anti-CD45 antibody delivered 2.5- and 3.7-fold more radiation to marrow than to liver and lungs, respectively. The ratios previously observed with 131I-antiCD45 antibody were 2.5-and 2.2-fold more radiation to marrow than to liver and lungs, respectively. Conclusions: This study shows that 90Y-anti-CD45 antibody can deliver relatively selective radiation to hematopoietic tissues, with similar ratios of radiation delivered to target versus nontarget organs, as compared with the 131I immunoconjugate in the same animal model.

  4. SU-E-I-80: Beta-Minus Emitting Radiotracers Improves Molecular Endoscopy

    SciTech Connect

    Carpenter, C; Ma, X; Sun, C; Pratx, G; Cheng, Z; Xing, L

    2014-06-01

    Purpose: Molecular Endoscopy using Cerenkov Luminescence can be used to monitor the distribution of many clinically-available PET and SPECT probes for endoscopic applications. A main limitation of Cerenkov is its limited sensitivity to small concentrations of radiotracer when using light guides s. Herein we demonstrate that the use of a high energy beta emitting radioisotope, exemplified here with 90Y provides superior sensitivity to 18F because of its higher light output and its lack of corresponding gamma emission. Methods: A series of phantom experiments were performed to compare the sensitivity and noise of the CLE system for imaging 90Y and 18F. Three vials of known concentrations of 90Y (0.008 μCi, 0.08 μCi, 1 μCi) were placed in centrifuge tubes and isolated from each other. One vial of 18F (100 μCi) was placed in the imaging chamber and imaged over the course of decay (19 hours, 43 minutes, or ∼10 half-lives). Image time-points were formed from 5-minute integrations. Results: Using an SNR of 10 to define the noise-floor, the 90Y minimum detectable activity was 0.056 μCi. To the contrast, the minimum detectable activity for 18F was 11.63 μCi. These data demonstrate a 207-fold improvement in SNR of 90Y compared to 18F, when controlled for activity. Conclusion: This study demonstrated that a pure β- radionuclide such as 90Y be used is superior to 18F for Cerenkov Endoscopy. Further study is needed to demonstrate its utility in preclinical studies, endoscopic applications, intraoperative, and radiotherapy applications.

  5. Monte Carlo simulation of liver cancer treatment with 166Ho-loaded glass microspheres

    NASA Astrophysics Data System (ADS)

    da Costa Guimarães, Carla; Moralles, Maurício; Roberto Martinelli, José

    2014-02-01

    Microspheres loaded with pure beta-emitter radioisotopes are used in the treatment of some types of liver cancer. The Instituto de Pesquisas Energéticas e Nucleares (IPEN) is developing 166Ho-loaded glass microspheres as an alternative to the commercially available 90Y microspheres. This work describes the implementation of a Monte Carlo code to simulate both the irradiation effects and the imaging of 166Ho and 90Y sources localized in different parts of the liver. Results obtained with the code and perspectives for the future are discussed.

  6. Current Role of Selective Internal Irradiation With Yttrium-90 Microspheres in the Management of Hepatocellular Carcinoma: A Systematic Review

    SciTech Connect

    Lau, Wan Yee; Lai, Eric C.H.; Leung, Thomas W.T.

    2011-10-01

    Purpose: This article reviews the role of selective internal irradiation (SIR) with yttrium-90 ({sup 90}Y) microspheres for hepatocellular carcinoma (HCC). Methods and Materials: Studies were identified by searching Medline and PubMed databases for articles from 1990 to 2009 using the keywords 'selective internal irradiation,' 'hepatocellular carcinoma,' 'therapeutic embolization,' and 'yttrium-90.' Results: {sup 90}Y microspheres are a safe and well-tolerated therapy for unresectable HCC (median survival range, 7 -21.6 months). The evidence was limited to cohort studies and comparative studies with historical control. {sup 90}Y microspheres have been reported to downstage unresectable HCC to allow for salvage treatments with curative intent, act as a bridging therapy before liver transplantation, and treat HCC with curative intent for patients who are not surgical candidates because of comorbidities. Conclusions: {sup 90}Y microsphere is recommended as an option of palliative therapy for large or multifocal HCC without major portal vein invasion or extrahepatic spread. It can also be used for recurrent unresectable HCC, as a bridging therapy before liver transplantation, as a tumor downstaging treatment, and as a curative treatment for patients with associated comorbidities who are not candidates for surgery.

  7. Measurement of K Shell Photoelectric Cross Sections at a K Edge--A Laboratory Experiment

    ERIC Educational Resources Information Center

    Nayak, S. V.; Badiger, N. M.

    2007-01-01

    We describe in this paper a new method for measuring the K shell photoelectric cross sections of high-Z elemental targets at a K absorption edge. In this method the external bremsstrahlung (EB) photons produced in the Ni target foil by beta particles from a weak[superscript 90]Sr-[superscript 90]Y beta source are passed through an elemental target…

  8. Production, PET performance and dosimetric considerations of 134Ce/134La, an Auger electron and positron-emitting generator for radionuclide therapy

    NASA Astrophysics Data System (ADS)

    Lubberink, Mark; Lundqvist, Hans; Tolmachev, Vladimir

    2002-02-01

    We propose the use of the Auger electron and positron-emitting generator 134Ce/134La (half-lives 3.16 d and 6.45 min) for radionuclide therapy. It combines emission of high-energy beta particles with Auger electrons. The high-energy beta particles have similar energies as those emitted by 90Y. Many cancer patients receiving radionuclide therapy have both bulk tumours, which are best treated with high-energy beta particles, and single spread cells or micrometastasis, which are preferably treated with low-energy electrons such as Auger and conversion electrons. Furthermore, the positron-emitting 134La can be used to study kinetics and dosimetry using PET. Production and PET performance were investigated and theoretical dosimetry calculations were made. PET resolution, recovery and quantitative accuracy were slightly degraded for 134La compared to 18F. 134Ce/134La absorbed doses to single cells were higher than absorbed doses from 90Y and 111In. Absorbed doses to spheres representing bulk tumours were almost as high as for 90Y, and a factor 10 higher than for 111In. Whole-body absorbed doses, based on kinetics of the somatostatin analogue octreotide, were higher for 134Ce/134La than for 90Y because of the 134La annihilation photons. This initial study of the therapeutic possibilities of 134Ce/134La is encouraging and justifies further investigations.

  9. Gemcitabine and Oxaliplatin, but Not Sorafenib or Paclitaxel, Have a Synergistic Effect with Yttrium-90 in Reducing Hepatocellular Carcinoma and Cholangiocarcinoma Cell Line Viability.

    PubMed

    Edeline, Julien; Coulouarn, Cédric; Crouzet, Laurence; Pracht, Marc; Lepareur, Nicolas; Clément, Bruno; Garin, Etienne

    2015-12-01

    Synergy between yttrium-90 (90Y) and antineoplastic drugs was investigated. Viability of HepaRG (hepatocellular carcinoma) and HuCCT1 (cholangiocarcinoma) cells was studied through a tetrazolium dye reduction assay. A combination index (CI) was calculated, with CI < 1 denoting synergy and CI > 1 denoting antagonism. In HepaRG cells, gemcitabine showed synergy with 90Y (CI = 0.70 [95% confidence interval = 0.65-0.75]), whereas oxaliplatin (CI = 1.15 [1.08-1.21]), paclitaxel (CI = 1.26 [1.15-1.37]), and sorafenib (CI = 1.77 [1.65-1.89]) showed antagonism. In HuCCT1 cells, gemcitabine (CI = 0.54 [0.50-0.58]) and oxaliplatin (CI = 0.86 [0.82-0.90]) showed synergy with 90Y, whereas paclitaxel (CI = 1.18 [1.09-1.27]) and sorafenib (CI = 1.21 [1.12-1.30]) showed antagonism. These results suggest that gemcitabine and oxaliplatin should be tested in combination with 90Y radioembolization for treatment of liver cancer. PMID:26596183

  10. CALIBRATION OF THERMOLUMINESCENCE AND FILM DOSEMETERS FOR SKIN DOSES FROM HIGH-ACTIVITY MICROPARTICLES.

    PubMed

    Eakins, J S; Hager, L G; Tanner, R J

    2016-09-01

    The use of EXT-RAD™ extremity TLDs and radiochromic film to measure doses from primarily beta-emitting microparticles is discussed. Specific calibration techniques have been developed, using both Monte Carlo modelling and experiments. Results for a (90)Sr/(90)Y microparticle are presented to illustrate the general techniques and to demonstrate reasonable agreement between the dosimetry methods.

  11. A Systematic Review on the Safety and Effectiveness of yttrium-90 Radioembolization for Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis

    PubMed Central

    Jia, Zhongzhi; Jiang, Guomin; Tian, Feng; Zhu, Chunfu; Qin, Xihu

    2016-01-01

    Background/Aim: Over the past two decades, several advances have been made in the management of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT). Yttrium-90 (90Y) radioembolization has recently been made a treatment option for patients with HCC and PVTT. However, there is still a need to systematicly evaluate the outcomes of 90Y radioembolization for HCC and PVTT. We aimed to assess the safety and effectiveness of 90Y radioembolization for HCC and PVTT. We performed a systematic review of clinical trials, clinical studies, and abstracts from conferences that qualified for analysis. Materials and Methods: PubMed, EMBASE, Cochrane Database of Systematic Review, CINAHL, and the “gray” literature (Google Scholar) were searched for all reports (1991-2016) related to 90Y radioembolization for HCC and PVTT. Results: A total of 14 clinical studies and three abstracts from conferences including 722 patients qualified for the analysis. The median length of follow-up was 7.2 months; the median time to progression was 5.6 months, and median disease control rate was 74.3%. Radiological response data were reported in five studies, and the median reported value of patients with complete response, partial response, stable disease, and progressive disease were 3.2%, 16.5%, 31.3%, and 28%, respectively. The median survival was 9.7 months for all patients, including the median overall survival (OS) were 12.1, 6.1 months of Child-Pugh class A and B patients, and the median OS were 6.1, 13.4 months of main and branch PVTT patients, respectively. The common toxicities were fatigue, nausea/vomiting, abdominal pain, mostly not requiring medical intervention needed no medication intervention. Conclusions: 90Y radioembolization is a safe and effective treatment for HCC and PVTT. PMID:27748320

  12. Influence of total-body mass on the scaling of S-factors for patient-specific, blood-based red-marrow dosimetry

    NASA Astrophysics Data System (ADS)

    Traino, A. C.; Ferrari, M.; Cremonesi, M.; Stabin, M. G.

    2007-09-01

    To perform patient-specific, blood-based red-marrow dosimetry, dose conversion factors (the S factors in the MIRD formalism) have to be scaled by patients' organ masses. The dose to red marrow includes both self-dose and cross-irradiation contributions. Linear mass scaling for the self-irradiation term only is usually applied as a first approximation, whereas the cross-irradiation term is considered to be mass independent. Recently, the need of a mass scaling correction on both terms, not necessarily linear and dependent on the radionuclide, has been highlighted in the literature. S-factors taking into account different mass adjustments of organs are available in the OLINDA/EXM code. In this paper, a general algorithm able to fit the mass-dependent factors Srm<--tb and Srm<--rm is suggested and included in a more general equation for red-marrow dose calculation. Moreover, parameters to be considered specifically for therapeutic radionuclides such as 131I, 90Y and 177Lu are reported. The red-marrow doses calculated by the traditional and new algorithms are compared for 131I in ablation therapy (14 pts), 177Lu- (13 pts) and 90Y- (11 pts) peptide therapy for neuroendocrine tumours, and 90Y-Zevalin therapy for NHL (21 pts). The range of differences observed is as follows: -36% to -10% for 131I ablation, -22% to 5% for 177Lu-DOTATATE, -9% to 11% for 90Y-DOTATOC and -8% to 6% for 90Y-Zevalin. All differences are mostly due to the activity in the remainder of the body contributing to cross-irradiation. This paper quantifies the influence of mass scaling adjustment on usually applied therapies and shows how to derive the appropriate parameters for other radionuclides and radiopharmaceuticals.

  13. Patient-Specific Dosimetry of Pretargeted Radioimmunotherapy Using CC49 Fusion Protein in Patients with Gastrointestinal Malignancies.

    SciTech Connect

    Shen, Shang; Forero, Andres; LoBuglio, Albert F.; Breitz, H; Khazaeli, M B.; Fisher, Darrell R.; Wang, W Q.; Meredith, Ruby F.

    2005-04-01

    Patient-Specific Dosimetry of Pretargeted Radioimmunotherapy Using CC49 Fusion Protein in Patients with Gastrointestinal Malignancies. Shen S, Forero A, Lobuglio AF, Breitz H, Khazaeli MB, Fisher DR, Wang W, Meredith RF. Department of Radiation Oncology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama, and Radioisotopes Program at Pacific Northwest National Laboratory, Richland, Washington. Pretargeted radioimmunotherapy (RIT) using CC49 fusion protein, comprised of CC49-(scFv)(4) and streptavidin, in conjunction with (90)Y/(111)In-DOTA-biotin (DOTA = dodecanetetraacetic acid) provides a new opportunity to improve efficacy by increasing the tumor-to-normal tissue dose ratio. To our knowledge, the patient-specific dosimetry of pretargeted (90)Y/(111)In-DOTA-biotin after CC49 fusion protein in patients has not been reported previously. METHODS: Nine patients received 3-step pretargeted RIT: (a) 160 mg/m(2) of CC49 fusion protein, (b) synthetic clearing agent (sCA) at 48 or 72 h later, and (c) (90)Y/(111)In-DOTA-biotin 24 h after the sCA administration. Sequential whole-body (111)In images were acquired immediately and at 2-144 h after injection of (90)Y/(111)In-DOTA-biotin. Geometric-mean quantification with background and attenuation correction was used for liver and lung dosimetry. Effective point source quantification was used for spleen, kidneys, and tumors. Organ and tumor (90)Y doses were calculated based on (111)In imaging data and the MIRD formalism using patient-specific organ masses determined from CT images. Patient-specific marrow doses were determined based on radioactivity concentration in the blood. RESULTS: The (90)Y/(111)In-DOTA-biotin had a rapid plasma clearance, which was biphasic with <10% residual at 8 h. Organ masses ranged from 1,263 to 3,855 g for liver, 95 to 1,009 g for spleen, and 309 to 578 g for kidneys. The patient-specific mean (90)Y dose (cGy/37 MBq, or rad/mCi) was 0.53 (0.32-0.78) to whole body

  14. Cerenkov Counter for In-Situ Groundwater Monitoring of 90Sr

    PubMed Central

    Runkle, Robert C.; Brodzinski, Ronald L.; Jordan, David V.; Hartman, John S.; Hensley, Walter K.; Maynard, Melody A.; Sliger, William A.; Smart, John E.; Todd, Lindsay C.

    2005-01-01

    Groundwater contamination from 90Sr is an environmental challenge posed to present and former nuclear weapons related sites. Traditional methods of extracting groundwater samples and performing laboratory analyses are expensive, time-consuming and induce significant disposal challenges. The authors present here a prototype counter capable of measuring 90Sr groundwater concentrations in-situ at or below the drinking water limit of 8 pCi/liter. The 90Y daughter of 90Sr produces high-energy electrons, which can create Cerenkov light. Photomultiplier tubes convert the Cerenkov light into an electronic pulse, which then undergoes signal processing with standard electronics. Strontium-90 concentrations near the drinking water limit can be measured in a matter of hours if it is in secular equilibrium with the 90Y daughter. The prototype counter is compact, can be deployed in an American Standard 6-inch, well while operated by a single person, and transmits the results to a central monitoring location.

  15. Current status of transarterial radioembolization

    PubMed Central

    Mahnken, Andreas H

    2016-01-01

    Unresectable primary and secondary liver malignancies present a major problem in the treatment of solid tumors. Transarterial radioembolization (TARE) is an increasingly used technique for treating various types of malignant liver tumors. This approach is appealing, as the mechanism of action is independent from other loco-regional treatments and potentially complementary to systemic therapies. There are two commercially available products in use for TARE: 90Y-resin and 90Y-glass microspheres. Currently available data indicates TARE so be safe and effective in hepatocellular carcinoma (HCC) and metastatic liver disease. In HCC the results compare well with chemoembolization, while the role of TARE in combination with kinase inhibitors has yet to be established. Current data on TARE in metastatic liver disease is promising, but there is a strong need for prospective randomized trials comparing TARE and modern chemotherapeutic regimen to support the growing role of TARE in metastatic liver disease. PMID:27247711

  16. A method for energy window optimization for quantitative tasks that includes the effects of model-mismatch on bias: application to Y-90 bremsstrahlung SPECT imaging.

    PubMed

    Rong, Xing; Du, Yong; Frey, Eric C

    2012-06-21

    Quantitative Yttrium-90 ((90)Y) bremsstrahlung single photon emission computed tomography (SPECT) imaging has shown great potential to provide reliable estimates of (90)Y activity distribution for targeted radionuclide therapy dosimetry applications. One factor that potentially affects the reliability of the activity estimates is the choice of the acquisition energy window. In contrast to imaging conventional gamma photon emitters where the acquisition energy windows are usually placed around photopeaks, there has been great variation in the choice of the acquisition energy window for (90)Y imaging due to the continuous and broad energy distribution of the bremsstrahlung photons. In quantitative imaging of conventional gamma photon emitters, previous methods for optimizing the acquisition energy window assumed unbiased estimators and used the variance in the estimates as a figure of merit (FOM). However, for situations, such as (90)Y imaging, where there are errors in the modeling of the image formation process used in the reconstruction there will be bias in the activity estimates. In (90)Y bremsstrahlung imaging this will be especially important due to the high levels of scatter, multiple scatter, and collimator septal penetration and scatter. Thus variance will not be a complete measure of reliability of the estimates and thus is not a complete FOM. To address this, we first aimed to develop a new method to optimize the energy window that accounts for both the bias due to model-mismatch and the variance of the activity estimates. We applied this method to optimize the acquisition energy window for quantitative (90)Y bremsstrahlung SPECT imaging in microsphere brachytherapy. Since absorbed dose is defined as the absorbed energy from the radiation per unit mass of tissues in this new method we proposed a mass-weighted root mean squared error of the volume of interest (VOI) activity estimates as the FOM. To calculate this FOM, two analytical expressions were

  17. Method for preparing radionuclide-labeled chelating agent-ligand complexes

    DOEpatents

    Meares, Claude F.; Li, Min; DeNardo, Sally J.

    1999-01-01

    Radionuclide-labeled chelating agent-ligand complexes that are useful in medical diagnosis or therapy are prepared by reacting a radionuclide, such as .sup.90 Y or .sup.111 In, with a polyfunctional chelating agent to form a radionuclide chelate that is electrically neutral; purifying the chelate by anion exchange chromatography; and reacting the purified chelate with a targeting molecule, such as a monoclonal antibody, to form the complex.

  18. Model-Based Radiation Dose Correction for Yttrium-90 Microsphere Treatment of Liver Tumors With Central Necrosis

    SciTech Connect

    Liu, Ching-Sheng; Lin, Ko-Han; Lee, Rheun-Chuan; Tseng, Hsiou-Shan; Wang, Ling-Wei; Huang, Pin-I; Chao, Liung-Sheau; Chang, Cheng-Yen; Yen, Sang-Hue; Tung, Chuan-Jong; Wang, Syh-Jen; Oliver Wong, Ching-yee

    2011-11-01

    Purpose: The objectives of this study were to model and calculate the absorbed fraction {phi} of energy emitted from yttrium-90 ({sup 90}Y) microsphere treatment of necrotic liver tumors. Methods and Materials: The tumor necrosis model was proposed for the calculation of {phi} over the spherical shell region. Two approaches, the semianalytic method and the probabilistic method, were adopted. In the former method, the range--energy relationship and the sampling of electron paths were applied to calculate the energy deposition within the target region, using the straight-ahead and continuous-slowing-down approximation (CSDA) method. In the latter method, the Monte Carlo PENELOPE code was used to verify results from the first method. Results: The fraction of energy, {phi}, absorbed from {sup 90}Y by 1-cm thickness of tumor shell from microsphere distribution by CSDA with complete beta spectrum was 0.832 {+-} 0.001 and 0.833 {+-} 0.001 for smaller (r{sub T} = 5 cm) and larger (r{sub T} = 10 cm) tumors (where r is the radii of the tumor [T] and necrosis [N]). The fraction absorbed depended mainly on the thickness of the tumor necrosis configuration, rather than on tumor necrosis size. The maximal absorbed fraction {phi} that occurred in tumors without central necrosis for each size of tumor was different: 0.950 {+-} 0.000, and 0.975 {+-} 0.000 for smaller (r{sub T} = 5 cm) and larger (r{sub T} = 10 cm) tumors, respectively (p < 0.0001). Conclusions: The tumor necrosis model was developed for dose calculation of {sup 90}Y microsphere treatment of hepatic tumors with central necrosis. With this model, important information is provided regarding the absorbed fraction applicable to clinical {sup 90}Y microsphere treatment.

  19. Cerenkov Luminescence Endoscopy: Improved Molecular Sensitivity with β−-Emitting Radiotracers

    PubMed Central

    Carpenter, Colin M.; Ma, Xiaowei; Liu, Hongguang; Sun, Conroy; Pratx, Guillem; Wang, Jing; Gambhir, Sanjiv S.; Xing, Lei; Cheng, Zhen

    2015-01-01

    Cerenkov luminescence endoscopy (CLE) is an optical technique that captures the Cerenkov photons emitted from highly energetic moving charged particles (β+ or β−) and can be used to monitor the distribution of many clinically available radioactive probes. A main limitation of CLE is its limited sensitivity to small concentrations of radiotracer, especially when used with a light guide. We investigated the improvement in the sensitivity of CLE brought about by using a β− radiotracer that improved Cerenkov signal due to both higher β-particle energy and lower γ noise in the imaging optics because of the lack of positron annihilation. Methods The signal-to-noise ratio (SNR) of 90Y was compared with that of 18F in both phantoms and small-animal tumor models. Sensitivity and noise characteristics were demonstrated using vials of activity both at the surface and beneath 1 cm of tissue. Rodent U87MG glioma xenograft models were imaged with radiotracers bound to arginine-glycine-aspartate (RGD) peptides to determine the SNR. Results γ noise from 18F was demonstrated by both an observed blurring across the field of view and a more pronounced fall-off with distance. A decreased γ background and increased energy of the β particles resulted in a 207-fold improvement in the sensitivity of 90Y compared with 18F in phantoms. 90Y-bound RGD peptide produced a higher tumor-to-background SNR than 18F in a mouse model. Conclusion The use of 90Y for Cerenkov endoscopic imaging enabled superior results compared with an 18F radiotracer. PMID:25300598

  20. Patient selection for personalized peptide receptor radionuclide therapy using Ga-68 somatostatin receptor PET/CT.

    PubMed

    Kulkarni, Harshad R; Baum, Richard P

    2014-01-01

    Neuroendocrine tumors are malignant solid tumors originating from neuroendocrine cells dispersed throughout the body. Differentiated neuroendocrine tumors overexpress somatostatin receptors (SSTRs), which enable the diagnosis using radiolabeled somatostatin analogues. Internalization and retention within the tumor cell are important for peptide receptor radionuclide therapy using the same peptide. The use of the same DOTA-peptide for SSTR PET/CT using (68)Ga and for peptide receptor radionuclide therapy using therapeutic radionuclides like (177)Lu and (90)Y offers a unique theranostic advantage.

  1. Anti-CD45 radioimmunotherapy without TBI before transplantation facilitates persistent haploidentical donor engraftment.

    PubMed

    Orozco, Johnnie J; Kenoyer, Aimee; Balkin, Ethan R; Gooley, Ted A; Hamlin, Donald K; Wilbur, D Scott; Hylarides, Mark D; Frost, Sofia H L; Mawad, Raya; O'Donnell, Paul; Sandmaier, Brenda M; Fuchs, Ephraim J; Luznik, Leo; Green, Damian J; Gopal, Ajay K; Press, Oliver W; Pagel, John M

    2016-01-21

    Many patients with hematologic malignancies cannot tolerate hematopoietic cell transplantation (HCT), whereas others may not have a compatible human leukocyte antigen-matched donor. To overcome these limitations, we optimized a conditioning regimen employing anti-CD45 radioimmunotherapy (RIT) replacing total body irradiation (TBI) before haploidentical HCT in a murine model. Mice received 200 to 400 μCi (90)Y-anti-CD45 antibody (30F11), with or without fludarabine (5 days starting day -8), with cyclophosphamide (CY; days -2 and +2) for graft-versus-host disease prophylaxis, and 1.5 × 10(7) haploidentical donor bone marrow cells (day 0). Haploidentical bone marrow transplantation (BMT) with 300 μCi (90)Y-anti-CD45 RIT and CY, without TBI or fludarabine, led to mixed chimeras with 81.3 ± 10.6% mean donor origin CD8(+) cells detected 1 month after BMT, and remained stable (85.5 ± 11% mean donor origin CD8(+) cells) 6 months after haploidentical BMT. High chimerism levels were induced across multiple hematopoietic lineages 28 days after haploidentical BMT with 69.3 ± 14.1%, 75.6 ± 20.2%, and 88.5 ± 11.8% CD3(+) T cells, B220(+) B cells, and CD11b(+) myeloid cells, respectively. Fifty percent of SJL leukemia-bearing mice treated with 400 μCi (90)Y-DOTA-30F11, CY, and haploidentical BMT were cured and lived >200 days. Mice treated with 200 μCi (90)Y-DOTA-30F11 had a median overall survival of 73 days, while untreated leukemic mice had a median overall survival of 34 days (P < .001, Mantel-Cox test). RIT-mediated haploidentical BMT without TBI may increase treatment options for aggressive hematologic malignancies. PMID:26576864

  2. Methods and means of checking thermoluminescent and radiophotoluminescent dosimeters

    SciTech Connect

    Fominykh, V.I.; Oborin, A.V.; Sebekin, A.P.; Uryaev, I.A.

    1987-06-01

    The authors discuss methods of checking thermoluminescent and radiophotoluminescent dosimeters which are used often in monitoring radiation safety in various areas including nuclear power stations. When the dosimeters are checked in the fields of standard beta-ray sources, it is recommended that the standard absorbed-dose or equivalent-dose measures for beta radiation should be sources of /sup 90/Sr + /sup 90/Y, /sup 204/Tl, and /sup 147/Pm. Various safety guidelines are discussed.

  3. Feasibility of EBT Gafchromic films for comparison exercises among standard beta radiation fields.

    PubMed

    Benavente, J A; Meira-Belo, L C; Reynaldo, S R; da Silva, T A

    2012-12-01

    The feasibility of using radiochromic films to verify the metrological coherence among standard beta radiation fields was evaluated. Exercises were done between two Brazilian metrology laboratories in beta fields from (90)Sr/(90)Y, (85)Kr and (147)Pm radiation sources. Results showed that the radiochromic film was useful for field mapping aiming uniformity and alignment verification and it was not reliable for absorbed dose measurements only for (147)Pm beta field.

  4. Dosimetric calibration of solid state detectors with low energy β sources

    NASA Astrophysics Data System (ADS)

    Fidanzio, Andrea; Pia Toni, Maria; Capote, Roberto; Pena, Juan; Pasciuti, Katia; Bovi, Maurizio; Perrone, Franco; Azario, Luigi; Lazzeri, Mauro; Gaudino, Diego; Piermattei, Angelo

    2008-01-01

    A PTW Optidos plastic scintillation and a PTW natural diamond detectors were calibrated in terms of absorbed dose to water with β fields produced by 90Sr + 90Y and 85Kr reference sources. Each source was characterized at the Italian National Metrological Institute - the Istituto Nazionale di Metrologia delle Radiazioni Ionizzanti of ENEA (ENEA-INMRI) - for two different series, 1 and 2, of ISO reference β-particle radiation fields. Beam flattening filters were used for the series 1 β fields to give uniform absorbed dose rates over a large area at a source-to-reference plane distance of 30 cm. The series 2 β fields were produced at source-to-reference plane distance of 10 cm, without the beam flattening filters, in order to obtain higher absorbed dose rates. The reference absorbed dose rate values were directly determined by the Italian national standard for β-particle dosimetry (a PTW extrapolation ionization chamber) for the series 1 β fields and by a calibrated transfer standard chamber, (a Capintec thin fixed-volume parallel plate ionization chamber) for the series 2 β fields. Finally the two solid state detectors were calibrated in terms of absorbed dose to water with the series 2 β field. The expanded uncertainties of the calibration coefficients obtained for the plastic scintillation dosimeter were 10% and 12% (2SD) for the 90Sr + 90Y and the 85Kr sources, respectively. The expanded uncertainties obtained for the diamond dosimeter were 10% (2SD) and 16% (2SD) for the 90Sr + 90Y and the 85Kr sources, respectively. The good results obtained with the 90Sr + 90Y and the 85Kr β sources encourage to implement this procedure to calibrate this type of detectors at shorter distances and with other β sources of interest in brachytherapy, for example the 106Ru source.

  5. 75 FR 20010 - In the Matter of: Certain Licensees Requesting Unescorted Access to Radioactive Material; Order...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-16

    ... accordance with the NRC E Filing rule (72 FR 49139, August 28, 2007). The E Filing process requires... Pm-147 400 11,000 Pu-238 0.6 16 Pu-239/Be 0.6 16 Ra-226 0.4 11 Se-75 2 54 Sr-90 (Y-90) 10 270 Tm-170... the following sources outside the safes: Cf-252, 0.12 TBq (3.2 Ci); Co-60, 0.18 TBq (4.9 Ci), and...

  6. Comparison of ⁹⁰Y and ¹⁷⁷Lu measurement capability in UK and European hospitals.

    PubMed

    Fenwick, Andrew; Baker, Michaela; Ferreira, Kelley; Keightley, John

    2014-05-01

    Comparison exercises involving (90)Y and (177)Lu were performed during 2009 and 2012, respectively, to assess the measurement capability of hospitals in the UK and Europe. The results from the measurement of a typical liquid solution of (90)Y show that only 40% of participants could measure the solution to within 5% of the certificated value and that a significant -6% bias was present due to the use of non-standard geometries for the calibration of equipment. The results from the measurement of a standard liquid solution of (177)Lu show that 81% of participants could measure to within 5% of the certificated value and in fact 65% of these results were within 2% of the certificated value, showing administered activities can be far more accurately measured for (177)Lu than for (90)Y and that (177)Lu has a far smaller geometry dependence. These studies were performed to identify specific measurement issues in the user community and to identify areas where future research should be focused. In addition to this the work allows the participants to adjust measurement practice and identify key measurement issues.

  7. Dose Rate Calibration of a Commercial Beta-Particle Irradiator Used In Archeological and Geological Dating

    SciTech Connect

    Bernal, S.M.

    2004-10-31

    The 801E Multiple Sample Irradiator, manufactured by Daybreak Nuclear Systems, is capable of exposing up to 30 samples to beta radiation by placing each sample one by one directly beneath a heavily shielded ceramic Sr-90/Y-90 source and opening a specially designed shutter. Daybreak Nuclear Systems does not provide the {sup 90}Sr/{sup 90}Y dose rate to the sample because of variations of up to 20% in the nominal activity of the beta sources (separately manufactured by AEA Technology). Thus it is left to the end user to determine. Here aluminum oxide doped with carbon (Al{sub 2}O{sub 3}:C), in the form of Landauer's Luxel{trademark}, was irradiated to different known doses using a calibrated {sup 90}Sr/{sup 90}Y beta particle irradiator, and the OSL signal monitored after each irradiation to generate a calibration curve. Comparison of the OSL Signal from the unknown 801E Irradiator dose with the calibration curve enabled the dose and therefore dose rate to be determined. The timing accuracy of the 801E Irradiator was also evaluated and found to be +/- 0.5 seconds. The dose rate of the beta source was found to be 0.147 +/- 0.007 Gy/s.

  8. In situ, high sensitivity, measurement of 90strontium in ground water using Cherenkov light

    NASA Astrophysics Data System (ADS)

    Bowyer, T. W.; Geelhood, B. D.; Hossbach, T. W.; Hansen, R.; Wilcox, W. A.

    2000-03-01

    The measurement of 90Sr in soils and ground water is important for characterization and remediation of radioactively contaminated sites. Measuring the 90Sr content to a few pCi/g of soil has been accomplished based on a design of scintillating fibers in a multilayered configuration measuring the high-energy beta emitted from 90Y decay (when in secular equilibrium with 90Sr), but has not been applied to water because the technique is sensitive to only the first few mm of soil. The volume of the source to which the detector is sensitive limits the theoretical sensitivity of such a detector, unless chemical preprocessing to strip the 90Sr from the water is performed. 90Sr activity in water can be quantified by detecting the high-energy beta particle by the Cherenkov light it produces when the high-energy beta from 90Y passes through the medium. We have used this phenomenon to sensitively measure 90Sr ( 90Y) from a volume of water large enough (765 cm 3) to make very sensitive measurements with short count times. For counting intervals of about 1000 s, we were able to achieve a minimum detectable concentration (MDC) (at 4.65 σ above background) of 14 pCi/L, and for 3000 s counts the MDC dropped to the drinking water limit of 8 pCi/L.

  9. Dose-rate distribution of {sup 32}P-glass microspheres for intra-arterial brachytherapy

    SciTech Connect

    Guimaraes, Carla C.; Moralles, Mauricio; Sene, Frank F.; Martinelli, Jose R.

    2010-02-15

    Purpose: The intra-arterial administration of radioactive glass microspheres is an alternative therapy option for treating primary hepatocellular carcinoma, the main cause of liver cancer death, and metastatic liver cancer, another important kind of cancer induced in the liver. The technique involves the administration of radioactive microspheres in the hepatic artery, which are trapped preferentially in the tumor. Methods: In this work the GEANT4 toolkit was used to calculate the radial dose-rate distributions in water from {sup 32}P-loaded glass microspheres and also from {sup 90}Y-loaded glass microspheres. To validate the toolkit for this application, the authors compared the dose-rate distribution of {sup 32}P and {sup 90}Y point sources in water with data from the International Commission on Radiation Units and Measurements report 72. Results: Tables of radial dose-rate distributions are provided for practical use in brachytherapy planning with these microspheres. Conclusions: The simulations with the microspheres show that the shape of the beta ray energy spectra with respect to the {sup 32}P and {sup 90}Y sources is significantly modified by the glass matrix.

  10. The multichain interleukin 2 receptor: A target for immunotherapy in lymphoma, autoimmune disorders, and organ allografts

    SciTech Connect

    Waldmann, T.A. )

    1990-01-12

    The use of chemotherapeutic agents has cured some types of human cancer. However, many types of cancer either are initially unresponsive or subsequently acquire resistance to chemotherapy. Many in vitro studies have shown selective high-affinity binding of monoclonal antibodies to tumor cells. However, such monoclonal antibodies have to data been relatively ineffective. In the case selected for presentation, the authors used the anti-Tac monoclonal antibody. This antibody is directed against the receptor for IL-2, a receptor expressed on ATL cells but not resting cells. The authors developed alternative cytotoxic agents that could be conjugated to anti-Tac and are effective when bound to the surface of Tac-expressing cells. In one case, they showed that {sup 212}Bi, an {alpha}-emitting radionuclide, conjugated to anti-Tac was well suited for this role. In parallel studies, they bound the {beta}-emitting {sup 90}Y to anti-Tac using chelates that did not permit elution of radiolabeled yttrium from the monoclonal antibody. Rhesus monkeys that received xenografts of cynomolgus hearts showed a marked prolongation of xenograft survival following administration of {sup 90}Y-labeled anti-Tac. Thus, {sup 212}Bi-labeled anti-Tac and {sup 90}Y-labeled anti-Tac are potentially effective and specific immunocytotoxic agents for the elimination of Tac-expressing cells.

  11. RAPID DETERMINATION OF RADIOSTRONTIUM IN SEAWATER SAMPLES

    SciTech Connect

    Maxwell, S.

    2013-01-16

    A new method for the determination of radiostrontium in seawater samples has been developed at the Savannah River National Laboratory (SRNL) that allows rapid preconcentration and separation of strontium and yttrium isotopes in seawater samples for measurement. The new SRNL method employs a novel and effective pre-concentration step that utilizes a blend of calcium phosphate with iron hydroxide to collect both strontium and yttrium rapidly from the seawater matrix with enhanced chemical yields. The pre-concentration steps, in combination with rapid Sr Resin and DGA Resin cartridge separation options using vacuum box technology, allow seawater samples up to 10 liters to be analyzed. The total {sup 89}Sr + {sup 90}Sr activity may be determined by gas flow proportional counting and recounted after ingrowth of {sup 90}Y to differentiate {sup 89}Sr from {sup 90}Sr. Gas flow proportional counting provides a lower method detection limit than liquid scintillation or Cerenkov counting and allows simultaneous counting of samples. Simultaneous counting allows for longer count times and lower method detection limits without handling very large aliquots of seawater. Seawater samples up to 6 liters may be analyzed using Sr Resin for {sup 89}Sr and {sup 90}Sr with a Minimum Detectable Activity (MDA) of 1-10 mBq/L, depending on count times. Seawater samples up to 10 liters may be analyzed for {sup 90}Sr using a DGA Resin method via collection and purification of {sup 90}Y only. If {sup 89}Sr and other fission products are present, then {sup 91}Y (beta energy 1.55 MeV, 58.5 day half-life) is also likely to be present. {sup 91}Y interferes with attempts to collect {sup 90}Y directly from the seawater sample without initial purification of Sr isotopes first and {sup 90}Y ingrowth. The DGA Resin option can be used to determine {sup 90}Sr, and if {sup 91}Y is also present, an ingrowth option with using DGA Resin again to collect {sup 90}Y can be performed. An MDA for {sup 90}Sr of <1 m

  12. Comparison of the targeting characteristics of various radioimmunoconjugates for radioimmunotherapy of neuroblastoma: dosimetry calculations incorporating cross-organ beta doses.

    PubMed

    Ugur, O; Kostakoglu, L; Hui, E T; Fisher, D R; Garmestani, K; Gansow, O A; Cheung, N K; Larson, S M

    1996-01-01

    To optimize the efficacy of radioimmunotherapy (RIT), the ideal antibody-radioisotope combinations should be used to deliver the highest tumor and the lowest normal tissue doses. In a mouse model, tumor and critical organ-absorbed doses delivered by different radioimmunoconjugates were calculated and compared. We used a Medical Internal Radiation Dosimetry (MIRD)-style mouse dosimetry model that incorporates cross-organ beta doses to make refined estimates of the radiation absorbed dose to tissues. Biodistribution data from neuroblastoma xenografted nude mice were used to estimate tumor, organ and bone marrow absorbed dose values for 90Y-3F8, 131I-3F8 and 131I-F(ab')2 fragments. Immunoreactive fractions of the radiolabeled antibodies were comparable. Although tumor uptake of the radioiodinated and radiometal labeled 3F8 was much higher than that of the radioiodinated F(ab')2 fragments (maximum percent injected dose per gram values were 39.4, 33.2 and 20.1 for 131I-3F8, 90Y-3F8 and 131I-F(ab')2, respectively), tumor to nontumor ratios were higher for radioiodinated fragments (with the exception of tumor to kidney ratio). For the minimum tumor dose necessary for complete ablation, the bone marrow received 195, 278 and 401 cGy for 131I-F(ab')2, 131I-3F8 and 90Y-3F8, respectively. Tumor doses were 50.1, 232 and 992 cGy/MBq for 131I-F(ab')2, 131I-3F8 and 90Y-3F8, respectively. Tumor to bone marrow dose, which is defined as the therapeutic index, was 21.5, 14.7 and 10.4 for 131I-F(ab')2, 131I-3F8 and 90Y-3F8. 131I-F(ab')2 fragments produced the highest therapeutic index but also the lowest tumor dose for radioimmunotherapy. Radiometal conjugated IgG produced the highest tumor dose but also the lowest therapeutic index.

  13. Fine-Resolution Voxel S Values for Constructing Absorbed Dose Distributions at Variable Voxel Size

    PubMed Central

    Dieudonné, Arnaud; Hobbs, Robert F.; Bolch, Wesley E.; Sgouros, George; Gardin, Isabelle

    2010-01-01

    This article presents a revised voxel S values (VSVs) approach for dosimetry in targeted radiotherapy, allowing dose calculation for any voxel size and shape of a given SPECT or PET dataset. This approach represents an update to the methodology presented in MIRD pamphlet no. 17. Methods VSVs were generated in soft tissue with a fine spatial sampling using the Monte Carlo (MC) code MCNPX for particle emissions of 9 radionuclides: 18F, 90Y, 99mTc, 111In, 123I, 131I, 177Lu, 186Re, and 201Tl. A specific resampling algorithm was developed to compute VSVs for desired voxel dimensions. The dose calculation was performed by convolution via a fast Hartley transform. The fine VSVs were calculated for cubic voxels of 0.5 mm for electrons and 1.0 mm for photons. Validation studies were done for 90Y and 131I VSV sets by comparing the revised VSV approach to direct MC simulations. The first comparison included 20 spheres with different voxel sizes (3.8–7.7 mm) and radii (4–64 voxels) and the second comparison a hepatic tumor with cubic voxels of 3.8 mm. MC simulations were done with MCNPX for both. The third comparison was performed on 2 clinical patients with the 3D-RD (3-Dimensional Radiobiologic Dosimetry) software using the EGSnrc (Electron Gamma Shower National Research Council Canada)-based MC implementation, assuming a homogeneous tissue-density distribution. Results For the sphere model study, the mean relative difference in the average absorbed dose was 0.20% ± 0.41% for 90Y and −0.36% ± 0.51% for 131I (n = 20). For the hepatic tumor, the difference in the average absorbed dose to tumor was 0.33% for 90Y and −0.61% for 131I and the difference in average absorbed dose to the liver was 0.25% for 90Y and −1.35% for 131I. The comparison with the 3D-RD software showed an average voxel-to-voxel dose ratio between 0.991 and 0.996. The calculation time was below 10 s with the VSV approach and 50 and 15 h with 3D-RD for the 2 clinical patients. Conclusion This new

  14. Tumor lysis syndrome in the era of novel and targeted agents in patients with hematologic malignancies: a systematic review.

    PubMed

    Howard, Scott C; Trifilio, Steven; Gregory, Tara K; Baxter, Nadine; McBride, Ali

    2016-03-01

    Effective new treatments are now available for patients with hematologic malignancies. However, their propensity to cause tumor lysis syndrome (TLS) has not been systematically examined. A literature search identified published Phase I-III clinical trials of monoclonal antibodies (otlertuzumab, brentuximab, obinutuzumab, ibritumomab, ofatumumab); tyrosine kinase inhibitors (alvocidib [flavopiridol], dinaciclib, ibrutinib, nilotinib, dasatinib, idelalisib, venetoclax [ABT-199]); proteasome inhibitors (oprozomib, carfilzomib); chimeric antigen receptor (CAR) T cells; and the proapoptotic agent lenalidomide. Abstracts from major congresses were also reviewed. Idelalisib and ofatumumab had no reported TLS. TLS incidence was ≤5 % with brentuximab vedotin (for anaplastic large-cell lymphoma), carfilzomib and lenalidomide (for multiple myeloma), dasatinib (for acute lymphoblastic leukemia), and oprozomib (for various hematologic malignancies). TLS incidences were 8.3 and 8.9 % in two trials of venetoclax (for chronic lymphocytic leukemia [CLL]) and 10 % in trials of CAR T cells (for B-cell malignancies) and obinutuzumab (for non-Hodgkin lymphoma). TLS rates of 15 % with dinaciclib and 42 and 53 % with alvocidib (with sequential cytarabine and mitoxantrone) were seen in trials of acute leukemias. TLS mitigation was employed routinely in clinical trials of alvocidib and lenalidomide. However, TLS mitigation strategies were not mentioned or stated only in general terms for many studies of other agents. The risk of TLS persists in the current era of novel and targeted therapy for hematologic malignancies and was seen to some extent with most agents. Our findings underscore the importance of continued awareness, risk assessment, and prevention to reduce this serious potential complication of effective anticancer therapy. PMID:26758269

  15. Combined sorafenib and yttrium-90 radioembolization for the treatment of advanced hepatocellular carcinoma

    PubMed Central

    Salman, A.; Simoneau, E.; Hassanain, M.; Chaudhury, P.; Boucher, L.M.; Valenti, D.; Cabrera, T.; Nudo, C.; Metrakos, P.

    2016-01-01

    Background and Aims In this pilot study, we assessed the safety and tolerability of combining sorafenib with 90Y radioembolization for the treatment of unresectable hepatocellular carcinoma (hcc). Methods The study, conducted prospectively during 2009–2012, included eligible patients with unresectable hcc and a life expectancy of at least 12 weeks. Each patient received sorafenib (400 mg twice daily) for 6–8 weeks before 90Y treatment. Safety and tolerability were assessed. Results Of the 40 patients enrolled, 29 completed treatment (combined therapy). In the initial cohort, the most common cause of hcc was hepatitis C (32.5%), and most patients were staged Child A (82.5%). The 29 patients who completed the study had similar baseline characteristics. Grades 1 and 2 toxicities accounted for 77.8% of all adverse events reported. The most common toxicities reported were fatigue (19.0%), alteration in liver function (7.9%), and diarrhea (6.3%). There were 12 grade 3 and 2 grade 4 toxicity events reported. One patient died of liver failure within 30 days after treatment. During the study, the sorafenib dose was reduced in 6 patients (20.7%), and sorafenib had to be interrupted in 4 patients (13.8%) and discontinued in 4 patients (13.8%). The disease control rate was 72.4% per the modified Response Evaluation Criteria in Solid Tumors, and tumour necrosis was observed in 82.8% of patients. Overall survival in patients undergoing combined therapy was 12.4 months. Conclusions Preliminary results demonstrate the safety and tolerability of combining 90Y radioembolization and sorafenib for advanced hcc. A larger prospective study is needed to determine the extent of the survival benefit. PMID:27803608

  16. Intrahepatic Flow Redistribution in Patients Treated with Radioembolization

    SciTech Connect

    Spreafico, Carlo Morosi, Carlo; Maccauro, Marco; Romito, Raffaele; Lanocita, Rodolfo Civelli, Enrico M.; Sposito, Carlo Bhoori, Sherrie; Chiesa, Carlo; Frigerio, Laura F.; Lorenzoni, Alice; Cascella, Tommaso Marchianò, Alfonso; Mazzaferro, Vincenzo

    2015-04-15

    IntroductionIn planning Yttrium-90 ({sup 90}Y)-radioembolizations, strategy problems arise in tumours with multiple arterial supplies. We aim to demonstrate that tumours can be treated via one main feeding artery achieving flow redistribution by embolizing accessory vessels.MethodsOne hundred {sup 90}Y-radioembolizations were performed on 90 patients using glass microspheres. In 19 lesions/17 patients, accessory branches were found feeding a minor tumour portion and embolized. In all 17 patients, the assessment of the complete perfusion was obtained by angiography and single photon emission computerized tomography–computerized tomography (SPECT–CT). Dosimetry, toxicity, and tumor response rate of the patients treated after flow redistribution were compared with the 83 standard-treated patients. Seventeen lesions in 15 patients with flow redistribution were chosen as target lesions and evaluated according to mRECIST criteria.ResultsIn all patients, the complete tumor perfusion was assessed immediately before radioembolization by angiography in all patients and after the {sup 90}Y-infusion by SPECT–CT in 15 of 17 patients. In the 15 assessable patients, the response rate in their 17 lesions was 3 CR, 8 PR, and 6 SD. Dosimetric and toxicity data, as well tumour response rate, were comparable with the 83 patients with regular vasculature.ConclusionsAll embolization procedures were performed successfully with no complications, and the flow redistribution was obtained in all cases. Results in term of toxicity, median dose administered, and radiological response were comparable with standard radioembolizations. Our findings confirmed the intratumoral flow redistribution after embolizing the accessory arteries, which makes it possible to treat the tumour through its single main feeding artery.

  17. Neutron Activated Samarium-153 Microparticles for Transarterial Radioembolization of Liver Tumour with Post-Procedure Imaging Capabilities

    PubMed Central

    Hashikin, Nurul Ab. Aziz; Yeong, Chai-Hong; Abdullah, Basri Johan Jeet; Ng, Kwan-Hoong; Chung, Lip-Yong; Dahalan, Rehir; Perkins, Alan Christopher

    2015-01-01

    Introduction Samarium-153 (153Sm) styrene divinylbenzene microparticles were developed as a surrogate for Yttrium-90 (90Y) microspheres in liver radioembolization therapy. Unlike the pure beta emitter 90Y, 153Sm possess both therapeutic beta and diagnostic gamma radiations, making it possible for post-procedure imaging following therapy. Methods The microparticles were prepared using commercially available cation exchange resin, Amberlite IR-120 H+ (620–830 μm), which were reduced to 20–40 μm via ball mill grinding and sieve separation. The microparticles were labelled with 152Sm via ion exchange process with 152SmCl3, prior to neutron activation to produce radioactive 153Sm through 152Sm(n,γ)153Sm reaction. Therapeutic activity of 3 GBq was referred based on the recommended activity used in 90Y-microspheres therapy. The samples were irradiated in 1.494 x 1012 n.cm-2.s-1 neutron flux for 6 h to achieve the nominal activity of 3.1 GBq.g-1. Physicochemical characterisation of the microparticles, gamma spectrometry, and in vitro radiolabelling studies were carried out to study the performance and stability of the microparticles. Results Fourier Transform Infrared (FTIR) spectroscopy of the Amberlite IR-120 resins showed unaffected functional groups, following size reduction of the beads. However, as shown by the electron microscope, the microparticles were irregular in shape. The radioactivity achieved after 6 h neutron activation was 3.104 ± 0.029 GBq. The specific activity per microparticle was 53.855 ± 0.503 Bq. Gamma spectrometry and elemental analysis showed no radioactive impurities in the samples. Radiolabelling efficiencies of 153Sm-Amberlite in distilled water and blood plasma over 48 h were excellent and higher than 95%. Conclusion The laboratory work revealed that the 153Sm-Amberlite microparticles demonstrated superior characteristics for potential use in hepatic radioembolization. PMID:26382059

  18. Factors affecting ultraviolet-A photon emission from β-irradiated human keratinocyte cells

    NASA Astrophysics Data System (ADS)

    Le, M.; Mothersill, C. E.; Seymour, C. B.; Ahmad, S. B.; Armstrong, A.; Rainbow, A. J.; McNeill, F. E.

    2015-08-01

    The luminescence intensity of 340+/- 5 nm photons emitted from HaCaT (human keratinocyte) cells was investigated using a single-photon-counting system during cellular exposure to 90Y β-particles. Multiple factors were assessed to determine their influence upon the quantity and pattern of photon emission from β-irradiated cells. Exposure of 1× {{10}4} cells/5 mL to 703 μCi resulted in maximum UVA photoemission at 44.8× {{10}3}+/- 2.5× {{10}3} counts per second (cps) from live HaCaT cells (background: 1-5 cps); a 16-fold increase above cell-free controls. Significant biophoton emission was achieved only upon stimulation and was also dependent upon presence of cells. UVA luminescence was measured for 90Y activities 14 to 703 μCi where a positive relationship between photoemission and 90Y activity was observed. Irradiation of live HaCaT cells plated at various densities produced a distinct pattern of emission whereby luminescence increased up to a maximum at 1× {{10}4} cells/5 mL and thereafter decreased. However, this result was not observed in the dead cell population. Both live and dead HaCaT cells were irradiated and were found to demonstrate different rates of photon emission at low β activities (⩽400 μCi). Dead cells exhibited greater photon emission rates than live cells which may be attributable to metabolic processes taking place to modulate the photoemissive effect. The results indicate that photon emission from HaCaT cells is perturbed by external stimulation, is dependent upon the activity of radiation delivered, the density of irradiated cells, and cell viability. It is postulated that biophoton emission may be modulated by a biological or metabolic process.

  19. Factors affecting ultraviolet-A photon emission from β-irradiated human keratinocyte cells.

    PubMed

    Le, M; Mothersill, C E; Seymour, C B; Ahmad, S B; Armstrong, A; Rainbow, A J; McNeill, F E

    2015-08-21

    The luminescence intensity of 340±5 nm photons emitted from HaCaT (human keratinocyte) cells was investigated using a single-photon-counting system during cellular exposure to (90)Y β-particles. Multiple factors were assessed to determine their influence upon the quantity and pattern of photon emission from β-irradiated cells. Exposure of 1 x 10(4) cells/5 mL to 703 μCi resulted in maximum UVA photoemission at 44.8 x 10(3)±2.5 x 10(3) counts per second (cps) from live HaCaT cells (background: 1-5 cps); a 16-fold increase above cell-free controls. Significant biophoton emission was achieved only upon stimulation and was also dependent upon presence of cells. UVA luminescence was measured for (90)Y activities 14 to 703 μCi where a positive relationship between photoemission and (90)Y activity was observed. Irradiation of live HaCaT cells plated at various densities produced a distinct pattern of emission whereby luminescence increased up to a maximum at 1 x 10(4) cells/5 mL and thereafter decreased. However, this result was not observed in the dead cell population. Both live and dead HaCaT cells were irradiated and were found to demonstrate different rates of photon emission at low β activities (⩽400 μCi). Dead cells exhibited greater photon emission rates than live cells which may be attributable to metabolic processes taking place to modulate the photoemissive effect. The results indicate that photon emission from HaCaT cells is perturbed by external stimulation, is dependent upon the activity of radiation delivered, the density of irradiated cells, and cell viability. It is postulated that biophoton emission may be modulated by a biological or metabolic process.

  20. Computer Modeling of Yttrium-90-Microsphere Transport in the Hepatic Arterial Tree to Improve Clinical Outcomes

    SciTech Connect

    Kennedy, Andrew S.; Kleinstreuer, Clement; Basciano, Christopher A.; Dezarn, William A.

    2010-02-01

    Purpose: Radioembolization (RE) via yttrium-90 ({sup 90}Y) microspheres is an effective and safe treatment for unresectable liver malignancies. However, no data are available regarding the impact of local blood flow dynamics on {sup 90}Y-microsphere transport and distribution in the human hepatic arterial system. Methods and Materials: A three-dimensional (3-D) computer model was developed to analyze and simulate blood-microsphere flow dynamics in the hepatic arterial system with tumor. Supplemental geometric and flow data sets from patients undergoing RE were also available to validate the accuracy of the computer simulation model. Specifically, vessel diameters, curvatures, and branching patterns, as well as blood flow velocities/pressures and microsphere characteristics (i.e., diameter and specific gravity), were measured. Three-dimensional computer-aided design software was used to create the vessel geometries. Initial trials, with 10,000 noninteracting microspheres released into the hepatic artery, used resin spheres 32-{mu}m in diameter with a density twice that of blood. Results: Simulations of blood flow subject to different branch-outlet pressures as well as blood-microsphere transport were successfully carried out, allowing testing of two types of microsphere release distributions in the inlet plane of the main hepatic artery. If the inlet distribution of microspheres was uniform (evenly spaced particles), a greater percentage would exit into the vessel branch feeding the tumor. Conversely, a parabolic inlet distribution of microspheres (more particles around the vessel center) showed a high percentage of microspheres exiting the branch vessel leading to the normal liver. Conclusions: Computer simulations of both blood flow patterns and microsphere dynamics have the potential to provide valuable insight on how to optimize {sup 90}Y-microsphere implantation into hepatic tumors while sparing normal tissue.

  1. 3D dosimetry estimation for selective internal radiation therapy (SIRT) using SPECT/CT images: a phantom study

    NASA Astrophysics Data System (ADS)

    Debebe, Senait A.; Franquiz, Juan; McGoron, Anthony J.

    2015-03-01

    Selective Internal Radiation Therapy (SIRT) is a common way to treat liver cancer that cannot be treated surgically. SIRT involves administration of Yttrium - 90 (90Y) microspheres via the hepatic artery after a diagnostic procedure using 99mTechnetium (Tc)-macroaggregated albumin (MAA) to detect extrahepatic shunting to the lung or the gastrointestinal tract. Accurate quantification of radionuclide administered to patients and radiation dose absorbed by different organs is of importance in SIRT. Accurate dosimetry for SIRT allows optimization of dose delivery to the target tumor and may allow for the ability to assess the efficacy of the treatment. In this study, we proposed a method that can efficiently estimate radiation absorbed dose from 90Y bremsstrahlung SPECT/CT images of liver and the surrounding organs. Bremsstrahlung radiation from 90Y was simulated using the Compton window of 99mTc (78keV at 57%). 99mTc images acquired at the photopeak energy window were used as a standard to examine the accuracy of dosimetry prediction by the simulated bremsstrahlung images. A Liqui-Phil abdominal phantom with liver, stomach and two tumor inserts was imaged using a Philips SPECT/CT scanner. The Dose Point Kernel convolution method was used to find the radiation absorbed dose at a voxel level for a three dimensional dose distribution. This method will allow for a complete estimate of the distribution of radiation absorbed dose by tumors, liver, stomach and other surrounding organs at the voxel level. The method provides a quantitative predictive method for SIRT treatment outcome and administered dose response for patients who undergo the treatment.

  2. Comparative Study of Staging Systems for Hepatocellular Carcinoma in 428 Patients Treated with Radioembolization

    PubMed Central

    Memon, Khairuddin; Kulik, Laura M.; Lewandowski, Robert J.; Wang, Edward; Wang, Jonathan; Ryu, Robert K.; Hickey, Ryan; Vouche, Michael; Baker, Talia; Ganger, Daniel; Gates, Vanessa L; Habib, Ali; Mulcahy, Mary F.; Salem, Riad

    2014-01-01

    Purpose To compare the utility of different staging systems and analyzed independent predictors of survival in patients with hepatocellular carcinoma (HCC) treated with 90Y radioembolization. Materials and Methods 428 HCC patients were treated with 90Y from 2004-2011. All patients were staged prospectively by Child-Turcotte-Pugh[CTP], United Network for Organ Sharing, Barcelona Clinic Liver Cancer [BCLC], Okuda classification, Cancer of the Liver Italian Program [CLIP], Groupe d'Etude et de Traitement du Carcinome Hepatocellulaire, Chinese University Prognostic Index and the Japan Integrated System; their ability to predict survival was assessed. Staging systems were compared using cox-regression model, linear trend test, Akaike information criterion (AIC) and Concordance Index (C-index). Uni/Multivariate analyses were employed to assess independent predictors of survival. Results When tested independently, all staging systems provided significant ability to discriminate early (long survival) from advanced disease (worse survival). CLIP provided the most accurate information in predicting survival outcomes (AIC=2993, C-index=0.8503); CTP was least informative (AIC=3074, C-index=0.6445). Independent predictors of survival included ECOG 0 (HR:0.56, CI:0.34-0.93); non-infiltrative tumors (HR:0.62, CI:0.44-0.89); absence of portal venous thrombosis (HR:0.60, CI:0.40-0.89); absence of ascites (HR:0.56, CI:0.40-0.76); albumin ≥2.8 g/dL (HR:0.72, CI:0.55-0.94); alkaline phosphatase ≤200 U/L (HR:0.68, CI:0.50-0.92); and AFP ≤200 ng/mL (HR:0.67, CI:0.51-0.86). Conclusion CLIP was most accurate in predicting HCC survival. Given that not all patients receive the recommended BCLC treatment strategy, this information is relevant for clinical trial design and predicting long-term outcomes following 90Y. PMID:24613269

  3. Synthesis, characterization, and evaluation of radiometal-containing peptide nucleic acids.

    PubMed

    Stephan, Holger; Foerster, Christian; Gasser, Gilles

    2014-01-01

    Peptide nucleic acids (PNAs) have very attractive properties for applications in nuclear medicine. Because PNAs have high selectivity for DNA/RNA recognition, resistance to nuclease/protease degradation, and high thermal and radiolytic stabilities, PNA bioconjugates could transform the areas of diagnostic and therapeutic nuclear medicine. In this book chapter, we report on the current developments towards the preparation of radiometal-containing PNA constructs and summarize the protocols for labeling these probes with (99m)Tc, (111)In, (64)Cu, (90)Y, and (177)Lu.

  4. CCR 20th anniversary commentary: Radioactive Drones for B-cell lymphoma.

    PubMed

    Knox, Susan J; Levy, Ronald

    2015-02-01

    In a study published in the March 1, 1996, issue of Clinical Cancer Research, Knox and colleagues (1) demonstrated the safety and efficacy of Yttirium-90 ((90)Y)-anti-CD20 monoclonal antibody therapy, as well as the benefit of preinfusion of unlabeled antibody on radiolabeled antibody biodistribution. Subsequent clinical trials with this radiolabeled antibody led to regulatory approval of this treatment for B-cell lymphoma. See related article by Knox et al., Clin Cancer Res 1996;2(3) Mar 1996; 457-70.

  5. Radioembolization of the Spleen: A Revisited Approach for the Treatment of Malignant Lymphomatous Splenomegaly

    SciTech Connect

    Muylle, Kristoff; Nguyen, Jasmine; Wind, Alexandre de; Meuleman, Nathalie; Delatte, Philippe; Vanderlinden, Bruno; Roelandts, Martine; Van der Stappen, Anja; Bron, Dominique; Flamen, Patrick

    2013-08-01

    Intraarterial administration of {sup 90}Y microspheres to the spleen in patients with malignant lymphoma was mentioned once in the literature in 1973. This case study illustrates the potential indication of selective internal radiotherapy in a heavily pretreated patient with highly refractory disease with a marginal zone lymphoma in leukemic phase and symptomatic splenomegaly. We describe the clinical course of disease; the biological and clinical response to the treatment after radioembolization; and simulation and dosimetry by multimodal imaging via single-photon emission computed tomography and computed tomography. The advantages of radioembolization for the management of lymphomatous splenomegaly are discussed.

  6. Separation of yttrium-90 and strontium-90 on papers impregnated with ionizable crown ethers

    SciTech Connect

    Wai, C.M.; Du, H.S. )

    1990-11-01

    It has been reported recently that lariat crown ethers with an attached carboxylate group and a suitable cavity size can be made highly selective for the extraction of trivalent lanthanides (1,2). The extraction is reversible with respect to pH and requires no special counteranions. This report describes a simple chromatographic method of separating {sup 90}Y from {sup 90}Sr by using papers impregnated with ionizable crown ethers sym-dibenzo-16-crown-5-oxyacetic acid (I) and its analogue 2-(sym-dibenzo-16-crown-5-oxy)stearic acid (II).

  7. Safety and Efficacy Assessment of Flow Redistribution by Occlusion of Intrahepatic Vessels Prior to Radioembolization in the Treatment of Liver Tumors

    SciTech Connect

    Bilbao, Jose I.; Garrastachu, Puy; Herraiz, Maria J.; Rodriguez, Macarena; Inarrairaegui, Mercedes; Rodriguez, Javier; Hernandez, Carmen; Cuesta, Antonio Martinez de la; Arbizu, Javier; Sangro, Bruno

    2010-06-15

    We evaluated the feasibility, safety, and efficacy of radioembolization (administered from one or two vascular points) after the redistribution of arterial blood flow in the liver in patients with hepatic neoplasms and arterial anatomic peculiarities (AAP). Twenty-four patients with liver neoplasms and AAP (graded according to Michel's classification) were included in the study. During pretreatment angiographic planning, all extrahepatic vessels that could feed the tumor were embolized and the intrahepatic vessels occluded in order to redistribute blood flow. The distribution of microspheres was initially assessed by using technetium-99m-labeled macroaggregated albumin ({sup 99m}Tc-MAA) from one of two vascular points before the administration of yttrium-90 ({sup 90}Y)-radiolabeled resin microspheres. Perfusion of lesions situated in the redistributed segments (L-RS) and nonredistributed segments (L-NRS) were compared by assessing the distribution of {sup 99m}Tc-MAA by SPECT/CT. Perfusion was graded as normal, reduced, or absent. {sup 90}Y resin microspheres were then injected from the same arterial sites as {sup 99m}Tc-MAA and the tumor response recorded 3 months later. The tumor response in L-RS was compared with that in L-NRS and graded as better, similar, or worse. Among 11 patients with type I AAP in whom mainly vessels in segments I-III or IV were occluded, perfusion of L-RS was graded as similar (n = 7) or reduced (n = 4). Among the remaining 13 patients with AAP types III (n = 3), V (n = 4), VIII (n = 3), and others (n = 3) in which aberrant arteries were occluded, perfusion of L-RS was graded as similar (n = 9), reduced (n = 3), or absent (n = 1). Overall, {sup 99m}Tc-MAA was present in the L-RS of 95.8% patients and the distribution of {sup 99m}Tc-MAA in L-RS and L-NRS were graded as similar in 66.6% of patients. Compared with lesions in the L-NRS, tumor response in L-RS was similar in 23 cases and worse in 1 case. No complications were recorded after the

  8. Ophthalmic applicators: An overview of calibrations following the change to SI units

    SciTech Connect

    Holmes, Shannon M.; Micka, John A.; DeWerd, Larry A.

    2009-05-15

    Since the NIST dose to water standard for {sup 90}Sr/{sup 90}Y ophthalmic applicators was introduced, numerous sources have undergone calibration either at NIST or at the University of Wisconsin Accredited Dosimetry Calibration Laboratory (UWADCL). From 1997 to 2008, 222 of these beta-emitting sources were calibrated at the UWADCL, and prior reference source strength values were available for 149 of these sources. A survey of UWADCL ophthalmic applicator calibrations is presented here, demonstrating an average discrepancy of -19% with a standard deviation of {+-}16% between prior reference values and the NIST-traceable UWADCL absorbed dose to water calibrations. Values ranged from -49% to +42%.

  9. Radionuclide therapy in neuroendocrine tumours: a systematic review.

    PubMed

    Gulenchyn, K Y; Yao, X; Asa, S L; Singh, S; Law, C

    2012-05-01

    The purpose of this systematic review was to investigate the effects of therapeutic radiopharmaceuticals in patients with different types of advanced neuroendocrine tumour (NETs). A literature search was carried out in MEDLINE and EMBASE from January 1998 to November 2010. The Cochrane Library (to Issue 10, 2010) and the Standards and Guidelines Evidence Inventory of Cancer Guidelines, including over 1100 English-language cancer guidelines from January 2003 to June 2010, were also checked. No existing systematic reviews or clinical practice guidelines based on a systematic review or randomised controlled trials focusing on this topic were found. Twenty-four fully published articles were abstracted and summarised: 16 articles focused on five peptide receptor radionuclide therapy ((111)In-DTPAOC, (90)Y-DOTALAN, (90)Y-DOTATOC, (90)Y-DOTATATE, and (177)Lu-DOTATATE) and eight focused on (131)I-MIBG treatment. Limited evidence from a historical comparison of studies in one centre supported that (177)Lu-DOTATATE might be associated with greater clinical outcomes compared with (90)Y-DOTATOC or (111)In-DTPAOC. The severe toxicities for (177)Lu-DOTATATE included hepatic insufficiency in 0.6%, myelodysplastic syndrome in 0.8% and renal insufficiency in 0.4% of patients in this study. Insufficient evidence suggested efficacy of (131)I-MIBG in adult NET patients, but the overall tumour response rate from (131)I-MIBG was 27-75% for malignant neuroblastoma, paraganglioma or pheochromocytoma. Haematological toxicities were the main severe side-effects after (131)I-MIBG and 4% of patients developed secondary malignancies in one study. To date, peptide receptor radionuclide therapy seems to be an acceptable option and is relatively safe in adult advanced NET patients with receptor uptake positive on scintigraphy, but patients' renal function must be monitored. (131)I-MIBG may be effective for malignant neuroblastoma, paraganglioma or pheochromocytoma, but its side-effects need to be

  10. OSL response bleaching of BeO samples, using fluorescent light and blue LEDs

    NASA Astrophysics Data System (ADS)

    Groppo, D. P.; Caldas, L. V. E.

    2016-07-01

    The optically stimulated luminescence (OSL) is widely used as a dosimetric technique for many applications. In this work, the OSL response bleaching of BeO samples was studied. The samples were irradiated using a beta radiation source (90Sr+90Y); the bleaching treatments (fluorescent light and blue LEDs) were performed, and the results were compared. Various optical treatment time intervals were tested until reaching the complete bleaching of the OSL response. The best combination of the time interval and bleaching type was analyzed.

  11. Analysis of beta-decay data acquired at the Physikalisch-Technische Bundesanstalt: Evidence of a solar influence

    NASA Astrophysics Data System (ADS)

    Sturrock, P. A.; Steinitz, G.; Fischbach, E.; Parkhomov, A.; Scargle, J. D.

    2016-11-01

    According to an article entitled Disproof of solar influence on the decay rates of 90Sr/90Y by Kossert and Nähle of the Physikalisch-Technische Bundesanstalt (PTB) [1], the PTB measurements show no evidence of variability. We show that, on the contrary, those measurements reveal strong evidence of variability, including an oscillation at 11 year-1 that is suggestive of an influence of internal solar rotation. An analysis of radon beta-decay data acquired at the Geological Survey of Israel (GSI) Laboratory for the same time interval yields strong confirmation of this oscillation.

  12. Safety of knee radiosynovectomy with yttrium - 90

    NASA Astrophysics Data System (ADS)

    Kempińska, M.; Lass, P.; Ćwikła, J. B.; Żbikowski, P.

    2011-09-01

    Radioisotope knee synovectomy is based on an Yttrium - 90 citrate injection (185 - 222 MBq) into the knee joint cavity. The performance of procedure needs participation of a nuclear medicine specialist as well as an orthopedist or a rheumatologist and a technologist, who prepares radiopharmaceuticals. The ionization doses for patients and personnel depend not only on the injected activity, but also on the method and process of injection and the radioactivity measurement procedure used. The aim of this study is the evaluation of the degree of radiation exposure of patients and medical personnel during the performance of therapy with 90Y.

  13. Separation and Purification and Beta Liquid Scintillation Analysis of Sm-151 in Savannah River Site and Hanford Site DOE High Level Waste

    SciTech Connect

    Dewberry, R.A.

    2001-02-13

    This paper describes development work to obtain a product phase of Sm-151 pure of any other radioactive species so that it can be determined in US Department of Energy high level liquid waste and low level solid waste by liquid scintillation {beta}-spectroscopy. The technique provides separation from {mu}Ci/ml levels of Cs-137, Pu alpha and Pu-241 {beta}-decay activity, and Sr-90/Y-90 activity. The separation technique is also demonstrated to be useful for the determination of Pm-147.

  14. CCR 20th anniversary commentary: Radioactive Drones for B-cell lymphoma.

    PubMed

    Knox, Susan J; Levy, Ronald

    2015-02-01

    In a study published in the March 1, 1996, issue of Clinical Cancer Research, Knox and colleagues (1) demonstrated the safety and efficacy of Yttirium-90 ((90)Y)-anti-CD20 monoclonal antibody therapy, as well as the benefit of preinfusion of unlabeled antibody on radiolabeled antibody biodistribution. Subsequent clinical trials with this radiolabeled antibody led to regulatory approval of this treatment for B-cell lymphoma. See related article by Knox et al., Clin Cancer Res 1996;2(3) Mar 1996; 457-70. PMID:25646179

  15. Patient selection for personalized peptide receptor radionuclide therapy using Ga-68 somatostatin receptor PET/CT.

    PubMed

    Kulkarni, Harshad R; Baum, Richard P

    2014-01-01

    Neuroendocrine tumors are malignant solid tumors originating from neuroendocrine cells dispersed throughout the body. Differentiated neuroendocrine tumors overexpress somatostatin receptors (SSTRs), which enable the diagnosis using radiolabeled somatostatin analogues. Internalization and retention within the tumor cell are important for peptide receptor radionuclide therapy using the same peptide. The use of the same DOTA-peptide for SSTR PET/CT using (68)Ga and for peptide receptor radionuclide therapy using therapeutic radionuclides like (177)Lu and (90)Y offers a unique theranostic advantage. PMID:25029937

  16. Relevance of PET for pretherapeutic prediction of doses in peptide receptor radionuclide therapy.

    PubMed

    Blaickner, Matthias; Baum, Richard P

    2014-01-01

    Personalized dosimetry in radionuclide therapy has gained much attention in recent years. This attention has also an impact on peptide receptor radionuclide therapy (PRRT). This article reviews the PET-based imaging techniques that can be used for pretherapeutic prediction of doses in PRRT. More specifically the usage of (86)Y, (90)Y, (68)Ga, and (44)Sc are discussed: their characteristics for PET acquisition, the available peptides for labeling, the specifics of the imaging protocols, and the experiences gained from phantom and clinical studies. These techniques are evaluated with regard to their usefulness for dosimetry predictions in PRRT, and future perspectives are discussed.

  17. Peptide receptor radionuclide therapy for advanced neuroendocrine tumors.

    PubMed

    Bodei, Lisa; Cremonesi, Marta; Kidd, Mark; Grana, Chiara M; Severi, Stefano; Modlin, Irvin M; Paganelli, Giovanni

    2014-08-01

    Peptide receptor radionuclide therapy (PRRT) consists of the systemic administration of a synthetic peptide, labeled with a suitable β-emitting radionuclide, able to irradiate tumors and their metastases via internalization through a specific receptor (usually somatostatin S2), over-expressed on the cell membrane. After almost 2 decades of experience, PRRT, with either (90)Y-octreotide or (177)Lu-octreotate, has established itself to be an efficient and effective therapeutic modality. As a treatment, it is relatively safe up to the known thresholds of absorbed and bio-effective isotope dosages and the renal and hematological toxicity profiles are acceptable if adequate protective measures are undertaken.

  18. Tumor vascular disruption using various radiation types

    PubMed Central

    2014-01-01

    The feasibility of disrupting a tumor’s vascular structure with various radiation types and radionuclides is investigated. Calculated absorbed dose profiles for photons and 4He ions suggest that low-energy beta-gamma and alpha emitting radionuclides can deposit sufficient absorbed dose to disrupt a tumor’s vascular structure while minimizing the dose outside the blood vessel. Candidate radionuclides uniformly distributed in microspheres are theoretically investigated with respect to their vascular disruption potential and to offer an alternative to 90Y microsphere therapy. Requisite activities of candidate low-energy beta-gamma and alpha emitting radionuclides to facilitate vascular disruption are calculated. PMID:24749005

  19. Environmental, health and safety assessment of decommissioning radioisotope thermoelectric generators (RTGs) in northwest Russia.

    PubMed

    Standring, W J F; Dowdall, M; Sneve, M; Selnaes, Ø G; Amundsen, I

    2007-09-01

    This paper presents findings from public health and environmental assessment work that has been conducted as part of a joint Norwegian-Russian project to decommission radioisotope thermoelectric generators (RTG) in northwest Russia. RTGs utilise heat energy from radioactive isotopes, in this case 90Sr and its daughter nuclide 90Y, to generate electricity as a power source. Different accident scenarios based on the decommissioning process for RTGs are assessed in terms of possible radiation effects to humans and the environment. Doses to humans and biota under the worst-case scenario were lower than threshold limits given in ICRP and IAEA literature.

  20. Induction of osteosarcomas in mouse lumbar vertebrae by repeated external beta-irradiation

    SciTech Connect

    Ootsuyama, A.; Tanooka, H.

    1989-03-15

    Besides skin tumors, osteosarcomas were induced at high frequency in the lumbar vertebrae of ICR mice by repeated local external irradiation of the back with /sup 90/Sr-/sup 90/Y beta-rays when irradiation was repeated three times a week until tumors appeared. The optimum dose range for osteosarcoma induction was 250-350 cGy per exposure at the surface of the back, or 125-175 cGy at the depth of the center of the bone. With the same irradiation schedule, the optimal dose of radiation for induction of osteosarcomas was much lower than that for induction of skin tumors.

  1. Initial clinical evaluation of radiolabeled MX-DTPA humanized BrE-3 antibody in patients with advanced breast cancer.

    PubMed

    Kramer, E L; Liebes, L; Wasserheit, C; Noz, M E; Blank, E W; Zabalegui, A; Melamed, J; Furmanski, P; Peterson, J A; Ceriani, R L

    1998-07-01

    To evaluate radiometal-labeled humanized BrE-3 (huBrE-3) monoclonal antibody as a radioimmunolocalization and therapeutic agent in breast cancer patients, tumor localization, pharmacokinetics, radiation dosimetry, and immunogenicity of (111)In-labeled combined 1-p-isothiocyanatobenzyl 3-methyl- and 1-p-isothiocyanatobenzyl 4-methyldiethylenetriamine pentaacetic acid (MX-DTPA) huBrE-3 were studied. Seven women with BrE-3 antigen-positive, metastatic breast carcinoma underwent (111)In huBrE-3 infusion (5 mCi; 50 mg), followed by serial gamma camera imaging and plasma sampling. Region of interest analysis of images was used to make radiation absorbed dose estimates for (111)In huBrE-3. Data were extrapolated to 90Y huBrE-3. Human anti-human antibody (HAHA) response was measured in serum samples obtained up to 3 months after infusion. Patients tolerated infusions well. Seventy-six percent of 105 known sites of disease were identified on planar and single-photon emission computed tomography scans. For six of seven patients, a biexponential model fit the plasma time-activity curve best with an average T1/2alpha=10.6+/-8.5 (SD) h and average T1/2beta=114.2+/-39.2 h. Radiation absorbed dose estimates for (111)In huBrE-3 for whole body averaged 0.53+/-.08 rads/mCi. Dose estimates for 90Y huBrE-3 for marrow averaged 8.4+/-11.9 rads/mCi, and for tumors, 70+/-31.5 rads/mCi. Liver radioactivity uptake averaged 19.7+/-8.8% injected dose at 24 h after infusion, translating into an average radiation absorbed dose 21.1+/-12 rads/90Y mCi administered. Only one of seven patients demonstrated a low level of HAHA response. Although the plasma half-lives are longer and marrow dose higher for radiolabeled huBrE-3 compared with the murine construct, the excellent tumor localization, good tumor dosimetry, and low immunogenicity support the use of 90Y-huBrE-3 antibody for radioimmunotherapy of breast cancer.

  2. Preliminary studies of an 18-crown-6 ether modified magnetic cation exchange polymer in rapid (90)Sr bioassay.

    PubMed

    Hrdina, Amy; Lai, Edward; Li, Chunsheng; Sadi, Baki; Kramer, Gary

    2011-08-01

    A cation exchange polymer resin embedded with magnetic nanoparticles and modified with crown ether was developed for urinalysis to rapidly monitor levels of (90)Sr exposure in humans who have been involved in a nuclear event. Invention of the resin matrix of 2-acrylamido-2-methyl-1-propanesulfonic acid cross-linked with divinylbenzene incorporated a Sr(2+) chelating agent, di-tert-butyl-cyclohexano-18-crown-6 through surface immobilization using a molecular modifier 1-octanol. The performance of these magnetic cation exchange resin particles was investigated by separating (90)Sr in the presence of (90)Y progeny. Masking agents and precipitants were examined to ascertain that sodium hydroxide at pH 7.5 was capable of selectively removing 89 ± 2% (90)Y before subsequent (90)Sr uptake. Preliminary investigations in rapid urinalysis were successful in isolating 83 ± 2% (90)Sr when pH was optimized to 9, with a sample turnover time <2 h, which is promising for radiological emergencies.

  3. Using naturally occurring radionuclides to determine drinking water age in a community water system

    DOE PAGES

    Waples, James T.; Bordewyk, Jason K.; Knesting, Kristina M.; Orlandini, Kent A.

    2015-07-22

    Drinking water quality in a community water system is closely linked to the age of water from initial treatment to time of delivery. However, water age is difficult to measure with conventional chemical tracers; particularly in stagnant water, where the relationship between disinfectant decay, microbial growth, and water age is poorly understood. Using radionuclides that were naturally present in source water, we found that measured activity ratios of 90Y/90Sr and 234Th/238U in discrete drinking water samples of known age accurately estimated water age up to 9 days old (σest: ± 3.8 h, P < 0.0001, r2 = 0.998, n =more » 11) and 25 days old (σest: ± 13.3 h, P < 0.0001, r2 = 0.996, n = 12), respectively. Moreover, 90Y-derived water ages in a community water system (6.8 × 104 m3 d–1 capacity) were generally consistent with water ages derived from an extended period simulation model. Radionuclides differ from conventional chemical tracers in that they are ubiquitous in distribution mains and connected premise plumbing. The ability to measure both water age and an analyte (e.g., chemical or microbe) in any water sample at any time allows for new insight into factors that control drinking water quality.« less

  4. Practical Vascular Anatomy in the Preparation of Radioembolization

    SciTech Connect

    Paprottka, P. M.; Jakobs, T. F.; Reiser, M. F.; Hoffmann, R. T.

    2012-06-15

    As the incidence of primary and metastatic liver cancer continues to increase, the use of minimally invasive techniques as a treatment option is becoming more common. Radioembolization, a form of intra-arterial brachytherapy, is a technique where particles of glass or resin, impregnated with the isotope {sup 90}yttrium ({sup 90}Y), are infused through a catheter directly into the hepatic arteries. This modality is based on the fact that hepatic malignancies receive their blood supply from the hepatic artery, whereas normal hepatocytes are perfused mostly from the portal circulation, which allows delivery of high doses to the tumor vasculature with relative sparing of normal liver tissue. This has been shown to be effective for both primary and metastatic tumors. A variety of complications may be related to hepatic intra-arterial treatments, especially to the gastroduodenal region. These complications are known to come from inadvertent extrahepatic infusion of {sup 90}Y particles, through arteries originating from the hepatic arterial branches such as the falciform artery, cystic artery, arteries from the pancreaticoduodenal arcade, gastroduodenal artery, or right gastric artery. Surgeons and interventional radiologists rely on accurate imaging and assessment of the hepatic arterial supply. It is important to know the common anatomic variations and technical considerations before radioembolization. We recommend an aggressive occlusion of all the above-mentioned arteries; further, clinicians should watch out for any other aberrant branches, and if in doubt, they ought to be coiled.

  5. Beta shapefactor determinations by the cutoff energy yield method

    NASA Astrophysics Data System (ADS)

    Grau Carles, A.

    2005-10-01

    The measurement of spectral deformations due to the forbiddenness of β transitions is commonly resolved by fitting a Kurie plot to experimental data. However, the autoabsorption of the sample and the presence of electromagnetic interferences frequently modify the expected spectral shape, making the determination of the shapefactor function inaccurate in semiconductor and magnetic spectrometers. Although the problem of autoabsorption is not present in liquid-scintillation samples, the sum-coincidence process for pulses and the poor resolution of scintillation spectrometers complicate the deconvolution of the spectra. The goal of this paper is to measure shapefactor functions by making use of observables, such as the maximum point or the cutoff energy yield, which are invariant under resolution changes. As a test of the method, the shapefactor coefficients of the six β-emitters, 36Cl, 204Tl, 210Bi, 89Sr, 90Y and 32P are determined from the analysis of the liquid-scintillation pulse-height spectra. Although the results for 210Bi, 89Sr and 90Y are in good agreement with theory, the measured shapefactors for 36Cl and 204Tl exhibit similar deviations from theory than those referenced in the literature for the Kurie plots.

  6. Autoradiography-based, three-dimensional calculation of dose rate for murine, human-tumor xenografts.

    PubMed

    Koral, K F; Kwok, C S; Yang, F E; Brown, R S; Sisson, J C; Wahl, R L

    1993-11-01

    A Fast Fourier Transform method for calculating the three-dimensional dose rate distribution for murine, human-tumor xenografts is outlined. The required input includes evenly-spaced activity slices which span the tumor. Numerical values in these slices are determined by quantitative 125I autoradiography. For the absorbed dose-rate calculation, we assume the activity from both 131I- and 90Y-labeled radiopharmaceuticals would be distributed as is measured with the 125I label. Two example cases are presented: an ovarian-carcinoma xenograft with an IgG 2ak monoclonal antibody and a neuroblastoma xenograft with meta-iodobenzylguanidine (MIBG). Considering all the volume elements in a tumor, we show, by comparison of histograms and also relative standard deviations, that the measured 125I activity and the calculated 131I dose-rate distributions, are similarly non-uniform and that they are more non-uniform than the calculated 90Y dose-rate distribution. However, the maximum-to-minimum ratio, another measure of non-uniformity, decreases by roughly an order of magnitude from one distribution to the next in the order given above. PMID:8298569

  7. The determination of the rate of conjugation immunoglobuline with bifunctional chelator

    NASA Astrophysics Data System (ADS)

    Málek, Z.; Miler, V.; Budský, F.

    2006-01-01

    The work was performed under the GACR project: "Technology of preparation of radionuclides and their labelled compounds for nuclear medicine and pharmacy with the use of the reactor LVR-15" reg. no. 104/03/0499. Imaging of cell’s antigens with the use of labelled immunoglobulines allows imaging of specific receptors on cell membrane and specific tumours. It is necessary to carry out the labelling of the immunoglobulines with radionuclides of suitable physical properties, which form cations (e.g., 111In, 90Y, 177Lu) that form very strong chelates of sufficiently high stability constant preventing the dissociation of complexes or the radionuclide under “in-vivo” conditions. The immunoglobuline must be conjugated with the bifunctional chelator (BCH), which contains both chelating unit and reactive group for binding to the immunoglobuline. In our laboratory we have conjugated human IgG and monoclonal antibody CD20 with diethylenetriamine pentaacetic acid dianhydride (cDTPAA). Radionuclides 90Y and 177Lu prepared on the LVR-15 reactor in NRI Rez were used for labelling. After conjugation and labelling the yields in relation to the amount of isotopic carrier have been determined.

  8. Shape-Controlled Synthesis of Isotopic Yttrium-90-Labeled Rare Earth Fluoride Nanocrystals for Multimodal Imaging.

    PubMed

    Paik, Taejong; Chacko, Ann-Marie; Mikitsh, John L; Friedberg, Joseph S; Pryma, Daniel A; Murray, Christopher B

    2015-09-22

    Isotopically labeled nanomaterials have recently attracted much attention in biomedical research, environmental health studies, and clinical medicine because radioactive probes allow the elucidation of in vitro and in vivo cellular transport mechanisms, as well as the unambiguous distribution and localization of nanomaterials in vivo. In addition, nanocrystal-based inorganic materials have a unique capability of customizing size, shape, and composition; with the potential to be designed as multimodal imaging probes. Size and shape of nanocrystals can directly influence interactions with biological systems, hence it is important to develop synthetic methods to design radiolabeled nanocrystals with precise control of size and shape. Here, we report size- and shape-controlled synthesis of rare earth fluoride nanocrystals doped with the β-emitting radioisotope yttrium-90 ((90)Y). Size and shape of nanocrystals are tailored via tight control of reaction parameters and the type of rare earth hosts (e.g., Gd or Y) employed. Radiolabeled nanocrystals are synthesized in high radiochemical yield and purity as well as excellent radiolabel stability in the face of surface modification with different polymeric ligands. We demonstrate the Cerenkov radioluminescence imaging and magnetic resonance imaging capabilities of (90)Y-doped GdF3 nanoplates, which offer unique opportunities as a promising platform for multimodal imaging and targeted therapy.

  9. Beta planar source quality assurance with the Fricke xylenol gel dosimeter

    NASA Astrophysics Data System (ADS)

    Alva-Sánchez, Mirko S.; de Oliveira, Lucas N.; Petchevist, Paulo C.; Moreira, Marco V.; de Almeida, Adelaide

    2014-03-01

    Beta therapy is employed in post surgery to treat lesions such as pterygia, keloid and glioblastoma. The beta source most used for these purposes is 90/90Y, whose quality assurance is a challenge, because the detectors currently used for this evaluation do not satisfy the spatial resolution, the effective atomic number and the tissue equivalent conditions. The Fricke xylenol gel (FXG) has been used in several applications in radiotherapy due to its better characteristics. This dosimeter is associated with the Fe(II) to Fe(III) oxidation, post ionizing irradiation, being the final Fe(III) concentration linearly depended on the absorbed dose. The goal of this present work is to show that the FXG, with atomic effective number (Zeff) of 7.75 and high resolution (<1 mm), accomplishes quality assurance for rectangular and square planar 90Sr/90Y sources. In order to demonstrate the quality assurance, calibration curves, percentage depth dose and beam profile from exposed FXG samples were analyzed and from these results, we demonstrate the potential use of the FXG dosimeter for beta source quality control.

  10. Safety of Radioembolization with {sup 90}Yttrium Resin Microspheres Depending on Coiling or No-Coiling of Aberrant/High-Risk Vessels

    SciTech Connect

    Paprottka, P. M. E-mail: philipp.paprottka@med.uni-muenchen.de; Paprottka, K. J. Walter, A.; Haug, A. R.; Trumm, C. G.; Lehner, S. Fendler, W. P.; Jakobs, T. F.; Reiser, M. F.; Zech, C. J.

    2015-08-15

    PurposeTo evaluate the safety of radioembolization (RE) with {sup 90}Yttrium ({sup 90}Y) resin microspheres depending on coiling or no-coiling of aberrant/high-risk vessels.Materials and MethodsEarly and late toxicity after 566 RE procedures were analyzed retrospectively in accordance with the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE v3.0). For optimal safety, aberrant vessels were either coil embolized (n = 240/566, coiling group) or a more peripheral position of the catheter tip was chosen to treat right or left liver lobes (n = 326/566, no-coiling group).ResultsClinically relevant late toxicities (≥Grade 3) were observed in 1 % of our overall cohort. The no-coiling group had significantly less “any” (P = 0.0001) or “clinically relevant” (P = 0.0003) early toxicity. There was no significant difference (P > 0.05) in delayed toxicity in the coiling versus the no-coiling group. No RE-induced liver disease was noted after all 566 procedures.ConclusionRE with {sup 90}Y resin microspheres is a safe and effective treatment option. Performing RE without coil embolization of aberrant vessels prior to treatment could be an alternative for experienced centers.

  11. Kidney dosimetry in ¹⁷⁷Lu and ⁹⁰Y peptide receptor radionuclide therapy: influence of image timing, time-activity integration method, and risk factors.

    PubMed

    Guerriero, F; Ferrari, M E; Botta, F; Fioroni, F; Grassi, E; Versari, A; Sarnelli, A; Pacilio, M; Amato, E; Strigari, L; Bodei, L; Paganelli, G; Iori, M; Pedroli, G; Cremonesi, M

    2013-01-01

    Kidney dosimetry in (177)Lu and (90)Y PRRT requires 3 to 6 whole-body/SPECT scans to extrapolate the peptide kinetics, and it is considered time and resource consuming. We investigated the most adequate timing for imaging and time-activity interpolating curve, as well as the performance of a simplified dosimetry, by means of just 1-2 scans. Finally the influence of risk factors and of the peptide (DOTATOC versus DOTATATE) is considered. 28 patients treated at first cycle with (177)Lu DOTATATE and 30 with (177)Lu DOTATOC underwent SPECT scans at 2 and 6 hours, 1, 2, and 3 days after the radiopharmaceutical injection. Dose was calculated with our simplified method, as well as the ones most used in the clinic, that is, trapezoids, monoexponential, and biexponential functions. The same was done skipping the 6 h and the 3 d points. We found that data should be collected until 100 h for (177)Lu therapy and 70 h for (90)Y therapy, otherwise the dose calculation is strongly influenced by the curve interpolating the data and should be carefully chosen. Risk factors (hypertension, diabetes) cause a rather statistically significant 20% increase in dose (t-test, P < 0.10), with DOTATATE affecting an increase of 25% compared to DOTATOC (t-test, P < 0.05).

  12. Radioisotope research, production, and processing at the University of Missouri Research Reactor

    SciTech Connect

    Ehrhardt, G.J.; Ketring, A.R.; Ja, Wei; Ma, D.; Zinn, K.; Lanigan, J.

    1995-12-31

    The University of Missouri Research Reactor (MURR) is a 10 MW, light-water-cooled and moderated research reactor which first achieved criticality in 1996 and is currently the highest powered university-owned research reactor in the U.S. For many years a major supplier of reactor-produced isotopes for research and commercial purposes, in the last 15 years MURR has concentrated on development of reactor-produced beta-particle emitters for experimental use in nuclear medicine therapy of cancer and rheumatoid arthritis. MURR has played a major role in the development of bone cancer pain palliation with the agents {sup 153}Sm EDTMP and {sup 186}Re/{sup 188}Re HEDP, as well as in the use of {sup 186}Re, {sup 177}Lu, {sup 166}Ho, and {sup 105}Rh for radioimmunotherapy and receptor-agent-guided radiotherapy. MURR is also responsible for the development of therapeutic, {sup 90}Y-labeled glass microspheres for the treatment of liver tumors, a product ({sup 90}Y Therasphere{trademark}) which is currently an approved drug in Canada. MURR has also pioneered the development of {sup 188}W/{sup 188}Re and {sup 99}Mo/{sup 99m}Tc gel generators, which make the use of low specific activity {sup 188}W and {sup 99}Mo practical for such isotope generators.

  13. A new catheter for tumor targeting with radioactive microspheres in representative hepatic artery systems. Part I: impact of catheter presence on local blood flow and microsphere delivery.

    PubMed

    Kleinstreuer, C; Basciano, C A; Childress, E M; Kennedy, A S

    2012-05-01

    Building on previous studies in which the transport and targeting of (90)Y microspheres for liver tumor treatment were numerically analyzed based on medical data sets, this two-part paper discusses the influence of an anchored, radially adjustable catheter on local blood flow and microsphere delivery in an idealized hepatic artery system (Part I). In Part II a patient-inspired case study with necessary conditions for optimal targeting of radioactive microspheres (i.e., yttrium 90) onto liver tumors is presented. A new concept of optimal catheter positioning is introduced for selective targeting of two daughter-vessel exits potentially connected to liver tumors. Assuming laminar flow in rigid blood vessels with an anchored catheter in three controlled positions, the transient three-dimensional (3D) transport phenomena were simulated employing user-enhanced engineering software. The catheter position as well as injection speed and delivery function may influence fluid flow and particle transport. Although the local influences of the catheter may not be negligible, unique cross-sectional particle release zones exist, with which selectively the new controlled targeting methodology would allow optimal microsphere delivery. The insight gained from this analysis paves the way for improved design and testing of a smart microcatheter (SMC) system as well as new investigations leading to even more successful treatment with (90)Y microspheres or combined internal radiation and chemotherapy.

  14. Effectiveness Evaluation of Skin Covers against Intravascular Brachytherapy Sources Using VARSKIN3 Code

    PubMed Central

    Baghani, H R; Nazempour, A R; Aghamiri, S M R; Hosseini Daghigh, S M; Mowlavi, A A

    2013-01-01

    Background and Objective: The most common intravascular brachytherapy sources include 32P, 188Re, 106Rh and 90Sr/90Y. In this research, skin absorbed dose for different covering materials in dealing with these sources were evaluated and the best covering material for skin protection and reduction of absorbed dose by radiation staff was recognized and recommended. Method: Four materials including polyethylene, cotton and two different kinds of plastic were proposed as skin covers and skin absorbed dose at different depths for each kind of the materials was calculated separately using the VARSKIN3 code. Results: The results suggested that for all sources, skin absorbed dose was minimized when using polyethylene. Considering this material as skin cover, maximum and minimum doses at skin surface were related to 90Sr/90Y and 106Rh, respectively. Conclusion: polyethylene was found the most effective cover in reducing skin dose and protecting the skin. Furthermore, proper agreement between the results of VARSKIN3 and other experimental measurements indicated that VRASKIN3 is a powerful tool for skin dose calculations when working with beta emitter sources. Therefore, it can be utilized in dealing with the issue of radiation protection. PMID:25505758

  15. Simulation of beta radiator handling procedures in nuclear medicine by means of a movable hand phantom.

    PubMed

    Blunck, Ch; Becker, F; Urban, M

    2011-03-01

    In nuclear medicine therapies, people working with beta radiators such as (90)Y may be exposed to non-negligible partial body doses. For radiation protection, it is important to know the characteristics of the radiation field and possible dose exposures at relevant positions in the working area. Besides extensive measurements, simulations can provide these data. For this purpose, a movable hand phantom for Monte Carlo simulations was developed. Specific beta radiator handling scenarios can be modelled interactively with forward kinematics or automatically with an inverse kinematics procedure. As a first investigation, the dose distribution on a medical doctor's hand injecting a (90)Y solution was measured and simulated with the phantom. Modelling was done with the interactive method based on five consecutive frames from a video recorded during the injection. Owing to the use of only one camera, not each detail of the radiation scenario is visible in the video. In spite of systematic uncertainties, the measured and simulated dose values are in good agreement.

  16. Cement As a Waste Form for Nuclear Fission Products: The Case of (90)Sr and Its Daughters.

    PubMed

    Dezerald, Lucile; Kohanoff, Jorge J; Correa, Alfredo A; Caro, Alfredo; Pellenq, Roland J-M; Ulm, Franz J; Saúl, Andrés

    2015-11-17

    One of the main challenges faced by the nuclear industry is the long-term confinement of nuclear waste. Because it is inexpensive and easy to manufacture, cement is the material of choice to store large volumes of radioactive materials, in particular the low-level medium-lived fission products. It is therefore of utmost importance to assess the chemical and structural stability of cement containing radioactive species. Here, we use ab initio calculations based on density functional theory (DFT) to study the effects of (90)Sr insertion and decay in C-S-H (calcium-silicate-hydrate) in order to test the ability of cement to trap and hold this radioactive fission product and to investigate the consequences of its β-decay on the cement paste structure. We show that (90)Sr is stable when it substitutes the Ca(2+) ions in C-S-H, and so is its daughter nucleus (90)Y after β-decay. Interestingly, (90)Zr, daughter of (90)Y and final product in the decay sequence, is found to be unstable compared to the bulk phase of the element at zero K but stable when compared to the solvated ion in water. Therefore, cement appears as a suitable waste form for (90)Sr storage.

  17. Rapid method to determine 89Sr/90Sr in large concrete samples

    DOE PAGES

    Maxwell, Sherrod L.; Culligan, Brian; Hutchison, Jay B.; Utsey, Robin C.; Sudowe, Ralf; McAlister, Daniel R.

    2016-03-24

    Here, a new rapid method has been developed that provides high quality low-level measurements of 89,90Sr in concrete samples with an MDA (Minimum Detectable Activity) of <1 mBq g-1. The new method is fast, meets new decommissioning regulatory limits and is robust even if refractory particles are present. The method utilizes a rapid fusion to ensure total dissolution of samples and rapid preconcentration and separation of 89,90Sr from 5-10 g concrete samples. When, the 89Sr/90Sr ratio is high, Sr can be isolated from up to 5g concrete samples, total 89/90Sr measured, and then 90Sr determined via 90Y separated after amore » period of ingrowth. Another approach allows the immediate determination of 90Sr in 10 g concrete aliquots without waiting for 90Y ingrowth, in instances where the shorter lived 89Sr is unlikely to be encountered.« less

  18. Determination of strontium-90 in water and urine samples using ion chromatography.

    PubMed

    Cobb, J; Warwick, P; Carpenter, R C; Morrison, R T

    1994-08-01

    A semi-automated method was developed for the determination of 90Sr in water and urine samples using ion chromatography. Yttrium-90 in secular equilibrium with 90Sr was initially extracted from the sample solution buffered to pH 5 using a high-capacity iminodiacetate chelating resin. At this pH, transition metals, lanthanides and actinides were extracted by the resin. The extracted metals were then transferred on to a separator column where they were separated and eluted as weak acid anionic complexes. The transition metals were eluted first by using a pyridine-2,6-dicarboxylate eluent, then the lanthanides, actinides and 90Y were eluted from the column by using an oxalate-diglycolate eluent. The fraction containing 90Y was then collected and beta-counted. For water samples, a minimum of sample preparation was required prior to chromatography, whereas an oxalate coprecipitation was included as a preconcentration step for urine samples. The derived recoveries for 90Sr for surface water, rain water and urine samples were 91.7 +/- 1.8, 91.9 +/- 1.6 and 90.0 +/- 2.7%, respectively, and the minimum detectable activity using gas flow proportional counting was 8 mBq.

  19. Cement As a Waste Form for Nuclear Fission Products: The Case of (90)Sr and Its Daughters.

    PubMed

    Dezerald, Lucile; Kohanoff, Jorge J; Correa, Alfredo A; Caro, Alfredo; Pellenq, Roland J-M; Ulm, Franz J; Saúl, Andrés

    2015-11-17

    One of the main challenges faced by the nuclear industry is the long-term confinement of nuclear waste. Because it is inexpensive and easy to manufacture, cement is the material of choice to store large volumes of radioactive materials, in particular the low-level medium-lived fission products. It is therefore of utmost importance to assess the chemical and structural stability of cement containing radioactive species. Here, we use ab initio calculations based on density functional theory (DFT) to study the effects of (90)Sr insertion and decay in C-S-H (calcium-silicate-hydrate) in order to test the ability of cement to trap and hold this radioactive fission product and to investigate the consequences of its β-decay on the cement paste structure. We show that (90)Sr is stable when it substitutes the Ca(2+) ions in C-S-H, and so is its daughter nucleus (90)Y after β-decay. Interestingly, (90)Zr, daughter of (90)Y and final product in the decay sequence, is found to be unstable compared to the bulk phase of the element at zero K but stable when compared to the solvated ion in water. Therefore, cement appears as a suitable waste form for (90)Sr storage. PMID:26513644

  20. Lobar Hepatocellular Carcinoma with Ipsilateral Portal Vein Tumor Thrombosis Treated with Yttrium-90 Glass Microsphere Radioembolization: Preliminary Results

    PubMed Central

    Pracht, M.; Edeline, J.; Lenoir, L.; Latournerie, M.; Mesbah, H.; Audrain, O.; Rolland, Y.; Clément, B.; Raoul, J. L.; Garin, E.; Boucher, E.

    2013-01-01

    Portal vein tumor thrombosis (PVTT) is a common complication of hepatocellular carcinoma (HCC) and has a negative impact on prognosis. This characteristic feature led to the rationale of the present trial designed to assess the efficacy and the safety of yttrium-90 glass-microsphere treatment for advanced-stage lobar HCC with ipsilateral PVTT. 18 patients with unresectable lobar HCC and ipsilateral PVTT were treated in our institution with 90Y-microS radioembolization. Patients were evaluated every 3 to 6 months for response, survival, and toxicity. Mean follow-up was 13.0 months (2.2–50.6). Outcomes were: complete response (n = 2), partial response (n = 13), stable disease (n = 1), and progressive disease (n = 2) giving a disease control rate of 88.9%. Four patients were downstaged. Treating lobar hepatocellular carcinoma with ipsilateral portal vein thrombosis with yttrium-90 glass-microsphere radioembolization is safe and efficacious. Further clinical trials are warranted to confirm these results and to compare 90Y-microS with sorafenib, taking into account not only survival but also the possibility of secondary surgery for putative curative intention after downstaging. PMID:23476792

  1. Using Naturally Occurring Radionuclides To Determine Drinking Water Age in a Community Water System.

    PubMed

    Waples, James T; Bordewyk, Jason K; Knesting, Kristina M; Orlandini, Kent A

    2015-08-18

    Drinking water quality in a community water system is closely linked to the age of water from initial treatment to time of delivery. However, water age is difficult to measure with conventional chemical tracers; particularly in stagnant water, where the relationship between disinfectant decay, microbial growth, and water age is poorly understood. Using radionuclides that were naturally present in source water, we found that measured activity ratios of (90)Y/(90)Sr and (234)Th/(238)U in discrete drinking water samples of known age accurately estimated water age up to 9 days old (σest: ± 3.8 h, P < 0.0001, r(2) = 0.998, n = 11) and 25 days old (σest: ± 13.3 h, P < 0.0001, r(2) = 0.996, n = 12), respectively. Moreover, (90)Y-derived water ages in a community water system (6.8 × 10(4) m(3) d(-1) capacity) were generally consistent with water ages derived from an extended period simulation model. Radionuclides differ from conventional chemical tracers in that they are ubiquitous in distribution mains and connected premise plumbing. The ability to measure both water age and an analyte (e.g., chemical or microbe) in any water sample at any time allows for new insight into factors that control drinking water quality.

  2. Isolation of strontium-90, yttrium-90, promethium-147, and cerium-144 from wet ashed urine by calcium oxalate coprecipitation and sequential solvent extraction

    SciTech Connect

    Kramer, G.H.; Davies, J.M.

    1982-01-01

    A method has been developed for separating low-level activities of the ..beta..-emitting isotopes strontium-90, yttrium-90, promethium-147, and cerium-144 from urine and aqueous solutions. They are subsequently estimated by direct counting of sources on planchets or by liquid scintillation counting. The radionuclides are separated from each other and from interfering elements by solvent extraction with HDEHP (di-2-ethylhexyl)phosphoric acid) in n-heptane. It is possible to separate the elements of interest with a minimum cross contamination by selecting appropriate pHs and solvent concentrations. Percentage recoveries for the above radionuclides are as follows: /sup 90/Sr, 100 +- 12; /sup 90/Y, 65 +- 4; /sup 147/Pm, 90 +- 8; /sup 144/Ce, 87 +- 11. The limits of detection are as follows: /sup 90/Sr, 0.6 pCi; /sup 90/Y, 0.7 pCi; /sup 147/Pm, 1.0 pCi; /sup 144/Ce, 0.8 pCi (1 pCi = 37 mBq). 16 references, 2 figures, 2 tables.

  3. Deposition of (90)YPO(4) and (144)CePO(4) radioisotopes on polymer surfaces for radiation delivery devices.

    PubMed

    Qu, Xin; Weinberger, Judah

    2002-01-01

    Intravascular irradiation with beta emitters inhibits restenosis in arteries after balloon angioplasty or stent implantation. Yttrium-90 ((90)Y, T(1/2)=64 h) and cerium-144 ((144)Ce, T(1/2)=286 d) emit beta particles (E(max)=2.28--3.50 MeV) having an ideal energy range for brachytherapy delivery system. In this article, a previously reported method for depositing (32)P on poly(ethylene terephtalate) (PET) surfaces is generalized and modifications that allow deposition of other beta-emitting radioisotopes, such as (90)Y and (144)Ce, are demonstrated. PET films were first coated with chitosan hydrogel and then adsorbed different amounts of phosphoric acid (PA) in aqueous solutions. Yttrium was deposited onto the surface as YPO(4) after the films were immersed in YCl(3) solutions. 1 muCi (90)YCl(3) (2 x 10(-9) g) was used in each sample as a tracer for measuring the deposition efficiency, which is defined as the percentage of YCl(3) deposited on the surface compared to the amount of YCl(3) in solutions before the deposition. In order to improve the safety of brachytherapy treatments, polyurethanes were used to seal the deposited radioisotopes on the surface to minimize the leakage of the isotopes into the patients. The generality of this method presented here for a wide variety of particular radioisotopic components allows design of a broad range of versatile radioisotope sources. PMID:11870641

  4. Luminescence properties after X-ray irradiation for dosimetry

    NASA Astrophysics Data System (ADS)

    Hong, Duk-Geun; Kim, Myung-Jin

    2016-05-01

    To investigate the luminescence characteristics after exposure to X-ray radiation, we developed an independent, small X-ray irradiation system comprising a Varian VF-50J mini X-ray generator, a Pb collimator, a delay shutter, and an Al absorber. With this system, the apparent dose rate increased linearly to 0.8 Gy/s against the emission current for a 50 kV anode potential when the shutter was delayed for an initial 4 s and the Al absorber was 300 µm thick. In addition, an approximately 20 mm diameter sample area was irradiated homogeneously with X rays. Based on three-dimensional (3D) thermoluminescence (TL) spectra, the small X-ray irradiator was considered comparable to the conventional 90Sr/90Y beta source even though the TL intensity from beta irradiation was higher than that from X-ray irradiation. The single aliquot regenerative (SAR) growth curve for the small X-ray irradiator was identical to that for the beta source. Therefore, we concluded that the characteristics of the small X-ray irradiator and the conventional 90Sr/90Y beta source were similar and that X ray irradiation had the potential for being suitable for use in luminescence dosimetry.

  5. Pretherapeutic radioembolization of CNS tumors: Methods, dosimetry and first clinical experience

    SciTech Connect

    Haldemann, A.R.; Roesler, H.; Noelpp, U.

    1994-05-01

    Our experience with transarterial radioembolization using 90Y resin particles ({null} 45-75 {mu}m) after selective catheterization of malignant tumors has shown good palliative results in patients with inoperable hepatocellular carcinoma. This method may be applicable for many inoperable tumors or symptomatic metastases, but selective tumor embolization must be documented prior to therapy. We have started examining highly vascularized tumors of the CNS that are routinely embolized mechanically with microparticles of different sizes in order to reduce the perioperative risk of hemorrhage. In 13 patients (5 meningiomas, 3 dural angiomas, 2 metastasis, 2 chemodectomas and 1 dural fibrosarcoma) 100 MBq 99mTc labelled macroaggregates of albumin ({null} 25-50 {mu}m) were injected intraarterially after transfemoral cathererization of the tumor-feeding artery. The activity in the area of embolization and in the lungs was then recorded using a gamma camera, and the pulmonary shunt rates calculated. In this ongoing study, we found three different patterns of embolization: (1) embolization with pulmonary shunt (up to 76% of injected activity; 3 patients), (2) embolization without pulmonary shunt but sometimes considerable peritumoral embolization (6 patients) and (3) superselective embolization without significant pulmonary or peritumoral embolization (5 patients). In patients of group (3) who would qualify for therapeutic radioembolization, dosimetric calculations resulted in tumor doses of 200-1000 Gy for 370 MBq 90Y resin particles.

  6. The analysis of feasibility and effectiveness of vascular targeting radiotherapy based on a model of tumor growth and angiogenesis

    NASA Astrophysics Data System (ADS)

    Ding, Yihong

    Targeting cytotoxic agents to tumor angiogenesis, instead of the tumor itself, is an attractive new approach in Radiation Oncology. Unlike tumor cells, endothelial cells are less likely to develop radio-resistance. Investigations have shown that radiation can cause a definite increase in cell permeability. Permeability changes in the tumor capillary endothelium can contribute to circulatory failure and serve as a site for clot formation. Therefore, radiation could initiate platelet aggregation and blood coagulation locally within the tumor vasculature, leading to tumor cell killing through depletion of oxygen and nutrients. In order to analyze the efficacy of a potential 90Y-labeled compound for vascular targeting radiotherapy and to evaluate the factors that may affect targets' absorbed dose, a tumor vasculature model including its angiogenesis process as a function of time and tumor growth are adopted and improved from the Liotta model. Its output is used to estimate targets' absorbed doses by Monte Carlo simulation. The results show that the effectiveness of vascular targeting therapy depends on the existence of available tumor endothelial cells and target expression. The alphavbeta3 antagonist model compound is less effective in the early stage tumors, which have very few vessels. Although a high administered dose, such as injecting of 2.1 mCi/kg to saturate all available binding sites, can destroy tumor endothelium network, the toxicity to bone marrow makes it impossible to inject such a dose. To a vascularized tumor, after giving one maximum allowable administered activity, 0.83 mCi/kg for the 90Y-labeled model compound, an average of 9.8%, 27.3%, 34.7% and 37.8% of endothelial cells would be killed when treatment starts at day 4, 7, 9 and 12 after tumor development, respectively. Therefore, recurrent treatment by vascular targeting therapy to well-vascularized tumor has the potential to slow down tumor growth or may even cause tumor regression at the primary

  7. Radioimmunotherapy with radioactive nanoparticles: Biological doses and treatment efficiency for vascularized tumors with or without a central hypoxic area

    SciTech Connect

    Bouchat, V.; Nuttens, V. E.; Michiels, C.; and others

    2010-04-15

    Purpose: Radioactive atoms attached to monoclonal antibodies are used in radioimmunotherapy to treat cancer while limiting radiation to healthy tissues. One limitation of this method is that only one radioactive atom is linked to each antibody and the deposited dose is often insufficient to eradicate solid and radioresistant tumors. In a previous study, simulations with the Monte Carlo N-Particle eXtended code showed that physical doses up to 50 Gy can be delivered inside tumors by replacing the single radionuclide by a radioactive nanoparticle of 5 nm diameter containing hundreds of radioactive atoms. However, tumoral and normal tissues are not equally sensitive to radiation, and previous works did not take account the biological effects such as cellular repair processes or the presence of less radiosensitive cells such as hypoxic cells. Methods: The idea is to adapt the linear-quadratic expression to the tumor model and to determine biological effective doses (BEDs) delivered through and around a tumor. This BED is then incorporated into a Poisson formula to determine the shell control probability (SCP) which predicts the cell cluster-killing efficiency at different distances ''r'' from the center of the tumor. BED and SCP models are used to analyze the advantages of injecting radioactive nanoparticles instead of a single radionuclide per vector in radioimmunotherapy. Results: Calculations of BED and SCP for different distances r from the center of a solid tumor, using the non-small-cell lung cancer as an example, were investigated for {sup 90}Y{sub 2} O{sub 3} nanoparticles. With a total activity of about 3.5 and 20 MBq for tumor radii of 0.5 and 1.0 cm, respectively, results show that a very high BED is deposited in the well oxygenated part of the spherical carcinoma. Conclusions: For either small or large solid tumors, BED and SCP calculations highlight the important benefit in replacing the single {beta}-emitter {sup 90}Y attached to each antibody by a {sup

  8. The patient as a radioactive source: an intercomparison of survey meters for measurements in nuclear medicine.

    PubMed

    Uhrhan, K; Drzezga, A; Sudbrock, F

    2014-11-01

    In this work, the radiation exposure in nuclear medicine is evaluated by measuring dose rates in the proximity of patients and those in close contact to sources like capsules and syringes. A huge number of different survey meters (SMs) are offered commercially. This topic has recently gained interest since dosemeters and active personal dosemeters (APD) for the new dose quantities (ambient and directional dose equivalent) have become available. One main concern is the practical use of SMs and APD in daily clinical routines. Therefore, the radiation field of four common radiopharmaceuticals containing (18)F, (90)Y, (99m)Tc and (131)I in radioactive sources or after application to the patient was determined. Measurements were carried out with different SMs and for several distances. Dose rates decline significantly with the distance to the patient, and with some restrictions, APD can be used as SMs.

  9. A new TDCR-LS counter using Channel photomultiplier tubes.

    PubMed

    Ivan, C; Cassette, P; Sahagia, Maria

    2008-01-01

    A new Triple to Double Coincidence Ratio (TDCR) liquid scintillation (LS) counter using recently available photodetectors, the Channel photomultiplier (CPM) tubes, was constructed and tested in the framework of a scientific cooperation between IFIN-HH and LNHB. The prototype LS counter uses 3CPM tubes arranged symmetrically in an optical chamber around a standard LS vial. The behavior of the prototype was first evaluated with a light emitting diode (LED) light pulser. The counter was then compared against a TDCR counter using conventional photomultiplier tubes, by measuring (55)Fe, (3)H, (63)Ni and (90)Sr/(90)Y LS sources prepared in commercial liquid scintillation cocktails. Although the observed detection efficiency was significantly lower than the one achieved with the traditional counter, we found a remarkable agreement on the activity determination using the two counters. Details on the prototype and the measurement results obtained are discussed in this paper.

  10. Experimental evidence for beta-decay as a source of chirality by enantiomer analysis

    NASA Technical Reports Server (NTRS)

    Bonner, W. A.

    1984-01-01

    Earlier experiments testing the Vester-Ulbricht beta-decay hypothesis for the origin of molecular chirality are reviewed, followed by descriptions of experiments involving attempted asymmetric radiolysis of DL-amino acids using quantitative gas chromotography as a probe for optical activity. The radiation sources included Sr-90-Y-90, C-14, and P-32 Bremsstrahlen, longitudinally polarized electrons from a linear accelerator and longitudinally polarized protons from a cyclotron. With the possible exception of the linear accelerator irradiations, these experiments failed to produce g.c.-detectable enantiomeric excesses, even at 50-70 percent gross radiolysis. Thus no unambiguous support for the Vester-Ulbricht hypothesis is found in any of the attempted asymmetric radiolyses performed to date. Radioracemization, a possible reason for these failures, is discussed.

  11. Interleukin 2 (IL 2) inhibitor in rheumatoid synovial fluid: Correlation with prognosis and soluble IL 2 receptor levels

    SciTech Connect

    Miossec, P.; Elhamiani, M.; Chichehian, B.; D'Angeac, A.D.; Sany, J.; Hirn, M. )

    1990-03-01

    A soluble activity inhibiting over 50% of the CTLL-2 cell line response to recombinant human interleukin 2 (IL 2) was found in 17 of 29 (59%) rheumatoid synovial fluids. To study the prognosis value of this activity, 16 rheumatoid synovial fluids were collected before a radiation synovectomy of the knee with 7 mCi of 90Y. Patients with a good clinical result after the synovectomy had a lower IL 2 inhibitory activity than those with a bad or incomplete result (P less than 0.01). Levels of inhibitory activity and of soluble IL 2 receptors were correlated with each other and with the response of the synovitis to the radiation synovectomy. These results extend the clinical usefulness of soluble IL 2 receptor measurements and indicate a correlation between the immune activation of the rheumatoid synovitis and its clinical activity.

  12. Cerenkov luminescence imaging of human breast cancer: a Monte Carlo simulations study

    NASA Astrophysics Data System (ADS)

    Boschi, F.; Pagliazzi, M.; Spinelli, A. E.

    2016-03-01

    Cerenkov luminescence imaging (CLI) is a novel molecular imaging technique based on the detection of Cerenkov light produced by beta particles traveling through biological tissues. In this paper we simulated using 18F and 90Y the possibility of detecting Cerenkov luminescence in human breast tissues, in order to evaluate the potential of the CLI technique in a clinical setting. A human breast digital phantom was obtained from an 18F-FDG CT-PET scan. The spectral features of the breast surface emission were obtained as well as the simulated images obtainable by a cooled CCD detector. The simulated images revealed a signal to noise ratio equal to 6 for a 300 s of acquisition time. We concluded that a dedicated human Cerenkov imaging detector can be designed in order to offer a valid low cost alternative to diagnostic techniques in nuclear medicine, in particular allowing the detection of beta-minus emitters used in radiotherapy.

  13. A 2D DNA lattice as an ultrasensitive detector for beta radiations.

    PubMed

    Dugasani, Sreekantha Reddy; Kim, Jang Ah; Kim, Byeonghoon; Joshirao, Pranav; Gnapareddy, Bramaramba; Vyas, Chirag; Kim, Taesung; Park, Sung Ha; Manchanda, Vijay

    2014-02-26

    There is growing demand for the development of efficient ultrasensitive radiation detectors to monitor the doses administered to individuals during therapeutic nuclear medicine which is often based on radiopharmaceuticals, especially those involving beta emitters. Recently biological materials are used in sensors in the nanobio disciplines due to their abilities to detect specific target materials or sites. Artificially designed two-dimensional (2D) DNA lattices grown on a substrate were analyzed after exposure to pure beta emitters, (90)Sr-(90)Y. We studied the Raman spectra and reflected intensities of DNA lattices at various distances from the source with different exposure times. Although beta particles have very low linear energy transfer values, the significant physical and chemical changes observed throughout the extremely thin, ∼0.6 nm, DNA lattices suggested the feasibility of using them to develop ultrasensitive detectors of beta radiations.

  14. Fluorescence and phosphorescence of photomultiplier window materials under electron irradiation

    NASA Technical Reports Server (NTRS)

    Viehmann, W.; Eubanks, A. G.; Bredekamp, J. H.

    1974-01-01

    The fluorescence and phosphorescence of photomultiplier window materials under electron irradiation were investigated using a Sr-90/Y-90 beta emitter as the electron source. Spectral emission curves of UV grade, optical grade, and electron-irradiated samples of MGF2 and LiF, CaF2, BaF2, sapphire, fused silica, and UV transmitting glasses were obtained over the spectral range of 200 nm to 650 nm. Fluorescence yields, expressed as the number of counts in a solid angle of 2 pi steradian per 1MeV of incident electron energy deposited, were determined on these materials utilizing photomultiplier tubes with cesium telluride, bialkali, and trialkali (S-20) photocathodes, respectively.

  15. Cerenkov Counter for In-situ Groundwater Monitoring of Sr90

    SciTech Connect

    Runkle, Robert C.; Brodzinski, Ronald L.; Jordan, David V.; Hartman, John S.; Hensley, Walter K.; Maynard, Melody A.; Sliger, William A.; Smart, John E.; Todd, Lindsay C.

    2005-01-15

    Groundwater contamination from 90Sr is an environmental challenge posed to present and former nuclear weapons related sites. Traditional methods of extracting groundwater samples and performing laboratory analyses are expensive, time consuming and induce significant disposal challenges. We present here a prototype counter capable of measuring in-situ 90Sr groundwater concentrations at or above the drinking water limit of 8 pCi/L. The beta-decay of 90Sr, and its daughter 90Y, emits high-energy electrons which create Cerenkov light. Photomultiplier tubes convert the Cerenkov light into an electronic pulse which then undergoes signal processing with standard electronics. Concentrations near the drinking water limit can be measured in a matter of hours if they exist in secular equilibrium. The prototype counter is compact, can be operated by a single person and transmits the results to a central monitoring location.

  16. INTEGRATED CIRCUITS FROM MOBILE PHONES AS POSSIBLE EMERGENCY OSL/TL DOSIMETERS.

    PubMed

    Sholom, S; McKeever, S W S

    2016-09-01

    In this article, optically stimulated luminescence (OSL) data are presented from integrated circuits (ICs) extracted from mobile phones. The purpose is to evaluate the potential of using OSL from components in personal electronic devices such as smart phones as a means of emergency dosimetry in the event of a large-scale radiological incident. ICs were extracted from five different makes and models of mobile phone. Sample preparation procedures are described, and OSL from the IC samples following irradiation using a (90)Sr/(90)Y source is presented. Repeatability, sensitivity, dose responses, minimum measureable doses, stability and fading data were examined and are described. A protocol for measuring absorbed dose is presented, and it was concluded that OSL from these components is a viable method for assessing dose in the days following a radiological incident. PMID:26516131

  17. Experimental determination of the dose deposition profile of a 90Sr beta source.

    PubMed

    Gaza, R; Bulur, E; McKeever, S W S; Soares, C G

    2006-01-01

    Three different methods for characterising the dose deposition profile of a (90)Sr/(90)Y radioactive source are described: GAFChromic film dosimetry, Thermoluminescence (TL) and Optically Stimulated Luminescence (OSL). For the film measurements, GAFChromic film samples were stacked at different depths between polyethylene terephthalate (PET) foils. For TL, the thickness of a TLD-500 dosemeter was gradually reduced by polishing and the TL from chips of different thickness was used in conjunction with a mathematical model based on the exponential attenuation of dose inside the crystal to determine the decay constant for the dose-depth profile. Finally, an OSL reader with confocal stimulation / detection capabilities was used to map the two-dimensional dose distribution in TLD-500 dosemeters as a function of depth. The shapes of the dose deposition profiles obtained from all the investigated methods are in good agreement. PMID:16644945

  18. Use of a Si(Li) detector as β spectrometer.

    PubMed

    Dryák, P; Kovář, P

    2014-05-01

    The aim of this work is to demonstrate the capability of a Si(Li) detector for the measurement of β spectra, despite the energy absorption in air and in the Be window. A simple source holder fixes the source on the symmetry axis at 3mm from the detector window. The β-sources are produced by evaporation on a plastic backing plate. Absorbing materials between the source and the sensitive volume of the detector are 3 mm of air, a Be window, 0.1 μm Si and 20 nm of gold. A model of the detector was created for β spectra simulation using the MCNP 4A code. Experimental spectra of (14)C, (147)Pm, (204)Tl, (90)Sr/(90)Y were compared with simulated spectra.

  19. Structure alterations in Al-Y-based metallic glasses with La and Ni addition

    NASA Astrophysics Data System (ADS)

    Shi, X. M.; Wang, X. D.; Yu, Q.; Cao, Q. P.; Zhang, D. X.; Zhang, J.; Hu, T. D.; Lai, L. H.; Xie, H. L.; Xiao, T. Q.; Jiang, J. Z.

    2016-03-01

    The atomic structures of Al89Y11, Al90Y6.5La3.5, and Al82.8Y6.07Ni8La3.13 metallic glasses have been studied by using high energy X-ray diffraction, X-ray absorption fine structure combined with the ab initio molecular dynamics and reverse Monte Carlo simulations. It is demonstrated that the partial replacement of Y atoms by La has limited improvement of the glass forming ability (GFA), although La atoms reduce the ordering around Y atoms and also the fractions of icosahedron-like polyhedra centered by Al atoms. In contrast, Ni atoms can significantly improve the GFA, which are inclined to locate in the shell of polyhedra centered by Al, Y, and La atoms, mainly forming Ni-centered icosahedron-like polyhedra to enhance the spatial connectivity between clusters and suppress the crystallization.

  20. Influence of voxel size on specific absorbed fractions and S-values in a mouse voxel phantom.

    PubMed

    Mohammadi, A; Kinase, S

    2011-02-01

    Photon and electron specific absorbed fractions (SAFs) and S-values have been evaluated using mouse voxel phantoms. In voxel phantoms, it is important to choose the voxel size carefully since it affects the accuracy of results. In this study, two mouse voxel phantoms were constructed, with cubic voxels, one with 0.1-mm sides and the other with 0.4-mm sides. The sources were considered to be distributed uniformly in the main organs and the radiation transport was simulated using the Monte Carlo code EGS4. It was found that the effect of voxel size on SAFs for self-irradiation was not high (<10 %) for electrons and photons. However, it was appreciable for cross-irradiation especially for electrons. The effect of voxel size was investigated on S-values for some beta emitters such as (131)I, (153)Sm, (188)Re and (90)Y.

  1. [The adaptive strategy of rodent populations living in conditions of radioactive and chemical environmental pollution].

    PubMed

    Liubashevskiĭ, N M; Starichenko, V I

    2010-01-01

    The comparative analysis of demographic, morphological and physiological processes in mouselike rodents in pollution zones (90Sr + 90Y, 137Cs) on East-Ural radioactive track (EURT) and (Cu + Cd + Pb + Zn + SO2) on a site near copper-smelting factory is carried out. The direct (not mediated) defeat of animals by an irradiation leads to inherited adaptation (density preservation, tolerance increase to pollution, migration decrease and so forth). The mediated defeat of animals at pollution by metals influences animals as a result of degradation of a vegetative cover, reducing a forage reserve, shelters and reproduction places. Population is decreasing, migration is increasing. Hence, population reacts onto direct defeat of animals or on inhabitancy locuses degradation, id est unspecifically, without dependence from the physical and chemical nature of pollution.

  2. A digital instrument for nondestructive measurements of coating thicknesses by beta backscattering

    NASA Astrophysics Data System (ADS)

    Farcasiu, D. M.; Apostolescu, T.; Bozdog, H.; Badescu, E.; Bohm, V.; Stanescu, S. P.; Jianu, A.; Bordeanu, C.; Cracium, M. V.

    1992-02-01

    The elements of nondestructive gauging of coatings applied on various metal bases are presented. The intensity of the backscattered beta radiations is related to the thickness of the coating. With a fixed measuring geometry and radioactive sources (147Pm, 204Tl, 90Sr+90Y) the intensity of the backscattered beta particles is dependent on the following parameters: coating thickness, atomic number of the coating material and of the base, the beta particle energy and the surface finish. It can be used for the measurement of a wide range of coating thicknesses provided that the difference between the coating and the support atomic numbers is at least 20%. Fields of application include electronics, electrotechnique and so on.

  3. Application and Dosimetric Requirements for Gallium-68-labeled Somatostatin Analogues in Targeted Radionuclide Therapy for Gastroenteropancreatic Neuroendocrine Tumors.

    PubMed

    Taïeb, David; Garrigue, Philippe; Bardiès, Manuel; Abdullah, Ahmad Esmaeel; Pacak, Karel

    2015-10-01

    Neuroendocrine tumors (NETs) are associated with variable prognosis, with grade 1 and 2 NETs having more favorable outcomes than grade 3. Patients with gastroenteropancreatic (GEP)-NET need individualized interdisciplinary evaluations and treatment. New treatment options have become available with significant improvements in progression-free survival. Peptide receptor radionuclide therapy (PRRT) using (90)Y or (177)Lu-labeled somatostatin analogues (SSTa) has also shown promise in the treatment of advanced progressive NETs. (68)Ga-1,4,7,10-tetraazacyclodecane-1,4,7,10-tetraacetic acid (DOTA)-SSTa can be used as companion imaging agents to assist in radionuclide therapy selection. (68)Ga-DOTA-SSTa PET/computed tomography might also provide information for prognosis, tumor response assessment to PRRT, and internal dosimetry.

  4. DOSE MEASUREMENTS TO THE LENS IN NUCLEAR MEDICINE AND IN FLUOROSCOPY-GUIDED INTERVENTIONAL PROCEDURES: ANALYSIS OF THE RESULTS AND ASSESSMENT OF THE EFFECTIVENESS OF PROTECTIVE EYEWEAR ANTI-X.

    PubMed

    Sarti, G; Busca, F; Carpano, L; Dottore, F Del; Dall'ara, D; Sanniti, S

    2016-09-01

    The new limit of 20 mSv to the lens raises the need for further assessment of the equivalent dose to the lens for nuclear medicine and interventional radiology operators. (a) A measurement campaign was performed in nuclear medicine, (b) a routine monitoring was organised in interventional procedures and (c) the effectiveness of protective eyewear was assessed. In nuclear medicine, for photon fields, the adequacy of Hp(0.07) of dosemeter worn on the trunk is confirmed; with (90)Y, the annual values of Hp(3) measured in therapeutic session are <5 mSv. In interventional procedures, routine monitoring of the dose to the lens must be maintained where the values of Hp(0.07) dosemeter worn on the trunk are higher than one-third of the new limits. The measures carried out have shown that the attenuation factor mean of the protective glasses is equal to ∼4 (range 1.7-11.4).

  5. Bikini Atoll ionizing radiation survey, May 1985-May 1986

    SciTech Connect

    Shingleton, K.L.; Cate, J.L.; Trent, M.G.; Robison, W.L.

    1987-10-01

    Between 1946 and 1958, the United States conducted 23 nuclear tests at the Bikini Atoll in the Marshall Islands, which resulted in extensive radioactive contamination of a number of islands in the atoll and prevented the timely resettlement of the native population. Although the external dose rates from beta and gamma radiation have been previously determined by aerial survey and a variety of ground measurement techniques, technical constraints limited the assessment of external beta dose rates that result from the /sup 137/Cs and /sup 90/Sr//sup 90/Y contamination on the islands. Now, because of the recent development of very thin thermoluminescent dosimeters (TLDs), the external beta dose rates can be measured. 18 refs., 7 figs., 5 tabs.

  6. Detecting Distance between Injected Microspheres and Target Tumor via 3D Reconstruction of Tissue Sections

    SciTech Connect

    Carson, James P.; Kuprat, Andrew P.; Colby, Sean M.; Davis, Cassi A.; Basciano, Christopher; Greene, Kevin; Feo, John T.; Kennedy, Andrew

    2012-08-28

    One treatment increasing in use for solid tumors in the liver is radioembolization via the delivery of 90Y microspheres to the vascular bed within or near the location of the tumor. It is desirable as part of the treatment for the microspheres to embed preferentially in or near the tumor. This work details an approach for analyzing the deposition of microspheres with respect to the location of the tumor. The approach used is based upon thin-slice serial sectioning of the tissue sample, followed by high resolution imaging, microsphere detection, and 3-D reconstruction of the tumor surface. Distance from the microspheres to the tumor was calculated using a fast deterministic point inclusion method.

  7. Society of Nuclear Medicine--57th annual meeting.

    PubMed

    Searle, Ben

    2010-08-01

    The 57th Annual Meeting of the Society of Nuclear Medicine, held in Salt Lake City, UT, USA, included topics covering new developments in imaging agents and radiopharmaceutical therapies in the field of nuclear medicine. This conference report highlights selected presentations related to imaging of the brain, the prediction of heart disease, and the detection and treatment of various cancers. Investigational drugs discussed include TF-2 plus [68Ga]IMP-288 and TF-2 plus [111In]IMP-288 (both Immunomedics Inc), [11C]PBR-170 (Royal Prince Alfred Hospital/Australian Nuclear Science & Technology Organization), [11C]LY-2795050 (Eli Lilly & Co), yttrium (90Y) clivatuzumab tetraxetan (Garden State Cancer Center/Immunomedics Inc), [18F]LMI-1195 (Lantheus Medical Imaging Inc), fluciclovine (18F) (GE Healthcare/Nihon Medi-Physics Co Ltd), [99mTc]MIP-1340 and [99mTc]MIP-1407 (both Molecular Insight Pharmaceuticals Inc).

  8. Threshold-like dose of local beta irradiation repeated throughout the life span of mice for induction of skin and bone tumors

    SciTech Connect

    Ootsuyama, A.; Tanooka, H. )

    1991-01-01

    The backs of female ICR mice were irradiated with beta rays from 90Sr-90Y three times a week throughout life. Previously we observed 100% tumor incidence at five different dose levels ranging from 1.5 to 11.8 Gy per exposure, but no tumor on repeated irradiation with 1.35 Gy for 300 days. In the present study, delay of tumor development was again seen at a dose of 1.5 Gy per exposure, with further delay at 1.0 Gy. The final tumor incidence was 100% with these two doses. At 0.75 Gy per exposure, no tumor appeared within 790 days after the start of irradiation, but one osteosarcoma and one squamous cell carcinoma did finally appear. These findings indicate a threshold-like response of tumor induction in this repeated irradiation system and further suggest that the apparent threshold may be somewhat less than 0.75 Gy per exposure.

  9. A rapid bioassay method for the determination of 90Sr in human urine sample.

    PubMed

    Sadi, Baki B; Li, Chunsheng; Jodayree, Sara; Lai, Edward P C; Kochermin, Vera; Kramer, Gary H

    2010-06-01

    A rapid bioassay method has been developed for the determination of (90)Sr in human urine samples. The method is based on on-cartridge decolourisation of urine sample, separation of (90)Y from (90)Sr on an anion exchange resin column and by determination of (90)Sr using a liquid scintillation analyser (LSA). Separation of (90)Y from (90)Sr was achieved through selective complexation of yttrium with phosphate and subsequent retention of the anionic yttrium phosphate species on anion exchange resin. A total recovery of 97 +/- 2 % was obtained for strontium with three washes. The minimum detectable activity for the method was 0.2 Bq or 40 Bq l(-1). Measurement accuracy (relative bias, B(r)) and repeatability (relative precision, S(B)) of the method for the determination of (90)Sr were found to be -1 and 4.7 %, respectively. Excellent linearity (r(2) > 0.999) was established over an activity range from 3.25 x 10(2) to 3.25 x 10(4) Bq l(-1). The method was also found to be very robust (S(B) < 5 %) against the matrix effect from different urine samples. Performance of the rapid bioassay method for sensitivity, accuracy and repeatability evaluated against the performance criteria for radiobioassay (ANSI N13.30) was found to be in compliant. Considering the simplicity, excellent analytical figures of merit, fast sample turnaround time (<1 h) and cost efficiency (<30 USD per sample) of the developed method, it is very promising as a rapid bioassay method for supporting the medical response to an emergency where internal contamination of (90)Sr is involved.

  10. Development and characterisation of a new Sr selective resin for the rapid determination of ⁹⁰Sr in environmental water samples.

    PubMed

    Surman, J J; Pates, J M; Zhang, H; Happel, S

    2014-11-01

    A new resin selective for Sr has been developed and characterised for the direct binding of (90)Sr from environmental waters with minimal pre-treatment. The new selective resin comprises of a mixture of two extractants, 4,4'(5')-bis-t-butylcyclohexano-18-crown-6 and di(2-ethyl-hexyl)phosphoric acid, sorbed onto Amberchrom CG-71. Sr uptake is shown to be high (the distribution weight coefficient Dw >100 mL g(-1)) across a range of environmentally realistic conditions (pH 2-8 and up to 11,500 mg L(-1) NaCl, 500 mg L(-1) Ca, 400 mg L(-1) K and 1300 mg L(-1) Mg). The Sr capacity of the resin is shown to be 7.7±0.4 mg g(-1), meaning that the resin has a sufficient capacity to quantitatively remove Sr from most environmental water samples. The reasonably fast uptake kinetics of the resin (95±4% of strontium bound within 30 min) results in a resin that is applicable to both batch- and column-type separation procedures. A range of potentially co-extracted radio-elements have been identified and an elution scheme has been developed to separate interferences, including (90)Y, from (90)Sr. The clean elution of (90)Sr permits immediate measurement by radiometric means, with no need for complicated spectral processing or waiting for secular equilibrium between (90)Sr and (90)Y. The characterised resin is applicable for use in rapid determination procedures, enabling the swift analysis of water samples required by monitoring schemes at contaminated nuclear sites and in the aftermath of nuclear accidents.

  11. Radiation Doses to Members of the U.S. Population from Ubiquitous Radionuclides in the Body: Part 1, Autopsy and In Vivo Data

    SciTech Connect

    Watson, David J.; Strom, Daniel J.

    2011-02-25

    This paper is part one of a three-part series investigating annual effective doses to residents of the United States from intakes of ubiquitous radionuclides, including radionuclides occurring naturally, radionuclides whose concentrations are technologically enhanced, and anthropogenic radionuclides. This series of papers explicitly excludes intakes from inhaling 222Rn, 220Rn, and their short-lived decay products; it also excludes intakes of radionuclides in occupational and medical settings. The goal of part one of this work was to review, summarize, and characterize all published and some unpublished data for U.S. residents on ubiquitous radionuclide concentrations in tissues and organs. Forty-five papers and reports were obtained and their data reviewed, and three data sets were obtained via private communication. The 45 radionuclides of interest are the 238U series (14 nuclides), the actinium series (headed by 235U; 11 nuclides), and the 232Th series (11 nuclides); primordial radionuclides 87Rb and 40 K; cosmogenic and fallout radionuclides 14C and 3H; and purely anthropogenic radionuclides 137Cs-137mBa, 129I, and 90Sr-90Y. Measurements judged to be relevant were available for only 15 of these radionuclides: 238U, 235U, 234U, 232Th, 230Th, 228Th, 228Ra, 226Ra, 210Pb, 210Po, 137Cs, 87Rb, 40K, 14C, and 3H. Recent and relevant measurements were not available for 129I and 90Sr-90Y. A total of 11,714 radionuclide concentration measurements were found in one or more tissues or organs from 14 States. Data on age, sex, geographic locations, height, and weight of subjects were available only sporadically. Too often authors did not provide meaningful values of uncertainty of measurements so that variability in data sets is confounded with measurement uncertainty. The following papers detail how these shortcomings are overcome to achieve the goals of the three-part series.

  12. Radioembolization of Symptomatic, Unresectable Neuroendocrine Hepatic Metastases Using Yttrium-90 Microspheres

    SciTech Connect

    Paprottka, Philipp M. Hoffmann, Ralf-T.; Haug, Alexander; Sommer, Wieland H.; Raessler, Franziska; Trumm, Christoph G.; Schmidt, Gerwin P.; Ashoori, Nima; Reiser, Maximilian F.; Jakobs, Tobias F.

    2012-04-15

    Purpose: To evaluate safety, efficacy, and symptom-control of radioembolization in patients with unresectable liver metastases from neuroendocrine tumors (NETLMs). Materials and Methods: Forty-two patients (mean age of 62 years) with treatment-refractory NETLMs underwent radioembolization using yttrium-90 ({sup 90}Y) resin microspheres. Posttreatment tumor response was assessed by cross-sectional imaging using the Response Evaluation Criteria in Solid Tumors (RECIST) and tumor-marker levels. Laboratory and clinical toxicities and clinical symptoms were monitored. Results: The median activity delivered was 1.63 GBq (range 0.63-2.36). Imaging follow-up using RECIST at 3-month follow-up demonstrated partial response, stable disease, and progressive disease in 22.5, 75.0, and 2.5% of patients, respectively. In 97.5% of patients, the liver lesions appeared hypovascular or partially necrotic. The mean follow-up was 16.2 months with 40 patients (95.2%) remaining alive. The median decrease in tumor-marker levels at 3 months was 54.8% (chromogranin A) and 37.3% (serotonin), respectively. There were no acute or delayed toxicities greater than grade 2 according to Common Terminology Criteria for Adverse Events [CTCAE (v3.0)]. No radiation-induced liver disease was noted. Improvement of clinical symptoms 3 months after treatment was observed in 36 of 38 symptomatic patients. Conclusion: Radioembolization with {sup 90}Y-microspheres is a safe and effective treatment option in patients with otherwise treatment-refractory NETLMs. Antitumoral effect is supported by good local tumor control, decreased tumor-marker levels, and improved clinical symptoms. Further investigation is warranted to define the role of radioembolization in the treatment paradigm for NETLMs.

  13. Modular syntheses of H₄octapa and H₂dedpa, and yttrium coordination chemistry relevant to ⁸⁶Y/⁹⁰Y radiopharmaceuticals.

    PubMed

    Price, Eric W; Cawthray, Jacqueline F; Adam, Michael J; Orvig, Chris

    2014-05-21

    The ligands H2dedpa, H4octapa, p-SCN-Bn-H2dedpa, and p-SCN-Bn-H4octapa were synthesized using a new protection chemistry approach, with labile tert-butyl esters replacing the previously used methyl esters as protecting groups for picolinic acid moieties. Additionally, the ligands H2dedpa and p-SCN-Bn-H2dedpa were synthesized using nosyl protection chemistry for the first time. The use of tert-butyl esters allows for deprotection at room temperature in trifluoroacetic acid (TFA), which compares favorably to the harsh conditions of refluxing HCl (6 M) or LiOH that were previously required for methyl ester cleavage. H4octapa has recently been shown to be a very promising (111)In and (177)Lu ligand for radiopharmaceutical applications; therefore, coordination chemistry studies with Y(3+) are described to assess its potential for use with (86)Y/(90)Y. The solution chemistry of H4octapa with Y(3+) is shown to be suitable via solution NMR studies of the [Y(octapa)](-) complex and density functional theory (DFT) calculations of the predicted structure, suggesting properties similar to those of the analogous In(3+) and Lu(3+) complexes. The molecular electrostatic potential (MEP) was mapped onto the molecular surface of the DFT-calculated coordination structures, suggesting very similar and even charge distributions between both the Lu(3+) and Y(3+) complexes of octapa(4-), and coordinate structures between 8 (ligand only) and 9 (ligand and one H2O). Potentiometric titrations determined H4octapa to have a formation constant (log K(ML)) with Y(3+) of 18.3 ± 0.1, revealing high thermodynamic stability. This preliminary work suggests that H4octapa may be a competent ligand for future (86)Y/(90)Y radiopharmaceutical applications.

  14. Lipoprotein Particle Profiles Mark Familial and Sporadic Human Longevity

    PubMed Central

    Heijmans, Bastiaan T; Beekman, Marian; Houwing-Duistermaat, Jeanine J; Cobain, Mark R; Powell, Jonathan; Blauw, Gerard Jan; van der Ouderaa, Frans; Westendorp, Rudi G. J; Slagboom, P. Eline

    2006-01-01

    Background Genetic and biochemical studies have indicated an important role for lipid metabolism in human longevity. Ashkenazi Jewish centenarians and their offspring have large low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles as compared with control individuals. This profile also coincided with a lower prevalence of disease. Here, we investigate whether this observation can be confirmed for familial longevity in an outbred European population and whether it can be extended to sporadic longevity in the general population. Methods and Findings NMR-measured lipoprotein profiles were analyzed in 165 families from the Leiden Longevity Study, consisting of 340 long-lived siblings (females >91 y, males >89 y), 511 of their offspring, and 243 partners of the offspring. Offspring had larger (21.3 versus 21.1 nm; p = 0.020) and fewer (1,470 versus 1,561 nmol/l; p = 0.011) LDL particles than their same-aged partners. This effect was even more prominent in the long-lived siblings (p < 10−3) and could be pinpointed to a reduction specifically in the concentration of small LDL particles. No differences were observed for HDL particle phenotypes. The mean LDL particle sizes in 259 90-y-old singletons from a population-based study were similar to those in the long-lived siblings and thus significantly larger than in partners of the offspring, suggesting that the relevance of this phenotype extends beyond familial longevity. A low concentration of small LDL particles was associated with better overall health among both long-lived siblings (p = 0.003) and 90-y-old singletons (p = 0.007). Conclusions Our study indicates that LDL particle profiles mark both familial and sporadic human longevity already in middle age. PMID:17194192

  15. Uncertainties in electron-absorbed fractions and lung doses from inhaled beta-emitters.

    PubMed

    Farfán, Eduardo B; Bolch, Wesley E; Huston, Thomas E; Rajon, Didier A; Huh, Chulhaeng; Bolch, W Emmett

    2005-01-01

    The computer code LUDUC (Lung Dose Uncertainty Code), developed at the University of Florida, was originally used to investigate the range of potential doses from the inhalation of either plutonium or uranium oxides. The code employs the ICRP Publication 66 Human Respiratory Tract model; however, rather than using simple point estimates for each of the model parameters associated with particle deposition, clearance, and lung-tissue dosimetry, probability density functions are ascribed to these parameters based upon detailed literature review. These distributions are subsequently sampled within LUDUC using Latin hypercube sampling techniques to generate multiple (e.g., approximately 1,000) sets of input vectors (i.e., trials), each yielding a unique estimate of lung dose. In the present study, the dosimetry component of the ICRP-66 model within LUDUC has been extended to explicitly consider variations in the beta particle absorbed fraction due to corresponding uncertainties and biological variabilities in both source and target tissue depths and thicknesses within the bronchi and bronchioles of the thoracic airways. Example dose distributions are given for the inhalation of absorption Type S compounds of 90Sr (Tmax = 546 keV) and 90Y (Tmax = 2,284 keV) as a function of particle size. Over the particle size range of 0.001 to 1 microm, estimates of total lung dose vary by a factor of 10 for 90Sr particles and by a factor of 4 to 10 for 90Y particles. As the particle size increases to 10 microm, dose uncertainties reach a factor of 100 for both radionuclides. In comparisons to identical exposures scenarios run by the LUDEP 2.0 code, Reference Man doses for inhaled beta-emitters were shown to provide slightly conservative estimates of lung dose compared to those in this study where uncertainties in lung airway histology are considered.

  16. Neuroendocrine tumor targeting: study of novel gallium-labeled somatostatin radiopeptides in a rat pancreatic tumor model.

    PubMed

    Froidevaux, Sylvie; Eberle, Alex N; Christe, Martine; Sumanovski, Lazar; Heppeler, Axel; Schmitt, Jörg S; Eisenwiener, Klaus; Beglinger, Christoph; Mäcke, Helmut R

    2002-04-20

    Somatostatin analogs labeled with radionuclides are of considerable interest in the diagnosis and therapy of SSTR-expressing tumors, such as gastroenteropancreatic, small cell lung, breast and frequently nervous system tumors. In view of the favorable physical characteristics of the Ga isotopes (67)Ga and (68)Ga, enabling conventional tumor scintigraphy, PET and possibly internal radiotherapy, we focused on the development of a Ga-labeled somatostatin analog suitable for targeting SSTR-expressing tumors. For this purpose, 3 somatostatin analogs, OC, TOC and TATE were conjugated to the metal chelator DOTA and labeled with the radiometals (111)In, (90)Y and (67)Ga. They were then evaluated for their performance in the AR4-2J pancreatic tumor model by testing SSTR2-binding affinity, internalization/externalization in isolated cells and biodistribution in tumor-bearing nude mice. Surprisingly, we found that, compared to (111)In or (90)Y, labeling with (67)Ga considerably improved the biologic performance of the tested somatostatin analogs with respect to SSTR2 affinity and tissue distribution. (67)Ga-labeled DOTA-somatostatin analogs were rapidly excreted from nontarget tissues, leading to excellent tumor-to-nontarget tissue uptake ratios. Of interest for radiotherapeutic application, [(67)Ga]DOTATOC was strongly internalized by AR4-2J cells. Furthermore, our results suggest a link between the radioligand charge and its kidney retention. The excellent tumor selectivity of Ga-DOTA somatostatin analogs together with the different applications of Ga in nuclear oncology suggests that Ga-DOTA somatostatin analogs will become an important tool in the management of SSTR-positive tumors.

  17. Dosimetry Model for Radioactivity Localized to Intestinal Mucosa

    SciTech Connect

    Fisher, Darrell R.; Rajon, Didier; Breitz, Hazel B.; Goris, Michael L.; Bolch, Wesley E.; Knox, Susan J.

    2004-06-30

    This paper provides a new model for calculating radiation absorbed dose to the full thickness of the small and large intestinal walls, and to the mucosal layers. The model was used to estimate the intestinal radiation doses from yttrium-90-labeled-DOTA-biotin binding to NR-LU-10-streptavidin in patients. We selected model parameters from published data and observations and used the model to calculate energy absorbed fractions using the EGS4 radiation transport code. We determined the cumulated 90Y activity in the small and large intestines of patients from gamma camera images and calculated absorbed doses to the mucosal layer and to the whole intestinal wall. The mean absorbed dose to the wall of the small intestine was 16.2 mGy/MBq (60 cGy/mCi) administered from 90Y localized in the mucosa and 70 mGy/MBq (260 cGy/mCi) to the mucosal layer within the wall. Doses to the large intestinal wall and to the mucosa of the large intestine were lower than those for small intestine by a factor of about 2.5. These doses are greater by factors of about 5 to 6 than those that would have been calculated using the standard MIRD models that assume the intestinal activity is in the bowel contents. The specific uptake of radiopharmaceuticals in mucosal tissues may lead to dose-related intestinal toxicities. Tissue dosimetry at the sub-organ level is useful for better understanding intestinal tract radiotoxicity and associated dose-response relationships.

  18. TH-C-17A-02: New Radioluminescence Strategies Based On CRET (Cerenkov Radiation Energy Transfer) for Imaging and Therapy

    SciTech Connect

    Volotskova, O; Sun, C; Pratx, G; Xing, L

    2014-06-15

    Purpose: Cerenkov photons are produced when charged particles, emitted from radionuclides, travel through a media with a speed greater than that of the light in the media. Cerenkov radiation is mostly in the UV/Blue region and, thus, readily absorbed by biological tissue. Cerenkov Radiation Energy Transfer (CRET) is a wavelength-shifting phenomenon from blue Cerenkov light to more penetrating red wavelengths. We demonstrate the feasibility of in-depth imaging of CRET light originating from radionuclides realized by down conversion of gold nanoclusters (AuNCs, a novel particle composed of few atoms of gold coated with serum proteins) in vivo. Methods: Bovine Serum Albumin, Human Serum Albumin and Transferrin conjugated gold nanoclusters were synthesized, characterized and examined for CRET. Three different clinically used radiotracers: 18F-FDG, 90Y and 99mTc were used. Optical spectrum (440–750 nm) was recorded by sensitive bioluminescence imaging system at physiological temperature. Dose dependence (activity range from 0.5 up to 800uCi) and concentration dependence (0.01 to 1uM) studies were carried out. The compound was also imaged in a xenograft mouse model. Results: Only β+ and β--emitting radionuclides (18F-FDG, 90Y) are capable of CRET; no signal was found in 99mTc (γ-emitter). The emission peak of CRET by AuNCs was found to be ∼700 nm and was ∼3 fold times of background. In vitro studies showed a linear dependency between luminescence intensity and dose and concentration. CRET by gold nanoclusters was observed in xenografted mice injected with 100uCi of 18F-FDG. Conclusion: The unique optical, transport and chemical properties of AuNCs (gold nanoclusters) make them ideal candidates for in-vivo imaging applications. Development of new molecular imaging probes will allow us to achieve substantially improved spatiotemporal resolution, sensitivity and specificity for tumor imaging and detection.

  19. A preclinical model of CD38-pretargeted radioimmunotherapy for plasma cell malignancies

    PubMed Central

    Green, Damian J.; Orgun, Nural N.; Jones, Jon C.; Hylarides, Mark D.; Pagel, John M.; Hamlin, Donald K.; Wilbur, D.S.; Lin, Yukang; Fisher, Darrell R.; Kenoyer, Aimee L.; Frayo, Shani L.; Gopal, Ajay K.; Orozco, Johnnie J.; Gooley, Theodore A.; Wood, Brent L.; Bensinger, William I.; Press, Oliver W.

    2014-01-01

    The vast majority of patients with plasma cell neoplasms die of progressive disease despite high response rates to novel agents. Malignant plasma cells are very radiosensitive, but the potential role of radioimmunotherapy (RIT) in the management of plasmacytomas and multiple myeloma (MM) has undergone only limited evaluation. Furthermore, CD38 has not been explored as a RIT target despite its uniform high expression on plasma cell malignancies. In this report, both conventional RIT (directly radiolabeled antibody) and streptavidin-biotin pretargeted RIT (PRIT) directed against the CD38 antigen, were assessed as approaches to deliver radiation doses sufficient for MM cell eradication. PRIT demonstrated biodistributions that were markedly superior to conventional RIT. Tumor-to-blood ratios as high as 638:1 were seen 24hr after PRIT, while ratios never exceeded 1:1 with conventional RIT. 90Yttrium absorbed dose estimates demonstrated excellent target-to-normal organ ratios (6:1 for the kidney, lung, liver; 10:1 for the whole body). Objective remissions were observed within 7 days in 100% of the mice treated with doses ranging from 800 µCi to 1200 µCi of anti-CD38 pretargeted 90Y-DOTA-biotin, including 100% complete remissions (no detectable tumor in treated mice compared to tumors that were 2982±2834% of initial tumor volume in control animals) by day 23. Furthermore, 100% of animals bearing NCI-H929 multiple myeloma tumor xenografts treated with 800 µCi of anti-CD38 pretargeted 90Y-DOTA-biotin achieved long-term myeloma-free survival (>70 days) compared to none (0%) of the control animals. PMID:24371230

  20. Modeling of dose to tumor and normal tissue from intraperitoneal radioimmunotherapy with alpha and beta emitters

    SciTech Connect

    Roeske, J.C.; Chen, G.T.; Atcher, R.W.; Pelizzari, C.A.; Rotmensch, J.; Haraf, D.; Montag, A.; Weichselbaum, R.R. )

    1990-12-01

    Dose distributions for normal and tumor tissues from intraperitoneally administered radiolabeled antibodies have been calculated for 90-Yttrium (90Y), 131-Iodine (131I), and 211-Astatine (211At). The dose calculations use data on the activity of intraperitoneal fluid administered, the percent injected dose/gm uptake by tumor, biological half life, and a model for diffusion of antibody/radionuclide complex into peritoneal tissues. Calculations are performed for planar and hemispherical tumor shapes, ranging in size to establish the influence of geometry on dose distribution. Calculations for tumor geometry obtained from biopsies are also performed. When the activity is concentrated on or near the tumor surface, the maximum dose to a planar tumor for a 20 mci administration of 90Y is approximately 60 Gy, and falls rapidly to 50% of this value within 1 mm. However, for a hemispherical tumor, the dose is a maximum of 26 Gy, with an average of approximately 20 Gy. The surface dose from 131I (130 mci) is 240 Gy, and diminishes to 20 Gy in .05 cm in the planar case, whereas a hemispherical tumor receives a dose of 90 Gy over a large fraction of the volume, with the distal portions receiving 40 Gy. The surface dose for an administration of 70 mci of 211 At is 450 Gy and decreases to 50% of this value in 30 microns. Both surface geometry and tumor size are important determinants in the heterogeneity of tumor dose, as are the dose administered, antibody uptake, biodistribution, and residence time factors. These initial studies suggest that the size of disease which may be effectively treated is much less than the range of the particle emitted by radiolabeled antibodies. Furthermore, therapy is ultimately limited by the degree to which the antibody/radionuclide complex can diffuse and permeate the tumor.

  1. Significant impact of transient deterioration of renal function on dosimetry in PRRT.

    PubMed

    Van Binnebeek, Sofie; Baete, Kristof; Terwinghe, Christelle; Vanbilloen, Bert; Haustermans, Karin; Mortelmans, Luc; Borbath, Ivan; Van Cutsem, Eric; Verslype, Chris; Mottaghy, Felix M; Verbruggen, Alfons; Deroose, Christophe M

    2013-01-01

    Peptide receptor radionuclide therapy (PRRT), with (90)Y-DOTATOC and (177)Lu-DOTATATE as most clinically used radiopeptides, is widely used in the management of metastatic neuroendocrine tumors. With respect to radiation dosimetry, the kidneys are the critical organ for (90)Y-DOTATOC. Renal irradiation is significant because of reabsorption of the radiopeptide from the proximal tubuli and the resulting retention in the interstitium, mainly in the inner cortical zone. The high energy and consequently wide range in tissue of the yttrium-90 beta particle result in high absorbed doses to the kidney cortex and medulla. Accurate renal dosimetry can help minimizing radiation nephropathy. We report a case of a 69-year-old candidate for PRRT with an acceptable kidney function at the time of screening. When performing (111)In-octreotide pretreatment dosimetry 3 weeks later, we observed a drastic deterioration in kidney function, caused by undisclosed non-steroidal anti-inflammatory drug intake. The calculated kidney biological effective dose (BED) was 153 Gy after four projected cycles. PRRT was canceled as our full-course BED limit is 37 Gy and the patient was switched to morphine analgesics. Renal function normalized after 3 months and repeated dosimetry yielded an acceptable kidney BED of 28 Gy after four projected cycles (7 Gy/cycle). This case emphasizes that acute kidney insufficiency can yield toxic kidney doses in a single therapy cycle, with an inherent risk of persistent renal insufficiency. All clinical factors which might influence kidney function should be verified at screening and before PRRT administration.

  2. Radioimmunotherapy of infectious diseases

    PubMed Central

    Dadachova, Ekaterina; Casadevall, Arturo

    2009-01-01

    The need for novel approaches to treat infectious diseases is obvious and urgent. This situation has renewed interest in using monoclonal antibodies (mAbs) in therapy of infectious diseases. During the last 5 years radioimmunotherapy (RIT), a modality developed for cancer treatment, has been successfully adapted for the treatment of experimental fungal (C. neoformans and H. capsulatum), bacterial (S. pneumoniae and B. anthracis) and viral (HIV-1) infections. RIT produced none or only transient hematological toxicity in experimental animals. Investigation of radiobiological mechanisms of RIT of infections showed that microbial cells are killed by both "direct hit" and "cross-fire" radiation. MAbs radiolabeled with either alpha- or beta-emitters stimulated apoptosis-like cell death, while only mAbs radiolabeled with alpha-emitter 213Bi also decreased the metabolic activity of microbial cells. The success of this approach in laboratory studies combined with earlier nuclear medicine experience on pre-clinical and clinical studies utilizing radiolabeled organism-specific antibodies for imaging of infections provides encouragement for feasibility of therapeutically targeting microbes with labeled antibodies. We envision that first the organism-specific mAbs will be radiolabeled with imaging radionuclides such as 99mTc or 111In to localize the sites of infection with SPECT followed by RIT with 188Re- or 90Y-labeled mAb, respectively. Also, immunoPET might be utilized for imaging of infection before treatment if such positron-emitting radionuclides as 86Y (matching pair for 90Y) or 124I (matching pair for 131I) are available. It might be possible to create a so-called “pan-antibody” which would recognize an antigen shared by a particular class of human pathogens such as fungi, for example. The availability of such antibodies would eliminate the necessity of having antibodies specific for each particular microorganism and would enormously enhance the development of RIT

  3. Histochemical Phosphatases and Metachromasia in Murine Tumours Induced by Bone Seeking Radionuclides

    PubMed Central

    Bland, M. R.; Loutit, J. F.; Sansom, Janet M.

    1974-01-01

    Tumours induced in mice, either CBA normal and chimaerical, or C3H, by 90Sr or 226Ra or plutonium have been examined histochemically with (1) diazotate fast red violet LB salt in naphthol AS-MX phosphate buffer at pH 8·6 and 5·2, (2) 1: 9 dimethyl methylene blue (Taylor). It is concluded: (a) The diagnosis of osteosarcoma is facilitated with Taylor's Blue which stains osteoid metachromatically. Cells of osteosarcoma, like normal osteoblasts, contain alkaline phosphatase but this may be lost by mutation either in the original tumour or subsequently on passage of the tumour serially to compatible hosts. (b) Osteosarcomata may contain giant-cells of two forms, bizarre tumour cells and osteoclasts; the latter contain acid phosphatase. Osteosarcomata which retain their osteoid on serial passage have few cells containing acid phosphatases. (c) Primitive mesenchymal cell tumours of angiomatous form may occur, if the bone marrow is irradiated, e.g. by 90Sr-90Y and Pu. These tumours lack osteoid and cells interpretable as osteoblasts or osteoclasts (though they destroy bone). (d) Tumours classifiable as fibrosarcomata occur rarely, and may be truly of fibroblastic origin or be mutated osteosarcomata. (e) Lymphomata also occur when the marrow is irradiated (90Sr-90Y and Pu). They may be generalized, when their cells may contain alkaline phosphatase or lack it. They may be localized to abdominal viscera, the reticulo-sarcomatous form, in which case the cells lack alkaline phosphatase. ImagesFig. 1Fig. 3Fig. 5Fig. 8Fig. 10Fig. 11Fig. 2Fig. 4Fig. 6Fig. 7Fig. 9Fig. 12 PMID:4133784

  4. A miniature MOSFET radiation dosimeter probe.

    PubMed

    Gladstone, D J; Lu, X Q; Humm, J L; Bowman, H F; Chin, L M

    1994-11-01

    Prototype miniature dosimeter probes have been designed, built, and characterized employing a small, radiation sensitive metal oxide semiconductor field effect transistor (MOSFET) chip to measure, in vivo, the total accumulated dose and dose rate as a function of time after internal administration of long range beta particle radiolabeled antibodies and in external high energy photon and electron beams. The MOSFET detector is mounted on a long narrow alumina substrate to facilitate electrical connection. The MOSFET, alumina substrate, and lead wires are inserted into a 16 gauge flexineedle, which, in turn, may be inserted into tissue. The radiation dosimeter probe has overall dimensions of 1.6 mm diam and 3.5 cm length. The MOSFET probe signals are read, stored, and analyzed using an automated data collection and analysis system. Initially, we have characterized the probe's response to long range beta particle emission from 90Y sources in solution and to high energy photon and electron beams from linear accelerators. Since the prototype has a finite substrate thickness, the angular dependence has been studied using beta particle emission from a 90Sr source. Temperature dependence and signal drift have been characterized and may be corrected for. Measurements made in spherical volumes containing 90Y with diameters less than the maximum electron range, to simulate anticipated geometries in animal models, agree well with Berger point kernel and EGS4 Monte Carlo calculations. The results from the prototype probes lead to design requirements for detection of shorter range beta particles used in radioimmunotherapy and lower photon energies used in brachytherapy. PMID:7891632

  5. Uncertainties in electron-absorbed fractions and lung doses from inhaled beta-emitters.

    PubMed

    Farfán, Eduardo B; Bolch, Wesley E; Huston, Thomas E; Rajon, Didier A; Huh, Chulhaeng; Bolch, W Emmett

    2005-01-01

    The computer code LUDUC (Lung Dose Uncertainty Code), developed at the University of Florida, was originally used to investigate the range of potential doses from the inhalation of either plutonium or uranium oxides. The code employs the ICRP Publication 66 Human Respiratory Tract model; however, rather than using simple point estimates for each of the model parameters associated with particle deposition, clearance, and lung-tissue dosimetry, probability density functions are ascribed to these parameters based upon detailed literature review. These distributions are subsequently sampled within LUDUC using Latin hypercube sampling techniques to generate multiple (e.g., approximately 1,000) sets of input vectors (i.e., trials), each yielding a unique estimate of lung dose. In the present study, the dosimetry component of the ICRP-66 model within LUDUC has been extended to explicitly consider variations in the beta particle absorbed fraction due to corresponding uncertainties and biological variabilities in both source and target tissue depths and thicknesses within the bronchi and bronchioles of the thoracic airways. Example dose distributions are given for the inhalation of absorption Type S compounds of 90Sr (Tmax = 546 keV) and 90Y (Tmax = 2,284 keV) as a function of particle size. Over the particle size range of 0.001 to 1 microm, estimates of total lung dose vary by a factor of 10 for 90Sr particles and by a factor of 4 to 10 for 90Y particles. As the particle size increases to 10 microm, dose uncertainties reach a factor of 100 for both radionuclides. In comparisons to identical exposures scenarios run by the LUDEP 2.0 code, Reference Man doses for inhaled beta-emitters were shown to provide slightly conservative estimates of lung dose compared to those in this study where uncertainties in lung airway histology are considered. PMID:15596988

  6. Radiosynoviorthesis in hemophilic joints with yttrium-90 citrate and rhenium-186 sulfide and long term results.

    PubMed

    Teyssler, Petr; Taborska, Katerina; Kolostova, Katarina; Bobek, Vladimir

    2013-01-01

    Repeated bleeding in the joint cavities is the most annoying symptom and often has disabling effects in patients with hemophilia (PWH). Our aim was to study the effect of radiosynovectomy (RSO) with beta particle-emitting radiocolloids in the treatment of hemorhagic arthropathy. We have treated 22 joints from 18 patients with hemophilia A, from April 2008 to February 2012, 5 knees, 11 elbows and 6 ankles. Joints were divided into two Groups, those treated with yttrium-90-citrate ((90)Y-C) (5 knees, 2 of them twice)-Group I and those with rhenium-186-sulfide ((186)Re-S) (11 elbows, 1 of them treated twice and 6 ankles)-Group II. A total of 25 treatments. Follow-up period was 3 months, 1 year and 3 years. Results showed a favourable subjective and a better objective result in all 5 joints of Group I and in 15/17 joints of Group II, respectively. Follow-up after 3 months showed significant improvement in Hemophilia Join Health Score (HJHS) after 20 treatments and steady score after 5 treatments. After 1 year, 19 treated joints had improved for the first time, 3 remained steady and 3 were not examined. After 3 years, 9 treated joints were HJHS steady, while 16 were not examined. One year after treatment, 13/14 joints of patients, aged 6-23 years showed better HJHS score, while 9/11 joints of patients aged 26-51 years, showed better HJHS. Synovial membrane thickness as measured by MRI in 8 joints, before and 3 months after treatment was not related to prognosis. In conclusion, in a small group of hemophilic patients with hemorrhagic arthropathy treated with (90)Y-C and with (186)Re-S, our study showed good results irrespective of age in 22/25 treatments after 3 months or 1 year. The thickness of synovial membrane in the 8 joints studied was not related to prognosis.

  7. IN-SITU, LONG-TERM MONITORING SYSTEM FOR RADIOACTIVE CONTAMINANTS

    SciTech Connect

    James S. Durham; Stephen W.S. McKeever; Mark S. Akselrod

    2002-10-01

    This report presents the results of the first phase of the project entitled ''In-situ, Long-term Monitoring System for Radioactive Contaminants.'' Phase one of this effort included four objectives, each with specific success criteria. The first objective was to produce dosimetry grade fibers and rods of aluminum oxide. The success criterion for this milestone was the production of aluminum oxide rods and fibers that have a minimum measurable dose (MMD) of 100 mrem or less. This milestone was completed and the MMD for the rods was measured to be 1.53 mrem. Based on the MMD, the ability of the sensor to measure {sup 137}Cs, {sup 90}Sr/{sup 90}Y, and {sup 99}Tc was evaluated. It was determined that the sensor can measure the release limit of these radionuclides (50 pCi/cm{sup 3}) in 150 h, 200 h, and 54,000 h, respectively. The monitor is adequate for measuring {sup 137}Cs and {sup 90}Sr/{sup 90}Y but is unsuitable for measuring {sup 99}Tc in soil. The second objective was to construct a prototype sensor (dosimeter and fiber optic channel). There were three success criteria for this milestone: (1) Perform measurements with the sensor for both gamma and beta radiation with a standard deviation of 10% or less; (2) Demonstrate the ability of the sensor to discriminate between gamma and beta radiation; and (3) Obtain similar or relatable results for differing lengths of fiber optic cable. These milestones were met. The sensor was able to measure gamma radiation repeatedly with a standard deviation of 3.15% and beta radiation with a standard deviation of 2.85%. Data is presented that demonstrates that an end cap can be used to discriminate between beta plus gamma radiation using beta radiation from a {sup 90}Sr/{sup 90}Y source, and gamma radiation alone. It is shown that some amount of attenuation occurs in longer fiber optic cables, but it is unclear if the attenuation is due to poor alignment of the dosimeter and the cable. This issue will be investigated further when

  8. Energy Differential Response of Cancer Cells for Low Dose Irradiation:Impact of Monoenergetic Brachytherapy Sources

    SciTech Connect

    Gueye, Paul; Prilepskiy, Yuriy; Keppel, Cynthia; Britten, R

    2010-06-01

    Purpose: The purpose of this work was to evaluate the energy differential response of cancer cells under identical dose exposure to asses the relevancy of mono-energetic sources for Brachytherapy treatments. Method and Materials: An electron energy spectrum impinging on lived breast cancer cell lines (MDA321) was obtained by placing a 19.65 {micro}Ci {sup 90}Sr/{sup 90}Y radioactive source in front of a non-uniform magnetic field constructed from two 5.08 x 5.0 cm x 2.54 cm neodimium ion permanent dipole magnets with a 1 cm separation gap. The cell lines were placed on the exit pole face of the magnet and were subsequently irradiated with different electron energies ranging from about 0.75 MeV to 1.85 MeV. The energy distribution was accurately measured with a scintillating fiber detector system that provided a 0.5% agreement with ICRU and a 5% energy resolution. The dosimetry was performed using a series of data acquired with a {sup 9}Sr/{sup 90}Y 4.5 mCi SIA-6 eye applicator, 6-21 MeV fixed energies from a Varian 2100 EX linac, EBT Gafchromic and Kodak ERT2 films, and an ion chamber detector. The accuracy of the dose rate obtained at different locations along and away from the magnet inside the cell containers was within 10.7%. Results: The cell lines were irradiated with a 0.5-4 Gy dose range. The data indicate a very strong differential energy response for electrons around 1 MeV (more lethal) compare to those with lesser or greater energy and a survival rate of at most 10% at very low dose (0.5-2 Gy). Conclusion: Mono-energetic Brachytherapy sources may provide a new pathway for radio-therapy treatment optimizations following a dedicated study showing very unusual high lethality in a specific energy window for MDA321 breast cancer cells.

  9. Radiation doses to members of the U.S. population from ubiquitous radionuclides in the body: Part 1, autopsy and in vivo data.

    PubMed

    Watson, David J; Strom, Daniel J

    2011-04-01

    This paper is Part 1 of a three-part series investigating steady-state effective dose rates to residents of the United States from intakes of ubiquitous radionuclides, including radionuclides occurring naturally, radionuclides whose concentrations are technologically enhanced, and anthropogenic radionuclides. This series of papers explicitly excludes intakes from inhaling (222)Rn, (220)Rn, and their short-lived decay products; it also excludes intakes of radionuclides in occupational and medical settings. In this work, it is assumed that instantaneous dose rates in target organs are proportional to steady-state radionuclide concentrations in source regions. The goal of Part 1 of this work was to review, summarize, and characterize all published and some unpublished data for U.S. residents on ubiquitous radionuclide concentrations in tissues and organs. Forty-five papers and reports were obtained and their data reviewed, and three data sets were obtained via private communication. The 45 radionuclides of interest are the (238)U series (14 nuclides), the actinium series (headed by (235)U; 11 nuclides), and the (232)Th series (11 nuclides); primordial radionuclides (87)Rb and (40)K; cosmogenic and fallout radionuclides (14)C and (3)H; and purely anthropogenic radionuclides (137)Cs-(137m)Ba, (129)I, and (90)Sr-(90)Y. Measurements judged to be relevant were available for only 15 of these radionuclides: (238)U, (235)U, (234)U, (232)Th, (230)Th, (228)Th, (228)Ra, (226)Ra, (210)Pb, (210)Po, (137)Cs, (87)Rb, (40)K, (14)C, and (3)H. Recent and relevant measurements were not available for (129)I and (90)Sr-(90)Y. A total of 11,741 radionuclide concentration measurements were found in one or more tissues or organs from 14 states. Data on age, gender, geographic locations, height, and weight of subjects were available only sporadically. Too often authors did not provide meaningful values of uncertainty of measurements, so that variability in data sets is confounded with

  10. Evaluation of a deterministic grid-based Boltzmann solver (GBBS) for voxel-level absorbed dose calculations in nuclear medicine

    NASA Astrophysics Data System (ADS)

    Mikell, Justin; Cheenu Kappadath, S.; Wareing, Todd; Erwin, William D.; Titt, Uwe; Mourtada, Firas

    2016-06-01

    To evaluate the 3D Grid-based Boltzmann Solver (GBBS) code ATTILA ® for coupled electron and photon transport in the nuclear medicine energy regime for electron (beta, Auger and internal conversion electrons) and photon (gamma, x-ray) sources. Codes rewritten based on ATTILA are used clinically for both high-energy photon teletherapy and 192Ir sealed source brachytherapy; little information exists for using the GBBS to calculate voxel-level absorbed doses in nuclear medicine. We compared DOSXYZnrc Monte Carlo (MC) with published voxel-S-values to establish MC as truth. GBBS was investigated for mono-energetic 1.0, 0.1, and 0.01 MeV electron and photon sources as well as 131I and 90Y radionuclides. We investigated convergence of GBBS by analyzing different meshes ({{M}0},{{M}1},{{M}2} ), energy group structures ({{E}0},{{E}1},{{E}2} ) for each radionuclide component, angular quadrature orders (≤ft. {{S}4},{{S}8},{{S}16}\\right) , and scattering order expansions ({{P}0} –{{P}6} ); higher indices imply finer discretization. We compared GBBS to MC in (1) voxel-S-value geometry for soft tissue, lung, and bone, and (2) a source at the interface between combinations of lung, soft tissue, and bone. Excluding Auger and conversion electrons, MC agreed within  ≈5% of published source voxel absorbed doses. For the finest discretization, most GBBS absorbed doses in the source voxel changed by less than 1% compared to the next finest discretization along each phase space variable indicating sufficient convergence. For the finest discretization, agreement with MC in the source voxel ranged from  ‑3% to  ‑20% with larger differences at lower energies (‑3% for 1 MeV electron in lung to  ‑20% for 0.01 MeV photon in bone); similar agreement was found for the interface geometries. Differences between GBBS and MC in the source voxel for 90Y and 131I were  ‑6%. The GBBS ATTILA was benchmarked against MC in the nuclear medicine regime. GBBS can be a

  11. Preclinical Evaluation of 86Y-Labeled Inhibitors of Prostate-Specific Membrane Antigen for Dosimetry Estimates

    PubMed Central

    Banerjee, Sangeeta Ray; Foss, Catherine A.; Pullambhatla, Mrudula; Wang, Yuchuan; Srinivasan, Senthamizhchelvan; Hobbs, Robert F.; Baidoo, Kwamena E.; Brechbiel, Martin W.; Nimmagadda, Sridhar; Mease, Ronnie C.; Sgouros, George; Pomper, Martin G.

    2016-01-01

    86Y (half-life = 14.74 h, 33% β+) is within an emerging class of positron-emitting isotopes with relatively long physical half-lives that enables extended imaging of biologic processes. We report the synthesis and evaluation of 3 low-molecular-weight compounds labeled with 86Y for imaging the prostate-specific membrane antigen (PSMA) using PET. Impetus for the study derives from the need to perform dosimetry estimates for the corresponding 90Y-labeled radiotherapeutics. Methods Multistep syntheses were used in preparing 86Y-4–6. PSMA inhibition constants were evaluated by competitive binding assay. In vivo characterization using tumor-bearing male mice was performed by PET/CT for 86Y-4–6 and by biodistribution studies of 86Y-4 and 86Y-6 out to 24 h after injection. Quantitative whole-body PET scans were recorded to measure the kinetics for 14 organs in a male baboon using 86Y-6. Results Compounds 86Y-4–6 were obtained in high radiochemical yield and purity, with specific radioactivities of more than 83.92 GBq/µmol. PET imaging and biodistribution studies using PSMA-positive PC-3 PIP and PSMA-negative PC-3 flu tumor-bearing mice revealed that 86Y-4–6 had high site-specific uptake in PSMA-positive PC-3 PIP tumor starting at 20 min after injection and remained high at 24 h. Compound 86Y-6 demonstrated the highest tumor uptake and retention, with 32.17 ± 7.99 and 15.79 ± 6.44 percentage injected dose per gram (%ID/g) at 5 and 24 h, respectively. Low activity concentrations were associated with blood and normal organs, except for the kidneys, a PSMA-expressing tissue. PET imaging in baboons reveals that all organs have a 2-phase (rapid and slow) clearance, with the highest uptake (8 %ID/g) in the kidneys at 25 min. The individual absolute uptake kinetics were used to calculate radiation doses using the OLINDA/EXM software. The highest mean absorbed dose was received by the renal cortex, with 1.9 mGy per MBq of 86Y-6. Conclusion Compound 86Y-6 is a promising

  12. PET imaging of tumor angiogenesis in mice with VEGF-A-targeted (86)Y-CHX-A″-DTPA-bevacizumab.

    PubMed

    Nayak, Tapan K; Garmestani, Kayhan; Baidoo, Kwamena E; Milenic, Diane E; Brechbiel, Martin W

    2011-02-15

    Bevacizumab is a humanized monoclonal antibody that binds to tumor-secreted vascular endothelial growth factor (VEGF)-A and inhibits tumor angiogenesis. In 2004, the antibody was approved by the US Food and Drug Administration (FDA) for the treatment of metastatic colorectal carcinoma in combination with chemotherapy. This report describes the preclinical evaluation of a radioimmunoconjugate, (86)Y-CHX-A″-DTPA-bevacizumab, for potential use in Positron Emission Tomography (PET) imaging of VEGF-A tumor angiogenesis and as a surrogate marker for (90)Y-based radioimmunotherapy. Bevacizumab was conjugated to CHX-A″-DTPA and radiolabeled with (86)Y. In vivo biodistribution and PET imaging studies were performed on mice bearing VEGF-A-secreting human colorectal (LS-174T), human ovarian (SKOV-3) and VEGF-A-negative human mesothelioma (MSTO-211H) xenografts. Biodistribution and PET imaging studies demonstrated highly specific tumor uptake of the radioimmunoconjugate. In mice bearing VEGF-A-secreting LS-174T, SKOV-3 and VEGF-A-negative MSTO-211H tumors, the tumor uptake at 3 days postinjection was 13.6 ± 1.5, 17.4 ± 1.7 and 6.8 ± 0.7 % ID/g, respectively. The corresponding tumor uptake in mice coinjected with 0.05 mg cold bevacizumab were 5.8 ± 1.3, 8.9 ± 1.9 and 7.4 ± 1.0 % ID/g, respectively at the same time point, demonstrating specific blockage of the target in VEGF-A-secreting tumors. The LS-174T and SKOV3 tumors were clearly visualized by PET imaging after injecting 1.8-2.0 MBq (86)Y-CHX-A″-DTPA-bevacizumab. Organ uptake quantified by PET closely correlated (r(2) = 0.87, p = 0.64, n = 18) to values determined by biodistribution studies. This preclinical study demonstrates the potential of the radioimmunoconjugate, (86)Y-CHX-A″-DTPA-bevacizumab, for noninvasive assessment of the VEGF-A tumor angiogenesis status and as a surrogate marker for (90)Y-CHX-A″-DTPA-bevacizumab radioimmunotherapy.

  13. Comparison of internal dose estimates obtained using organ-level, voxel S value, and Monte Carlo techniques

    SciTech Connect

    Grimes, Joshua; Celler, Anna

    2014-09-15

    Purpose: The authors’ objective was to compare internal dose estimates obtained using the Organ Level Dose Assessment with Exponential Modeling (OLINDA/EXM) software, the voxel S value technique, and Monte Carlo simulation. Monte Carlo dose estimates were used as the reference standard to assess the impact of patient-specific anatomy on the final dose estimate. Methods: Six patients injected with{sup 99m}Tc-hydrazinonicotinamide-Tyr{sup 3}-octreotide were included in this study. A hybrid planar/SPECT imaging protocol was used to estimate {sup 99m}Tc time-integrated activity coefficients (TIACs) for kidneys, liver, spleen, and tumors. Additionally, TIACs were predicted for {sup 131}I, {sup 177}Lu, and {sup 90}Y assuming the same biological half-lives as the {sup 99m}Tc labeled tracer. The TIACs were used as input for OLINDA/EXM for organ-level dose calculation and voxel level dosimetry was performed using the voxel S value method and Monte Carlo simulation. Dose estimates for {sup 99m}Tc, {sup 131}I, {sup 177}Lu, and {sup 90}Y distributions were evaluated by comparing (i) organ-level S values corresponding to each method, (ii) total tumor and organ doses, (iii) differences in right and left kidney doses, and (iv) voxelized dose distributions calculated by Monte Carlo and the voxel S value technique. Results: The S values for all investigated radionuclides used by OLINDA/EXM and the corresponding patient-specific S values calculated by Monte Carlo agreed within 2.3% on average for self-irradiation, and differed by as much as 105% for cross-organ irradiation. Total organ doses calculated by OLINDA/EXM and the voxel S value technique agreed with Monte Carlo results within approximately ±7%. Differences between right and left kidney doses determined by Monte Carlo were as high as 73%. Comparison of the Monte Carlo and voxel S value dose distributions showed that each method produced similar dose volume histograms with a minimum dose covering 90% of the volume (D90

  14. Radiation doses to members of the U.S. population from ubiquitous radionuclides in the body: Part 1, autopsy and in vivo data.

    PubMed

    Watson, David J; Strom, Daniel J

    2011-04-01

    This paper is Part 1 of a three-part series investigating steady-state effective dose rates to residents of the United States from intakes of ubiquitous radionuclides, including radionuclides occurring naturally, radionuclides whose concentrations are technologically enhanced, and anthropogenic radionuclides. This series of papers explicitly excludes intakes from inhaling (222)Rn, (220)Rn, and their short-lived decay products; it also excludes intakes of radionuclides in occupational and medical settings. In this work, it is assumed that instantaneous dose rates in target organs are proportional to steady-state radionuclide concentrations in source regions. The goal of Part 1 of this work was to review, summarize, and characterize all published and some unpublished data for U.S. residents on ubiquitous radionuclide concentrations in tissues and organs. Forty-five papers and reports were obtained and their data reviewed, and three data sets were obtained via private communication. The 45 radionuclides of interest are the (238)U series (14 nuclides), the actinium series (headed by (235)U; 11 nuclides), and the (232)Th series (11 nuclides); primordial radionuclides (87)Rb and (40)K; cosmogenic and fallout radionuclides (14)C and (3)H; and purely anthropogenic radionuclides (137)Cs-(137m)Ba, (129)I, and (90)Sr-(90)Y. Measurements judged to be relevant were available for only 15 of these radionuclides: (238)U, (235)U, (234)U, (232)Th, (230)Th, (228)Th, (228)Ra, (226)Ra, (210)Pb, (210)Po, (137)Cs, (87)Rb, (40)K, (14)C, and (3)H. Recent and relevant measurements were not available for (129)I and (90)Sr-(90)Y. A total of 11,741 radionuclide concentration measurements were found in one or more tissues or organs from 14 states. Data on age, gender, geographic locations, height, and weight of subjects were available only sporadically. Too often authors did not provide meaningful values of uncertainty of measurements, so that variability in data sets is confounded with

  15. Evaluation of a deterministic grid-based Boltzmann solver (GBBS) for voxel-level absorbed dose calculations in nuclear medicine

    NASA Astrophysics Data System (ADS)

    Mikell, Justin; Cheenu Kappadath, S.; Wareing, Todd; Erwin, William D.; Titt, Uwe; Mourtada, Firas

    2016-06-01

    To evaluate the 3D Grid-based Boltzmann Solver (GBBS) code ATTILA ® for coupled electron and photon transport in the nuclear medicine energy regime for electron (beta, Auger and internal conversion electrons) and photon (gamma, x-ray) sources. Codes rewritten based on ATTILA are used clinically for both high-energy photon teletherapy and 192Ir sealed source brachytherapy; little information exists for using the GBBS to calculate voxel-level absorbed doses in nuclear medicine. We compared DOSXYZnrc Monte Carlo (MC) with published voxel-S-values to establish MC as truth. GBBS was investigated for mono-energetic 1.0, 0.1, and 0.01 MeV electron and photon sources as well as 131I and 90Y radionuclides. We investigated convergence of GBBS by analyzing different meshes ({{M}0},{{M}1},{{M}2} ), energy group structures ({{E}0},{{E}1},{{E}2} ) for each radionuclide component, angular quadrature orders (≤ft. {{S}4},{{S}8},{{S}16}\\right) , and scattering order expansions ({{P}0} -{{P}6} ); higher indices imply finer discretization. We compared GBBS to MC in (1) voxel-S-value geometry for soft tissue, lung, and bone, and (2) a source at the interface between combinations of lung, soft tissue, and bone. Excluding Auger and conversion electrons, MC agreed within  ≈5% of published source voxel absorbed doses. For the finest discretization, most GBBS absorbed doses in the source voxel changed by less than 1% compared to the next finest discretization along each phase space variable indicating sufficient convergence. For the finest discretization, agreement with MC in the source voxel ranged from  -3% to  -20% with larger differences at lower energies (-3% for 1 MeV electron in lung to  -20% for 0.01 MeV photon in bone); similar agreement was found for the interface geometries. Differences between GBBS and MC in the source voxel for 90Y and 131I were  -6%. The GBBS ATTILA was benchmarked against MC in the nuclear medicine regime. GBBS can be a viable

  16. Evaluation of a deterministic grid-based Boltzmann solver (GBBS) for voxel-level absorbed dose calculations in nuclear medicine.

    PubMed

    Mikell, Justin; Cheenu Kappadath, S; Wareing, Todd; Erwin, William D; Titt, Uwe; Mourtada, Firas

    2016-06-21

    To evaluate the 3D Grid-based Boltzmann Solver (GBBS) code ATTILA (®) for coupled electron and photon transport in the nuclear medicine energy regime for electron (beta, Auger and internal conversion electrons) and photon (gamma, x-ray) sources. Codes rewritten based on ATTILA are used clinically for both high-energy photon teletherapy and (192)Ir sealed source brachytherapy; little information exists for using the GBBS to calculate voxel-level absorbed doses in nuclear medicine. We compared DOSXYZnrc Monte Carlo (MC) with published voxel-S-values to establish MC as truth. GBBS was investigated for mono-energetic 1.0, 0.1, and 0.01 MeV electron and photon sources as well as (131)I and (90)Y radionuclides. We investigated convergence of GBBS by analyzing different meshes ([Formula: see text]), energy group structures ([Formula: see text]) for each radionuclide component, angular quadrature orders ([Formula: see text], and scattering order expansions ([Formula: see text]-[Formula: see text]); higher indices imply finer discretization. We compared GBBS to MC in (1) voxel-S-value geometry for soft tissue, lung, and bone, and (2) a source at the interface between combinations of lung, soft tissue, and bone. Excluding Auger and conversion electrons, MC agreed within  ≈5% of published source voxel absorbed doses. For the finest discretization, most GBBS absorbed doses in the source voxel changed by less than 1% compared to the next finest discretization along each phase space variable indicating sufficient convergence. For the finest discretization, agreement with MC in the source voxel ranged from  -3% to  -20% with larger differences at lower energies (-3% for 1 MeV electron in lung to  -20% for 0.01 MeV photon in bone); similar agreement was found for the interface geometries. Differences between GBBS and MC in the source voxel for (90)Y and (131)I were  -6%. The GBBS ATTILA was benchmarked against MC in the nuclear medicine regime. GBBS can be a

  17. Evaluation of a deterministic grid-based Boltzmann solver (GBBS) for voxel-level absorbed dose calculations in nuclear medicine.

    PubMed

    Mikell, Justin; Cheenu Kappadath, S; Wareing, Todd; Erwin, William D; Titt, Uwe; Mourtada, Firas

    2016-06-21

    To evaluate the 3D Grid-based Boltzmann Solver (GBBS) code ATTILA (®) for coupled electron and photon transport in the nuclear medicine energy regime for electron (beta, Auger and internal conversion electrons) and photon (gamma, x-ray) sources. Codes rewritten based on ATTILA are used clinically for both high-energy photon teletherapy and (192)Ir sealed source brachytherapy; little information exists for using the GBBS to calculate voxel-level absorbed doses in nuclear medicine. We compared DOSXYZnrc Monte Carlo (MC) with published voxel-S-values to establish MC as truth. GBBS was investigated for mono-energetic 1.0, 0.1, and 0.01 MeV electron and photon sources as well as (131)I and (90)Y radionuclides. We investigated convergence of GBBS by analyzing different meshes ([Formula: see text]), energy group structures ([Formula: see text]) for each radionuclide component, angular quadrature orders ([Formula: see text], and scattering order expansions ([Formula: see text]-[Formula: see text]); higher indices imply finer discretization. We compared GBBS to MC in (1) voxel-S-value geometry for soft tissue, lung, and bone, and (2) a source at the interface between combinations of lung, soft tissue, and bone. Excluding Auger and conversion electrons, MC agreed within  ≈5% of published source voxel absorbed doses. For the finest discretization, most GBBS absorbed doses in the source voxel changed by less than 1% compared to the next finest discretization along each phase space variable indicating sufficient convergence. For the finest discretization, agreement with MC in the source voxel ranged from  -3% to  -20% with larger differences at lower energies (-3% for 1 MeV electron in lung to  -20% for 0.01 MeV photon in bone); similar agreement was found for the interface geometries. Differences between GBBS and MC in the source voxel for (90)Y and (131)I were  -6%. The GBBS ATTILA was benchmarked against MC in the nuclear medicine regime. GBBS can be a

  18. Three-dimensional radiobiological dosimetry of kidneys for treatment planning in peptide receptor radionuclide therapy

    SciTech Connect

    Baechler, Sebastien; Hobbs, Robert F.; Boubaker, Ariane; Buchegger, Franz; He Bin; Frey, Eric C.; Sgouros, George

    2012-10-15

    Purpose: Peptide receptor radionuclide therapy (PRRT) delivers high absorbed doses to kidneys and may lead to permanent nephropathy. Reliable dosimetry of kidneys is thus critical for safe and effective PRRT. The aim of this work was to assess the feasibility of planning PRRT based on 3D radiobiological dosimetry (3D-RD) in order to optimize both the amount of activity to administer and the fractionation scheme, while limiting the absorbed dose and the biological effective dose (BED) to the renal cortex. Methods: Planar and SPECT data were available for a patient examined with {sup 111}In-DTPA-octreotide at 0.5 (planar only), 4, 24, and 48 h post-injection. Absorbed dose and BED distributions were calculated for common therapeutic radionuclides, i.e., {sup 111}In, {sup 90}Y and {sup 177}Lu, using the 3D-RD methodology. Dose-volume histograms were computed and mean absorbed doses to kidneys, renal cortices, and medullae were compared with results obtained using the MIRD schema (S-values) with the multiregion kidney dosimetry model. Two different treatment planning approaches based on (1) the fixed absorbed dose to the cortex and (2) the fixed BED to the cortex were then considered to optimize the activity to administer by varying the number of fractions. Results: Mean absorbed doses calculated with 3D-RD were in good agreement with those obtained with S-value-based SPECT dosimetry for {sup 90}Y and {sup 177}Lu. Nevertheless, for {sup 111}In, differences of 14% and 22% were found for the whole kidneys and the cortex, respectively. Moreover, the authors found that planar-based dosimetry systematically underestimates the absorbed dose in comparison with SPECT-based methods, up to 32%. Regarding the 3D-RD-based treatment planning using a fixed BED constraint to the renal cortex, the optimal number of fractions was found to be 3 or 4, depending on the radionuclide administered and the value of the fixed BED. Cumulative activities obtained using the proposed simulated

  19. Differences in 3D dose distributions due to calculation method of voxel S-values and the influence of image blurring in SPECT

    NASA Astrophysics Data System (ADS)

    Pacilio, Massimiliano; Amato, Ernesto; Lanconelli, Nico; Basile, Chiara; Torres, Leonel Alberto; Botta, Francesca; Ferrari, Mahila; Cornejo Diaz, Nestor; Coca Perez, Marco; Fernández, María; Lassmann, Michael; Vergara Gil, Alex; Cremonesi, Marta

    2015-03-01

    This study compares 3D dose distributions obtained with voxel S values (VSVs) for soft tissue, calculated by several methods at their current state-of-the-art, varying the degree of image blurring. The methods were: 1) convolution of Dose Point Kernel (DPK) for water, using a scaling factor method; 2) an analytical model (AM), fitting the deposited energy as a function of the source-target distance; 3) a rescaling method (RSM) based on a set of high-resolution VSVs for each isotope; 4) local energy deposition (LED). VSVs calculated by direct Monte Carlo simulations were assumed as reference. Dose distributions were calculated considering spheroidal clusters with various sizes (251, 1237 and 4139 voxels of 3 mm size), uniformly filled with 131I, 177Lu, 188Re or 90Y. The activity distributions were blurred with Gaussian filters of various widths (6, 8 and 12 mm). Moreover, 3D-dosimetry was performed for 10 treatments with 90Y derivatives. Cumulative Dose Volume Histograms (cDVHs) were compared, studying the differences in D95%, D50% or Dmax (ΔD95%, ΔD50% and ΔDmax) and dose profiles. For unblurred spheroidal clusters, ΔD95%, ΔD50% and ΔDmax were mostly within some percents, slightly higher for 177Lu with DPK (8%) and RSM (12%) and considerably higher for LED (ΔD95% up to 59%). Increasing the blurring, differences decreased and also LED yielded very similar results, but D95% and D50% underestimations between 30-60% and 15-50%, respectively (with respect to 3D-dosimetry with unblurred distributions), were evidenced. Also for clinical images (affected by blurring as well), cDVHs differences for most methods were within few percents, except for slightly higher differences with LED, and almost systematic for dose profiles with DPK (-1.2%), AM (-3.0%) and RSM (4.5%), whereas showed an oscillating trend with LED. The major concern for 3D-dosimetry on clinical SPECT images is more strongly represented by image blurring than by differences among the VSVs

  20. [166Dy]Dy/166Ho hydroxide macroaggregates: an in vivo generator system for radiation synovectomy.

    PubMed

    Ferro-Flores, G; Hernández-Oviedo, O; Arteaga de Murphy, C; Tendilla, J I; Monroy-Guzmán, F; Pedraza-López, M; Aldama-Alvarado, K

    2004-12-01

    Radiation synovectomy is an effective treatment in patients suffering from inflammatory-rheumatoid and degenerative joint diseases. The aim of this work was to examine the feasibility of preparing dysprosium-166 (166Dy)/holmium-166(166Ho) hydroxide macroaggregates ([166Dy]Dy/166Ho-HM) as an in vivo generator for radiation synovectomy evaluating whether the stability of 166Dy-HM and 166Ho-HM complexes is maintained when the daughter 166Ho is formed. The Monte Carlo (MCNP4B) theoretical depth dose profile for the in vivo [166Dy]Dy/166Ho generator system in a joint model was calculated and compared with that produced by 90Y, 153Sm and 166Ho. 166Dy was obtained by neutron irradiation of enriched 164Dy2O3 in a Triga Mark III reactor. Macroaggregates were prepared by reaction of [166Dy]DyCl3 with 0.5 M NaOH in an ultrasonic bath. [166Dy]Dy/166Ho-HM was obtained with radiochemical purity >99.5% and with the majority of particles in the 2-5 microm range. In vitro studies demonstrated that the radio-macroaggregates are stable in saline solution and human serum without a significant change in the particle size over 14 d, suggesting that no translocation of the daughter nucleus occurs subsequent to beta- decay of 166Dy. Biological studies in normal rats demonstrated high retention in the knee joint even 7 d after [166Dy]Dy/166Ho-HM administration. The Monte Carlo (MCNP4B) theoretical depth dose profiles in a joint model, showed that the in vivo [166Dy]Dy/166Ho generator system would produce 25% and 50% less radiation dose to the articular cartilage and bone surface, respectively, than that produced by 90Y or pure 166Ho in a treatment with the same therapeutic dose to the synovium surface. Despite that 153Sm showed the best depth dose profile sparing doses to healthy tissues, the use of 166Dy could provide the advantage of being applied in patients that cannot be reached within a few hours from a nuclear reactor and to produce less radiation exposure to the medical personnel

  1. GaP betavoltaic cells as a power source

    NASA Technical Reports Server (NTRS)

    Pool, F. S.; Stella, Paul M.; Anspaugh, B.

    1991-01-01

    Maximum power output for the GaP cells of this study was found to be on the order of 1 microW. This resulted from exposure to 200 and 40 KeV electrons at a flux of 2 x 10(exp 9) electrons/sq cm/s, equivalent to a 54 mCurie source. The efficiencies of the cells ranged from 5 to 9 percent for 200 and 40 KeV electrons respectively. The lower efficiency at higher energy is due to a substantial fraction of energy deposition in the substrate, further than a diffusion length from the depletion region of the cell. Radiation damage was clearly observed in GaP after exposure to 200 KeV electrons at a fluence of 2 x 10(exp 12) electrons/sq cm. No discernable damage was observed after exposure to 40 KeV electrons at the same fluence. Analysis indicates that a GaP betavoltaic system would not be practical if limited to low energy beta sources. The power available would be too low even in the ideal case. By utilizing high activity beta sources, such as Sr-90/Y-90, it may be possible to achieve performance that could be suitable for some space power applications. However, to utilize such a source the problem of radiation damage in the beta cell material must be overcome.

  2. Molecularly imprinted polymers for (90)Sr urine bioassay.

    PubMed

    Bahraini, Negar; Lai, Edward P C; Li, Chunsheng; Sadi, Baki B; Kramer, Gary H

    2011-08-01

    A molecularly imprinted polymer (MIP) comprising dicyclohexano-18-crown-6 (DCH18C6) was synthesized as a Sr-selective sorbent for urine bioassay purposes. MIP particles (326 ± 2 nm diameter) were formed using acetone and acetonitrile (1:3 v/v) as the porogen, methacrylic acid (MAA) as the functional monomer and ethylene glycol dimethacrylate (EGDMA) as the cross-linker. The DCH18C6-MIP particles were impregnated with additional DCH18C6 and treated further with NaOH to attain better binding affinity for Sr(2+). The effects of pH, ionic strength and amount of particles were evaluated for optimal extraction of (90)Sr(2+) from urine samples, as measured by liquid scintillation analysis (LSA). After up to 94% of (90)Y was removed by precipitation with TiO(2), DCH18C6-MIP particles were applied for selective SPE of (90)Sr remaining in the urine matrix for final LSA.

  3. Radium-228 determination of natural waters via concentration on manganese dioxide and separation using Diphonix ion exchange resin.

    PubMed

    Nour, S; El-Sharkawy, A; Burnett, W C; Horwitz, E P

    2004-12-01

    The objective of this work was to establish a new procedure for 228Ra determination of natural waters via preconcentration of radium on MnO2 and separation of its daughter, 228Ac, using Diphonix ion exchange resin. Following removal of potential interferences via passage through an initial Diphonix Resin column, the first daughter of 228Ra, 228Ac, is isolated by chromatographic separation via a second Diphonix column. A holding time of > 30 h for 228Ac ingrowth in between the two column separations ensures secular equilibrium. Barium-133 is used as a yield tracer. Actinium-228 is eluted from the second Diphonix Resin with 5 ml 1M 1-Hydroxyethane-1,1-diphosphonic acid (HEDPA) and quantified by addition of scintillation cocktail and LSC counting. Radium (and 133Ba) from the load and rinse solutions from the 2nd Diphonix column may be prepared for alpha spectrometry (for determination of 223Ra, 224Ra, and 226Ra) by BaSO4 microprecipitation and filtration. Decontamination tests indicate that U, Th, and Ra series nuclides do not interfere with these measurements, although high contents of 90Sr (90Y) require additional treatment for accurate measurement of 228Ra. Addition of stable Sr as a "hold back" carrier during the initial MnO2 preconcentration step was shown to remove most 90Sr interference.

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

    SciTech Connect

    Mueller, 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 {sup 227}Th and {sup 228}Th 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 {sup 144}Ce+{sup 144}Pr (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 {sup 144}Ce 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 {sup 144}Ce+{sup 144}Pr in rats and for external {sup 90}Sr+{sup 90}Y irradiation in mice. We conclude that the processes involved in the induction of local and systemic bone sarcomas by radiation may be quite different. 35 refs., 1 fig., 3 tabs.

  5. Beta-decay, Bremsstrahlen, and the origin of molecular chirality

    NASA Technical Reports Server (NTRS)

    Bonner, W. A.; Yi, L.

    1984-01-01

    A brief review is presented of the Vester-Ulbricht beta-decay Bremsstrahlen hypothesis for the origin of optical activity, and of subsequent experiments designed to test it. Certain experiments along these lines, begun in 1974 and involving the irradiation of racemic and optically active amino acids in a 61.7 KCi Sr-90-Y-90 Bremsstrahlen source, have now been completed and are described. After 10.89 years of irradiation with a total Bremsstrahlen dose of 2.5 x 10 to the 9th rads, crystalline DL-leucine, norleucine, and norvaline suffered 47.2, 33.6, and 27.4 percent radiolysis, respectively, but showed no evidence whatsoever of asymmetric degradation. Dand L-Leucine underwent about 48 percent radiolysis and showed 2.4-2.9 percent radioracemization. Other samples in solution were too severely degraded to analyze. Probable intrinsic reasons for the failure of the Vester-Ulbricht mechanism to afford asymmetric radiolysis in the present and related experiments involving beta-decay Bremsstrahlen are enumerated.

  6. Spin-isovector giant resonances induced by (n,p) reactions on heavy nuclei

    NASA Astrophysics Data System (ADS)

    Long, S. A.; Spicer, B. M.; Raywood, K. J.; Abegg, R.; Alford, W. P.; Celler, A.; Frekers, D.; Green, P. E.; Häusser, O.; Helmer, R. L.; Henderson, R. S.; Hicks, K. H.; Jackson, K. P.; Jeppesen, R. G.; King, N. S.; Miller, C. A.; Moinester, M. A.; Officer, V. C.; Shute, G. G.; Trudel, A.; Vetterli, M. C.; Yavin, A. I.; Yen, S.

    1998-06-01

    Double differential cross sections from the 120Sn(n,p)120In and 181Ta(n,p)181Hf reactions at 298 MeV and the 238U(n,p)238Pa reaction at 318 MeV have been measured for excitation energies up to 50 MeV in the residual nucleus. These data, together with the previously published data from the 90Zr(n,p)90Y and 208Pb(n,p)208Tl reactions at 198 MeV, have been analyzed for spin-isovector resonances of multipolarities less than 7, using the multipole decomposition method. The strengths due to spin-isovector excitations of multipolarity less than 4 have been extracted. The anomalous behavior of the extracted spin-isovector quadrupole strength with target mass number is discussed with reference to the calculations of Leonardi et al. The cross section due to quasifree processes was calculated and subtracted from the data. The data after this subtraction were reanalyzed for spin-isovector resonances and the strengths due to multipolarities up to 3 were extracted. The strengths due to spin-isovector dipole and octupole excitations were compared to values calculated, for 1ħω transitions only, using the sum rules of Macfarlane. The behavior with target mass number is well represented by these sum rules.

  7. Effectiveness of Repeat Angiographic Assessment in Patients Designated for Radioembolization Using Yttrium-90 Microspheres With Initial Extrahepatic Accumulation of Technitium-99m Macroaggregated Albumin: A Single Center's Experience

    SciTech Connect

    Dudeck, Oliver Wilhelmsen, Skadi; Ulrich, Gerhard; Loewenthal, David; Pech, Maciej; Amthauer, Holger; Ricke, Jens

    2012-10-15

    Purpose: To evaluate the efficacy of a workflow consisting of repeat assessment in patients planned for yttrium-90 ({sup 90}Y) radioembolization in case of nontarget visceral technetium-99m ({sup 99m}Tc)-macroaggregated albumin (MAA) accumulation despite initial prophylactic coil embolization of nonhepatic arteries. Materials and Methods: In 341 patients with primary and secondary liver cancer, pretreatment hepatic angiograms, as well as single-photon emission computed tomography coregistered with magnetic resonance imaging scans, were obtained. Extrahepatic tracer deposition was identified in 33 patients (9.7%) necessitating repeat assessment. Images were reviewed to correlate the site of MAA accumulation with causative gastrointestinal vessels, and repeat angiograms served as reference standard. Results: At repeat angiography, the source of extrahepatic flow was identified and eliminated in 31 of 33 patients (93.9%). In 20 patients (60.6%), successful embolization of nontarget vessels was achieved, in 13 patients (39.4%), MAA was administered more distally. Afterward, extrahepatic MAA deposition was eliminated in 30 patients (90.9%). Conclusion: The algorithm of repeat assessment in case of extrahepatic MAA accumulation has proven highly effective to eliminate extrahepatic shunting, thus decreasing the risk of postradioembolization complications due to inadvertent visceral microsphere deposition.

  8. The neoplastic transformation potential of mammography X rays and atomic bomb spectrum radiation.

    PubMed

    Heyes, G J; Mill, A J

    2004-08-01

    Considerable controversy currently exists regarding the biological effectiveness of 29 kVp X rays which are used for mammography screening. This issue must be resolved to enable proper evaluation of radiation risks from breast screening. Here a definitive assessment of the biological effectiveness of 29 kVp X rays compared to the quality of radiation to which the atomic bomb survivors were exposed is presented for the first time. The standard radiation sources used were (a) an atomic bomb simulation spectrum and (b) 2.2 MeV electrons from a strontium-90/yttrium-90 (90Sr/90Y) radioactive source. The biological end point used was neoplastic transformation in vitro in CGL1 (HeLa x human fibroblast hybrid) cells. No significant difference was observed for the biological effectiveness of the two high-energy sources for neoplastic transformation. A limiting relative biological effectiveness (RBE(M)) of 4.42 +/- 2.02 was observed for neoplastic transformation by 29 kVp X rays compared to these two sources. This compares with values of 4.67 +/- 3.93 calculated from previously published data and 3.58 +/- 1.77 when the reference radiation was 200 and 220 kVp X rays. This suggests that the risks associated with mammography screening may be approximately five times higher than previously assumed and that the risk-benefit relationship of mammography exposures may need to be re-examined. PMID:15387138

  9. Visualizing the origins of selfish de novo mutations in individual seminiferous tubules of human testes.

    PubMed

    Maher, Geoffrey J; McGowan, Simon J; Giannoulatou, Eleni; Verrill, Clare; Goriely, Anne; Wilkie, Andrew O M

    2016-03-01

    De novo point mutations arise predominantly in the male germline and increase in frequency with age, but it has not previously been possible to locate specific, identifiable mutations directly within the seminiferous tubules of human testes. Using microdissection of tubules exhibiting altered expression of the spermatogonial markers MAGEA4, FGFR3, and phospho-AKT, whole genome amplification, and DNA sequencing, we establish an in situ strategy for discovery and analysis of pathogenic de novo mutations. In 14 testes from men aged 39-90 y, we identified 11 distinct gain-of-function mutations in five genes (fibroblast growth factor receptors FGFR2 and FGFR3, tyrosine phosphatase PTPN11, and RAS oncogene homologs HRAS and KRAS) from 16 of 22 tubules analyzed; all mutations have known associations with severe diseases, ranging from congenital or perinatal lethal disorders to somatically acquired cancers. These results support proposed selfish selection of spermatogonial mutations affecting growth factor receptor-RAS signaling, highlight its prevalence in older men, and enable direct visualization of the microscopic anatomy of elongated mutant clones.

  10. On application of low doses from beta radiation source in OSL retrospective dosimetry

    NASA Astrophysics Data System (ADS)

    Przegietka, K.; Chruscinska, A.

    2014-11-01

    The paper reports on three levels of dose rates obtainable from single beta source: (133±3) mGy/s, (17.8±0.3) mGy/s and (1.94±0.04) mGy/s, as calibrated for quartz sand grains. These values were achieved for different attenuation stages of beta radiation emitted by standard 90Sr/90Y source with the nominal activity of 1.48 GBq attached to an automatic luminescence reader. Lower dose rates give opportunity for exact dosing, which is especially required in luminescence dating applied to young samples as well as in environmental dosimetry. Moreover new method for determining time lag in opening the source in the Riso beta irradiator is presented. This allowed to resolve the contradiction appearing in the literature. The time delay was found to be (0.15±0.01) s per single irradiation. For improving accuracy the dose rate correction is suggest to be taken into account for irradiations shorter than 30 s.

  11. Visualizing the origins of selfish de novo mutations in individual seminiferous tubules of human testes

    PubMed Central

    Maher, Geoffrey J.; McGowan, Simon J.; Giannoulatou, Eleni; Verrill, Clare; Goriely, Anne; Wilkie, Andrew O. M.

    2016-01-01

    De novo point mutations arise predominantly in the male germline and increase in frequency with age, but it has not previously been possible to locate specific, identifiable mutations directly within the seminiferous tubules of human testes. Using microdissection of tubules exhibiting altered expression of the spermatogonial markers MAGEA4, FGFR3, and phospho-AKT, whole genome amplification, and DNA sequencing, we establish an in situ strategy for discovery and analysis of pathogenic de novo mutations. In 14 testes from men aged 39–90 y, we identified 11 distinct gain-of-function mutations in five genes (fibroblast growth factor receptors FGFR2 and FGFR3, tyrosine phosphatase PTPN11, and RAS oncogene homologs HRAS and KRAS) from 16 of 22 tubules analyzed; all mutations have known associations with severe diseases, ranging from congenital or perinatal lethal disorders to somatically acquired cancers. These results support proposed selfish selection of spermatogonial mutations affecting growth factor receptor-RAS signaling, highlight its prevalence in older men, and enable direct visualization of the microscopic anatomy of elongated mutant clones. PMID:26858415

  12. Pixel-based parametric source depth map for Cerenkov luminescence imaging

    NASA Astrophysics Data System (ADS)

    Altabella, L.; Boschi, F.; Spinelli, A. E.

    2016-01-01

    Optical tomography represents a challenging problem in optical imaging because of the intrinsically ill-posed inverse problem due to photon diffusion. Cerenkov luminescence tomography (CLT) for optical photons produced in tissues by several radionuclides (i.e.: 32P, 18F, 90Y), has been investigated using both 3D multispectral approach and multiviews methods. Difficult in convergence of 3D algorithms can discourage to use this technique to have information of depth and intensity of source. For these reasons, we developed a faster 2D corrected approach based on multispectral acquisitions, to obtain source depth and its intensity using a pixel-based fitting of source intensity. Monte Carlo simulations and experimental data were used to develop and validate the method to obtain the parametric map of source depth. With this approach we obtain parametric source depth maps with a precision between 3% and 7% for MC simulation and 5-6% for experimental data. Using this method we are able to obtain reliable information about the source depth of Cerenkov luminescence with a simple and flexible procedure.

  13. Response of ionization chamber based pocket dosimeter to beta radiation.

    PubMed

    Kumar, Munish; Gupta, Anil; Pradhan, S M; Bakshi, A K; Chougaonkar, M P; Babu, D A R

    2013-12-01

    Quantitative estimate of the response of ionization chamber based pocket dosimeters (DRDs) to various beta sources was performed. It has been established that the ionization chamber based pocket dosimeters do not respond to beta particles having energy (Emax)<1 MeV and same was verified using (147)Pm, (85)Kr and (204)Tl beta sources. However, for beta particles having energy >1 MeV, the DRDs exhibit measureable response and the values are ~8%, ~14% and ~27% per mSv for natural uranium, (90)Sr/(90)Y and (106)Ru/(106)Rh beta sources respectively. As the energy of the beta particles increases, the response also increases. The response of DRDs to beta particles having energy>1 MeV arises due to the fact that the thickness of the chamber walls is less than the maximum range of beta particles. This may also be one of the reasons for disparity between doses measured with passive/legal dosimeters (TLDs) and DRDs in those situations in which radiation workers are exposed to mixed field of gamma photons and beta particles especially at uranium processing plants, nuclear (power and research) reactors, waste management facilities and fuel reprocessing plants etc. The paper provides the reason (technical) for disparity between the doses recorded by TLDs and DRDs in mixed field of photons and beta particles.

  14. Current Challenges in Personal Dosimetry at the U.S. DOE Hanford Site

    SciTech Connect

    Rathbone, Bruce A. ); McDonald, Joseph C. ); Traub, Richard J. )

    2002-10-01

    Abstract - This paper presents an overview of the dosimetry system, dose equivalent calculation methodology, and QA/QC practices used at the U.S. Department of Energy Hanford site. It describes some of the problems encountered in accurately measuring dose equivalent quantities under a broad range of field conditions that do not necessarily correlate with laboratory calibration conditions and the approach taken to solve these problems. Personnel at Hanford are monitored with a combination of Harshaw model 8825 and 8816 thermoluminescent dosimeters and CR-39? track etch dosimeters. Extremities are monitored using the ICN MeasuRing loaded with a Harshaw XD740 chipstrate TLD. All dosimeters employ LiF:Mg,Ti elements that are read onsite with Harshaw model 8800 and 6600 TLD readers. CR-39? dosimeters are electrochemically etched in non-commercial etch chambers and counted with an automated track counting system developed by Pacific Northwest National Laboratory. Problems with over response of the 8825 with respect to Hp(0.07), under response of the 8825 with respect to Hp(3), and over response of the 8825 with respect to Hp(10) in Hanford's 90Sr/90Y beta radiation fields are discussed. Approaches to measurement of the operational quantities for field conditions and algorithm solutions to the above problems are described. Methods used to calibrate the ring dosimeter for Hanford field conditions together with limitations of the ring dosimeter in measuring Hp(0.07) for extremities, particularly when covered with protective clothing, are also discussed.

  15. Apoferritin-Templated Yttrium Phosphate Nanoparticle Conjugates for Radioimmunotherapy of Cancers

    SciTech Connect

    Wu, Hong; Wang, Jun; Wang, Zheming; Fisher, Darrell R.; Lin, Yuehe

    2008-05-01

    We report a templated-synthetic approach based on apoferritin to prepare radionuclide nanoparticle (NP) conjugates. Non-radioactive yttrium (89Y) was used as model target and surrogate for radioyttrium (90Y) to prepare the nanoparticle conjugate. The center cavity and multiple channel structure of apoferritin offer a fast and facile method to precipitate yttrium phosphate by diffusing yttrium and phosphate ions into the cavity of apofrritin, resulting a core-shell nanocomposite. The yttrium phosphate/apoferritin nanoparticle was functionalized with biotin for further application. The synthesized nanoparticle was characterized by transmission electron microscopy (TEM) and x-ray photoelectron spectroscopy (XPS). We found that the resulting nanoparticles were uniform in size, with a diameter of around 8 nm. We tested the pre-targeting capability of the biotin-modified yttrium phosphate/apoferritin nanoparticle (yttrium phosphate/apoferritin nanoparticle) conjugate with streptavidin-modified magnetic beads and with aid of biotin-modified fluorecein isothiocyanate (FITC) tracer. This work shows that an yttrium phosphate NP conjugate provides a fast, simple and efficient method to prepare radioactive yttrium conjugate for applications in radioimmunotherapy of cancer.

  16. Apoferritin-templated yttrium phosphate nanoparticle conjugates for radioimmunotherapy of cancers.

    PubMed

    Wu, Hong; Wang, Jun; Wang, Zhemin; Fisher, Darrell R; Lin, Yuehe

    2008-05-01

    We report a templated-synthetic approach based on protein-cage of apoferritin to prepare radionuclide nanoparticle (NP) conjugates. Non-radioactive yttrium (89Y) was used as a model target and surrogate for radioyttrium (90Y) to prepare the nanoparticle conjugate. The center cavity and multiple channel structure of apoferritin offer a fast and facile method to precipitate yttrium phosphate by diffusing yttrium and phosphate ions into the cavity of apoferritin, resulting a core-shell nanoparticle. The yttrium phosphate/apoferritin nanoparticle was functionalized with biotin for further application. The synthesized nanoparticle was characterized by transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS). We found that the resulting nanoparticles were uniform in size, with a diameter of around 8 nm. We tested the pre-targeting capability of the biotin-modified yttrium phosphate/apoferritin nanoparticle conjugate with streptavidin-modified magnetic beads and with aid of streptavidin-modified fluorescein isothiocyanate (FITC) tracer. This work shows that an yttrium phosphate NP conjugate provides a fast, simple and efficient method to prepare radioactive yttrium conjugate for potential applications in radioimmunotherapy of cancer.

  17. Electrochemical and catalytic properties of Ni/BaCe0.75Y0.25O3-δ anode for direct ammonia-fueled solid oxide fuel cells.

    PubMed

    Yang, Jun; Molouk, Ahmed Fathi Salem; Okanishi, Takeou; Muroyama, Hiroki; Matsui, Toshiaki; Eguchi, Koichi

    2015-04-01

    In this study, Ni/BaCe0.75Y0.25O3-δ (Ni/BCY25) was investigated as an anode for direct ammonia-fueled solid oxide fuel cells. The catalytic activity of Ni/BCY25 for ammonia decomposition was found to be remarkably higher than Ni/8 mol % Y2O3-ZrO2 and Ni/Ce0.90Gd0.10O1.95. The poisoning effect of water and hydrogen on ammonia decomposition reaction over Ni/BCY25 was evaluated. In addition, an electrolyte-supported SOFC employing BaCe0.90Y0.10O3-δ (BCY10) electrolyte and Ni/BCY25 anode was fabricated, and its electrochemical performance was investigated at 550-650 °C with supply of ammonia and hydrogen fuel gases. The effect of water content in anode gas on the cell performance was also studied. Based on these results, it was concluded that Ni/BCY25 was a promising anode for direct ammonia-fueled SOFCs. An anode-supported single cell denoted as Ni/BCY25|BCY10|Sm0.5Sr0.5CoO3-δ was also fabricated, and maximum powder density of 216 and 165 mW cm(-2) was achieved at 650 and 600 °C, for ammonia fuel, respectively.

  18. Macrodosimetry and microdosimetry in radioimmunotherapy. Final report, July 15, 1989 -- July 14, 1992

    SciTech Connect

    Leichner, P.K.

    1991-12-01

    This report summarizes research in beta-particle dosimetry, quantitative single-photon emission computed tomography (SPECT), the clinical implementation of these two areas of research in radioimmunotherapy (RIT), and postgraduate training provided since the inception of this grant on July 15, 1989. To improve beta-particle dosimetry, a point source function was developed that is valid for a wide range of beta emitters. Analytical solutions for beta-particle dose rates within out outside slabs of finite thickness were validated in experimental tumors and are now being used in clinical RIT. Quantitative SPECT based on the circular harmonic transform (CHT) algorithm was validated in phantom, experimental, and clinical studies. This has led to improved macrodosimetry in clinical RIT. In dosimetry at the multi-cellular level studies were made of the HepG2 human hepatoblastoma grown subcutaneously in nude mice. Histologic sections and autoradiographs were prepared to quantitate activity distributions of radiolabeled antibodies. Absorbed-dose calculations are being carried out for {sup 131}I and {sup 90}Y beta particles for these antibody distributions.

  19. Targeted therapy using alpha emitters.

    PubMed

    Vaidyanathan, G; Zalutsky, M R

    1996-10-01

    Radionuclides such as 211At and 212Bi which decay by the emission of alpha-particles are attractive for certain applications of targeted radiotherapy. The tissue penetration of 212Bi and 211At alpha-particles is equivalent to only a few cell diameters, offering the possibility of combining cell-specific targeting with radiation of similar range. Unlike the beta-particles emitted by radionuclides such as 131I and 90Y, alpha-particles are radiation of high linear energy transfer and thus greater biological effectiveness. Several approaches have been explored for targeted radiotherapy with 212Bi- and 211At-labelled substances including colloids, monoclonal antibodies, metabolic precursors, receptor-avid ligands and other lower molecular weight molecules. An additional agent which exemplifies the promise of alpha-emitting radiopharmaceuticals is meta-[211At]astatobenzylguanidine. The toxicity of this compound under single-cell conditions, determined both by [3H]thymidine incorporation and by limiting dilution clonogenic assays, for human neuroblastoma cells is of the order of 1000 times higher than that of meta-[131I] iodobenzylguanidine. For meta-[211At] astatobenzylguanidine, the Do value was equivalent to only 6-7 211At atoms bound per cell. These results suggest that meta-[211At] astatobenzylguanidine might be valuable for the targeted radiotherapy of micrometastatic neuroblastomas.

  20. Radionuclide therapy beyond radioiodine.

    PubMed

    Gabriel, Michael

    2012-10-01

    For decades, Iodine-131 has been used for the treatment of patients with thyroid cancer. In recent years, increasingly, other radiopharmaceuticals are in clinical use in the treatment of various malignant diseases. Although in principle these therapies-as in all applications of radionuclides-special radiation protection measures are required, a separate nuclear medicine therapy department is not necessary in many cases due to the lower or lack of gamma radiation. In the following article, four different radionuclide therapies are more closely presented which are emerging in the last years. One of them is the "Peptide Receptor Radionuclide Therapy," the so-called PRRT in which radiolabeled somatostatin (SST)-receptor(R) ligands are used in patients with neuroendocrine tumors. On the basis of radiolabeled antibodies against CD20-positive cells, the so-called radioimmunotherapy is used in the treatment of certain forms of malignant lymphoma. In primary or secondary liver tumors, the (90)Y-labeled particles can be administered. Last but not the least, the palliative approach of bone-seeking radiopharmaceuticals is noted in patients with painful bone metastases.

  1. [Neuroendocrine tumors: Peptide receptors radionuclide therapy (PRRT)].

    PubMed

    Papamichail, Dimitris G; Exadaktylou, Paraskevi E; Chatzipavlidou, Vasiliki D

    2016-01-01

    Neuroendocrine tumors (neuroendocrine tumors-NET) are a heterogeneous group of neoplasms with a common embryological origin and diverse biological behavior, derived from cells of the neuroendocrine system, the system APUD (amine precursor uptake and decarboxylation). They are characterized by overexpression of all five somatostatin receptors (SSTR1-SSTR5), particularly type 2 (SST2). Surgical resection of the tumor is the treatment option, with a possibility of complete remission in patients with limited disease. Somatostatin analogs (octreotide and lanreotide) are the treatment of choice in patients with residual disease, particularly when it comes to NET non-pancreatic origin. Systemic chemotherapy is administered primarily to patients with poorly differentiated carcinomas. PRRT treatment is recommended in case of non-responsiveness of the disease. The ideal candidates for PRRT are patients with unresectable disease of high and intermediate differentiation. Somatostatine analogs radiolabelled with Indium-111 ((111)In), Yttrium-90 ((90)Y), Lutetium-177 ((177)Lu) and Bismuth-213 ((213)Bi), are selectively concentrated in the tumor cells, causing maximum tissue damage to tumors and with fewer effects on healthy tissue and the immune system. In the current review, it was demonstrated that patients with unresectable grade 1 or 2 disease showed increased PFS (progression free survival) and OS (overall survival), while quality of life was improved after PRRT treatment as compared to somatostatin analogs, chemotherapy and other targeted therapies. PMID:27035909

  2. Results of fibre and toner flotation depending on oleic acid dosage.

    PubMed

    Trumic, Maja S; Trumic, Milan Z; Vujic, Bogdana; Andric, Ljubisa; Bogdanovic, Grozdanka

    2016-09-01

    The literature was reviewed with respect to deinking flotation methods with toner samples, specifically emphasizing the speciation of copy machine and laser printing, which produce an increasing quantity of paper that is difficult to recycle. Speciation here refers to the physical-chemical characteristics of the toner, which change because of the polymerization (fusion) and oxidation process, due to exposure to heat, light and oxygen (air) during the printing process. To simulate the deinking flotation, after the ideal disintegration process, samples of toner were prepared in order to provide free toner particles. Synthetic toner has iron content and the same physical-chemical features as free disintegrated printed toner particles.We report the toner (I) and fibre (Y) recovery and the brightness (B) of laboratory filter pads formed of deinked product as deinking efficiencies. The application of oleic acid as the collector in the flotation stage gives a better flotation recovery in alkaline than in acidic conditions. The highest brightness (BF = 93.66%) and flotation recoveries (I = 90, Y = 92.82%) were achieved during testing at an oleic acid concentration of 3.38·10(-6) mol l(-1), which is the lowest dose used. This makes the use of oleic acid economical and environmentally friendly. PMID:27354017

  3. Photomultiplier window materials under electron irradiation - Fluorescence and phosphorescence

    NASA Technical Reports Server (NTRS)

    Viehmann, W.; Eubanks, A. G.; Pieper, G. F.; Bredekamp, J. H.

    1975-01-01

    The fluorescence and phosphorescence of photomultiplier window materials under electron irradiation have been investigated using a Sr-90/Y-90 beta emitter as the electron source. Spectral emission curves of UV-grade, optical-grade, and electron-irradiated samples of MgF2 and LiF, and of CaF2, BaF2, sapphire, fused silica, and UV-transmitting glasses were obtained over the 200-650-nm spectral range. Fluorescence yields were determined on these materials utilizing photomultiplier tubes with cesium telluride, bialkali, and trialkali (S-20) photocathodes, respectively. Optical-grade MgF2 and LiF, as well as electron-irradiated UV-grade samples of these two materials, show enhanced fluorescence due to color-center formation and associated emission bands in the blue and red wavelength regions. Large variations in fluorescence intensities were found in UV-grade sapphire samples of different origins, particularly in the red end of the spectrum, presumably due to various amounts of chromium-ion content. Phosphorescence decay with time is best described by a sum of exponential terms, with time constants ranging from a few minutes to several days.

  4. Design and Construction of A Cerenkov Counter for In Situ Monitoring of Sr-90 in Groundwater

    SciTech Connect

    Brodzinski, Ronald L.; Runkle, Robert C.; Hartman, John S.; Ashbaker, Eric D.; Douglas, Matthew; Jordan, David V.; McCormick, Kathleen R.; Sliger, William A.; Todd, Lindsay C.

    2008-07-01

    Migration of groundwater contamination from beneath the U.S. Department of Energy’s Hanford Site into the Columbia River creates a need for in situ 90Sr monitoring. The prototype monitor discussed here is designed for deployment inside a monitoring well and provides near-real-time determination of the 90Sr concentration in a two-liter groundwater sample. The measurement is made by direct detection of Cerenkov light generated in the water by beta decay of the 90Y daughter. This manuscript presents results from a prototype monitor that was designed by a parametric Monte Carlo simulation study. Calibration and testing results of the as-built system show near perfect agreement between simulated predictions and experimental results. Downwell and laboratory tests demonstrate that the prototype monitor is sensitive to 90Sr at concentrations below drinking water standards of 8 pCi/l (0.3 Bq/l) at the 90% confidence level in measurement times of less than four hours.

  5. Robustness of plastic scintillation microspheres in the continuous measurement of different river waters.

    PubMed

    Tarancón, A; Novella, O; Batlle, M; Pujadas, M; Cros, J; García, J F

    2016-08-01

    Plastic scintillation microspheres (PSm) represent one of the most promising options for monitoring alpha and beta radioactivity in river water. For that reason, a study of the stability of PSm packed into a cell against the continuous flow of river water with different degrees of turbidity was performed over a period of 100h. The results showed that the volume of the cell became stable after 15h of pumping and continued to be stable throughout the 100h of the experiment. During this period of time, the detection efficiency of the PSm, in terms of efficiency*volume, presented mean values of 0.75(3)% for (3)H and 272(11)% for (90)Sr/(90)Y. No dependence on flow time or river water type was observed. The background was also constant for 100h and for the different water types, although (222)Rn should be removed from the water beforehand to prevent its accumulation in the PSm. Since PSm did not present any degradation throughout the whole experiment, PSm can undoubtedly be used for monitoring radioactivity with low reagent consumption, low waste generation and low maintenance costs. PMID:27235888

  6. Determination of immunoreactive fraction of radiolabeled monoclonal antibodies: what is an appropriate method?

    PubMed

    Konishi, Shota; Hamacher, Klaus; Vallabhajosula, Shankar; Kothari, Paresh; Bastidas, Diago; Bander, Neil; Goldsmith, Stanley

    2004-12-01

    Determination of the immunoreactive fraction (IF) of radiolabeled monoclonal antibodies (MAb) is essential to the understanding of the effects of radiolabeling and subsequent target-specific tumor localization. There has been generally no accepted method of determining the IF of MAbs. The conventional method is based on a radioimmunoassay technique in which the fraction of radiolabeled MAb bound to antigen under conditions of "antigen excess" is determined. Lindmo et al. introduced a modified method in which the IF is determined by extrapolation to conditions representing "infinite antigen excess." Although the Lindmo method, in principle, is insensitive to experimental parameters, it does not always provide a reliable estimate of IF. We, therefore, evaluated an alternate method in which percent cell bound fraction is measured under conditions of fixed antigen concentration and various dilutions of radiolabeled MAb. We developed a mathematical equation to estimate immunoreactivity. J591 MAb specific for prostate-specific membrane antigen was radiolabeled with (111)In, (90)Y and (177)Lu to specific activities of 1-20 mCi/mg. We compared the effect of several experimental conditions on the determination of IF using all three different methods. The Lindmo method requires careful optimization of experimental conditions for each radiolabeled MAb. The alternate method, based on a fixed antigen concentration, appears to be practical and may provide a more reliable measure of immunoreactivity.

  7. Bone Marrow Recovery and Subsequent Chemotherapy Following Radiolabeled Anti-Prostate-Specific Membrane Antigen Monoclonal Antibody J591 in Men with Metastatic Castration-Resistant Prostate Cancer

    PubMed Central

    Tagawa, Scott T.; Akhtar, Naveed H.; Nikolopoulou, Anastasia; Kaur, Gurveen; Robinson, Brian; Kahn, Renee; Vallabhajosula, Shankar; Goldsmith, Stanley J.; Nanus, David M.; Bander, Neil H.

    2013-01-01

    Radioimmunotherapy (RIT) has demonstrated efficacy with acceptable toxicity leading to approval in non-Hodgkin’s lymphoma, but has been slower to develop for the treatment of advanced solid tumors. Prostate cancer (PC) represents a good candidate for RIT based upon high exposure to circulating antibodies at common disease sites with a specific, highly expressed cell-surface antigen of prostate-specific membrane antigen. Four phase I and II trials utilizing 177Lu- or 90Y-J591 have been reported. Long-term toxicity and chemotherapy administration was analyzed. As expected, the only serious toxicity observed was myelosuppression. Grade 4 thrombocytopenia occurred in 33.3% without significant hemorrhage and grade 4 neutropenia occurred in 17.3% with 0.07% febrile neutropenia. Nearly all subjects (97.3%) recovered to grade 0 or 1 platelets and all had complete neutrophil recovery. The majority (81.3%) received chemotherapy at any time, with 61.3% receiving chemotherapy following RIT. Ten subjects underwent bone marrow biopsies at some point in their disease course following RIT for low counts; all had diffuse PC infiltration without evidence of myelodysplasia or leukemia. As expected, myelosuppression occurs following therapeutic doses of RIT for men with metastatic castration-resistant PC. However, toxicity is predictable and self-limited, with the majority of patients who do not refuse able to receive cytotoxic chemotherapy following RIT. PMID:23986881

  8. Bone marrow recovery and subsequent chemotherapy following radiolabeled anti-prostate-specific membrane antigen monoclonal antibody j591 in men with metastatic castration-resistant prostate cancer.

    PubMed

    Tagawa, Scott T; Akhtar, Naveed H; Nikolopoulou, Anastasia; Kaur, Gurveen; Robinson, Brian; Kahn, Renee; Vallabhajosula, Shankar; Goldsmith, Stanley J; Nanus, David M; Bander, Neil H

    2013-01-01

    Radioimmunotherapy (RIT) has demonstrated efficacy with acceptable toxicity leading to approval in non-Hodgkin's lymphoma, but has been slower to develop for the treatment of advanced solid tumors. Prostate cancer (PC) represents a good candidate for RIT based upon high exposure to circulating antibodies at common disease sites with a specific, highly expressed cell-surface antigen of prostate-specific membrane antigen. Four phase I and II trials utilizing (177)Lu- or (90)Y-J591 have been reported. Long-term toxicity and chemotherapy administration was analyzed. As expected, the only serious toxicity observed was myelosuppression. Grade 4 thrombocytopenia occurred in 33.3% without significant hemorrhage and grade 4 neutropenia occurred in 17.3% with 0.07% febrile neutropenia. Nearly all subjects (97.3%) recovered to grade 0 or 1 platelets and all had complete neutrophil recovery. The majority (81.3%) received chemotherapy at any time, with 61.3% receiving chemotherapy following RIT. Ten subjects underwent bone marrow biopsies at some point in their disease course following RIT for low counts; all had diffuse PC infiltration without evidence of myelodysplasia or leukemia. As expected, myelosuppression occurs following therapeutic doses of RIT for men with metastatic castration-resistant PC. However, toxicity is predictable and self-limited, with the majority of patients who do not refuse able to receive cytotoxic chemotherapy following RIT.

  9. Retrospective dosimetry using OSL of tooth enamel and dental repair materials irradiated under wet and dry conditions.

    PubMed

    Geber-Bergstrand, Therése; Bernhardsson, Christian; Mattsson, Sören; Rääf, Christopher L

    2012-11-01

    Following a radiological or nuclear emergency event, there is a need for quick and reliable dose estimations of potentially exposed people. In situations where dosimeters are not readily available, the dose estimations must be carried out using alternative methods. In the present study, the optically stimulated luminescence (OSL) properties of tooth enamel and different dental repair materials have been examined. Specimens of the materials were exposed to gamma and beta radiation in different types of liquid environments to mimic the actual irradiation situation in the mouth. Measurements were taken using a Risø TL/OSL reader, and irradiations were made using a (90)Sr/(90)Y source and a linear accelerator (6 MV photons). Results show that the OSL signal from tooth enamel decreases substantially when the enamel is kept in a wet environment. Thus, tooth enamel is not reliable for retrospective dose assessment without further studies of the phenomenon. Dental repair materials, on the other hand, do not exhibit the same effect when exposed to liquids. In addition, dose-response and fading measurements of the dental repair materials show promising results, making these materials highly interesting for retrospective dosimetry. The minimum detectable dose for the dental repair materials has been estimated to be 20-185 mGy. PMID:22972601

  10. Optically stimulated luminescence: Searching for new dosimetric materials

    NASA Astrophysics Data System (ADS)

    Yoshimura, E. M.; Yukihara, E. G.

    2006-09-01

    Optically stimulated luminescence (OSL) is increasingly being used as a dosimetric technique in various fields such as medical, environmental and space dosimetry, and sediment and archaeological dating. Nevertheless few compounds are suitable as OSL materials. In this work, a survey was made of various insulators, searching for candidates for new OSL dosimeters. Natural and synthetic crystals and glasses from numerous sources are included. Luminescence was stimulated with blue LEDs (470 nm) and with IR laser (830 nm) provided by an automatic reader. Irradiation was performed with a 90Sr/ 90Y beta source, and the emitted light was measured with a photomultiplier tube, protected with suitable optical filters. Thermoluminescence (TL) of the samples was also measured, with the same equipment, to evaluate the thermal and optical stability of the defects related to OSL and TL. Among the various investigated materials, Al 2O 3:Cr, Mg, Fe, MgAl 2O 4 spinels, Mg 2SiO 4:Tb, and natural fluorite show potential as OSL dosimeters. Some materials, as barium aluminoborate glasses, although showing intense OSL signals, present a high fading at room temperature. In that situation the OSL signal is related to low temperature TL peaks that also fade at room temperature. None of the investigated materials was specially prepared to be used as an OSL dosimeter, which means that work can be done, mainly in the impurity nature and content, in order to improve OSL signals and to overcome some of the shortcomings that were noticed.

  11. Robustness of plastic scintillation microspheres in the continuous measurement of different river waters.

    PubMed

    Tarancón, A; Novella, O; Batlle, M; Pujadas, M; Cros, J; García, J F

    2016-08-01

    Plastic scintillation microspheres (PSm) represent one of the most promising options for monitoring alpha and beta radioactivity in river water. For that reason, a study of the stability of PSm packed into a cell against the continuous flow of river water with different degrees of turbidity was performed over a period of 100h. The results showed that the volume of the cell became stable after 15h of pumping and continued to be stable throughout the 100h of the experiment. During this period of time, the detection efficiency of the PSm, in terms of efficiency*volume, presented mean values of 0.75(3)% for (3)H and 272(11)% for (90)Sr/(90)Y. No dependence on flow time or river water type was observed. The background was also constant for 100h and for the different water types, although (222)Rn should be removed from the water beforehand to prevent its accumulation in the PSm. Since PSm did not present any degradation throughout the whole experiment, PSm can undoubtedly be used for monitoring radioactivity with low reagent consumption, low waste generation and low maintenance costs.

  12. Time-specific measurements of energy deposition from radiation fields in simulated sub-micron tissue volumes

    SciTech Connect

    Famiano, M.A.

    1997-07-07

    A tissue-equivalent spherical proportional counter is used with a modified amplifier system to measure specific energy deposited from a uniform radiation field for short periods of time ({approximately}1 {micro}s to seconds) in order to extrapolate to dose in sub-micron tissue volumes. The energy deposited during these time intervals is compared to biological repair processes occurring within the same intervals after the initial energy deposition. The signal is integrated over a variable collection time which is adjusted with a square-wave pulse. Charge from particle passages is collected on the anode during the period in which the integrator is triggered, and the signal decays quickly to zero after the integrator feedback switch resets; the process repeats for every triggering pulse. Measurements of energy deposited from x rays, {sup 137}Cs gamma rays, and electrons from a {sup 90}Sr/{sup 90}Y source for various time intervals are taken. Spectral characteristics as a function of charge collection time are observed and frequency plots of specific energy and collection time-interval are presented. In addition, a threshold energy flux is selected for each radiation type at which the formation of radicals (based on current measurements) in mammalian cells equals the rate at which radicals are repaired.

  13. Extremity exposure in nuclear medicine: preliminary results of a European study.

    PubMed

    Sans Merce, M; Ruiz, N; Barth, I; Carnicer, A; Donadille, L; Ferrari, P; Fulop, M; Ginjaume, M; Gualdrini, G; Krim, S; Mariotti, F; Ortega, X; Rimpler, A; Vanhavere, F; Baechler, S

    2011-03-01

    The Work Package 4 of the ORAMED project, a collaborative project (2008-11) supported by the European Commission within its seventh Framework Programme, is concerned with the optimisation of the extremity dosimetry of medical staff in nuclear medicine. To evaluate the extremity doses and dose distributions across the hands of medical staff working in nuclear medicine departments, an extensive measurement programme has been started in 32 nuclear medicine departments in Europe. This was done using a standard protocol recording all relevant information for radiation exposure, i.e. radiation protection devices and tools. This study shows the preliminary results obtained for this measurement campaign. For diagnostic purposes, the two most-used radionuclides were considered: (99m)Tc and (18)F. For therapeutic treatments, Zevalin(®) and DOTATOC (both labelled with (90)Y) were chosen. Large variations of doses were observed across the hands depending on different parameters. Furthermore, this study highlights the importance of the positioning of the extremity dosemeter for a correct estimate of the maximum skin doses.

  14. Development of the Japanese reference man model for age-specific phantoms.

    PubMed

    Kawamura, Hisao

    2012-03-01

    Recent interest in improving methods for calculating radiation doses to atomic bomb survivors necessitates reinforcing the data on masses of organs of the Japanese population in 1945, including those that are not calculated by DS02, as well as increasing the number of phantoms for different ages. Reference is made to published data on the masses of organs in normal Japanese subjects of 0-90 y of age with more than 5000 samples during 1970-80, as well as the weight and size of the total body. The first Japanese Reference Man model, primarily based on these data and following the ICRP Reference Man concept, is briefly explained. It provides a set of reference values for males and females of six age groups, i.e. 3 months, 1, 5, 10, 15 and 20-50 y. To consider the organ masses of the Japanese population in 1945, the data during the period 1970-80 are compared with the literature data of normal Japanese reported in 1952. Differences between the two sets of organ data in adults are discussed in relation to changes in the national status of nutrition. Additional organ masses of current interest for the Japanese population in 1945 are preliminarily considered.

  15. 142-Sm - a suitable positron emitter for uptake monitoring in 153-Sm EDTMP therapy

    SciTech Connect

    Beyer, G.J.; Donath, A.; Morel, C.

    1996-05-01

    The positron emitting isotopes {sup 86}Y and 83Sr are favoured candidates for monitoring the individual nuclide uptake in bone metastases with PET when {sup 90}Y or {sup 89}Sr are used in the therapy. It therefore seemed to be logical to propose the short-lived positron emitter {sup 142}Sm to perform the in vivo dosimetry in case cf {sup 153}Sm EDTMP therapy. {sup 142}Sm (72 min, 50 % positron branching) forms the 40 sec {sup 142}Pm with 95% positron decay rate. Three aspects will be discussed in the paper: the production of several GBq of the {sup 142}Sm in the required high quality, systematic studies of the biokinetic behaviour of radio-lanthanides with EDTMP as ligand and first dynamic PET studies using rabbits as animal model. Spallation reaction of 1 GeV protons interacting with a 100/g/cm{sup 2} Ta target in combination with an on line isotope separation process was used for the production of the radionuclides. The on line isotope separator facility ISOLDE at CERN provides excellent possibilities to produce {sup 142}Sm in multi GBq quantities, isotopically clean and carrier free. All other radio-lanthanides used in the study were produced at the ISOLDE facility as well. Using a number of long-lived radio-lanthanides we studied systematically the biokinetics of the lanthanides at different EDTMP concentrations and established clear relationships between biokinetics, EDTMP concentration and the ionic radius of the radioisotope used.

  16. Therapeutic radionuclides in nuclear medicine: current and future prospects.

    PubMed

    Yeong, Chai-Hong; Cheng, Mu-hua; Ng, Kwan-Hoong

    2014-10-01

    The potential use of radionuclides in therapy has been recognized for many decades. A number of radionuclides, such as iodine-131 ((131)I), phosphorous-32 ((32)P), strontium-90 ((90)Sr), and yttrium-90 ((90)Y), have been used successfully for the treatment of many benign and malignant disorders. Recently, the rapid growth of this branch of nuclear medicine has been stimulated by the introduction of a number of new radionuclides and radiopharmaceuticals for the treatment of metastatic bone pain and neuroendocrine and other malignant or non-malignant tumours. Today, the field of radionuclide therapy is enjoying an exciting phase and is poised for greater growth and development in the coming years. For example, in Asia, the high prevalence of thyroid and liver diseases has prompted many novel developments and clinical trials using targeted radionuclide therapy. This paper reviews the characteristics and clinical applications of the commonly available therapeutic radionuclides, as well as the problems and issues involved in translating novel radionuclides into clinical therapies.

  17. Rapid screening of radioactivity in food for emergency response.

    PubMed

    Bari, A; Khan, A J; Semkow, T M; Syed, U-F; Roselan, A; Haines, D K; Roth, G; West, L; Arndt, M

    2011-06-01

    This paper describes the development of methods for the rapid screening of gross alpha (GA) and gross beta (GB) radioactivity in liquid foods, specifically, Tang drink mix, apple juice, and milk, as well as screening of GA, GB, and gamma radioactivity from surface deposition on apples. Detailed procedures were developed for spiking of matrices with (241)Am (alpha radioactivity), (90)Sr/(90)Y (beta radioactivity), and (60)Co, (137)Cs, and (241)Am (gamma radioactivity). Matrix stability studies were performed for 43 days after spiking. The method for liquid foods is based upon rapid digestion, evaporation, and flaming, followed by gas proportional (GP) counting. For the apple matrix, surface radioactivity was acid-leached, followed by GP counting and/or gamma spectrometry. The average leaching recoveries from four different apple brands were between 63% and 96%, and have been interpreted on the basis of ion transport through the apple cuticle. The minimum detectable concentrations (MDCs) were calculated from either the background or method-blank (MB) measurements. They were found to satisfy the required U.S. FDA's Derived Intervention Levels (DILs) in all but one case. The newly developed methods can perform radioactivity screening in foods within a few hours and have the potential to capacity with further automation. They are especially applicable to emergency response following accidental or intentional contamination of food with radioactivity.

  18. Application and dosimetric requirements for 68Ga-labeled somatostatin analogues in targeted radionuclide therapy for gastroenteropancreatic neuroendocrine tumors

    PubMed Central

    Taïeb, David; Garrigue, Philippe; Bardiès, Manuel; Esmaeel, Abdullah Ahmad; Pacak, Karel

    2015-01-01

    Neuroendocrine tumors (NETs) are associated with variable prognosis, with grade 1 and 2 NETs having a more favorable outcome than G3 ones (also called carcinoma). GEP-NET patients need highly individualized interdisciplinary evaluations and treatment. New treatment options have become available (i.e., sunitinib, mTOR inhibitors) with significant improvements in progression-free survival. Peptide receptor radionuclide therapy (PRRT) using 90Y or 177Lu-labeled somatostatin analogs has also shown promise in the treatment of advanced progressive NETs but randomized clinical trials comparing with other modalities are still lacking. SST-targeting represents the essence of theranostics. 68Ga-DOTA-SSTa can be used as companion imaging agents to assist in such a radionuclide therapy selection. 68Ga-DOTA-SSTa PET/CT might also provide critical information for prognosis, tumor response assessement to PRRT, and internal dosimetry. It is also expected that the development of novel receptor-targeting radiopharmaceuticals will contribute to the development of molecular-based personalized medicine approaches. PMID:26384594

  19. Development of A phantom for ophthalmic beta source applicator quality control using TL dosimetry

    NASA Astrophysics Data System (ADS)

    Barbosa, N. A.; da Rosa, L. A. R.; Braz, D.

    2015-11-01

    Concave eye applicators with 90Sr/90Y and 106Ru/106Rh beta ray sources are usually used in brachytherapy for the treatment of superficial intraocular tumors as uveal melanoma with thickness up to 5 mm. The calculation of the dose delivered to the eye is carried out based on the data present in the beta source calibration certificate. Therefore, it would be interesting to have a system that could evaluate that dose. In this work, an eye phantom to be used with 106Ru/106Rh betatherapy applicators was developed in solid water. This phantom can hold nine micro-cube thermoluminescent (TL) dosimeters, TLD-100. The characteristics of the TL response of the dosimeters, namely reproducibility and individual sensitivity, were determined for a 60Co source. Using Monte Carlo code MCNPX, the dose to a water eye was determined at different depths. Exposing the eye phantom with TL dosimeters to the 106Ru/106Rh applicator, it is possible to assess calibration factors using the dose values obtained by Monte Carlo simulation to each depth. Using mean calibration factors, dose values obtained by TL dosimetry were compared to the data present in the applicators certificate. Mean differences for both applicators were lower than ±10%, maximum value 17% and minimum value 0.08%. Considering that the certificate values present an uncertainty of ±20%, the calibration procedure and the developed phantom are validated and can be applied.

  20. Downstream Hepatic Arterial Blood Pressure Changes Caused by Deployment of the Surefire AntiReflux Expandable Tip

    SciTech Connect

    Rose, Steven C. Kikolski, Steven G.; Chomas, James E.

    2013-10-15

    Purpose: The purpose of this work was to evaluate blood pressure changes caused by deployment of the Surefire antireflux expandable tip. The pressure measurements are relevant because they imply changes in hepatoenteric arterial blood flow within this liver compartment during hepatic artery delivery of cytotoxic agents. Methods: After positioning the Surefire antireflux system in the targeted hepatic artery, blood pressure was obtained initially with the tip collapsed (or through a femoral artery sheath), then again after the tip was expanded before chemoembolization or yttrium 90 ({sup 90}Y) radioembolization. Results: Eighteen patients with liver malignancy underwent 29 procedures in 29 hepatic arteries (3 common hepatic, 22 lobar, 4 segmental). Systolic, diastolic, and mean blood pressure were all decreased by a mean of 29 mm Hg (p = 0.000004), 14 mm Hg (p = 0.0000004), and 22 mm Hg (p = 0.00000001), respectively. Conclusion: When the Surefire expandable tip is deployed to prevent retrograde reflux of agents, it also results in a significant decrease in blood pressure in the antegrade distribution, potentially resulting in hepatopedal blood flow in vessels that are difficult to embolize, such as the supraduodenal arteries.

  1. Radioimmunotherapy with radioactive nanoparticles: First results of dosimetry for vascularized and necrosed solid tumors

    SciTech Connect

    Bouchat, V.; Nuttens, V. E.; Lucas, S.; Michiels, C.; Masereel, B.; Feron, O.; Gallez, B.; Borght, T. Vander

    2007-11-15

    Radioimmunotherapy uses monoclonal antibodies that are still labeled with only one radioactive atom. The aim of this paper is to assess, by means of MCNPX simulations, the doses delivered around and throughout a solid tumor when the radioactive atom linked to each antibody is replaced by a 5 nm diameter nanoparticle composed of numerous radionuclides. A new model for a spherical vascularized tumor has been developed in which the antibody distributions inside the tumor can be uniform or heterogeneous. It is also possible to simulate a central necrotic core inside the tumor where the concentration of radiolabeled antibodies is assumed to be zero. Dosimetry calculations have been performed for the beta-emitting radionuclide {sup 90}Y{sub 2}O{sub 3}. Preliminary results show that the irregularity of vasculature and the presence of a necrotic core have a noticeable influence on the deposited dose profiles. Moreover, with a total activity of 5 and 34 MBq for tumor radii of 0.5 and 1.0 cm, respectively, viable tumor cells can receive doses of up to 50 Gy, even if high nonuniformity of the total activity is observed in the tumor. These simulations still require accurate information about antibody characteristics and necrosis sizes but clearly confirm that the use of monoclonal antibodies conjugated to nanoparticles could lead to a considerable enhancement of treatment efficacy against cancer.

  2. Effect of quench on alpha/beta pulse shape discrimination of liquid scintillation cocktails.

    PubMed

    DeVol, Timothy A; Theisen, Christopher D; DiPrete, David P

    2007-05-01

    The objectives of this paper are (1) to illustrate that knowledge of the external quench parameter is insufficient to properly setup a pulse shape discriminating liquid scintillation counter (LSC) for quantitative measurement, (2) to illustrate dependence on pulse shape discrimination on the radionuclide (more than just radiation and energy), and (3) to compare the pulse shape discrimination (PSD) of two commercial instruments. The effects various quenching agents, liquid scintillation cocktails, radionuclides, and LSCs have on alpha/beta pulse shape discriminating liquid scintillation counting were quantified. Alpha emitting radionuclides (239)Pu and (241)Am and beta emitter (90)Sr/(90)Y were investigated to quantify the nuclide dependence on alpha/beta pulse shape discrimination. Also, chemical and color quenching agents, nitromethane, nitric acid, and yellow dye impact on alpha/beta pulse shape discrimination using PerkinElmer Optiphase "HiSafe" 2 and 3, and Ultima Gold AB liquid scintillation cocktails were determined. The prepared samples were counted on the PerkinElmer Wallac WinSpectral 1414 alpha/beta pulse shape discriminating LSC. It was found that for the same level of quench, as measured by the external quench parameter, different quench agents influenced the pulse shape discrimination and the pulse shape discrimination parameters differently. The radionuclide also affects alpha/beta pulse shape discrimination. By comparison with the PerkinElmer Tri-carb 3150 TR/AB, the Wallac 1414 exhibited better pulse shape discrimination capability under the same experimental conditions. PMID:17440321

  3. Radium-228 determination of natural waters via concentration on manganese dioxide and separation using Diphonix ion exchange resin.

    PubMed

    Nour, S; El-Sharkawy, A; Burnett, W C; Horwitz, E P

    2004-12-01

    The objective of this work was to establish a new procedure for 228Ra determination of natural waters via preconcentration of radium on MnO2 and separation of its daughter, 228Ac, using Diphonix ion exchange resin. Following removal of potential interferences via passage through an initial Diphonix Resin column, the first daughter of 228Ra, 228Ac, is isolated by chromatographic separation via a second Diphonix column. A holding time of > 30 h for 228Ac ingrowth in between the two column separations ensures secular equilibrium. Barium-133 is used as a yield tracer. Actinium-228 is eluted from the second Diphonix Resin with 5 ml 1M 1-Hydroxyethane-1,1-diphosphonic acid (HEDPA) and quantified by addition of scintillation cocktail and LSC counting. Radium (and 133Ba) from the load and rinse solutions from the 2nd Diphonix column may be prepared for alpha spectrometry (for determination of 223Ra, 224Ra, and 226Ra) by BaSO4 microprecipitation and filtration. Decontamination tests indicate that U, Th, and Ra series nuclides do not interfere with these measurements, although high contents of 90Sr (90Y) require additional treatment for accurate measurement of 228Ra. Addition of stable Sr as a "hold back" carrier during the initial MnO2 preconcentration step was shown to remove most 90Sr interference. PMID:15388106

  4. Review of recent advances in radiochromic materials for 3D dosimetry

    NASA Astrophysics Data System (ADS)

    Jordan, Kevin

    2010-11-01

    Recent papers concerning radiochromic films, plastics and hydrogels for 3D dosimetry are summarized. The utility of Presage", a radiochromic plastic, with optical CT readout was demonstrated for the following applications: motion and gated treatment delivery, commissioning of small fields for radiosurgery, 192Ir high dose rate brachytherapy source commissioning and as a 3D insert for IMRT credentialing tests with Radiological Physics Centre (RPC) phantoms. Preliminary performance for characterizing microbeams from a synchrotron with optic projection tomography readout demonstrated resolution of an 83 micron diameter beam. Hydrogel chemistries based on nonionic micelles for leuco malachite green and leuco crystal violet demonstrated that low diffusion gels can be designed by choosing product dyes that are poorly soluble and water and tend to remain in the micelles. Turnbull blue chemistry has been successfully adapted to form a non-difffusing gel as well. The performance of ferrous xylenol orange hydrogel layers doped with boron to form neutron dosimeters demonstrated another practical application. Polymerization hydrogels are alternate materials that can be read with optical CT scanners. High dose gradient applications in brachytherapy with 90Sr/90Y sources and proton dosimetry are presented for comparison.

  5. Relationships between tumor size and curablity for uniformly targeted therapy with beta-emitting radionuclides

    SciTech Connect

    O`Donoghue, J.A.; Bardies, M.; Wheldon, T.E. |

    1995-10-01

    Targeted radionuclide therapy is a new form of radiotherapy that differs in some important respects from external beam irradiation. One of the most important differences is due to the finite range of ionizing beta particles emitted as a result of radionuclide disintegration. The effects of particle range have important implications for the curability of tumors. We used a mathematical model to examine tumor curability and its relationship to tumor size for 22 beta-emitting radionuclides that may have therapeutic potential. The model assumed a uniform distribution of radionuclide throughout. For targeted radionuclide therapy, the relationship between tumor curability and tumor size is different from that for conventional external beam radiotherapy. With targeted radionuclides, there is an optimal tumor size for cure. Tumors smaller than the optimal size are less vulnerable to irradiation from radionuclides because a substantial proportion of the disintegration energy escapes and is deposited outside the tumor volume. We found an optimal tumor size for radiocurability by each of the 22 radionuclides considered. Optimal cure diameters range from less than 1 mm for short-range emitters such as {sup 199}Au and {sup 33}P to several centimeters for long-range emitters such as {sup 90}Y and {sup 188}Re. The energy emitted per disintegration may be used to predict optimal cure size for uniform distributions of radionuclide. 17 refs., 8 figs., 3 tabs.

  6. Use of Yttrium-90 Microspheres in the Treatment of Unresectable Hepatic Metastases From Breast Cancer

    SciTech Connect

    Coldwell, Douglas M. Kennedy, Andrew S.; Nutting, Charles W.

    2007-11-01

    Purpose: Therapy for patients with unresectable liver metastases from breast cancer that were refractory to multiple treatment regimens was performed using radioactive microspheres. High doses of radiation were delivered to tumors from these permanently implanted yttrium-90 ({sup 90}Y) microspheres, delivered through the hepatic arterial vessels. Methods and Materials: Women from three institutions were selected for treatment, after screening that demonstrated vascular access to all tumors and after imaging confirmed that microspheres would be implanted only in the liver tumors. All patients were followed with laboratory and imaging studies at regular intervals until death. Toxicities, both acute and late were recorded, and actuarial survival determined. Results: A total of 44 women were treated from April 2002 to April 2005. Median follow-up of these women was 14 months (1-42 months). No treatment-related procedure deaths or radiation related veno-occlusive liver failures were found. Computed tomographic imaging partial response was 47% and positron emission tomographic response 95%. Conclusion: In this group of heavily pretreated patients, radioactive microspheres produced an encouraging median survival, with acceptable toxicity and a significant objective response rate, suggesting that further investigation of this approach is warranted.

  7. [Usage, effectiveness and safety of abiraterone in prostate cancer].

    PubMed

    Caro Teller, J M; Cortijo Cascajares, S; Escribano Valenciano, I; Serrano Garrote, O; Ferrari Piquero, J M

    2014-04-01

    Fundamento y objetivo: Tras la comercialización de abiraterona, inhibidor de la síntesis de andrógenos, el objetivo del estudio fue analizar el uso, la respuesta y la seguridad de abiraterona en la población de un hospital de tercer nivel. Material y métodos: Se realizó un estudio observacional retrospectivo en el que se incluyeron todos los pacientes que iniciaron tratamiento con abiraterona en un periodo de 21 meses. Se recogieron variables demográficas, diagnósticas, terapéuticas y clínicas. La respuesta se evaluó de acuerdo con la reducción del PSA con respecto al basal. Para evaluar la seguridad se registraron todas las reacciones adversas secundarias al tratamiento. Resultados: Se incluyó un total de 45 pacientes de los que, fueron evaluables con respecto a la efectividad del fármaco el 88,89%. La mediana de PSA basal era de 457,31 (rango 9032- 2,81). La reducción de PSA fue ≥50%, ≥90% y.

  8. Recommendations for Radioembolization of Hepatic Malignancies Using Yttrium-90 Microsphere Brachytherapy: A Consensus Panel Report from the Radioembolization Brachytherapy Oncology Consortium

    SciTech Connect

    Kennedy, Andrew; Nag, Subir . E-mail: subir.nag@kp.org; Salem, Riad; Murthy, Ravi; McEwan, Alexander J.; Nutting, Charles; Benson, Al; Espat, Joseph; Bilbao, Jose Ignacio; Sharma, Ricky A.; Thomas, James P.; Coldwell, Douglas

    2007-05-01

    Purpose: To standardize the indications, techniques, multimodality treatment approaches, and dosimetry to be used for yttrium-90 (Y90) microsphere hepatic brachytherapy. Methods and Materials: Members of the Radioembolization Brachytherapy Oncology Consortium met as an independent group of experts in interventional radiology, radiation oncology, nuclear medicine, medical oncology, and surgical oncology to identify areas of consensus and controversy and to issue clinical guidelines for Y90 microsphere brachytherapy. Results: A total of 14 recommendations are made with category 2A consensus. Key findings include the following. Sufficient evidence exists to support the safety and effectiveness of Y90 microsphere therapy. A meticulous angiographic technique is required to prevent complications. Resin microsphere prescribed activity is best estimated by the body surface area method. By virtue of their training, certification, and contribution to Y90 microsphere treatment programs, the disciplines of radiation oncology, nuclear medicine, and interventional radiology are all qualified to use Y90 microspheres. The panel strongly advocates the creation of a treatment registry with uniform reporting criteria. Initiation of clinical trials is essential to further define the safety and role of Y90 microspheres in the context of currently available therapies. Conclusions: Yttrium-90 microsphere therapy is a complex procedure that requires multidisciplinary management for safety and success. Practitioners and cooperative groups are encouraged to use these guidelines to formulate their treatment and dose-reporting policies.

  9. Preparation and validation of gross alpha/beta samples used in EML`s quality assessment program

    SciTech Connect

    Scarpitta, S.C.

    1997-10-01

    A set of water and filter samples have been incorporated into the existing Environmental Measurements Laboratory`s (EML) Quality Assessment Program (QAP) for gross alpha/beta determinations by participating DOE laboratories. The participating laboratories are evaluated by comparing their results with the EML value. The preferred EML method for measuring water and filter samples, described in this report, uses gas flow proportional counters with 2 in. detectors. Procedures for sample preparation, quality control and instrument calibration are presented. Liquid scintillation (LS) counting is an alternative technique that is suitable for quantifying both the alpha ({sup 241}Am, {sup 230}Th and {sup 238}Pu) and beta ({sup 90}Sr/{sup 90}Y) activity concentrations in the solutions used to prepare the QAP water and air filter samples. Three LS counting techniques (Cerenkov, dual dpm and full spectrum analysis) are compared. These techniques may be used to validate the activity concentrations of each component in the alpha/beta solution before the QAP samples are actually prepared.

  10. Myeloid neoplasms after chemotherapy and PRRT: myth and reality.

    PubMed

    Bodei, Lisa; Modlin, Irvin M; Luster, Markus; Forrer, Flavio; Cremonesi, Marta; Hicks, Rodney J; Ezziddin, Samer; Kidd, Mark; Chiti, Arturo

    2016-08-01

    Peptide receptor radionuclide therapy (PRRT) with (90)Y-octreotide or (177)Lu-octreotate is an effective treatment for inoperable or metastatic neuroendocrine tumors (NETs), particularly well-differentiated gastroenteropancreatic or bronchopulmonary NETs. PRRT is generally extremely well tolerated, with modest toxicity to target organs, kidney and bone marrow. Nevertheless, a priori concerns regarding long-term effects lead clinicians such as Brieau and coworkers, in this ERC issue, to ascribe to the combination of alkylating agents and PRRT the apparently high occurrence (n=4) of myeloproliferative events (therapy-related myeloid neoplasms (t-MNs)) in a small cohort of 20 progressive, advanced digestive NETs treated with PRRT after chemotherapy. Anecdotal reports of myelotoxic events should be placed in the correct perspective of larger series, where the reported incidence of these events is ~2%, with the aim of promoting a balanced awareness of the issue and unbiased and reasonable overall conclusions. For a comprehensive definition of the issue, we provide an evaluation of the occurrence of t-MN in patients treated with various myelotoxic treatments. PMID:27353035

  11. Application of the CIEMAT-NIST method to plastic scintillation microspheres.

    PubMed

    Tarancón, A; Barrera, J; Santiago, L M; Bagán, H; García, J F

    2015-04-01

    An adaptation of the MICELLE2 code was used to apply the CIEMAT-NIST tracing method to the activity calculation for radioactive solutions of pure beta emitters of different energies using plastic scintillation microspheres (PSm) and (3)H as a tracing radionuclide. Particle quenching, very important in measurements with PSm, was computed with PENELOPE using geometries formed by a heterogeneous mixture of polystyrene microspheres and water. The results obtained with PENELOPE were adapted to be included in MICELLE2, which is capable of including the energy losses due to particle quenching in the computation of the detection efficiency. The activity calculation of (63)Ni, (14)C, (36)Cl and (90)Sr/(90)Y solutions was performed with deviations of 8.8%, 1.9%, 1.4% and 2.1%, respectively. Of the different parameters evaluated, those with the greatest impact on the activity calculation are, in order of importance, the energy of the radionuclide, the degree of quenching of the sample and the packing fraction of the geometry used in the computation.

  12. Experiments on the origin of molecular chirality by parity non-conservation during beta-decay

    NASA Technical Reports Server (NTRS)

    Bonner, W. A.

    1973-01-01

    Experiments are described to test a theory for the origin of optical activity wherein the longitudinally polarized electrons resulting from parity violation during radioactive beta decay, and their resulting circularly polarized Bremsstrahlung, might interact asymmetrically with organic matter to yield optically active products. Experiments involve subjecting a number of racemic and optically active amino acid samples to irradiation in a 61700 Ci90SR-90Y beta radiation source for a period of 1.34 years, then examining them for any asymmetric effects by means of optical rotatory dispersion and analytical gas chromatography. In the cases of D,L-leucine, norleucine, norvaline and proline as solids, of D,L-leucine in solution and of D,L-tyrosine in alkaline solution no optical rotation was observed during CRD measurements in the 250-630 nm spectral region. While slight differences were noted in the percent radiolysis of solid D- (12.7%) and L-leucine (16.2%) as determined by GC, no enrichment of either enantiomer was found.

  13. Feasibility study of CaSO4:Tb,Yb as a thermoluminescent dosimeter

    NASA Astrophysics Data System (ADS)

    Junot, Danilo O.; Santos, Max A.; Chagas, Marcos A. P.; Couto dos Santos, Marcos A.; Nunes, Luiz A. O.; Souza, Divanizia N.

    2014-02-01

    A new composite based on CaSO4, using terbium as dopant and ytterbium as co-dopant (CaSO4:Tb,Yb), was developed for employment as a thermoluminescent (TL) dosimeter. The crystals used in this work were grown using a production route based on the Yamashita method (Yamashita et al., 1968). Crystal powder was calcined at 600 °C for 1 h. Pellets were made by adding commercial and colorless glass to improve physical resistance and sintered at 700 °C for 6 h. All samples were irradiated by a beta source (90Sr/90Y) and received doses from 1 Gy to 5 Gy. TL analyses have been performed and characteristics such as sensitivity, reproducibility, linearity, and fading have been studied. The CaSO4:Tb,Yb pellets glow curves presented two peaks, the first at around 115 °C, and the second at around 200 °C. The highest intensity was shown for CaSO4:Tb,Yb with a concentration of 0.1 mol% of Tb and Yb together. In all the samples the TL response was proportional to the absorbed dose. Therefore, the CaSO4:Tb,Yb has potential to be used as a thermoluminescent dosimeter.

  14. Monoclonal antibodies reactive with human breast or ovarian carcinoma: In vivo applications

    SciTech Connect

    Thor, A.D.; Edgerton, S.M. )

    1989-10-01

    Monoclonal antibodies (MoAbs) are unique and useful bioprobes that allow in vivo targeting of membrane-associated or circulating antigens. Most of the clinical trials to date have used low dosages of radiolabeled MoAb given in a single dose. Newer studies have included antibody fragments, repeated injections, intraperitoneal (IP) administration, and other labels such as 90Y. Clinical MoAb trials are often arduous, expensive, and time-consuming to perform. Before human use, animal studies and extensive MoAb characterization are required. The production of pharmaceutical grade, radiolabeled MoAb is technically difficult and costly. Clinical trials require administrative and patient consent as well as extensive written protocols. These studies necessitate interdepartmental and intradepartmental cooperation and coordination. Furthermore, the use of in vivo radiolabeled probes impacts many levels of health care providers from janitorial, nursing, and technical staff to laboratories and physicians. Simple blood tests or disposal of body excretions may concern nursing or technical staff with the possibility of radiation exposure. The responsibility for study design, personnel involvement, and prospective use in patients without a definitive cancer diagnosis ultimately rests with the physician. While many issues have been addressed, additional clinical trials, consideration of safety issues, and standardization between institutions will be necessary before the use of radiolabeled MoAb for diagnosis, management, or therapy of human tumors becomes routine. Continued cooperation and funding should ensure its achievement. 136 references.

  15. Utilization of wavelength-shifting fibers coupled to ZnS(Ag) and plastic scintillator for simultaneous detection of alpha/beta particles

    NASA Astrophysics Data System (ADS)

    Ifergan, Y.; Dadon, S.; Israelashvili, I.; Osovizky, A.; Gonen, E.; Yehuda-Zada, Y.; Smadja, D.; Knafo, Y.; Ginzburg, D.; Kadmon, Y.; Cohen, Y.; Mazor, T.

    2015-06-01

    Low level radioactive surface contamination measurements require lightweight, large area and high efficiency detector. In most existing scintillation detectors there is a tradeoff between effective area and scintillation light collection. By using wavelength shifting (WLS) fibers the scintillation light may be collected efficiently also in a large area detector. In this study, WLS fibers were coupled to a beta sensitive plastic scintillator layer and to a alpha sensitive silver-activated zinc sulfide ZnS(Ag) layer for detecting both alpha and beta particles. The WLS fibers collect the scintillation light from the whole detector and transfer it to a single PMT. This first prototype unique configuration enables monitoring radioactive contaminated surfaces by both sides of the detector and provides high gamma rejection. In this paper, the detector structure, as well as the detector's measured linear response, will be described. The measured detection efficiency of 238Pu alpha particles (5.5 MeV) is ~63%. The measured detection efficiency for beta particles is ~89% for 90Sr-90Y (average energy of 195.8 keV, 934.8 keV), ~50% for 36Cl (average energy of 251.3 keV), and 35% for 137Cs (average energy of 156.8 keV).

  16. Thermoluminescence glow curve analysis of natural onyx from Turkey.

    PubMed

    Dogan, Tamer; Toktamış, Hüseyin; Yüksel, Mehmet; Topaksu, Mustafa; Yazici, A Necmeddin

    2015-02-01

    In this study, the thermoluminesce (TL) properties of natural onyx were determined after β-irradiation ((90)Sr/(90)Y) at room temperature. The effect of the additive dose and variable heating rate for TL glow peaks of the sample were investigated. Computerized glow curve deconvolution (CGCD) methods were used to determine the number of peaks and kinetic parameters related to the TL glow peaks in natural onyx from Turkey. It was also determined kinetic parameters of onyx by means of the variable heating rate (VHR) method. The sample was exposed to β-irradiation between 2.4 Gy and 2.457 kGy. The CGCD methods showed that the glow curve of sample is the superposition of at least six first order components which were ascribed as P1-P6. The dose responses of some peaks have similar patterns and they follow linearity. The effect of heating rates on the response of dosimetric glow peaks of sample was studied. The maximum TL peak intensities of glow curve are decreasing with increasing heating rate and maximum TL peak intensities at 1 °C/s drops to 20% of the initial value when the sample is read at 6 °C/s.

  17. Ultra low fluence rate photodynamic therapy: simulation of light emitted by the Cerenkov effect

    NASA Astrophysics Data System (ADS)

    Gonzales, Jonathan; Wang, Fred; Zamora, Genesis; Trinidad, Anthony; Marcu, Laura; Cherry, Simon; Hirschberg, Henry

    2014-03-01

    PDT has been shown to be most effective at low fluence rates. Many radionuclides used for both diagnostic and therapeutic purposes produce measurable amounts of visible radiation when they decay via the Cerenkov effect which occurs when a charged particle travels faster in a dielectric medium than the speed of light in that medium. Cerenkov radiation from radiopharmaceuticals could serve as a source of extended duration, low level "internal" light, to mediate PDT, with the ultimate goals of overcoming some its current limitations. Using laser light, we are exploring the effects of fluence rates that could be generated by Cerenkov radiation on PDT efficacy. ALA or TPPS2a mediated PDT of rat gliomas monolayers or multicell spheroids ( F98, C6) was performed with 410 nm laser light exposure over an extended period of 24-96hrs. Photosensitizers were delivered either as a bolus or continuously with light exposure. At fluence rate of 20μW/cm2 effective PDT was obtained as measured by decrease in cell viability or inhibition of spheroid growth. PDT is effective at ultra low fluence rates if given over long time periods. No lower threshold has been ascertained. Since the half-life of 90Y, a radionuclide with a high Cherenkov yield is 64 hrs it is a good candidate to supply sufficient light activation for PDT. The combination of radionuclide and photodynamic therapies could improve the effectiveness of cancer treatment by exploiting synergies between these two modalities.

  18. Therapeutic radionuclides in nuclear medicine: current and future prospects

    PubMed Central

    Yeong, Chai-Hong; Cheng, Mu-hua; Ng, Kwan-Hoong

    2014-01-01

    The potential use of radionuclides in therapy has been recognized for many decades. A number of radionuclides, such as iodine-131 (131I), phosphorous-32 (32P), strontium-90 (90Sr), and yttrium-90 (90Y), have been used successfully for the treatment of many benign and malignant disorders. Recently, the rapid growth of this branch of nuclear medicine has been stimulated by the introduction of a number of new radionuclides and radiopharmaceuticals for the treatment of metastatic bone pain and neuroendocrine and other malignant or non-malignant tumours. Today, the field of radionuclide therapy is enjoying an exciting phase and is poised for greater growth and development in the coming years. For example, in Asia, the high prevalence of thyroid and liver diseases has prompted many novel developments and clinical trials using targeted radionuclide therapy. This paper reviews the characteristics and clinical applications of the commonly available therapeutic radionuclides, as well as the problems and issues involved in translating novel radionuclides into clinical therapies. PMID:25294374

  19. Current challenges in personal dosimetry at the US DOE Hanford site.

    PubMed

    Rathbone, B A; McDonald, J C; Traub, R J

    2002-01-01

    An overview is presented of the dosimetry system, dose equivalent calculation methodology, and QA/QC practices used at the US Department of Energy Hanford site. It describes some of the problems encountered in accurately measuring dose equivalent quantities under a broad range of field conditions that do not necessarily correlate with laboratory calibration conditions and the approach taken to solve these problems. Personnel at Hanford are monitored with a combination of Harshaw model 8825 and 8816 thermoluminescence dosemeters and CR-39 etched track dosemeters. Extremities are monitored using the ICN MeasuRing loaded with a Harshaw XD740 chipstrate TLD. All dosemeters employ LiF:Mg,Ti elements that are read on-site with Harshaw model 8800 and 6600 TLD readers. CR-39 dosemeters are electrochemically etched in non-commercial etch chambers and counted with an automated track counting system developed by Pacific Northwest National Laboratory. Problems with over response of the 8825 with respect to Hp(0.07), under-response of the 8825 with respect to Hp(3), and over response of the 8825 with respect to Hp(10) in Hanford's 90Sr/90Y beta radiation fields are discussed. Approaches to measurement of the operational quantities for field conditions and algorithm solutions to the above problems are described. Methods used to calibrate the ring dosemeter for Hanford field conditions together with limitations of the ring dosemeter in measuring Hp(0.07) for extremities, particularly when covered with protective clothing, are also discussed. PMID:12382727

  20. Specific energy from Auger and conversion electrons of 131I, 188Re-anti-CD20 to a lymphocyte's nucleus

    NASA Astrophysics Data System (ADS)

    Torres-García, E.; Carrillo-Cazares, T. A.

    2011-01-01

    The typical radionuclides used to label anti-CD20 in the treatment of non-Hodgkin's lymphoma are 90Y, 131I, and 188Re, with the emission of beta particles, Auger electrons, and conversion electrons for the latter two. The aim of the present work was to calculate the contribution of high linear energy transfer radiation as Auger electrons (AE) and conversion electrons (CE) of 131I and 188Re-anti-CD20 to mean specific energy into the cell nucleus by Monte Carlo simulation (MCS), so as to infer therapeutic effectiveness on a dosimetric basis. MCS was used to quantify the frequency-mean specific energy into the cell nucleus, where the cell was modeled by two concentric spheres, considering two cell models. The results showed that 10% and 33% of the mean-specific energies (z¯) per disintegration imparted to the cell nucleus for both geometries are due to AE and CE; on the other hand, if the hit of AE and CE occurs, the contribution to (z¯) is about 64% and 86% for 131I and 188Re, respectively. According to the amount of specific energy from AE and CE into the cell nucleus by positive event, they can cause catastrophic effects in the nuclear DNA in the treatment of non-Hodgkin's lymphoma with 131I, 188Re-anti-CD20.

  1. Therapeutic Strategies in HCC: Radiation Modalities.

    PubMed

    Gallicchio, R; Nardelli, A; Mainenti, P; Nappi, A; Capacchione, D; Simeon, V; Sirignano, C; Abbruzzi, F; Barbato, F; Landriscina, M; Storto, G

    2016-01-01

    Patients with hepatocellular carcinoma (HCC) comply with an advanced disease and are not eligible for radical therapy. In this distressed scenario new treatment options hold great promise; among them transarterial chemoembolization (TACE) and transarterial metabolic radiotherapy (TAMR) have shown efficacy in terms of both tumor shrinking and survival. External radiation therapy (RTx) by using novel three-dimensional conformal radiotherapy has also been used for HCC patients with encouraging results while its role had been limited in the past for the low tolerance of surrounding healthy liver. The rationale of TAMR derives from the idea of delivering exceptional radiation dose locally to the tumor, with cell killing intent, while preserving normal liver from undue exposition and minimizing systemic irradiation. Since the therapeutic efficacy of TACE is being continuously disputed, the TAMR with (131)I Lipiodol or (90)Y microspheres has gained consideration providing adequate therapeutic responses regardless of few toxicities. The implementation of novel radioisotopes and technological innovations in the field of RTx constitutes an intriguing field of research with important translational aspects. Moreover, the combination of different therapeutic approaches including chemotherapy offers captivating perspectives. We present the role of the radiation-based therapies in hepatocellular carcinoma patients who are not entitled for radical treatment.

  2. Therapeutic Strategies in HCC: Radiation Modalities

    PubMed Central

    Gallicchio, R.; Nardelli, A.; Mainenti, P.; Nappi, A.; Capacchione, D.; Simeon, V.; Sirignano, C.; Abbruzzi, F.; Barbato, F.; Landriscina, M.

    2016-01-01

    Patients with hepatocellular carcinoma (HCC) comply with an advanced disease and are not eligible for radical therapy. In this distressed scenario new treatment options hold great promise; among them transarterial chemoembolization (TACE) and transarterial metabolic radiotherapy (TAMR) have shown efficacy in terms of both tumor shrinking and survival. External radiation therapy (RTx) by using novel three-dimensional conformal radiotherapy has also been used for HCC patients with encouraging results while its role had been limited in the past for the low tolerance of surrounding healthy liver. The rationale of TAMR derives from the idea of delivering exceptional radiation dose locally to the tumor, with cell killing intent, while preserving normal liver from undue exposition and minimizing systemic irradiation. Since the therapeutic efficacy of TACE is being continuously disputed, the TAMR with 131I Lipiodol or 90Y microspheres has gained consideration providing adequate therapeutic responses regardless of few toxicities. The implementation of novel radioisotopes and technological innovations in the field of RTx constitutes an intriguing field of research with important translational aspects. Moreover, the combination of different therapeutic approaches including chemotherapy offers captivating perspectives. We present the role of the radiation-based therapies in hepatocellular carcinoma patients who are not entitled for radical treatment. PMID:27563661

  3. VIDA: a voxel-based dosimetry method for targeted radionuclide therapy using Geant4.

    PubMed

    Kost, Susan D; Dewaraja, Yuni K; Abramson, Richard G; Stabin, Michael G

    2015-02-01

    We have developed the Voxel-Based Internal Dosimetry Application (VIDA) to provide patient-specific dosimetry in targeted radionuclide therapy performing Monte Carlo simulations of radiation transport with the Geant4 toolkit. The code generates voxel-level dose rate maps using anatomical and physiological data taken from individual patients. Voxel level dose rate curves are then fit and integrated to yield a spatial map of radiation absorbed dose. In this article, we present validation studies using established dosimetry results, including self-dose factors (DFs) from the OLINDA/EXM program for uniform activity in unit density spheres and organ self- and cross-organ DFs in the Radiation Dose Assessment Resource (RADAR) reference adult phantom. The comparison with reference data demonstrated agreement within 5% for self-DFs to spheres and reference phantom source organs for four common radionuclides used in targeted therapy ((131)I, (90)Y, (111)In, (177)Lu). Agreement within 9% was achieved for cross-organ DFs. We also present dose estimates to normal tissues and tumors from studies of two non-Hodgkin Lymphoma patients treated by (131)I radioimmunotherapy, with comparison to results generated independently with another dosimetry code. A relative difference of 12% or less was found between methods for mean absorbed tumor doses accounting for tumor regression.

  4. Targeted radionuclide therapies for pancreatic cancer.

    PubMed

    Shah, M; Da Silva, R; Gravekamp, C; Libutti, S K; Abraham, T; Dadachova, E

    2015-08-01

    Pancreatic malignancies, the fourth leading cause of cancer deaths, have an aggressive behavior with poor prognosis, resulting in a 5-year survival rate of only 4%. It is typically a silent malignancy until patients develop metastatic disease. Targeted radionuclide therapies of cancer such as radiolabeled peptides, which bind to the receptors overexpressed by cancer cells and radiolabeled antibodies to tumor-specific antigens provide a viable alternative to chemotherapy and external beam radiation of metastatic cancers. Multiple clinical trials of targeted radionuclide therapy of pancreatic cancer have been performed in the last decade and demonstrated safety and potential efficacy of radionuclide therapy for treatment of this formidable disease. Although a lot of progress has been made in treatment of pancreatic neuroendocrine tumors with radiolabeled (90)Y and (177)Lu somatostatin peptide analogs, pancreatic adenocarcinomas remain a major challenge. Novel approaches such as peptides and antibodies radiolabeled with alpha emitters, pre-targeting, bispecific antibodies and biological therapy based on the radioactive tumorlytic bacteria might offer a potential breakthrough in treatment of pancreatic adenocarcinomas.

  5. [Neuroendocrine tumors: Peptide receptors radionuclide therapy (PRRT)].

    PubMed

    Papamichail, Dimitris G; Exadaktylou, Paraskevi E; Chatzipavlidou, Vasiliki D

    2016-01-01

    Neuroendocrine tumors (neuroendocrine tumors-NET) are a heterogeneous group of neoplasms with a common embryological origin and diverse biological behavior, derived from cells of the neuroendocrine system, the system APUD (amine precursor uptake and decarboxylation). They are characterized by overexpression of all five somatostatin receptors (SSTR1-SSTR5), particularly type 2 (SST2). Surgical resection of the tumor is the treatment option, with a possibility of complete remission in patients with limited disease. Somatostatin analogs (octreotide and lanreotide) are the treatment of choice in patients with residual disease, particularly when it comes to NET non-pancreatic origin. Systemic chemotherapy is administered primarily to patients with poorly differentiated carcinomas. PRRT treatment is recommended in case of non-responsiveness of the disease. The ideal candidates for PRRT are patients with unresectable disease of high and intermediate differentiation. Somatostatine analogs radiolabelled with Indium-111 ((111)In), Yttrium-90 ((90)Y), Lutetium-177 ((177)Lu) and Bismuth-213 ((213)Bi), are selectively concentrated in the tumor cells, causing maximum tissue damage to tumors and with fewer effects on healthy tissue and the immune system. In the current review, it was demonstrated that patients with unresectable grade 1 or 2 disease showed increased PFS (progression free survival) and OS (overall survival), while quality of life was improved after PRRT treatment as compared to somatostatin analogs, chemotherapy and other targeted therapies.

  6. Electrochemical separation is an attractive strategy for development of radionuclide generators for medical applications.

    PubMed

    Chakravarty, Rubel; Dash, Ashutosh; Pillai, M R A

    2012-07-01

    Electrochemical separation techniques are not widely used in radionuclide generator technology and only a few studies have been reported [1-4]. Nevertheless, this strategy is useful when other parent-daughter separation techniques are not effective or not possible. Such situations are frequent when low specific activity (LSA) parent radionuclides are used for instance with adsorption chromatographic separations, which can result in lower concentration of the daughter radionuclide in the eluent. In addition, radiation instability of the column matrix in many cases can affect the performance of the generator when long lived parent radionuclides are used. Intricate knowledge of the chemistry involved in the electrochemical separation is crucial to develop a reproducible technology that ensures that the pure daughter radionuclide can be obtained in a reasonable time of operation. Crucial parameters to be critically optimized include the applied potential, choice of electrolyte, selection of electrodes, temperature of electrolyte bath and the time of electrolysis in order to ensure that the daughter radionuclide can be reproducibly recovered in high yields and high purity. The successful electrochemical generator technologies which have been developed and are discussed in this paper include the (90)Sr/(90)Y, (188)W/(188)Re and (99)Mo/(99m)Tc generators. Electrochemical separation not only acts as a separation technique but also is an effective concentration methodology which yields high radioactive concentrations of the daughter products. The lower consumption of reagents and minimal generation of radioactive wastes using such electrochemical techniques are compatible with 'green chemistry' principles.

  7. Monte Carlo studies for medical imaging detector optimization

    NASA Astrophysics Data System (ADS)

    Fois, G. R.; Cisbani, E.; Garibaldi, F.

    2016-02-01

    This work reports on the Monte Carlo optimization studies of detection systems for Molecular Breast Imaging with radionuclides and Bremsstrahlung Imaging in nuclear medicine. Molecular Breast Imaging requires competing performances of the detectors: high efficiency and high spatial resolutions; in this direction, it has been proposed an innovative device which combines images from two different, and somehow complementary, detectors at the opposite sides of the breast. The dual detector design allows for spot compression and improves significantly the performance of the overall system if all components are well tuned, layout and processing carefully optimized; in this direction the Monte Carlo simulation represents a valuable tools. In recent years, Bremsstrahlung Imaging potentiality in internal radiotherapy (with beta-radiopharmaceuticals) has been clearly emerged; Bremsstrahlung Imaging is currently performed with existing detector generally used for single photon radioisotopes. We are evaluating the possibility to adapt an existing compact gamma camera and optimize by Monte Carlo its performance for Bremsstrahlung imaging with photons emitted by the beta- from 90 Y.

  8. Radiolabeled Somatostatin Analogue Therapy Of Gastroenteropancreatic Cancer.

    PubMed

    Bodei, Lisa; Kwekkeboom, Dik J; Kidd, Mark; Modlin, Irvin M; Krenning, Eric P

    2016-05-01

    Peptide receptor radionuclide therapy (PRRT) has been utilized for more than two decades and has been accepted as an effective therapeutic modality in the treatment of inoperable or metastatic gastroenteropancreatic neuroendocrine neoplasms (NENs) or neuroendocrine tumors (NETs). The two most commonly used radiopeptides for PRRT, (90)Y-octreotide and (177)Lu-octreotate, produce disease-control rates of 68%-94%, with progression-free survival rates that compare favorably with chemotherapy, somatostatin analogues, and newer targeted therapies. In addition, biochemical and symptomatic responses are commonly observed. In general, PRRT is well tolerated with only low to moderate toxicity in most individuals. In line with the need to place PRRT in the therapeutic sequence of gastroenteropancreatic NENs, a recently sponsored phase III randomized trial in small intestine NENs treated with (177)Lu-octreotate vs high-dose octreotide long-acting release demonstrated that (177)Lu-octreotate significantly improved progression-free survival. Other strategies that are presently being developed include combinations with targeted therapies or chemotherapy, intra-arterial PRRT, and salvage treatments. Sophisticated molecular tools need to be incorporated into the management strategy to more effectively define therapeutic efficacy and for an early identification of adverse events. The strategy of randomized controlled trials is a key issue to standardize the treatment and establish the position of PRRT in the therapeutic algorithm of NENs. PMID:27067503

  9. Tumor dosimetry in radioimmunotherapy: Methods of calculation for beta particles

    SciTech Connect

    Leichner, P.K. ); Kwok, C.S. )

    1993-03-01

    Calculational methods of beta-particle dosimetry in radioimmunotherapy (RIT) are reviewed for clinical and experimental studies and computer modeling of tumors. In clinical studies, absorbed-dose estimates are usually based on the [ital in]-[ital vivo] quantitation of the activity in tumors from gamma camera images. Because of the limited spatial resolution of gamma cameras, clinical dosimetry is necessarily limited to the macroscopic level (macrodosimetry) and the MIRD formalism for absorbed-dose calculations is appropriate. In experimental RIT, tumor dimensions are often comparable to or smaller than the beta-particle range of commonly used radionuclides (for example, [sup 131]I, [sup 67]Cu, [sup 186]Re, [sup 188]Re, [sup 90]Y) and deviations from the equilibrium dose must be taken into account in absorbed-dose calculations. Additionally, if small tumors are growing rapidly at the time of RIT, the effects of tumor growth will need to be included in absorbed-dose estimates. In computer modeling of absorbed-dose distributions, analytical, numerical, and Monte Carlo methods have been used to investigate the consequences of uniform and nonuniform activity distributions and the effects of inhomogeneous media. Measurements and calculations of the local absorbed dose at the multicellular level have shown that variations in this dose are large. Knowledge of the absorbed dose is essential for any form of radiotherapy. Therefore, it is important that clinical, experimental, and theoretical investigations continue to provide information on tumor dosimetry that is necessary for a better understanding of the radiobiological effects of RIT.

  10. Lutetium-labelled peptides for therapy of neuroendocrine tumours.

    PubMed

    Kam, B L R; Teunissen, J J M; Krenning, E P; de Herder, W W; Khan, S; van Vliet, E I; Kwekkeboom, D J

    2012-02-01

    Treatment with radiolabelled somatostatin analogues is a promising new tool in the management of patients with inoperable or metastasized neuroendocrine tumours. Symptomatic improvement may occur with (177)Lu-labelled somatostatin analogues that have been used for peptide receptor radionuclide therapy (PRRT). The results obtained with (177)Lu-[DOTA(0),Tyr(3)]octreotate (DOTATATE) are very encouraging in terms of tumour regression. Dosimetry studies with (177)Lu-DOTATATE as well as the limited side effects with additional cycles of (177)Lu-DOTATATE suggest that more cycles of (177)Lu-DOTATATE can be safely given. Also, if kidney-protective agents are used, the side effects of this therapy are few and mild and less than those from the use of (90)Y-[DOTA(0),Tyr(3)]octreotide (DOTATOC). Besides objective tumour responses, the median progression-free survival is more than 40 months. The patients' self-assessed quality of life increases significantly after treatment with (177)Lu-DOTATATE. Lastly, compared to historical controls, there is a benefit in overall survival of several years from the time of diagnosis in patients treated with (177)Lu-DOTATATE. These findings compare favourably with the limited number of alternative therapeutic approaches. If more widespread use of PRRT can be guaranteed, such therapy may well become the therapy of first choice in patients with metastasized or inoperable neuroendocrine tumours.

  11. Treatment of low level radioactive liquid waste containing appreciable concentration of TBP degraded products.

    PubMed

    Valsala, T P; Sonavane, M S; Kore, S G; Sonar, N L; De, Vaishali; Raghavendra, Y; Chattopadyaya, S; Dani, U; Kulkarni, Y; Changrani, R D

    2011-11-30

    The acidic and alkaline low level radioactive liquid waste (LLW) generated during the concentration of high level radioactive liquid waste (HLW) prior to vitrification and ion exchange treatment of intermediate level radioactive liquid waste (ILW), respectively are decontaminated by chemical co-precipitation before discharge to the environment. LLW stream generated from the ion exchange treatment of ILW contained high concentrations of carbonates, tributyl phosphate (TBP) degraded products and problematic radio nuclides like (106)Ru and (99)Tc. Presence of TBP degraded products was interfering with the co-precipitation process. In view of this a modified chemical treatment scheme was formulated for the treatment of this waste stream. By mixing the acidic LLW and alkaline LLW, the carbonates in the alkaline LLW were destroyed and the TBP degraded products got separated as a layer at the top of the vessel. By making use of the modified co-precipitation process the effluent stream (1-2 μCi/L) became dischargeable to the environment after appropriate dilution. Based on the lab scale studies about 250 m(3) of LLW was treated in the plant. The higher activity of the TBP degraded products separated was due to short lived (90)Y isotope. The cement waste product prepared using the TBP degraded product was having good chemical durability and compressive strength.

  12. Monte Carlo feasibility study for image guided surgery: from direct beta minus detection to Cerenkov luminescence imaging

    NASA Astrophysics Data System (ADS)

    Gigliotti, C. R.; Altabella, L.; Boschi, F.; Spinelli, A. E.

    2016-07-01

    The goal of this work is to compare the performances of different beta minus detection strategies for image guided surgery or ex vivo tissue analysis. In particular we investigated Cerenkov luminescence imaging (CLI) with and without the use of a radiator, direct and indirect beta detection and bremsstrahlung imaging using beta emitters commonly employed in Nuclear Medicine. Monte Carlo simulations were implemented using the GAMOS plug-in for GEANT4 considering a slab of muscle and a radioactive source (32P or 90Y) placed at 0.5 mm depth. We estimated the gain that can be obtained in terms of produced photons using different materials placed on the slab used as Cerenkov radiators, we then focused on the number of exiting photons and their spatial distribution for the different strategies. The use of radiator to enhance Cerenkov signal reduces the spatial resolution because of the increased optical spread. We found that direct beta detection and CLI are best approaches in term of resolution while the use of a thin scintillator increases the signal but the spatial resolution is degraded. Bremsstrahlung presents lower signal and it does not represent the best choice for image guided surgery. CLI represents a more flexible approach for image guided surgery using or ex vivo tissue analysis using beta-emitter imaging.

  13. A 25-Year Experience of Gastroenteropancreatic Neuroendocrine Tumors and Somatostatin (Congeners) Analogs: From Symptom Control to Antineoplastic Therapy.

    PubMed

    O'Dorisio, Thomas M; Anthony, Lowell B

    2015-01-01

    Radioimmunoassay technology was utilized in the discovery of somatostatin and was quickly brought into therapeutics; however, it took the development of somatostatin congeners to solve its limitations of a short half-life. Therapeutic medical control of hyperhormonal states such as acromegaly, carcinoid syndrome and VIPoma significantly advanced from a nonspecific approach to one that specifically and effectively targeted the underlying pathophysiology. Clinical care was transformed from nonspecific symptom control to one of a significant improvement in not only quality of life, but also quantity of life. These data submitted to US and European regulatory authorities for approval included many investigative sites with no uniform protocol and multiple investigational new drugs, and have not been previously published. This review includes the original data demonstrating the transformational impact this class of agents had on specific disease subsets resulting in regulatory approval 25 years ago. Autoradiography techniques using somatostatin resulted in identifying, localizing and characterizing its receptor subtypes. Translating in vitro data to in vivo resulted in scintigraphic whole body and SPECT scans with (111)In-pentetreotide and was incorporated into standard clinical care 20 years ago. (68)Ga-octreotide congeners using PET scanning offers a major imaging advance. Peptide receptor radiotherapy has evolved over the last 2 decades and utilizes several therapeutic isotopes, including (90)Y and (177)Lu. PMID:26303712

  14. VIDA: A Voxel-Based Dosimetry Method for Targeted Radionuclide Therapy Using Geant4

    PubMed Central

    Dewaraja, Yuni K.; Abramson, Richard G.; Stabin, Michael G.

    2015-01-01

    Abstract We have developed the Voxel-Based Internal Dosimetry Application (VIDA) to provide patient-specific dosimetry in targeted radionuclide therapy performing Monte Carlo simulations of radiation transport with the Geant4 toolkit. The code generates voxel-level dose rate maps using anatomical and physiological data taken from individual patients. Voxel level dose rate curves are then fit and integrated to yield a spatial map of radiation absorbed dose. In this article, we present validation studies using established dosimetry results, including self-dose factors (DFs) from the OLINDA/EXM program for uniform activity in unit density spheres and organ self- and cross-organ DFs in the Radiation Dose Assessment Resource (RADAR) reference adult phantom. The comparison with reference data demonstrated agreement within 5% for self-DFs to spheres and reference phantom source organs for four common radionuclides used in targeted therapy (131I, 90Y, 111In, 177Lu). Agreement within 9% was achieved for cross-organ DFs. We also present dose estimates to normal tissues and tumors from studies of two non-Hodgkin Lymphoma patients treated by 131I radioimmunotherapy, with comparison to results generated independently with another dosimetry code. A relative difference of 12% or less was found between methods for mean absorbed tumor doses accounting for tumor regression. PMID:25594357

  15. Development of a dose algorithm for the modified panasonic UD-802 personal dosimeter used at three mile island

    SciTech Connect

    Miklos, J. A.; Plato, P.

    1988-01-01

    During the fall of 1981, the personnel dosimetry group at GPU Nuclear Corporation at Three Mile Island (TMI) requested assistance from The University of Michigan (UM) in developing a dose algorithm for use at TMI-2. The dose algorithm had to satisfy the specific needs of TMI-2, particularly the need to distinguish beta-particle emitters of different energies, as well as having the capability of satisfying the requirements of the American National Standards Institute (ANSI) N13.11-1983 standard. A standard Panasonic UD-802 dosimeter was modified by having the plastic filter over element 2 removed. The dosimeter and hanger consists of the elements with a 14 mg/cm/sup 2/ density thickness and the filtrations shown. The hanger on this dosimeter had a double open window to facilitate monitoring for low-energy beta particles. The dose algorithm was written to satisfy the requirements of the ANSI N13.11-1983 standard, to include /sup 204/Tl with mixtures of /sup 204/Tl with /sup 90/Sr//sup 90/Y and /sup 137/Cs, and to include 81- and 200-keV average energy X-ray spectra. Stress tests were conducted to observe the algorithm performance to low doses, temperature, humidity, and the residual response following high-dose irradiations. The ability of the algorithm to determine dose from the beta particles of /sup 147/Pm was also investigated.

  16. AGE DEPENDENCIES OF 90Sr INCORPORATION IN DENTAL TISSUES: COMPARATIVE ANALYSIS AND INTERPRETATION OF DIFFERENT KINDS OF MEASUREMENTS OBTAINED FOR RESIDENTS ON THE TECHA RIVER

    SciTech Connect

    Tolstykh, E I.; Shishkina, Elena A.; Degteva, M O.; Ivanov, Denis V.; Shved, Valentina A.; Bayankin, Sergey N.; Anspaugh, Lynn R.; Napier, Bruce A.; Wieser, Albrecht; Jacob, Peter

    2003-10-01

    Human teeth have been considered as dosimeters for decades. Methods include the in vivo measurement of 90Sr/90Y in teeth with a tooth-beta counter (TBC), the radiochemical determination of 90Sr in whole teeth, and the measurement of dose in teeth by use of electron paramagnetic resonance (EPR). Presented in this paper are results of 2,514 TBC measurements, 334 radiochemical measurements, and 218 EPR measurements for residents living in settlements along the Techa River. All three kinds of measurements indicate a sharp peak that corresponds to the uptake of 90Sr by tooth tissue. The results can be interpreted in terms of an intake function for 90Sr only if the period of calcification of each individual tooth is considered?such detail on a tooth by tooth basis is presented in this paper. The conclusion is reached that the TBC data are the most reliable in terms of reconstruction of 90Sr intake; this is due in part to the fact that the TBC measures four teeth (all at position 1) with essentially the same time periods of mineralization and because there are a large number of TBC measurements. The main utility of EPR measurements is considered to be the validation of estimates of external dose; but for this purpose teeth with 90Sr taken up into enamel must be avoided.

  17. Waste/Rock Interactions Technology Program. Status report on LWR spent-fuel leach tests

    SciTech Connect

    Katayama, Y.B.; Bradley, D.J.; Harvey, C.O.

    1980-11-01

    Spent fuels with burnups of 9000, 28,000 and 54,500 MWd/MTU have been leach tested at 25/sup 0/C. Three leach-test procedures (Paige, IAEA and static) were used. IAEA and static tests were conducted in five different solutions: deionized water, sodium bicarbonate, sodium chloride, calcium chloride and Waste Isolation Pilot Plant B brine solutions. Elemental leach data are reported based on the release of /sup 90/Sr/sup +90/Y, /sup 106/Ru, /sup 137/Cs, /sup 144/Ce, /sup 154/Eu, /sup 239 +240/Pu, /sup 125/Sb, /sup 244/Cm, /sup 129/I, /sup 99/Tc, and total uranium. This is the first report on /sup 129/I and /sup 99/Tc from spent fuel. Termination of the Paige test showed that the plateout (radionuclide adsorption) on the test apparatus had negligible effect on the leach rate of cesium and plutonium, but a major (up to a factor of 50 times) effect on the curium leach rate. Three-hundred additional days of leach testing by the IAEA procedure, from 467 to 769 d, showed a continuation of the leaching trends observed during the first 467 d. Results from the first two static leach test series, 2 and 8 d, gave the /sup 129/I and /sup 99/Tc release numbers.

  18. Therapeutic Strategies in HCC: Radiation Modalities.

    PubMed

    Gallicchio, R; Nardelli, A; Mainenti, P; Nappi, A; Capacchione, D; Simeon, V; Sirignano, C; Abbruzzi, F; Barbato, F; Landriscina, M; Storto, G

    2016-01-01

    Patients with hepatocellular carcinoma (HCC) comply with an advanced disease and are not eligible for radical therapy. In this distressed scenario new treatment options hold great promise; among them transarterial chemoembolization (TACE) and transarterial metabolic radiotherapy (TAMR) have shown efficacy in terms of both tumor shrinking and survival. External radiation therapy (RTx) by using novel three-dimensional conformal radiotherapy has also been used for HCC patients with encouraging results while its role had been limited in the past for the low tolerance of surrounding healthy liver. The rationale of TAMR derives from the idea of delivering exceptional radiation dose locally to the tumor, with cell killing intent, while preserving normal liver from undue exposition and minimizing systemic irradiation. Since the therapeutic efficacy of TACE is being continuously disputed, the TAMR with (131)I Lipiodol or (90)Y microspheres has gained consideration providing adequate therapeutic responses regardless of few toxicities. The implementation of novel radioisotopes and technological innovations in the field of RTx constitutes an intriguing field of research with important translational aspects. Moreover, the combination of different therapeutic approaches including chemotherapy offers captivating perspectives. We present the role of the radiation-based therapies in hepatocellular carcinoma patients who are not entitled for radical treatment. PMID:27563661

  19. Quality control assurance of strontium-90 in foodstuffs by LSC.

    PubMed

    Lopes, I; Mourato, A; Abrantes, J; Carvalhal, G; Madruga, M J; Reis, M

    2014-11-01

    A method based on the separation of Sr-90 by extraction chromatography and beta determination by Liquid Scintillation Counting (LSC) technique was used for strontium analysis in food samples. The methodology consisted in prior sample treatment (drying and incineration) followed by radiochemical separation of Sr-90 by extraction chromatography, using the Sr-resin. The chemical yield was determined by gravimetric method, adding stable strontium to the matrix. Beta activity (Sr-90/Y-90) was determined using a low background liquid scintillation spectrometer (Tri-Carb 3170 TR/SL, Packard). The accuracy and the precision of the method, was performed previously through recovery trials with Sr-90 spiked samples, using the same type of matrices (milk, complete meals, meat and vegetables). A reference material (IAEA_321) was now used to measure the accuracy of the procedure. Participation in interlaboratory comparison exercises was also performed in order to establish an external control on the measurements and to ensure the adequacy of the method. PMID:24560851

  20. Production and Clinical Applications of Radiopharmaceuticals and Medical Radioisotopes in Iran.

    PubMed

    Jalilian, Amir Reza; Beiki, Davood; Hassanzadeh-Rad, Arman; Eftekhari, Arash; Geramifar, Parham; Eftekhari, Mohammad

    2016-07-01

    -meta-iodobenzylguanidine for treatment of neuroblastoma, pheochromocytoma, and other neuroendocrine tumors has been steadily increasing in major academic university hospitals. Also (153)Sm-EDTMP, (177)Lu-EDTMP, (90)Y-citrate, (90)Y-hydroxyapatite colloid, (188/186)Re-sulfur colloid, and (188/186)Re-HEDP have been locally developed and now routinely available for bone pain palliation and radiosynovectomy. Cu-64 has been available to the nuclear medicine community for some time. With recent reports in diagnostic and therapeutic applications of this agent especially in the field of oncology, we anticipate an expansion in production and availability. The initiation of the production line for gallium-68 generator is one of the latest exciting developments. We are proud that Iran would be joining the club of few nations with production lines for this type of generator. There are also quite a number of SPECT and PET tracers at research and preclinical stage of development preliminarily introduced for possible future clinical applications. Availability of fluorine-18 tracers and gallium-68 generators would no doubt allow rapid dissemination of PET/CT practices in various parts of our large country even far from a cyclotron facility. Also, local production and availability of therapeutic radiopharmaceuticals are going to open exciting horizons in the field of nuclear medicine therapy. Given the available manpower, local infrastructure of SPECT imaging, and rapidly growing population, the production of Tc-99m generators and cold kit would continue to flourish in Iran. PMID:27237443

  1. IN-SITU, LONG-TERM MONITORING SYSTEM FOR RADIOACTIVE CONTAMINANTS

    SciTech Connect

    James S. Durham; Stephen W.S. McKeever; Mark S. Akselrod

    2002-10-01

    This report presents the results of the first phase of the project entitled ''In-situ, Long-term Monitoring System for Radioactive Contaminants.'' Phase one of this effort included four objectives, each with specific success criteria. The first objective was to produce dosimetry grade fibers and rods of aluminum oxide. The success criterion for this milestone was the production of aluminum oxide rods and fibers that have a minimum measureable dose (MMD) of 100 mrem or less. This milestone was completed and the MMD for the rods was measured to be 1.53 mrem. Based on the MMD, the ability of the sensor to measure {sup 137}Cs, {sup 90}Sr/{sup 90}Y, and {sup 99}Tc was evaluated. It was determined that the sensor can measure the release limit of these radionuclides (50 pCi/cm{sup 3}) in 150 h, 200 h, and 54,000 h, respectively. The monitor is adequate for measuring {sup 137}Cs and {sup 90}Sr/{sup 90}Y but is unsuitable for measuring {sup 99}Tc in soil. The second objective was to construct a prototype sensor (dosimeter and fiber optic channel). There were three success criteria for this milestone: (1) Perform measurements with the sensor for both gamma and beta radiation with a standard deviation of 10% or less; (2) Demonstrate the ability of the sensor to discriminate between gamma and beta radiation; and (3) Obtain similar or relatable results for differing lengths of fiber optic cable. These milestones were met. The sensor was able to measure gamma radiation repeatedly with a standard deviation of 3.15% and beta radiation with a standard deviation of 2.85%. Data is presented that demonstrates that an end cap can be used to discriminate between beta plus gamma and gamma radiation. It is shown that some amount of attenuation occurs in longer fiber optic cables, but it is unclear if the attenuation is due to poor alignment of the dosimeter and the cable. This issue will be investigated further when more dosimeters are available so that the dosimeters can be permanently

  2. A preclinical simulated dataset of S-values and investigation of the impact of rescaled organ masses using the MOBY phantom.

    PubMed

    Kostou, Theodora; Papadimitroulas, Panagiotis; Loudos, George; Kagadis, George C

    2016-03-21

    Nuclear medicine and radiation therapy, although well established, are still rapidly evolving, by exploiting animal models, aiming to define precise dosimetry in molecular imaging protocols. The purpose of the present study was to create a dataset based on the MOBY phantom for the calculation of organ-to-organ S-values of commonly used radionuclides. S-values of most crucial organs were calculated using specific biodistributions with a whole-body heterogeneous source. In order to determine the impact of the varying organs' size on the S-values, and based on the fact that the anatomic properties of the organs are correlated with S-values, dosimetric calculations were performed by simulating the MOBY-version 2 model with different whole-body masses. The GATE Monte Carlo simulation toolkit was used for all simulations. Two mouse models of different body masses were developed to calculate the S-values of eight commonly used radioisotopes in nuclear imaging studies, namely (18)F, (68)Ga, (131)I, (111)In, (177)Lu, and (99m)Tc, (90)Y and (188)Re. The impact of modified mass of the source organs in S-values was investigated with (18)F, and (90)Y in five different scalings of the source organs. Based on realistic preclinical exams, three mouse models, 22, 28 and 34 g, were used as input in the GATE simulator based on realistic preclinical exams to calculate the S-values of the six radioisotopes used. Whole body activity distributions were used as the source organ. The simulation procedure was validated in terms of extracting individual organ-to-organ S-values, and consequently in calculating the new S-values using a heterogeneous activity distribution as a source. The calculation was validated with (18)F source in a 30 g mouse model. For the generation of the new S-values with heterogeneous activity sources, four organs were used for the calculation of a single S-value. The absorbed doses per organ were compared with previously published reports. The validation procedure of

  3. A preclinical simulated dataset of S-values and investigation of the impact of rescaled organ masses using the MOBY phantom

    NASA Astrophysics Data System (ADS)

    Kostou, Theodora; Papadimitroulas, Panagiotis; Loudos, George; Kagadis, George C.

    2016-03-01

    Nuclear medicine and radiation therapy, although well established, are still rapidly evolving, by exploiting animal models, aiming to define precise dosimetry in molecular imaging protocols. The purpose of the present study was to create a dataset based on the MOBY phantom for the calculation of organ-to-organ S-values of commonly used radionuclides. S-values of most crucial organs were calculated using specific biodistributions with a whole-body heterogeneous source. In order to determine the impact of the varying organs’ size on the S-values, and based on the fact that the anatomic properties of the organs are correlated with S-values, dosimetric calculations were performed by simulating the MOBY-version 2 model with different whole-body masses. The GATE Monte Carlo simulation toolkit was used for all simulations. Two mouse models of different body masses were developed to calculate the S-values of eight commonly used radioisotopes in nuclear imaging studies, namely 18F, 68Ga, 131I, 111In, 177Lu, and 99mTc, 90Y and 188Re. The impact of modified mass of the source organs in S-values was investigated with 18F, and 90Y in five different scalings of the source organs. Based on realistic preclinical exams, three mouse models, 22, 28 and 34 g, were used as input in the GATE simulator based on realistic preclinical exams to calculate the S-values of the six radioisotopes used. Whole body activity distributions were used as the source organ. The simulation procedure was validated in terms of extracting individual organ-to-organ S-values, and consequently in calculating the new S-values using a heterogeneous activity distribution as a source. The calculation was validated with 18F source in a 30 g mouse model. For the generation of the new S-values with heterogeneous activity sources, four organs were used for the calculation of a single S-value. The absorbed doses per organ were compared with previously published reports. The validation procedure of 18F indicates

  4. Absorbed fractions for electrons in ellipsoidal volumes.

    PubMed

    Amato, E; Lizio, D; Baldari, S

    2011-01-21

    We applied a Monte Carlo simulation in Geant4 in order to calculate the absorbed fractions for monoenergetic electrons in the energy interval between 10 keV and 2 MeV, uniformly distributed in ellipsoids made from soft tissue. For each volume, we simulated a spherical shape, four oblate and four prolate ellipsoids, and one scalene shape. For each energy and for every geometrical configuration, an analytical relationship between the absorbed fraction and a 'generalized radius' was found, and the dependence of the fit parameters from electron energy is discussed and fitted by proper parametric functions. With the proposed formulation, the absorbed fraction for electrons in the 10-2000 keV energy range can be calculated for all volumes and for every ellipsoidal shape of practical interest. This method can be directly applied to evaluation of the absorbed fraction from the radionuclide emission of monoenergetic electrons, such as Auger or conversion electrons. The average deposited energy per disintegration in the case of extended beta spectra can be evaluated through integration. Two examples of application to a pure beta emitter such as (90)Y and to (131)I, whose emission include monoenergetic and beta electrons plus gamma photons, are presented. This approach represent a generalization of our previous studies, allowing a comprehensive treatment of absorbed fractions from electron and photon sources uniformly distributed in ellipsoidal volumes of any ellipticity and volume, in the whole range of practical interest for internal dosimetry in nuclear medicine applications, as well as in radiological protection estimations of doses from an internal contamination.

  5. Assessment of doses caused by electrons in thin layers of tissue-equivalent materials, using MCNP.

    PubMed

    Heide, Bernd

    2013-10-01

    Absorbed doses caused by electron irradiation were calculated with Monte Carlo N-Particle transport code (MCNP) for thin layers of tissue-equivalent materials. The layers were so thin that the calculation of energy deposition was on the border of the scope of MCNP. Therefore, in this article application of three different methods of calculation of energy deposition is discussed. This was done by means of two scenarios: in the first one, electrons were emitted from the centre of a sphere of water and also recorded in that sphere; and in the second, an irradiation with the PTB Secondary Standard BSS2 was modelled, where electrons were emitted from an (90)Sr/(90)Y area source and recorded inside a cuboid phantom made of tissue-equivalent material. The speed and accuracy of the different methods were of interest. While a significant difference in accuracy was visible for one method in the first scenario, the difference in accuracy of the three methods was insignificant for the second one. Considerable differences in speed were found for both scenarios. In order to demonstrate the need for calculating the dose in thin small zones, a third scenario was constructed and simulated as well. The third scenario was nearly equal to the second one, but a pike of lead was assumed to be inside the phantom in addition. A dose enhancement (caused by the pike of lead) of ∼113 % was recorded for a thin hollow cylinder at a depth of 0.007 cm, which the basal-skin layer is referred to in particular. Dose enhancements between 68 and 88 % were found for a slab with a radius of 0.09 cm for all depths. All dose enhancements were hardly noticeable for a slab with a cross-sectional area of 1 cm(2), which is usually applied to operational radiation protection.

  6. Two Realistic Beagle Models for Dose Assessment.

    PubMed

    Stabin, Michael G; Kost, Susan D; Segars, William P; Guilmette, Raymond A

    2015-09-01

    Previously, the authors developed a series of eight realistic digital mouse and rat whole body phantoms based on NURBS technology to facilitate internal and external dose calculations in various species of rodents. In this paper, two body phantoms of adult beagles are described based on voxel images converted to NURBS models. Specific absorbed fractions for activity in 24 organs are presented in these models. CT images were acquired of an adult male and female beagle. The images were segmented, and the organs and structures were modeled using NURBS surfaces and polygon meshes. Each model was voxelized at a resolution of 0.75 × 0.75 × 2 mm. The voxel versions were implemented in GEANT4 radiation transport codes to calculate specific absorbed fractions (SAFs) using internal photon and electron sources. Photon and electron SAFs were then calculated for relevant organs in both models. The SAFs for photons and electrons were compatible with results observed by others. Absorbed fractions for electrons for organ self-irradiation were significantly less than 1.0 at energies above 0.5 MeV, as expected for many of these small-sized organs, and measurable cross irradiation was observed for many organ pairs for high-energy electrons (as would be emitted by nuclides like 32P, 90Y, or 188Re). The SAFs were used with standardized decay data to develop dose factors (DFs) for radiation dose calculations using the RADAR Method. These two new realistic models of male and female beagle dogs will be useful in radiation dosimetry calculations for external or internal simulated sources. PMID:26222214

  7. Anti-CD45 Pretargeted Radioimmunotherapy using Bismuth-213: High Rates of Complete Remission and Long-Term Survival in a Mouse Myeloid Leukemia Xenograft Model

    SciTech Connect

    Pagel, John M; Kenoyer, Aimee L; Back, Tom; Hamlin, Donald K; Wilbur, D Scott; Fisher, Darrell R; Park, Steven I; Frayo, Shani; Axtman, Amanda; Orgun, Nural; Orozoco, Johnnie; Shenoi, Jaideep; Lin, Yukang; Gopal, Ajay K; Green, Damian J; Appelbaum, Frederick R; Press, Oliver W

    2011-07-21

    Pretargeted radioimmunotherapy (PRIT) using an anti-CD45 antibody (Ab)-streptavidin (SA) conjugate and DOTA-biotin labeled with β-emitting radionuclides has been explored as a strategy to decrease relapse and toxicity. α-emitting radionuclides exhibit high cytotoxicity coupled with a short path-length, potentially increasing the therapeutic index and making them an attractive alternative to β-emitting radionuclides for patients with Acute Myeloid Leukemia (AML). Accordingly, we have used 213Bi in mice with human leukemia xenografts. Results demonstrated excellent localization of 213Bi-DOTA-biotin to tumors with minimal uptake into normal organs. After 10 minutes, 4.5 ± 1.1% of the injected dose of 213Bi was delivered per gram of tumor. α imaging demonstrated uniform radionuclide distribution within tumor tissue 45 minutes after 213Bi-DOTA-biotin injection. Radiation absorbed doses were similar to those observed using a β-emitting radionuclide (90Y) in the same model. We conducted therapy experiments in a xenograft model using a single-dose of 213Bi-DOTA-biotin given 24 hours after anti-CD45 Ab-SA conjugate. Among mice treated with anti-CD45 Ab-SA conjugate followed by 800 μCi of 213Bi- or 90Y-DOTA-biotin, 80% and 20%, respectively, survived leukemia-free for >100 days with minimal toxicity. These data suggest that anti-CD45 PRIT using an α-emitting radionuclide may be highly effective and minimally toxic for treatment of AML.

  8. Methylation of SOCS3 is inversely associated with metabolic syndrome in an epigenome-wide association study of obesity

    PubMed Central

    Ali, Omar; Cerjak, Diana; Kent, Jack W.; James, Roland; Blangero, John; Carless, Melanie A.; Zhang, Yi

    2016-01-01

    ABSTRACT Epigenetic mechanisms, including DNA methylation, mediate the interaction between gene and environment and may play an important role in the obesity epidemic. We assessed the relationship between DNA methylation and obesity in peripheral blood mononuclear cells (PBMCs) at 485,000 CpG sites across the genome in family members (8-90 y of age) using a discovery cohort (192 individuals) and a validation cohort (1,052 individuals) of Northern European ancestry. After Bonferroni-correction (Pα=0.05 = 1.31 × 10−7) for genome-wide significance, we identified 3 loci, cg18181703 (SOCS3), cg04502490 (ZNF771), and cg02988947 (LIMD2), where methylation status was associated with body mass index percentile (BMI%), a clinical index for obesity in children, adolescents, and adults. These sites were also associated with multiple metabolic syndrome (MetS) traits, including central obesity, fat depots, insulin responsiveness, and plasma lipids. The SOCS3 methylation locus was also associated with the clinical definition of MetS. In the validation cohort, SOCS3 methylation status was found to be inversely associated with BMI% (P = 1.75 × 10−6), waist to height ratio (P = 4.18 × 10−7), triglycerides (P = 4.01 × 10−4), and MetS (P = 4.01 × 10−7), and positively correlated with HDL-c (P = 4.57 × 10−8). Functional analysis in a sub cohort (333 individuals) demonstrated SOCS3 methylation and gene expression in PBMCs were inversely correlated (P = 2.93 × 10−4) and expression of SOCS3 was positively correlated with status of MetS (P = 0.012). We conclude that epigenetic modulation of SOCS3, a gene involved in leptin and insulin signaling, may play an important role in obesity and MetS. PMID:27564309

  9. Dose calculation formalisms and consensus dosimetry parameters for intravascular brachytherapy dosimetry: Recommendations of the AAPM Therapy Physics Committee Task Group No. 149

    SciTech Connect

    Chiu-Tsao, Sou-Tung; Schaart, Dennis R.; Soares, Christopher G.; Nath, Ravinder

    2007-11-15

    Since the publication of AAPM Task Group 60 report in 1999, a considerable amount of dosimetry data for the three coronary brachytherapy systems in use in the United States has been reported. A subgroup, Task Group 149, of the AAPM working group on Special Brachytherapy Modalities (Bruce Thomadsen, Chair) was charged to develop recommendations for dose calculation formalisms and the related consensus dosimetry parameters. The recommendations of this group are presented here. For the Cordis {sup 192}Ir and Novoste {sup 90}Sr/{sup 90}Y systems, the original TG-43 formalism in spherical coordinates should be used along with the consensus values of the dose rate constant, geometry function, radial dose function, and anisotropy function for the single seeds. Contributions from the single seeds should be added linearly for the calculation of dose distributions from a source train. For the Guidant {sup 32}P wire system, the modified TG-43 formalism in cylindrical coordinates along with the recommended data for the 20 and 27 mm wires should be used. Data tables for the 6, 10, 14, 18, and 22 seed trains of the Cordis system, 30, 40, and 60 mm seed trains of the Novoste system, and the 20 and 27 mm wires of the Guidant system are presented along with our rationale and methodology for selecting the consensus data. Briefly, all available datasets were compared with each other and the consensus dataset was either an average of available data or the one obtained from the most densely populated study; in most cases this was a Monte Carlo calculation.

  10. Absorbed fractions for electrons in ellipsoidal volumes

    NASA Astrophysics Data System (ADS)

    Amato, E.; Lizio, D.; Baldari, S.

    2011-01-01

    We applied a Monte Carlo simulation in Geant4 in order to calculate the absorbed fractions for monoenergetic electrons in the energy interval between 10 keV and 2 MeV, uniformly distributed in ellipsoids made from soft tissue. For each volume, we simulated a spherical shape, four oblate and four prolate ellipsoids, and one scalene shape. For each energy and for every geometrical configuration, an analytical relationship between the absorbed fraction and a 'generalized radius' was found, and the dependence of the fit parameters from electron energy is discussed and fitted by proper parametric functions. With the proposed formulation, the absorbed fraction for electrons in the 10-2000 keV energy range can be calculated for all volumes and for every ellipsoidal shape of practical interest. This method can be directly applied to evaluation of the absorbed fraction from the radionuclide emission of monoenergetic electrons, such as Auger or conversion electrons. The average deposited energy per disintegration in the case of extended beta spectra can be evaluated through integration. Two examples of application to a pure beta emitter such as 90Y and to 131I, whose emission include monoenergetic and beta electrons plus gamma photons, are presented. This approach represent a generalization of our previous studies, allowing a comprehensive treatment of absorbed fractions from electron and photon sources uniformly distributed in ellipsoidal volumes of any ellipticity and volume, in the whole range of practical interest for internal dosimetry in nuclear medicine applications, as well as in radiological protection estimations of doses from an internal contamination.

  11. [Reference curves for assessing the physical growth of male Wistar rats].

    PubMed

    Cossio-Bolaños, Marco; Gómez Campos, Rossana; Vargas Vitoria, Rodrigo; Hochmuller Fogaça, Rosalvo Tadeu; de Arruda, Miguel

    2013-11-01

    Introducción: Las ratas Wistar son una de las cepas más populares y utilizadas cotidianamente para la investigación en el laboratorio sirviendo como una importante herramienta de investigación, por lo que, exige el control estricto de variables como la edad, el sexo y el peso corporal, y de esta forma poder extrapolar los resultados al modelo humano. Objetivo: Desarrollar curvas de referencia para valorar el crecimiento físico de ratas machos Wistar en función de la edad cronológica y la maduración somática desde una perspectiva no-invasiva. Metodología: Fueron estudiadas 731 ratas machos Wistar de forma transversal. Se evaluó la edad, peso corporal y la superficie corporal. Se utilizó el método LMS para construir curvas de percentil en función del peso y la maduración somática. Resultados: Las curvas de crecimiento físico propuestas sirven para realizar el seguimiento del crecimiento físico y el diagnóstico del estado nutricional de ratas machos de cepa Wistar. Los puntos de corte prepuestos son: P3, P10, P25, P50, P75, P90 y P97. Conclusión: Los resultados sugieren que los científicos de diversas áreas puedan usar tales referencias, con el objetivo de extrapolar las fases del crecimiento somático de la rata de laboratorio al modelo humano y es una alternativa no-invasiva para valorar el crecimiento y el estado nutricional.

  12. SU-E-J-03: A Comprehensive Comparison Between Alpha and Beta Emitters for Cancer Radioimmunotherapy

    SciTech Connect

    Huang, C.Y.; Guatelli, S; Oborn, B; Allen, B

    2014-06-01

    Purpose: The purpose of this study is to perform a comprehensive comparison of the therapeutic efficacy and cytotoxicity of alpha and beta emitters for Radioimmunotherapy (RIT). For each stage of cancer development, specific models were built for the separate objectives of RIT to be addressed:a) kill isolated cancer cells in transit in the lymphatic and vascular circulation,b) regress avascular cell clusters,c) regress tumor vasculature and tumors. Methods: Because of the nature of short range, high LET alpha and long energy beta radiation and heterogeneous antigen expression among cancer cells, the microdosimetric approach is essential for the RIT assessment. Geant4 based microdosimetric models are developed for the three different stages of cancer progression: cancer cells, cell clusters and tumors. The energy deposition, specific energy resulted from different source distribution in the three models was calculated separately for 4 alpha emitting radioisotopes ({sup 211}At, {sup 213}Bi, {sup 223}Ra and {sup 225}Ac) and 6 beta emitters ({sup 32}P, {sup 33}P, {sup 67}Cu, {sup 90}Y, {sup 131}I and {sup 177}Lu). The cell survival, therapeutic efficacy and cytotoxicity are determined and compared between alpha and beta emitters. Results: We show that internal targeted alpha radiation has advantages over beta radiation for killing isolated cancer cells, regressing small cell clusters and also solid tumors. Alpha particles have much higher dose specificity and potency than beta particles. They can deposit 3 logs more dose than beta emitters to single cells and solid tumor. Tumor control probability relies on deep penetration of radioisotopes to cancer cell clusters and solid tumors. Conclusion: The results of this study provide a quantitative understanding of the efficacy and cytotoxicity of RIT for each stage of cancer development.

  13. SU-E-T-116: Dose Response in the Treatment of Unresectable Cholangiocarcinoma with Yttrium-90 Microspheres

    SciTech Connect

    Yu, S; Green, G; Sehgal, V; Samford, G; Kuo, J; Imagawa, D; Fernando, D; Al-Ghazi, M

    2014-06-01

    Purpose: The purpose of this study is to assess the dose response of radioembolization using yttrium-90 (Y-90) microspheres in patients treated for unresectable cholangiocarcinoma. This study utilized partition dosimetry model for the dose calculation. The results show survival benefit with dose escalation. Methods: Between February 2009 and March 2013, ten patients with pathology proven unresectable cholangiocarcinoma were radioembolized with Y-90 microspheres. Patients underwent initial pre-treatment angiographic assessment for blood flow and 99mTc- MAA for lung shunt evaluation. Activity of Y-90 administration was calculated using the Body Surface Area (BSA) and target volumes which were determined by contouring the pre-treatment MRI/CT images using a radiation therapy treatment planning system. Medical Internal Radiation Dose (MIRD) method was used to assess the dosimetric results of Y90. Partition model based on the tumor to-liver activity uptake estimated from pretreatment 99mTc- MAA study was used to calculate the dose delivered to the target. The variables assessed included: administered dose, toxicity based on clinical changes, imaging based tumor response, and survival. Results: Ten patients were radioembolized with Y-90 microspheres to either one hepatic lobe or both left and right lobes. Patients were stratified by dose. Four patients who received dose greater than 140Gy (p < 0.05) all survived. The corresponding activity they received was greater than 35 mCi. Six out of ten patients died of disease with median survival of 18 weeks (range 12–81wks). Conclusion: Given the growing body of data for Y-90 microspheres in the context of cholangiocarcinoma, radioembolization may become an important treatment modality for an appropriately selected group of patients. Our study further substantiates past studies and shows additional evidence of a survival benefit with dose escalation.

  14. The effects of Ca2SiO4-Ca3(PO4)2 ceramics on adult human mesenchymal stem cell viability, adhesion, proliferation, differentiation and function.

    PubMed

    De Aza, Piedad N; García-Bernal, David; Cragnolini, Francesca; Velasquez, Pablo; Meseguer-Olmo, Luis

    2013-10-01

    Bioceramic samples with osteogenic properties, suitable for use in the regeneration of hard tissue, were synthesized. The materials consisting of α-tricalcium phosphate (αTCP) and also αTCP doped with either 1.5 wt.% or 3.0 wt.% of dicalcium silicate (C2S) in the system Dicalcium Silicate-Tricalcium Phosphate (C2S-TCP) were obtained by solid state reaction. All materials were composed of a single phase, αTCP in the case of a pure material, or solid solution of C2S in αTCP (αTCPss) for the doped αTCP. Viability, proliferation and in vitro osteoinductive capacity were investigated by seeding, adult mesenchymal stem cells of human origin (ahMSCs) which were CD73(+), CD90(+), CD105(+), CD34(-) and CD45(-) onto the 3 substrates for 30 days. Results show a non-cytotoxic effect after applying an indirect apoptosis test (Annexin V/7-AAD staining), so ahMSCs adhered, spread, proliferated and produced extracellular matrix (Heparan-sulfate proteoglycan (HS) and osteopontin (OP)) on all the ceramics studied. Finally, the cells lost the cluster differentiation marker expression CD73, CD90 y CD105 characteristic of ahMSCs and they showed an osteoblastic phenotype (Alkaline phosphatase activity (ALP), Osteocalcin production (OC), Collagen type I expression (Col-I), and production of mineralization nodules on the extracellular matrix). These observations were more evident in the αTCP ceramic doped with 1.5 wt.% C2S, indicating osteoblastic differentiation as a result of the increased concentration of solid solution of C2S in αTCP (αTCPss). Overall, these results suggest that the ceramics studied are cytocompatible and they are able to induce osteoblastic differentiation of undifferentiated ahMSCs.

  15. Retention of radioactive particles and associated effects in the filter-feeding marine mollusc Mytilus edulis.

    PubMed

    Jaeschke, B C; Lind, O C; Bradshaw, C; Salbu, B

    2015-01-01

    Radioactive particles are aggregates of radioactive atoms that may contain significant activity concentrations. They have been released into the environment from nuclear weapons tests, and from accidents and effluents associated with the nuclear fuel cycle. Aquatic filter-feeders can capture and potentially retain radioactive particles, which could then provide concentrated doses to nearby tissues. This study experimentally investigated the retention and effects of radioactive particles in the blue mussel, Mytilus edulis. Spent fuel particles originating from the Dounreay nuclear establishment, and collected in the field, comprised a U and Al alloy containing fission products such as (137)Cs and (90)Sr/(90)Y. Particles were introduced into mussels in suspension with plankton-food or through implantation in the extrapallial cavity. Of the particles introduced with food, 37% were retained for 70 h, and were found on the siphon or gills, with the notable exception of one particle that was ingested and found in the stomach. Particles not retained seemed to have been actively rejected and expelled by the mussels. The largest and most radioactive particle (estimated dose rate 3.18 ± 0.06 Gyh(-1)) induced a significant increase in Comet tail-DNA %. In one case this particle caused a large white mark (suggesting necrosis) in the mantle tissue with a simultaneous increase in micronucleus frequency observed in the haemolymph collected from the muscle, implying that non-targeted effects of radiation were induced by radiation from the retained particle. White marks found in the tissue were attributed to ionising radiation and physical irritation. The results indicate that current methods used for risk assessment, based upon the absorbed dose equivalent limit and estimating the "no-effect dose" are inadequate for radioactive particle exposures. Knowledge is lacking about the ecological implications of radioactive particles released into the environment, for example potential

  16. Use of radioactive substances in diagnosis and treatment of neuroendocrine tumors

    PubMed Central

    Kjaer, Andreas; Knigge, Ulrich

    2015-01-01

    Abstract Radionuclides are needed both for nuclear medicine imaging as well as for peptide-receptor radionuclide therapy (PRRT) of neuroendocrine tumors (NET). Imaging is important in the initial diagnostic work-up and for staging NETs. In therapy planning, somatostatin receptor imaging (SRI) is used when treatment is targeted at the somatostatin receptors as with the use of somatostatin analogues or PRRT. SRI with gamma camera technique using the tracer 111In-DTPA-octreotide has for many years been the backbone of nuclear imaging of NETs. However, increasingly PET tracers for SRI are now used. 68Ga-DOTATATE, 68Ga-DOTATOC and 68Ga-DOTANOC are the three most often used PET tracers. They perform better than SPECT tracers and should be preferred. FDG-PET is well suited for visualization of most of the somatostatin receptor-negative tumors prognostic in NET patients. Also 11C-5-HTP, 18F-DOPA and 123I-MIBG may be used in NET. However, with FDG-PET and somatostatin receptor PET at hand we see limited necessity of other tracers. PRRT is an important tool in the treatment of advanced NETs causing complete or partial response in 20% and minor response or tumor stabilization in 60% with response duration of up to 3 years. Grade 3–4 kidney or bone marrow toxicity is seen in 1.5% and 9.5%, respectively, but are completely or partly reversible in most patients. 177Lu-DOTATATE seems to have less toxicity than 90Y-DOTATOC. However, until now only retrospective, non-randomized studies have been performed and the role of PRRT in treatment of NETs remains to be established. PMID:25959100

  17. Preclinical evaluation of multistep targeting of diasialoganglioside GD2 using an IgG-scFv bispecific antibody with high affinity for GD2 and DOTA metal complex.

    PubMed

    Cheal, Sarah M; Xu, Hong; Guo, Hong-fen; Zanzonico, Pat B; Larson, Steven M; Cheung, Nai-Kong

    2014-07-01

    Bispecific antibodies (BsAb) have proven to be useful targeting vectors for pretargeted radioimmunotherapy (PRIT). We sought to overcome key PRIT limitations such as high renal radiation exposure and immunogenicity (e.g., of streptavidin-antibody fusions), to advance clinical translation of this PRIT strategy for diasialoganglioside GD2-positive [GD2(+)] tumors. For this purpose, an IgG-scFv BsAb was engineered using the sequences for the anti-GD2 humanized monoclonal antibody hu3F8 and C825, a murine scFv antibody with high affinity for the chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) complexed with β-particle-emitting radiometals such as (177)Lu and (90)Y. A three-step regimen, including hu3F8-C825, a dextran-based clearing agent, and p-aminobenzyl-DOTA radiolabeled with (177)Lu (as (177)Lu-DOTA-Bn; t1/2 = 6.71 days), was optimized in immunocompromised mice carrying subcutaneous human GD2(+) neuroblastoma (NB) xenografts. Absorbed doses for tumor and normal tissues were approximately 85 cGy/MBq and ≤3.7 cGy/MBq, respectively, with therapeutic indices (TI) of 142 for blood and 23 for kidney. A therapy study (n = 5/group; tumor volume, 240 ± 160 mm(3)) with three successive PRIT cycles (total (177)Lu: ∼33 MBq; tumor dose ∼3,400 cGy), revealed complete tumor response in 5 of 5 animals, with no recurrence up to 28 days after treatment. Tumor ablation was confirmed histologically in 4 of 5 mice, and normal organs showed minimal overall toxicities. All nontreated mice required sacrifice within 12 days (>1.0-cm(3) tumor volume). We conclude that this novel anti-GD2 PRIT approach has sufficient TI to successfully ablate subcutaneous GD2(+)-NB in mice while sparing kidney and bone marrow.

  18. Seasonal variation in the serum 25-hydroxyvitamin D levels of young and elderly active and inactive adults in São Paulo, Brazil

    PubMed Central

    Maeda, Sergio Setsuo; Saraiva, Gabriela Luporini; Hayashi, Lilian Fukusima; Cendoroglo, Maysa Seabra; Ramos, Luiz Roberto; Corrêa, Marcelo de Paula; Henrique de Mesquita, Carlos; Lazaretti-Castro, Marise

    2013-01-01

    Objective: To evaluate the 25-hydroxyvitamin D [25(OH)D] concentrations in individuals in the city of São Paulo belonging to different age groups and exhibiting specific behavioral characteristics and to correlate the 25(OH)D concentration with the level of UV radiation (UVR). Patients and Methods: A total of 591 individuals were included, distributed as follows: 177 were living in institutions (NURSING, 76.2 ± 9.0 y old), 243 were part of the community elderly (COMMUNITY, 79.6 ± 5.3 y old), 99 were enrolled in a physical activity program targeting the elderly (ACTIVE, 67.6 ± 5.4 y old) and 72 were young (YOUNG, 23.9 ± 2.8 y old). Blood samples from all individuals were collected throughout the year. UVR measurements were taken by an official meteorology institution. Results: The UVR values varied throughout the year, following a sinusoidal-like pattern. Because of the Earth’s orbit, we hypothesized that there would be cyclic patterns for the 25(OH)D and UVR values that repeat every 12 mo. The general formula is represented by the equation P1+P2⋅sin(−2⋅π12⋅(t−P3)) The mean 25(OH)D concentration and the amplitude of the variation were significantly higher for the YOUNG and ACTIVE groups than for the COMMUNITY and NURSING groups. The nadir for UVR was in June, whereas the nadir for the 25(OH)D concentration was in the spring, corresponding to a delay of one season. Conclusions: There was seasonal variation in the 25(OH)D concentration for all the groups studied; however, the amplitude of the variation was higher for the groups of young and physically active people, possibly due to the higher level of sunlight exposure for these groups. The lowest 25(OH)D concentration was detected in the spring. PMID:24494057

  19. Genetic Variants Influencing Biomarkers of Nutrition Are Not Associated with Cognitive Capability in Middle-Aged and Older Adults123

    PubMed Central

    Alfred, Tamuno; Ben-Shlomo, Yoav; Cooper, Rachel; Hardy, Rebecca; Deary, Ian J.; Elliott, Jane; Harris, Sarah E.; Hyppönen, Elina; Kivimaki, Mika; Kumari, Meena; Maddock, Jane; Power, Chris; Starr, John M.; Kuh, Diana; Day, Ian N.M.

    2013-01-01

    Several investigations have observed positive associations between good nutritional status, as indicated by micronutrients, and cognitive measures; however, these associations may not be causal. Genetic polymorphisms that affect nutritional biomarkers may be useful for providing evidence for associations between micronutrients and cognitive measures. As part of the Healthy Ageing across the Life Course (HALCyon) program, men and women aged between 44 and 90 y from 6 UK cohorts were genotyped for polymorphisms associated with circulating concentrations of iron [rs4820268 transmembrane protease, serine 6 (TMPRSS6) and rs1800562 hemochromatosis (HFE)], vitamin B-12 [(rs492602 fucosyltransferase 2 (FUT2)], vitamin D ([rs2282679 group-specific component (GC)] and β-carotene ([rs6564851 beta-carotene 15,15'-monooxygenase 1 (BCMO1)]. Meta-analysis was used to pool within-study effects of the associations between these polymorphisms and the following measures of cognitive capability: word recall, phonemic fluency, semantic fluency, and search speed. Among the several statistical tests conducted, we found little evidence for associations. We found the minor allele of rs1800562 was associated with poorer word recall scores [pooled β on Z-score for carriers vs. noncarriers: −0.05 (95% CI: −0.09, −0.004); P = 0.03, n = 14,105] and poorer word recall scores for the vitamin D–raising allele of rs2282679 [pooled β per T allele: −0.03 (95% CI: −0.05, −0.003); P = 0.03, n = 16,527]. However, there was no evidence for other associations. Our findings provide little evidence to support associations between these genotypes and cognitive capability in older adults. Further investigations are required to elucidate whether the previous positive associations from observational studies between circulating measures of these micronutrients and cognitive performance are due to confounding and reverse causality. PMID:23468552

  20. Mutagenesis of tGCN5 core region reveals two critical surface residues F90 and R140

    SciTech Connect

    Mehta, Kinjal Rajesh; Chan, Yan M.; Lee, Man X.; Yang, Ching Yao; Voloshchuk, Natalya; Montclare, Jin Kim

    2010-09-24

    Research highlights: {yields} Mutagenesis of the tGCN5 core region reveals two residues important for function. {yields} Developed a fluorescent lysate-based activity assay to assess mutants. {yields} Surface-exposed residues F90 and R140 of tGCN5 are critical for H3 acetylation. -- Abstract: Tetrahymena General Control Non-Derepressor 5 (tGCN5) is a critical regulator of gene transcription via acetylation of histones. Since the acetylation ability has been attributed to the 'core region', we perform mutagenesis of residues within the tGCN5 'core region' in order to identify those critical for function and stability. Residues that do not participate in catalysis are identified, mutated and characterized for activity, structure and thermodynamic stability. Variants I107V, Q114L, A121T and A130S maintain the acetylation function relative to wild-type tGCN5, while variants F90Y, F112R and R140H completely abolish function. Of the three non-functional variants, since F112 is mutated into a non-homologous charged residue, a loss in function is expected. However, the remaining two variants are mutated into homologous residues, suggesting that F90 and R140 are critical for the activity of tGCN5. While mutation to homologous residue maintains acetylation of histone H3 for the majority of the variants, the two surface-exposed residues, F90 and R140, appear to be essential for tGCN5 function, structure or stability.

  1. Hsp90 phosphorylation, Wee1 and the cell cycle.

    PubMed

    Mollapour, Mehdi; Tsutsumi, Shinji; Neckers, Len

    2010-06-15

    Heat Shock Protein 90 (Hsp90) is an essential molecular chaperone in eukaryotic cells, and it maintains the functional conformation of a subset of proteins that are typically key components of multiple regulatory and signaling networks mediating cancer cell proliferation, survival, and metastasis. It is possible to selectively inhibit Hsp90 using natural products such as geldanamycin (GA) or radicicol (RD), which have served as prototypes for development of synthetic Hsp90 inhibitors. These compounds bind within the ADP/ATP-binding site of the Hsp90 N-terminal domain to inhibit its ATPase activity. As numerous N-terminal domain inhibitors are currently undergoing extensive clinical evaluation, it is important to understand the factors that may modulate in vivo susceptibility to these drugs. We recently reported that Wee1Swe1-mediated, cell cycle-dependent, tyrosine phosphorylation of Hsp90 affects GA binding and impacts cancer cell sensitivity to Hsp90 inhibition. This phosphorylation also affects Hsp90 ATPase activity and its ability to chaperone a selected group of clients, comprised primarily of protein kinases. Wee1 regulates the G2/M transition. Here we present additional data demonstrating that tyrosine phosphorylation of Hsp90 by Wee1Swe1 is important for Wee1Swe1 association with Hsp90 and for Wee1Swe1 stability. Yeast expressing non-phosphorylatable yHsp90-Y24F, like swe1∆ yeast, undergo premature nuclear division that is insensitive to G2/M checkpoint arrest. These findings demonstrate the importance of Hsp90 phosphorylation for proper cell cycle regulation. PMID:20519952

  2. Individual quantification of 89Sr and 90Sr in nuclear reactor effluent.

    PubMed

    Senaratne, U P; Jester, W A; Bleistein, C D

    1997-10-01

    An analytical method utilizing ion chromatography, a non-radioactive strontium carrier, and liquid scintillation spectroscopy to individually quantify 89Sr and 90Sr in nuclear reactor effluent is presented. It is observed that this method is less time consuming than traditional procedures for quantifying radio-strontium, deals comprehensively with separation and subsequent isotopic quantification of strontium, and avoids difficulties reported in previous research. The equipment, solutions and operating conditions for the chromatographic separation of strontium in aqueous solution are identified, and the strontium fraction is shown to elute between 7 and 7.5 min after injection. The beta spectra of 90Sr, 89Sr and 90Y are obtained using liquid scintillation spectroscopy, and the effects of quenching are shown to be negligible. The positions of the liquid scintillation windows within the combined beta spectra facilitating isotopic analysis of 89Sr and 90Sr are identified, followed by the system of equations to quantify 89Sr and 90Sr within a sample. The performance of the method is evaluated using five solutions representing effluent containing radio-strontium at known concentrations. It is observed that when the 89Sr and 90Sr concentrations each are approximately 37 Bq mL(-1) or more, the method over-estimates the 89Sr activity by 15-20% and under-estimates the 90Sr activity by 10-30%, while yielding the total radio-strontium activity to within 1-4% of expected. The lower limit of detection of the system for either 89Sr or 90Sr is shown to be approximately 0.8 Bq mL(-1) of effluent.

  3. Optically Stimulated Luminescence Response to Ionizing Radiation of Red Bricks (SiO2, Al2O3, and Fe2O3) Used as Building Materials

    SciTech Connect

    Bogard, James S; Espinosa Garcia, Guillermo

    2007-01-01

    Quartz is the most common mineral in our environment. It is found in granite, hydrothermal veins and volcanic rocks, as well as in sedimentary deposits derived from such solid materials. These sediments are also made into building materials, such as bricks and pottery. Thus the potential use of a dose reconstruction technique based on quartz grains is enormous, whether as a dating tool in archaeology and quaternary geology, or in nuclear accident dosimetry. This work describes the Optically Stimulated Luminescence (OSL) response of red brick to ionizing radiation. The bricks, from the state of Puebla, Mexico, represent another class of materials that can be used in retrospective dosimetry following nuclear or radiological incidents. The chemical composition of fifteen bricks (three samples from five different brick factories) was determined, using energy dispersive spectroscopy (EDS), be primarily SiO{sub 2}, Al{sub 2}O{sub 3} and Fe{sub 2}O{sub 3} and is believed to be representative for this common building material. Individual aliquots from these bricks were powdered in agate mortars and thermally annealed. Replicate samples of the aliquots were then irradiated with beta particles from a sealed source of {sup 90}Sr/{sup 90}Y. The OSL response was measured with a Daybreak Model 2200 High-Capacity OSL Reader System. We present here for this material the characteristic OSL response to beta particles; the reproducibility of the OSL response; the linearity of the response in the dose range 0.47 Gy to 47 Gy; and the fading characteristics.

  4. Yttrium-90 Radioembolization for Unresectable Standard-chemorefractory Intrahepatic Cholangiocarcinoma: Survival, Efficacy, and Safety Study

    SciTech Connect

    Rafi, Shoaib; Piduru, Sarat M.; El-Rayes, Bassel; Kauh, John S.; Kooby, David A.; Sarmiento, Juan M.; Kim, Hyun S.

    2013-04-15

    To assess the overall survival, efficacy, and safety of radioembolization with yttrium-90 (Y90) for unresectable standard-chemorefractory intrahepatic cholangiocarcinoma (ICC). Patients with unresectable standard-chemorefractory ICC treated with Y90 were studied. Survival was calculated from the date of first Y90 procedure. Tumor response was assessed with the Response Evaluation Criteria in Solid Tumors criteria on follow-up computed tomography or magnetic resonance imaging scans. National Cancer Institute Common Terminology Criteria (NCI CTCAE), version 3, were used for complications. Statistical analysis was performed by the Kaplan-Meier estimator by the log rank test. Nineteen patients underwent a total of 24 resin-based Y90 treatments. Median survival from the time of diagnosis and first Y90 procedure was 752 {+-} 193 [95 % confidence interval (CI) 374-1130] and 345 {+-} 128 (95 % CI 95-595) days, respectively. Median survival with Eastern Cooperative Oncology Group (ECOG) performance status 1 (n = 15) and ECOG performance status 2 (n = 4) was 450 {+-} 190 (95 % CI 78-822) and 345 {+-} 227 (95 % CI 0-790) days, respectively (p = .214). Patients with extrahepatic metastasis (n = 11) had a median survival of 404 {+-} 309 (95 % CI 0-1010) days versus 345 {+-} 117 (95 % CI 115-575) days for patients without metastasis (n = 8) (p = .491). No mortality was reported within 30 days from first Y90 radioembolization. One patient developed grade 3 thrombocytopenia as assessed by NCI CTCAE. Fatigue and transient abdominal pain were observed in 4 (21 %) and 6 (32 %) patients, respectively. Y90 radioembolization is effective for unresectable standard-chemorefractory ICC.

  5. Selective Internal Radiotherapy (SIRT) of Hepatic Tumors: How to Deal with the Cystic Artery

    SciTech Connect

    Theysohn, Jens M.; Mueller, Stefan; Schlaak, Joerg F.; Ertle, Judith; Schlosser, Thomas W.; Bockisch, Andreas; Lauenstein, Thomas C.

    2013-08-01

    PurposeSelective internal radiotherapy (SIRT) with the beta emitter yttrium-90 (Y90) is a rapidly developing therapy option for unresectable liver malignancies. Nontarget irradiation of the gallbladder is a complication of SIRT. Thus, we aimed to assess different strategies to avoid infusion of Y90 into the cystic artery (CA).MethodsAfter hepatic digital subtraction angiography and administration of technetium-99m-labeled human serum albumin ({sup 99}mTc-HSA), 295 patients with primary or secondary liver tumors underwent single-photon emission computed tomography/computed tomography (SPECT/CT). Different measures were taken before repeated Y90 mapping and SIRT to avoid unintended influx into the CA where necessary. Clinical symptoms, including pain, fever, or a positive Murphy sign, were assessed during patient follow-up.ResultsA significant {sup 99}mTc-HSA accumulation in the gallbladder wall (higher {sup 99}mTc-HSA uptake than in normal liver tissue) was seen in 20 patients. The following measures were taken to avoid unintended influx into the CA: temporary/permanent occlusion of the CA with gelfoam (n = 5)/microcoil (n = 1), induction of vasospasm with a microwire (n = 4), or altering catheter position (n = 10). Clinical signs of cholecystitis were observed in only one patient after temporary CA occlusion with gelfoam and were successfully treated by antibiotics. Cholecystectomy was not required for any patient.ConclusionIt is important to identify possible nontarget irradiation of the gallbladder. The risk for radiation-induced cholecystitis can be easily minimized by temporary or permanent CA embolization, vasospasm induction, or altering the catheter position.

  6. Optimizing radioimmunotherapy by matching dose distribution with tumor structure using 3D reconstructions of serial images.

    PubMed

    Flynn, A A; Pedley, R B; Green, A J; Boxer, G M; Boden, R; Begent, R H

    2001-10-01

    The biological effect of radioimmunotherapy (RIT) is most commonly assessed in terms of the absorbed radiation dose. In tumor, conventional dosimetry methods assume a uniform radionuclide and calculate a mean dose throughout the tumor. However, the vasculature of solid tumors tends to be highly irregular and the systemic delivery of antibodies is therefore heterogeneous. Tumor-specific antibodies preferentially localize in the viable, radiosensitive parts of the tumor whereas non-specific antibodies can penetrate into the necrosis where the dose is wasted. As a result, the observed biological effect can be very different to the predicted effect from conventional dose estimates. The purpose of this study is to assess the potential for optimizing the biological effect of RIT by matching the dose-distribution with tumor structure through the selection of appropriate antibodies and radionuclides. Storage phosphor plate technology was used to acquire images of the antibody distribution in serial tumor sections. Images of the distributions of a trivalent (TFM), bivalent (A5B7-IgG), monovalent (MFE-23) and a non-specific antibody (MOPC) were obtained. These images were registered with corresponding images showing tumor morphology. Serial images were reconstructed to form 3D maps of the antibody distribution and tumor structure. Convolution of the image of antibody distribution with beta dose point kernals generated dose-rate distributions for 14C, 131I and 90Y. These were statistically compared with the tumor structure. The highest correlation was obtained for the multivalent antibodies combined with 131I, due to specific retention in viable areas of tumor coupled with the fact that much of the dose was deposted locally. With decreasing avidity the correlation also decreased and with the non-specific antibody this correlation was negative, indicating higher concentrations in the necrotic regions. In conclusion, the dose distribution can be optimized in tumor by selecting

  7. Stable bifunctional chelates of metals used in radiotherapy.

    PubMed

    Moi, M K; DeNardo, S J; Meares, C F

    1990-02-01

    Monoclonal antibody technology allows the specificity of an antibody for its antigen to be used in targeting cancer cells. The conjugation of metals, particularly radionuclides such as 90Y or 67Cu, to monoclonal antibodies results in agents for radioimmunotherapy and other medical applications. Chelators that can hold radiometals with high stability under physiological conditions are essential to avoid excessive radiation damage to nontarget cells. Derivatives of polyazamacrocycles (bearing a C-substituted functional group for antibody attachment) can exhibit remarkable kinetic inertness; for example, the copper complex of the 14-membered 6-(p-nitrobenzyl)-1,4,8,11-tetraazacyclotetradecane-N,N',N'',N'''- tetraacetic acid is very stable in human serum under physiological conditions, and a conjugate of this complex with a monoclonal antibody has tested well in tumor-bearing mice. Desreux and coworkers [Loncin, M. F., Desreux, J. F., and Merciny, E. Inorg. Chem., 25: 2646-2648, 1986] have shown that complexes of lanthanides with 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid have formation constants that are several orders of magnitude higher than that of 1,4,8,11-tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid; thus the 12-membered macrocycle is the favored target for binding trivalent yttrium. We have developed a new synthetic route to these macrocycles via peptide synthesis and intramolecular tosylamide ring closure. Incubation of the 88Y-(III) complex of 2-p-nitrobenzyl-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''- tetraacetic acid for 18 days in serum results in loss of so little Y(III) from the complex (less than 0.5%) that the rate of loss cannot be measured under these conditions.

  8. Characterization of Fundamental Luminescence Properties of the Mars Soil Simulant JSC Mars-1 and Their Relevance to Absolute Dating of Martian Eolian Sediments

    NASA Astrophysics Data System (ADS)

    Lepper, Kenneth; McKeever, Stephen W. S.

    2000-04-01

    This report explores the potential for luminescence dating techniques to provide absolute age determinations of eolian sediments on the surface of Mars, including those incorporated in the martian polar ice caps. Fundamental thermally and optically stimulated luminescence properties of bulk samples of JSC Mars-1 soil simulant are reported and their relevance to the development of dating procedures is discussed. The radiation-induced luminescence signals (both thermoluminescence, TL, and optically stimulated luminescence, OSL) from JSC Mars-1 are found to have a wide dynamic dose-response range, with the luminescence increasing linearly to the highest doses used (936 Gy), following irradiation with 90Sr/ 90Y beta particles. The signals are also susceptible to solar resetting, with the OSL signals decreasing to <10% of their original levels within the first 20 min of exposure to sunlight. The TL signal also decays rapidly, being reduced to ˜15% within the first 20 min, but reaches a stable, nonzero level at long bleaching times. Neither the TL nor the OSL signals exhibit fading (i.e., loss of signal after irradiation before TL or OSL readout), nor do they exhibit significant sensitivity changes upon repeated irradiation and readout. These three properties (wide dynamic range, solar bleaching, and signal stability) form a stable base for future investigation of the material for luminescence dating and form a preliminary step toward development of dating protocols for terrestrial analogs of Mars surface materials. We conclude that luminescence dating, properly developed, holds the potential to be a valuable tool for absolute dating of martian eolian sediments

  9. Ki67 score as a potential predictor in the selection of liver-directed therapies for metastatic neuroendocrine tumors: a single institutional experience

    PubMed Central

    Singla, Smit; LeVea, Charles M.; Pokuri, Venkata K.; Attwood, Kristopher M.; Wach, Michael M.; Tomaszewski, Garin M.; Kuvshinoff, Boris

    2016-01-01

    Background Neuroendocrine tumors (NETs) metastatic to the liver are treated with transarterial radioembolization (TARE) using yttrium-90 (Y-90) microspheres or transarterial chemoembolization (TACE). However the criteria for patient selection are not well defined. We sought to determine if Ki67 score could help select patients for one therapy over the other in the management of hepatic neuroendocrine metastases. Methods Single institution analysis of patients treated with Y-90 or TACE between 2001 and 2014. Pathologists blinded to clinical information performed Ki67 staining. Data were analyzed using multivariate association for survival outcomes. Results Amongst 72 patients (male: 39, female: 33, median age: 57 years) with metastatic NET, the most common site of origin was small bowel (n=35, 49%), while pancreas constituted 32% (n=23). Forty-four patients were treated with Y-90 (61%) and 28 patients received TACE (39%). Ki67 score was available in 28 patients (64%) treated with Y-90 and 16 patients (57%) with TACE. Within Y-90 group, there was greater use of Sandostatin (95% vs. 75%, P=0.02) and less number of total treatments completed (89% vs. 46%, P<0.001). There was no significant difference in overall survival (OS) between Y-90 and TACE when used without selection (median, 69 vs. 82 months, P=0.47). When adjusted for Ki67, patients with Ki67 score ≥3% had better OS with Y-90 compared to TACE (HR, 0.1; CI, 0.01–0.9), however for Ki67 <3%, OS was better when treated with TACE compared to Y-90 (HR, 13.5; CI, 1.22–148.87). Conclusions There is significant interaction between Ki-67 score and liver-directed treatment benefit in patients with hepatic neuroendocrine metastases. Ki-67 score ≥3% predicts greater benefit with Y-90 and a Ki-67 score <3% predicts greater benefit with TACE. PMID:27284478

  10. Intra-Arterial Radionuclide Therapies for Liver Tumors.

    PubMed

    Bozkurt, Murat Fani; Salanci, Bilge Volkan; Uğur, Ömer

    2016-07-01

    Intra-arterial radionuclide therapies serve essentially as internal radiation treatment options for both primary and metastatic liver tumors, which imply delivering implantable radioactive microspheres into branches of hepatic arteries that feed liver tumors to provide a high dose of targeted radiation to tumor tissue, while sparing the healthy liver tissue from hazardous effects of radiation. The principle of this therapeutic option depends on the unique preferential arterial supply of malignant liver tumors in contrast with mostly portal venous supply of normal hepatocytes as well as excess amount of arterial neovascularization in the tumor bed. Therefore, intra-arterial radionuclide therapy can provide very high radiation exposure to tumor tissue, which is impossible to reach with external radiation therapy due to serious side effects and moreover, radiation can be targeted to tumor tissue selectively with less side effects. Yttrium-90 (Y-90), a high-energetic beta emitter is the most preferred radionuclide, which is used to label microspheres. Two types of Y-90 microspheres are commercially available that are made of resin and glass. Many studies in the literature have demonstrated that Y-90 microsphere therapy is an efficient and safe locoregional therapeutic option for unresectable primary and metastatic liver tumors such as hepatocellular carcinoma and liver metastases from colorectal cancer and breast cancer as well as neuroendocrine tumors. Furthermore, limited number of studies has reported its use in some relatively uncommon metastatic liver tumors from melanoma, pancreatic, renal, and lung cancer. Besides Y-90 microspheres, Iodine-131 lipiodol, Rhenium-188 lipiodol, Rhenium-188 microspheres, Holmium-166 chitosan, and Holmium-166 microspheres have been introduced as alternative radiopharmaceuticals for intra-arterial therapy for liver tumors. PMID:27237442

  11. Classification of structural lesions in magnetic resonance imaging. Surgical implications in drug-resistant epilepsy patients.

    PubMed

    Torres, C V; Pastor, J; Garcia-Navarrete, E; Pulido-Rivas, P; Sola, R G

    2015-09-16

    Introduccion. En la seleccion quirurgica del paciente con epilepsia farmacorresistente, el papel de la resonancia magnetica (RM) no se ha cuantificado hasta el momento. Presentamos la experiencia en nuestra Unidad de Cirugia de la Epilepsia. Pacientes y metodos. Se estudiaron retrospectivamente los pacientes intervenidos por epilepsia farmacorresistente. Distinguimos dos periodos: 1990-2000 (RM de 0,5 T) y 2001-2008 (RM de 1,5 T). La RM preoperatoria se clasifico en tres grupos: RM con lesion quirurgica (LQ), RM orientativa (LO) y RM normal (NL). Tambien se efectuo una clasificacion anatomopatologica similar. Se correlacionaron las distintas clasificaciones y los resultados quirurgicos. Resultados. Periodo 1990-2000: 151 pacientes. El 70% quedo en las clases de Engel I o II. Segun la RM, los resultados fueron: LQ, 87%; LO, 65%; y NL, 57%. Las diferencias fueron estadisticamente significativas. Periodo 2001-2008: 114 pacientes. El 89% quedo en las clases de Engel I o II. Segun la RM: LQ, 100%; LO, 90%; y NL, 81%. Las diferencias fueron estadisticamente significativas. Los pacientes con epilepsia del lobulo temporal y extratemporal con LQ tuvieron un 100% de control; con LO, el 95% con epilepsia del lobulo temporal y el 43% con estado epileptico; en aquellos pacientes sin lesion (NL), el 88% con epilepsia del lobulo temporal se controlo frente al 50% con estado epileptico. Conclusiones. La RM es una herramienta eficaz en la seleccion de candidatos quirurgicos en la epilepsia. La LQ asocia muy buen pronostico. En la epilepsia del lobulo temporal se pueden obtener muy buenos resultados (80-90% de control) a pesar de una RM normal. En el estado epileptico, las LO pueden tener peor resultado que la NL en la RM.

  12. Decay/ingrowth uncertainty correction of (210)Po/(210)Pb in seawater.

    PubMed

    Lin, Wuhui; Ma, Hao; Chen, Liqi; Zeng, Zhi; He, Jianhua; Zeng, Shi

    2014-11-01

    Due to increasing application of (210)Po/(210)Pb in studying particle dynamics, a consistent procedure and calculation to derive accurate and precise result of (210)Po and (210)Pb in seawater should be proposed in the framework of intercalibration by GEOTRACES. The associated uncertainty of radioactivity, which is a significant component of data report, plays a vital role in intercomparison and should be well evaluated. Although measurement uncertainty of laboratory result was well defined in ISO standards and IAEA technical documents, the decay/ingrowth uncertainty correction from laboratory result to in-situ result was less studied. It was demonstrated that the relative uncertainty of in-situ (210)Pb activity was independent of elapsed time and equal to relative uncertainty of laboratory measuring (210)Po activity at second spontaneous deposition date. The relative uncertainty of in-situ (210)Po activity decreases with in-situ activity ratio of (210)Po to (210)Pb and increases with elapsed time between sampling date and separation date, relative uncertainty of laboratory measuring (210)Po activity at first spontaneous deposition date and relative uncertainty of in-situ (210)Pb activity. It was more important to improve precision of (210)Po at first spontaneous deposition date than that of (210)Po at second spontaneous deposition date. To obtain a desirable relative uncertainty of in-situ (210)Po activity, the maximum allowing elapsed time for (210)Po, which was important for sampling strategy making and quality assurance, was calculated by in-situ activity ratio of (210)Po to (210)Pb and precision of analytical method for (210)Po. The methodology of decay/ingrowth uncertainty correction could also be applied for other radionuclide pairs ((234)Th/(238)U, (90)Y/(90)Sr, (210)Bi/(210)Pb), sample matrixes (aerosols), and disciplines. PMID:24992240

  13. Beta-radiation-induced resistance to MNNG initiation of papilloma but not carcinoma formation in mouse skin

    SciTech Connect

    Mitchel, R.E.; Gragtmans, N.J.; Morrison, D.P. )

    1990-02-01

    We have shown previously that the risk of tumor initiation, promotion, and progression in animals initiated with alkylating agents can be drastically altered by hyperthermia treatments. We show here that ionizing radiation can also alter the risk of tumor initiation by alkylating agents. Using a two-step skin tumorigenesis protocol in female SENCAR mice (initiation by MNNG, promotion with TPA), we exposed the dorsal skin of the mice to various doses of 90Sr/90Y beta radiation near the time of initiation. The radiation produced a dose-dependent reduction in the number of papillomas which appeared after TPA promotion, with about a 20% reduction in animals receiving 0.5 Gy surface dose just before initiation, about 50% reduction after 2.5 Gy, and greater than 80% at doses above 5 Gy. A dose of 2.5 Gy in animals initiated with DMBA produced no significant reduction. One skin hyperthermia treatment along with radiation in MNNG-initiated animals partially blocked the protective effect of radiation and increased the papilloma frequency. Radiation (2.5 Gy) given either 6 days before or after MNNG initiation was less effective but still reduced papilloma frequency about 20%. In sharp contrast to the marked reduction in papilloma formation, these same animals showed no change in carcinoma frequency with any of the doses or schedules of beta radiation. MNNG initiation alone produced three types of initiated cells. One type, produced in low yield, was promotion-independent with a high probability of progression to a carcinoma and appeared unaffected by the radiation. A second type, produced in intermediate yield, was promotion-dependent and also had a high progression probability, but was likewise unaffected by the radiation. The third and most abundant type was promotion-dependent with a very low progression probability.

  14. Yttrium-90 Resin Microsphere Radioembolization Using an Antireflux Catheter: An Alternative to Traditional Coil Embolization for Nontarget Protection

    SciTech Connect

    Morshedi, Maud M. Bauman, Michael Rose, Steven C. Kikolski, Steven G.

    2015-04-15

    PurposeSerious complications can result from nontarget embolization during yttrium-90 (Y-90) transarterial radioembolization. Hepatoenteric artery coil embolization has been traditionally performed to prevent nontarget radioembolization. The U.S. Food and Drug Administration–approved Surefire Infusion System (SIS) catheter, designed to prevent reflux, is an alternative to coils. The hypothesis that quantifiable SIS procedural parameters are comparable to coil embolization was tested.MethodsFourteen patients aged 36–79 years with colorectal, neuroendocrine, hepatocellular, and other predominantly bilobar hepatic tumors who underwent resin microsphere Y-90 radioembolization using only the SIS catheter (n = 7) versus only detachable coils (n = 7) for nontarget protection were reviewed retrospectively. Procedure time, fluoroscopy time, contrast dose, radiation dose, and cost were evaluated.ResultsMultivariate analysis identified significant cohort differences in the procedural parameters evaluated (F(10, 3) = 10.39, p = 0.04). Between-group comparisons of the pretreatment planning procedure in the SIS catheter group compared to the coil embolization group demonstrated a significant reduction in procedure time (102.6 vs. 192.1 min, respectively, p = 0.0004), fluoroscopy time (14.3 vs. 49.7 min, respectively, p = 0.0016), and contrast material dose (mean dose of 174.3 vs. 265.0 mL, respectively, p = 0.0098). Procedural parameters were not significantly different between the two groups during subsequent dose delivery procedures. Overall cost of combined first-time radioembolization procedures was significantly less in the SIS group ($4252) compared to retrievable coil embolization ($11,123; p = 0.001).ConclusionThe SIS catheter results in a reduction in procedure time, fluoroscopy time, and contrast material dose and may be an attractive cost-effective alternative to detachable coil embolization for prevention of nontarget radioembolization.

  15. Peptide receptor radionuclide therapy with somatostatin analogues in neuroendocrine tumors.

    PubMed

    Giovacchini, Giampiero; Nicolas, Guillaume; Forrer, Flavio

    2012-06-01

    Neuroendocrine tumors (NETs) are rare tumors with variable malignant behavior. The majority of NETs express increased levels of somatostatin (SST) receptors, particularly SST2 receptors. Radiolabeled peptides specific for the SST2 receptors may be used for diagnosis of NETs and for peptide receptor radionuclide therapy (PRRT). [(111)In-DTPA(0)]-octreotide has been the first peptide used for PRRT. This radiolabeled peptide, emitting Auger electrons, often induced symptomatic relief, but objective morphological responses were rarely documented. After the introduction of the chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) other peptides, primarily [DOTA(0),Tyr(3)]octreotate (DOTATATE) and [DOTA(0),Tyr(3)]octreotide (DOTATOC) were labeled with (90)Y or (177)Lu and used for therapy applications. The rate of objective response obtained with these radiolabeled peptides ranges between 6% and 46%, owing to differences in inclusion criteria adopted in different studies, length and type of therapy, and criteria of evaluation of the response. The present data in the literature do not allow defining the most suitable peptide and radionuclide for the treatment of NETs. Instead emerging evidence indicates that a combination of nuclides with different physical characteristics might be more effective than the use of a single nuclide. Kidney and bone marrow toxicity are the limiting factors for PRRT. Mild toxicity is often encountered while severe toxicity is rarer. Toxicity could be reduced and therapeutic efficacy enhanced by patient-specific dosimetry. Future directions include different issues of PRRT, such as defining the most suitable treatment scheme, evaluation of new peptides with different affinity profiles to other SST receptor subtypes, and reduction of toxicity. PMID:22292758

  16. Embolisation of the Gastroduodenal Artery is Not Necessary in the Presence of Reversed Flow Before Yttrium-90 Radioembolisation

    SciTech Connect

    Daghir, Ahmed A.; Gungor, Hatice; Haydar, Ali A.; Wasan, Harpreet S.; Tait, Nicholas P.

    2012-08-15

    Introduction: The gastroduodenal artery (GDA) is usually embolised to avoid nontarget dispersal before yttrium-90 (Y{sup 90}) radioembolisation to treat liver metastases. In a minority of patients, there is retrograde flow in the GDA. The purpose of this study was to determine if there is any increased risk from maintaining a patent GDA in patients with reversed flow. Materials and Methods: A retrospective review was performed of all patients undergoing Y{sup 90} radioembolisation at our institution. The incidence of toxicities arising from nontarget radioembolisation by way of the GDA (gastric/duodenal ulceration, gastric/duodenal bleeding, and pancreatitis) and death occurring within 2 months of treatment were compared between the reversed and the antegrade GDA groups. Results: Ninety-two patients underwent preliminary angiography. Reversed GDA flow was found on angiography in 14.1% of cases; the GDA was not embolised in these patients. The GDA was coiled in 55.7% of patients with antegrade GDA flow to prevent inadvertent dispersal of radioembolic material. There was no increased toxicity related to nontarget dispersal by way of the GDA, or increased early mortality, in patients with reversed GDA flow (P > 0.05). Conclusion: In patients with reversed GDA flow, maintenance of a patent GDA before administration of Y{sup 90} radioembolisation does not increase the risk of toxicity from nontarget dispersal. Therapeutic injection, with careful monitoring to identify early vascular stasis, may be safely performed beyond the origin of the patent GDA. A patent GDA with reversed flow provides forward drive for infused particles and may allow alternative access to the hepatic circulation.

  17. Radioisotope Production for Medical and Physics Applications

    NASA Astrophysics Data System (ADS)

    Mausner, Leonard

    2012-10-01

    Radioisotopes are critical to the science and technology base of the US. Discoveries and applications made as a result of the availability of radioisotopes span widely from medicine, biology, physics, chemistry and homeland security. The clinical use of radioisotopes for medical diagnosis is the largest sector of use, with about 16 million procedures a year in the US. The use of ^99Mo/^99mTc generator and ^18F make up the majority, but ^201Tl, ^123I, ^111In, and ^67Ga are also used routinely to perform imaging of organ function. Application of radioisotopes for therapy is dominated by use of ^131I for thyroid malignancies, ^90Y for some solid tumors, and ^89Sr for bone cancer, but production of several more exotic species such as ^225Ac and ^211At are of significant current research interest. In physics ^225Ra is of interest for CP violation studies, and the actinides ^242Am, ^249Bk, and ^254Es are needed as targets for experiments to create superheavy elements. Large amounts of ^252Cf are needed as a fission source for the CARIBU experiment at ANL. The process of radioisotope production is multidisciplinary. Nuclear physics input based on nuclear reaction excitation function data is needed to choose an optimum target/projectile in order to maximize desired isotope production and minimize unwanted byproducts. Mechanical engineering is needed to address issues of target heating, induced mechanical stress and material compatibility of target and claddings. Radiochemists are involved as well since chemical separation to purify the desired final radioisotope product from the bulk target and impurities is also usually necessary. Most neutron rich species are produced at a few government and university reactors. Other radioisotopes are produced in cyclotrons in the commercial sector, university/hospital based facilities, and larger devices at the DOE labs. The landscape of US facilities, the techniques involved, and current supply challenges will be reviewed.

  18. Comparison between beta radiation dose distribution due to LDR and HDR ocular brachytherapy applicators using GATE Monte Carlo platform.

    PubMed

    Mostafa, Laoues; Rachid, Khelifi; Ahmed, Sidi Moussa

    2016-08-01

    Eye applicators with 90Sr/90Y and 106Ru/106Rh beta-ray sources are generally used in brachytherapy for the treatment of eye diseases as uveal melanoma. Whenever, radiation is used in treatment, dosimetry is essential. However, knowledge of the exact dose distribution is a critical decision-making to the outcome of the treatment. The Monte Carlo technique provides a powerful tool for calculation of the dose and dose distributions which helps to predict and determine the doses from different shapes of various types of eye applicators more accurately. The aim of this work consisted in using the Monte Carlo GATE platform to calculate the 3D dose distribution on a mathematical model of the human eye according to international recommendations. Mathematical models were developed for four ophthalmic applicators, two HDR 90Sr applicators SIA.20 and SIA.6, and two LDR 106Ru applicators, a concave CCB model and a flat CCB model. In present work, considering a heterogeneous eye phantom and the chosen tumor, obtained results with the use of GATE for mean doses distributions in a phantom and according to international recommendations show a discrepancy with respect to those specified by the manufacturers. The QC of dosimetric parameters shows that contrarily to the other applicators, the SIA.20 applicator is consistent with recommendations. The GATE platform show that the SIA.20 applicator present better results, namely the dose delivered to critical structures were lower compared to those obtained for the other applicators, and the SIA.6 applicator, simulated with MCNPX generates higher lens doses than those generated by GATE. PMID:27499370

  19. Radioembolization as Locoregional Therapy of Hepatic Metastases in Uveal Melanoma Patients

    SciTech Connect

    Klingenstein, A.; Haug, A. R.; Zech, C. J.; Schaller, U. C.

    2013-02-15

    To retrospectively evaluate the overall survival, safety, and efficacy of metastatic uveal melanoma patients after radioembolization as salvage therapy. Thirteen patients were treated with radioembolization of branches of the hepatic artery with resin-based yttrium-90 ({sup 90}Y)-labelled microspheres. Twelve patients underwent a single application, and 1 patient underwent 4 interventions. Dosages from 644 to 2,450 MBq (mean activity 1,780) were applied. Treatment response was evaluated by way of liver magnetic resonance imaging and computed tomography (CT) as well as whole-body fluorodeoxyglucose positron emission tomography (PET)/CT with evaluation of percentage changes in SUV{sub max} before and at 2-3 months after therapy. Kaplan-Meier analysis was calculated to determine overall survival. Partial remission (PR) was observed in 8 (62 %), stable disease (SD) in 2 (15 %), and progressive disease (PD) in 3 (23 %) patients under terms of standard criteria and PR in 3 (23 %), SD in 3 (23 %), and PD in 7 (54 %) patients according to PET criteria. Neither RECIST nor PET criteria showed a significant difference in predicting overall survival (P = 0.12 and 0.11, respectively). Median survival time after radioembolization was 7 months. No acute toxicity with in-hospital morbidity was observed. One patient developed hepatomegaly, and 1 patient developed gastric ulceration. Throughout follow-up, progression of extrahepatic metastases was observed. Radioembolization may be a promising therapy in uveal melanoma patients with predominant hepatic metastases. At first follow-up, we observed PR or SD in 77 % patients under terms of standard criteria with an acceptable toxicity profile.

  20. Safety and efficacy of manual stepping and overlapping of {beta}-emitter for diffuse in-stent restenosis lesions

    SciTech Connect

    Kim, Han-Soo; Waksman, Ron; Chan, Rosanna C.; Pappas, Chrysoula K.; Bhargava, Balram; Ajani, Andrew E.; Bui, Anh B.; Yazdi, Hamid A.; Mintz, Gary S.; Satler, Lowell F.; Kent, Kenneth M.; Pichard, Augusto D

    2002-03-01

    Background: The effects of overlapping {beta}-emitter sources on the treatment of in-stent restenosis (ISR) lesions as a result of manual stepping are unknown. Methods and results: In the BETA WRIST (Beta Washington Radiation for In-stent Restenosis Trial), 17 out of the 50 patients who received radiation treatment had diffuse ISR in native coronaries that required manual stepping of the {beta}-emitter ({sup 90}Y) source in order to cover the lesion and the edges. Fourteen of those patients received radiation with an overlap of up to 3 mm in the middle of the stented segment. The prescribed dose was 20.6 Gy to a distance of 1.0 mm from the surface of the inflated balloon, and the calculated dose to the vessel wall at the overlapped area did not exceed 75 Gy. There was no difference in late total occlusion (7.1% vs. 9.0%, P=NS) and target lesion revascularization (28.5% vs. 27.2%, P=NS) between patients with stepping and those without stepping. At 6 months, there was no evidence of perforation or aneurysm at the overlapped segments. Quantitative coronary angiographic (QCA) analysis revealed significantly reduced late loss in the overlapped segment compared to the adjacent segment (P=.04). Serial (postradiation vs. follow-up) IVUS measurement showed larger mean lumen cross-sectional area (CSA) (P=.0035) and smaller mean intimal hyperplasia (IH) CSA (P=.0010) in the overlapped segment compared to the adjacent segment. Conclusion: Manual stepping of {beta}-emitter source with a short overlapped segment is safe for diffuse ISR. Further increase in lumen dimension and reduction in IH formation are observed at the overlapped segment.

  1. Radioembolization for hepatocellular carcinoma.

    PubMed

    Sangro, Bruno; Iñarrairaegui, Mercedes; Bilbao, Jose I

    2012-02-01

    Radioembolization is a form of brachytherapy in which intra-arterially injected (90)Y-loaded microspheres serve as sources for internal radiation purposes. It produces average disease control rates above 80% and is usually very well tolerated. Main complications do not result from the microembolic effect, even in patients with portal vein occlusion, but rather from an excessive irradiation of non-target tissues including the liver. All the evidence that support the use of radioembolization in HCC is based on retrospective series or non-controlled prospective studies. However, reliable data can be obtained from the literature, particularly since the recent publication of large series accounting for nearly 700 patients. When compared to the standard of care for the intermediate and advanced stages (transarterial embolization and sorafenib), radioembolization consistently provides similar survival rates. Two indications seem particularly appealing in the boundaries of these stages for first-line radioembolization. First, the treatment of patients straddling between the intermediate and advanced stages (intermediate patients with bulky or bilobar disease that are considered poor candidates for TACE, and advanced patients with solitary tumors invading a segmental or lobar branch of the portal vein). Second, the treatment of patients that are slightly above the criteria for resection, ablation or transplantation, for which downstaging could open the door for a radical approach. Radioembolization can also be used to treat patients progressing to TACE or sorafenib. With a number of clinical trials underway, the available evidence shows that it adds a significant value to the therapeutic weaponry against HCC of tertiary care centers dealing with this major cancer problem. PMID:21816126

  2. Variability of formulas to assess insulin sensitivity and their association with the Matsuda index.

    PubMed

    Henríquez, Sandra; Jara, Natalia; Bunout, Daniel; Hirsch, Sandra; de la Maza, María Pía; Leiva, Laura; Barrera, Gladys

    2013-01-01

    Objetivo: Evaluar la variabilidad individual de los índices HOMA y QUICKI para resistencia a insulina, utilizando tres muestras de sangre en ayunas obtenidas en un período de 30 minutos. Material y métodos: Se utilizaron datos provenientes de 80 participantes de 41.5 ± 15 años de edad (26 mujeres) a quienes se les efectuó una prueba de tolerancia a glucosa oral para calcular el índice de Matsuda. A cada participante se le tomaron tres muestras de sangre en ayunas en un período de 30 minutos y cuatro muestras a los 30, 60, 90 y 120 minutos después de una carga oral de 75 g de glucosa. En cada muestra se midieron los niveles de insulina y glucosa. Los índices HOMA y QUICKI se calcularon utilizando las nueve combinaciones posibles con las tres muestras obtenidas en ayunas. El índice de Matsuda se calculó utilizando todas las muestras. Resultados: Las medianas de los índices HOMA-IR, HOMA-?, QUICKI y Matsuda fueron 1,9, 117,9, 0,35 and 3,71 unidades arbitrarias, respectivamente. Los coeficientes de variación individual del HOMA-IR, HOMA-??y QUICKI fueron 11,8 (7,8-18,9), 15 (10,2-22,9) and 1,8 (8,8-21,9) %, respectivamente. Comparados con el índice de Matsuda, los valores de R2 para el HOMA-IR, HOMA-??y QUICKI fueron 0,46, 0,2 y 0,71, respectivamente. Conclusiones: De los índices que utilizan muestras en ayunas para determinar resistencia a insulina, el QUICKI es el que tiene el menor coeficiente de variación y la mejor correlación con el índice de Matsuda.

  3. Radiolabeled monoclonal antibodies in the diagnosis and treatment of malignant melanoma

    SciTech Connect

    Divgi, C.R.; Larson, S.M. )

    1989-10-01

    The use of antibodies directed against tumors has found increasing usefulness after the discovery by Kohler and Milstein of hybridoma technology, which made it possible to obtain monoclonal antibody (MoAb) that reacted specifically against a particular epitope on a particular antigen site. Relative tumor specificity and a lack of significant toxicity, together with the ability to link radionuclides (both halogens and metals) without significant deterioration of biologic behavioral characteristics such as immunoreactivity, have enabled widespread use of radiolabeled MoAbs in several malignancies, including and especially malignant melanoma. There is a significant body of data indicating that radiolabeled MoAbs directed against melanoma-associated antigens have an important role in the detection and therapy of metastatic malignant melanoma. Detection of visceral disease, while currently suboptimal, will in the future improve with optimization of SPECT imaging using 99mTc-labeled MoAb Fab fragments. This may result in an attenuated or absent antimouse response, especially after one injection, unless of course coinfused with either specific and/or nonspecific intact immunoglobulin (Ig). Radiolabeled fragments play an important role in radioimmunotherapy in metastatic melanoma. This role may be enhanced by the development of newer chelating agents that will decrease nonspecific hepatic uptake of radionuclide, enabling the use of beta-emitting radiometals such as 90Y. The recent report demonstrating diminished hepatic uptake of 99mTc-labeled anti-high molecular weight antigen (HMWA) Fab shows promise, since the same labeling technique can be used to deliver radiotherapeutic agents such as 186Re, which may be labeled to MoAb with methods similar to those used for 99mTc.82 references.

  4. Radon concentration in groundwater of the Yongin area in Korea by using LSC

    NASA Astrophysics Data System (ADS)

    Cho, Sooyoung; Lee, Kilyong; Yoon, Yoonyeol; Yun, Uk; Cho, Byungwook; Ha, kyoochul; Koo, Minho

    2015-04-01

    The precise determination of 222Rn concentration in ground water is very important to understand the interactions between the groundwater and surface water interactions because it has been used frequently as a tracer for many geohydrological processes. In this study, the measurement was based on the liquid scintillation counting technique using LKB Wallac Quantulus 1220 liquid scintillation counter(LSC) equipped with pulse shape analyzer(PSA). We have optimized the pulse-discrimination capabilities of the detector to achieve the best α/β separation, which made the lowest detection limit possible. LSC was calibrated to optimize the PSA with 241Am and 90Sr/90Y. The sample was collected from 100 groundwater sites in the Yoingin area, Korea. The relationship between chemical characteristics and depth was investigated in terms of EC, pH, and temperature. The concentration of 222Rn in ground water was measured to be about 0.6 to 678 Bq/l with an average of 217 Bq/L. However, there was no relationship between the Rn and other physicochemical components. The Rn concentration in ground water was 170 Bq/L, 210 Bq/L, 260 Bq/L for depth <50 m, 50-100 m, >100 m, respectively. When viewed from the average value, 222Rn in deep ground was relatively higher. It also was dependent on the geolocial legend: The high-Rn area corresponds to Jurassuc grabute and low-Rn to Sedunentary area. It was clearly demonstrated that the occurrence of radionuclides is closely related to radiogenic minerals. Key words: Grondwater, 222Rn, LSC, chemical characteristics, geolocial legend

  5. A free database of radionuclide voxel S values for the dosimetry of nonuniform activity distributions.

    PubMed

    Lanconelli, N; Pacilio, M; Lo Meo, S; Botta, F; Di Dia, A; Aroche, A Torres; Pérez, M A Coca; Cremonesi, M

    2012-01-21

    The increasing availability of SPECT/CT devices with advanced technology offers the opportunity for the accurate assessment of the radiation dose to the biological target volume during radionuclide therapy. Voxel dosimetry can be performed employing direct Monte Carlo radiation transport simulations, based on both morphological and functional images of the patient. On the other hand, for voxel dosimetry calculations the voxel S value method can be considered an easier approach than patient-specific Monte Carlo simulations, ensuring a good dosimetric accuracy at least for anatomic regions which are characterized by uniform density tissue. However, this approach has been limited because of the lack of tabulated S values for different voxel dimensions and radionuclides. The aim of this work is to provide a free dataset of values which can be used for voxel dosimetry in targeted radionuclide studies. Seven different radionuclides (89Sr, 90Y, 131I, 153Sm, 177Lu, 186Re, 188Re), and 13 different voxel sizes (2.21, 2.33, 2.4, 3, 3.59, 3.9, 4, 4.42, 4.8, 5, 6, 6.8 and 9.28 mm) are considered. Voxel S values are calculated performing simulations of monochromatic photon and electron sources in two different homogeneous tissues (soft tissue and bone) with DOSXYZnrc code, and weighting the contributions on the basis of the radionuclide emission spectra. The outcomes are validated by comparison with Monte Carlo simulations obtained with other codes (PENELOPE and MCNP4c) performing direct simulation of the radionuclide emission spectra. The differences among the different Monte Carlo codes are of the order of a few per cent when considering the source voxel and the bremsstrahlung tail, whereas the highest differences are observed at a distance close to the maximum continuous slowing down approximation range of electrons. These discrepancies would negligibly affect dosimetric assessments. The dataset of voxel S values can be freely downloaded from the website www.medphys.it.

  6. A design study for the analysis of 90Sr And 135,137Cs by ISA-AMS

    NASA Astrophysics Data System (ADS)

    Alary, Jean-François; Cousins, Lisa M.; Eliades, John; Hao, Changtong; Javahery, Gholamreza; Kieser, William E.; Litherland, Albert E.; Zhao, Xiaolei

    2013-04-01

    Extending the range of Accelerator Mass Spectrometry (AMS) to the fission products 90Sr and 135,137Cs would offer numerous advantages for non-proliferation surveillance activities. A new method for suppressing the interfering isobars 90Zr (and 90Y) and 135,137Ba using low kinetic energy (<20 eV) gas-phase reactions in an AMS injection line can help achieving this goal in a cost effective way [1]. The reactions occur in a radiofrequency quadrupole (RFQ) cell filled with a low pressure gas, part of a device known as the Isobar Separator for Anions (ISA). Combined with fluoridematrix assisted ionization, this method greatly improves the analytical capabilities of AMS for 90Sr and will enable the direct analysis of 135,137Cs below sub-parts per trillion levels. The ISA alone provides interference suppression factors of 4×10-6 for ZrF3-/SrF3- and 2×10-5 for BaF2-/CsF2-. The general performance improvement provided by the ISA, however, critically depends on the capacity of this device to transmit the wanted anions with a high efficiency and with a stable response to the natural variations of AMS targets. Based on recent SIMION-8.1 studies and on results of a parallel study on the attenuation of other anions, we have developed a pre-commercial design for the ISA. In this design, RFQ rods and split-flow turbo molecular pumps are configured to achieve full control of reaction time, ion energy and fragmentation pathways (chemical and kinetic reactions), and to improve beam transmission through the cell. The mechanical layout will be presented in 3D models using Solid Works; SIMION-8.1 simulations were used to illustrate the importance of optical matching of the RFQ and the front-end DC retardation section of the ISA.

  7. The response of thermally and optically stimulated luminescence from Al2O3:C to high-energy heavy charged particles

    NASA Technical Reports Server (NTRS)

    Gaza, R.; Yukihara, E. G.; McKeever, S. W. S.

    2004-01-01

    The thermoluminescence (TL) and optically stimulated luminescence (OSL) response of Al2O3 dosimeters to high-energy heavy charged particles (HCP) has been studied using the heavy ion medical accelerator at Chiba, Japan. The samples were Al2O3 single-crystal chips, of the type usually known as TLD-500, and Luxel(TM) dosimeters (Al2O3:C powder in plastic) from Landauer Inc. The samples were exposed to 4He (150 MeV/u), 12C (400 MeV/u), 28Si (490 MeV/us) and 56Fe (500 MeV/u) ions, with linear energy transfer values covering the range from 2.26 to 189 keV/micrometers in water and doses from 1 to 100 mGy (to water). A 90Sr/90Y beta source, calibrated against a 60Co secondary standard, was used for calibration purposes. For OSL, we used both continuous-wave OSL measurements (CW-OSL, using green light stimulation at 525 nm) and pulsed OSL measurements (POSL, using 532 nm stimulation from a Nd:YAG Q-switched laser). The efficiencies (eta HCP, gamma) of the different HCPs at producing OSL or TL were observed to depend not only upon the linear energy transfer (LET) of the HCP, but also upon the sample type (single crystal chip or Luxel(TM)) and the luminescence method used to define the signal--i.e. TL, CW-OSL initial intensity, CW-OSL total area, or POSL. Observed changes in shape of the decay curve lead to potential methods for extracting LET information of unknown radiation fields. A discussion of the results is given, including the potential use of OSL from Al2O3 in the areas of space radiation dosimetry and radiation oncology. c2004 Elsevier Ltd. All rights reserved.

  8. A free database of radionuclide voxel S values for the dosimetry of nonuniform activity distributions

    NASA Astrophysics Data System (ADS)

    Lanconelli, N.; Pacilio, M.; Lo Meo, S.; Botta, F.; Di Dia, A.; Torres Aroche, L. A.; Coca Pérez, M. A.; Cremonesi, M.

    2012-01-01

    The increasing availability of SPECT/CT devices with advanced technology offers the opportunity for the accurate assessment of the radiation dose to the biological target volume during radionuclide therapy. Voxel dosimetry can be performed employing direct Monte Carlo radiation transport simulations, based on both morphological and functional images of the patient. On the other hand, for voxel dosimetry calculations the voxel S value method can be considered an easier approach than patient-specific Monte Carlo simulations, ensuring a good dosimetric accuracy at least for anatomic regions which are characterized by uniform density tissue. However, this approach has been limited because of the lack of tabulated S values for different voxel dimensions and radionuclides. The aim of this work is to provide a free dataset of values which can be used for voxel dosimetry in targeted radionuclide studies. Seven different radionuclides (89Sr, 90Y, 131I, 153Sm, 177Lu, 186Re, 188Re), and 13 different voxel sizes (2.21, 2.33, 2.4, 3, 3.59, 3.9, 4, 4.42, 4.8, 5, 6, 6.8 and 9.28 mm) are considered. Voxel S values are calculated performing simulations of monochromatic photon and electron sources in two different homogeneous tissues (soft tissue and bone) with DOSXYZnrc code, and weighting the contributions on the basis of the radionuclide emission spectra. The outcomes are validated by comparison with Monte Carlo simulations obtained with other codes (PENELOPE and MCNP4c) performing direct simulation of the radionuclide emission spectra. The differences among the different Monte Carlo codes are of the order of a few per cent when considering the source voxel and the bremsstrahlung tail, whereas the highest differences are observed at a distance close to the maximum continuous slowing down approximation range of electrons. These discrepancies would negligibly affect dosimetric assessments. The dataset of voxel S values can be freely downloaded from the website www.medphys.it.

  9. Postoperative Strontium-90 Brachytherapy in the Prevention of Keloids: Results and Prognostic Factors

    SciTech Connect

    Viani, Gustavo A. Stefano, Eduardo J.; Afonso, Sergio L.; De Fendi, Ligia I.

    2009-04-01

    Purpose: The aim of this study was to evaluate the results of keloidectomy and strontium 90 brachytherapy in the prevention of keloid recurrence following excision and to identify outcome and the prognostic factors that predict keloid recurrence after irradiation. Methods and Materials: Data of 612 patients with 892 keloids treated between 1992 and 2006 were evaluated retrospectively. Brachytherapy was performed using a Sr-90Y surface applicator. Total dose was 20 Gy in 10 fractions. Results: With a median follow-up of 61 months, the overall recurrence-free response rate for all keloids was 87.6%. Multivariate analysis revealed the following prognostic factors for recurrence: keloid size > 5 cm (p < 0.0001), burn scars as the keloid etiology (p < 0.0001), and previous treatment (p < 0.0001). Outcome was not found to be significantly related to the interval between surgery and radiotherapy, sex, or age. Pruritus and skin reddening were the most common symptoms of keloids, but all signs and symptoms abated with time after treatment. Cosmetic results from the keloid treatment were considered good or excellent in 70.6% of the patients. Conclusion: Our study findings show that excision plus Sr-90 brachytherapy is effective in the eradication of keloids. Sr-90 radiotherapy (20 Gy in 10 fractions) achieved a similar local control rate, as have higher doses per fraction in other series. It also resulted in a good cosmetic rate and relief of symptoms. Our data further suggest that the initiation of postoperative irradiation within hours of surgical excision is not important to therapeutic outcome.

  10. Rapid determination of 226Ra in environmental samples

    SciTech Connect

    Maxwell, Sherrod L.; Culligan, Brian K.

    2012-02-04

    A new rapid method for the determination of {sup 228}Ra in natural water samples has been developed at the SRNL/EBL (Savannah River National Lab/ Environmental Bioassay Laboratory) that can be used for emergency response or routine samples. While gamma spectrometry can be employed with sufficient detection limits to determine {sup 228}Ra in solid samples (via {sup 228}Ac) , radiochemical methods that employ gas flow proportional counting techniques typically provide lower MDA (Minimal Detectable Activity) levels for the determination of {sup 228}Ra in water samples. Most radiochemical methods for {sup 228}Ra collect and purify {sup 228}Ra and allow for {sup 228}Ac daughter ingrowth for ~36 hours. In this new SRNL/EBL approach, {sup 228}Ac is collected and purified from the water sample without waiting to eliminate this delay. The sample preparation requires only about 4 hours so that {sup 228}Ra assay results on water samples can be achieved in < 6 hours. The method uses a rapid calcium carbonate precipitation enhanced with a small amount of phosphate added to enhance chemical yields (typically >90%), followed by rapid cation exchange removal of calcium. Lead, bismuth, uranium, thorium and protactinium isotopes are also removed by the cation exchange separation. {sup 228}Ac is eluted from the cation resin directly onto a DGA Resin cartridge attached to the bottom of the cation column to purify {sup 228}Ac. DGA Resin also removes lead and bismuth isotopes, along with Sr isotopes and {sup 90}Y. La is used to determine {sup 228}Ac chemical yield via ICP-MS, but {sup 133}Ba can also be used instead if ICP-MS assay is not available. Unlike some older methods, no lead or strontium holdback carriers or continual readjustment of sample pH is required.

  11. Decay/ingrowth uncertainty correction of (210)Po/(210)Pb in seawater.

    PubMed

    Lin, Wuhui; Ma, Hao; Chen, Liqi; Zeng, Zhi; He, Jianhua; Zeng, Shi

    2014-11-01

    Due to increasing application of (210)Po/(210)Pb in studying particle dynamics, a consistent procedure and calculation to derive accurate and precise result of (210)Po and (210)Pb in seawater should be proposed in the framework of intercalibration by GEOTRACES. The associated uncertainty of radioactivity, which is a significant component of data report, plays a vital role in intercomparison and should be well evaluated. Although measurement uncertainty of laboratory result was well defined in ISO standards and IAEA technical documents, the decay/ingrowth uncertainty correction from laboratory result to in-situ result was less studied. It was demonstrated that the relative uncertainty of in-situ (210)Pb activity was independent of elapsed time and equal to relative uncertainty of laboratory measuring (210)Po activity at second spontaneous deposition date. The relative uncertainty of in-situ (210)Po activity decreases with in-situ activity ratio of (210)Po to (210)Pb and increases with elapsed time between sampling date and separation date, relative uncertainty of laboratory measuring (210)Po activity at first spontaneous deposition date and relative uncertainty of in-situ (210)Pb activity. It was more important to improve precision of (210)Po at first spontaneous deposition date than that of (210)Po at second spontaneous deposition date. To obtain a desirable relative uncertainty of in-situ (210)Po activity, the maximum allowing elapsed time for (210)Po, which was important for sampling strategy making and quality assurance, was calculated by in-situ activity ratio of (210)Po to (210)Pb and precision of analytical method for (210)Po. The methodology of decay/ingrowth uncertainty correction could also be applied for other radionuclide pairs ((234)Th/(238)U, (90)Y/(90)Sr, (210)Bi/(210)Pb), sample matrixes (aerosols), and disciplines.

  12. Lutetium-177 Labeled Peptides: The European Institute of Oncology Experience.

    PubMed

    Carollo, Angela; Papi, Stefano; Chinol, Marco

    2016-01-01

    Peptide receptor radionuclide therapy (PRRT) using radiolabeled somatostatin analogues has shown encouraging results in various somatostatin receptor positive tumors. Partial remission rates up to 30% have been documented as well as significant improvements in quality of life and survival. This treatment takes advantage of the high specific binding of the radiolabeled peptide to somatostatin receptors overexpressed by the tumors thus being more effective on the tumor cells with less systemic side-effects. The development of macrocyclic chelators conjugated to peptides made possible the stable binding with various radionuclides. In particular 177Lu features favourable physical characteristics with a half-life of 6.7 days, emission of β- with energy of 0.5 MeV for treatment and γ-emissions suitable for imaging. The present contribution describes the learning process achieved at the European Institute of Oncology (IEO) since the first application of 90Y labeled peptides to the therapy of neuroendocrine tumors back in 1997. Continuous improvements led to the preparation of a safe 177Lu labeled peptide for human use. Our learning curve began with the identification of the optimal characteristics of the isotope paying attention to its chemical purity and specific activity along with the optimization of the parameters involved in the radiolabeling procedure. Also the radiation protection issues have been improved along the years and recently more and more attention has been devoted to the pharmaceutical aspects involved in the preparation. The overall issue of the quality has now been completed by drafting an extensive documentation with the goal to deliver a safe and reliable product to our patients.

  13. Efficacy of radiation synovectomy (radiosynovectomy or radiosynoviorthesis) with yttrium-90 in exudative inflammation of synovial membrane of knee joints in patients with rheumatic diseases – preliminary report

    PubMed Central

    Węgierska, Małgorzata; Barczyńska, Tacjana; Waszczak, Marzena; Żuchowski, Paweł; Jeka, Sławomir

    2016-01-01

    Objectives Hypertrophic and exudative synovitis of the knee is one of the earliest symptoms in rheumatic diseases. In the case of pharmacotherapy failure, other methods which directly remove the inflamed synovial membrane are used – synovectomies. Radiosynovectomy (RSV) is the radiopharmaceutical application of colloidal solution to joint cavities. In this study, the authors assessed the efficacy of knee radiosynovectomy with yttrium-90 (Y-90) in several groups of patients divided into certain rheumatic diseases. Material and methods The study group consisted of 70 patients aged from 29 to 65 years with hypertrophic and exudative synovitis of the knee in rheumatic diseases such as rheumatoid arthritis, osteoarthrosis and spondyloarthropathies. Radiopharmaceutical colloid of Y-90, with a radiation dose of 185-222 MBq in a volume of 2-3 ml, was administered to joint. Then the knee joint was immobilized for 72 h. During visits V1, V2, V3 and V4, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were measured and ultrasound of the knee was performed. Disease activity was evaluated by the WOMAC scale, HAQ and 100-mm visual analog scale (VAS). Results The most significant difference of synovial hypertrophy, before and after the procedure, was obtained in patients with rheumatoid arthritis. Variability of effusion before and after the procedure in all groups was comparable and statistically significant. The greatest improvement in variability of inflammatory parameters, before and 4 weeks after radiosynovectomy, was observed in patients with rheumatoid arthritis. Conclusions In the therapeutic algorithm radiosynovectomy should be located between conservative treatment and operative procedures. Radiosynovectomy does not require hospitalization or prolonged rehabilitation. Radiosynoviorthesis affects the patient's general condition, which is associated with eliminating pain and restoring joint function. PMID:27407269

  14. Evaluation of a reflective coating for an organic scintillation detector

    NASA Astrophysics Data System (ADS)

    Tarancón, A.; Marin, E.; Tent, J.; Rauret, G.; Garcia, J. F.

    2012-05-01

    A reflective coating based on white paint, black paint and varnish has been evaluated to determine its reflective capabilities and its potential use in radioactivity detectors based on organic scintillators. Three different white paints, all of which were based on TiO2, were also tested to determine the one with the best performance and lowest radioactivity content. In a first experiment, we evaluated the capability of the reflective coating by measuring 90Sr/90Y with PSm in a polyethylene vial partially painted with EJ510 (Eljen Technology) reflective paint, black paint and varnish. In a second experiment, we compared the performance of the EJ510 to that of other white paints used for artistic purposes (Vallejo and Rembrandt). The results showed that, when a vial was only partially painted with the white paints (keeping a window free of paint to allow photons to exit), the efficiency and spectral distribution of the painted vial was similar to that of a non-painted vial. This behavior showed the efficiency of the reflective coatings. In terms of reflection capabilities, all of the tested paints were equivalent; however, the background was higher for the EJ510 paint. Analyses using high-resolution gamma spectroscopy indicated the presence of natural radionuclides (40K, 226Ra and 228Ra) in the EJ510. On the basis of the results (high reflection capabilities and the absence of radioactive impurities) and its lower cost, the Vallejo paint was selected as the white reflective paint. The final structure of the reflective coating was composed of five white paint layers, a black paint (to avoid external light entrance) and a layer of varnish (to protect the paints).

  15. Production and characterization of spodumene dosimetric pellets prepared by a sol-gel route

    NASA Astrophysics Data System (ADS)

    Lima, H. R. B. R.; Nascimento, D. S.; Bispo, G. F. C.; Teixeira, V. C.; Valério, M. E. G.; Souza, S. O.

    2014-11-01

    Spodumene is an aluminosilicate that has shown good results for high-dose TL dosimetry for beta or gamma rays. Due to its chemical composition (LiAlSi2O6) it has potential to be used as a neutron dosimeter. The synthetic spodumene is usually produced by solid state reaction and conventional sol-gel, whose shortcomings arise from the need to employ high temperatures and high cost reagents, respectively. Proteic sol-gel method is promising, because it can reduce production costs and the possibility of environmental contamination. This work reports the production of the spodumene by the proteic sol-gel method using edible unflavored gelatin as a precursor. The product is characterized physically and morphologically, and investigated its applicability as a TL dosimeter. Two sets of samples were prepared using different sources of silicon, one with TEOS (Si(OC3H5)4) and one with SILICA (SiO2). The materials produced were characterized by X-ray diffraction, differential thermal analysis and thermogravimetry in order to evaluate the structural properties, as well as possible changes in physical or chemical properties depending on the temperature. The production of spodumene was successful, with generation of the crystals in the β-phase with tetragonal structure. Sintered pellets produced from these crystals were irradiated with a 90Sr-90Y source and their TL glow curves were evaluated. Although the samples prepared by the proteic sol-gel method with TEOS presented a lower forming temperature, the samples produced with SILICA showed higher sensitivity to radiation.

  16. Bacterial acyl-CoA mutase specifically catalyzes coenzyme B12-dependent isomerization of 2-hydroxyisobutyryl-CoA and (S)-3-hydroxybutyryl-CoA.

    PubMed

    Yaneva, Nadya; Schuster, Judith; Schäfer, Franziska; Lede, Vera; Przybylski, Denise; Paproth, Torsten; Harms, Hauke; Müller, Roland H; Rohwerder, Thore

    2012-05-01

    Coenzyme B(12)-dependent acyl-CoA mutases are radical enzymes catalyzing reversible carbon skeleton rearrangements in carboxylic acids. Here, we describe 2-hydroxyisobutyryl-CoA mutase (HCM) found in the bacterium Aquincola tertiaricarbonis as a novel member of the mutase family. HCM specifically catalyzes the interconversion of 2-hydroxyisobutyryl- and (S)-3-hydroxybutyryl-CoA. Like isobutyryl-CoA mutase, HCM consists of a large substrate- and a small B(12)-binding subunit, HcmA and HcmB, respectively. However, it is thus far the only acyl-CoA mutase showing substrate specificity for hydroxylated carboxylic acids. Complete loss of 2-hydroxyisobutyric acid degradation capacity in hcmA and hcmB knock-out mutants established the central role of HCM in A. tertiaricarbonis for degrading substrates bearing a tert-butyl moiety, such as the fuel oxygenate methyl tert-butyl ether (MTBE) and its metabolites. Sequence analysis revealed several HCM-like enzymes in other bacterial strains not related to MTBE degradation, indicating that HCM may also be involved in other pathways. In all strains, hcmA and hcmB are associated with genes encoding for a putative acyl-CoA synthetase and a MeaB-like chaperone. Activity and substrate specificity of wild-type enzyme and active site mutants HcmA I90V, I90F, and I90Y clearly demonstrated that HCM belongs to a new subfamily of B(12)-dependent acyl-CoA mutases. PMID:22433853

  17. Microscopic interpretation of the (t, 3He) reaction at 130 MeV on 90Zr and isovector monopole strength

    NASA Astrophysics Data System (ADS)

    Guillot, J.

    2007-08-01

    The 130-MeV primary tritium beam of the AGOR facility with an intensity of up to 108 pps and the Big Bite Spectrometer experimental setup have been used to study the (t, 3He) reaction between 0° and 5° lab angles on 12C and 90Zr targets. The standard ray-tracing procedure has allowed us to obtain excitation-energy spectra up to 30 MeV in six angular bins for each residual nucleus, with an average energy resolution of 350 keV. We have used the DWBA reaction mechanism model to reproduce those spectra and their angular distributions. In this approximation, the form factor was treated as a folding of an effective projectile-nucleon interaction with a transition density. The effective projectile-nucleon interaction has been adjusted to reproduce the 0° cross section of the 1+ ground state of 12B populated in the 12C(t, 3He) reaction. We have employed RPA wave functions of excited states to construct the form factors. This DWBA+RPA analysis is used to compare calculated and experimental cross sections directly and to discuss the giant resonance excitations in the 90Y nucleus. In this talk, we give some details on this analysis. We show that there are important contributions of L = 2 transitions in the observed cross sections for the 1+ final states that explain the previous difficulties in clearly identifying the monopole strength distributions. We then have a better indication of where the L = 0 part is located with this reaction and its microscopic analysis.

  18. Preparation and preclinical evaluation of humanised A33 immunoconjugates for radioimmunotherapy.

    PubMed Central

    King, D. J.; Antoniw, P.; Owens, R. J.; Adair, J. R.; Haines, A. M.; Farnsworth, A. P.; Finney, H.; Lawson, A. D.; Lyons, A.; Baker, T. S.

    1995-01-01

    A humanised IgG1/k version of A33 (hA33) has been constructed and expressed with yields up to 700 mg l-1 in mouse myeloma NS0 cells in suspension culture. The equilibrium dissociation constant of hA33 (KD = 1.3 nM) was shown to be equivalent to that of the murine antibody in a cell-binding assay. hA33 labelled with yttrium-90 using the macrocyclic chelator 12N4 (DOTA) was shown to localise very effectively to human colon tumour xenografts in nude mice, with tumour levels increasing as blood concentration fell up to 144 h. A Fab' variant of hA33 with a single hinge thiol group to facilitate chemical cross-linking has also been constructed and expressed with yields of 500 mg l-1. Trimaleimide cross-linkers have been used to produce a trivalent Fab fragment (hA33 TFM) that binds antigen on tumour cells with greater avidity than hA33 IgG. Cross-linkers incorporating 12N4 or 9N3 macrocycles have been used to produce hA33 TFM labelled stably and site specifically with yttrium-90 or indium-111 respectively. These molecules have been used to demonstrate that hA33 TFM is cleared more rapidly than hA33 IgG from the circulation of animals but does not lead to accumulation of these metallic radionuclides in the kidney. 90Y-labelled hA33 TFM therefore appears to be the optimal form of the antibody for radioimmunotherapy of colorectal carcinoma. Images Figure 3 PMID:8519646

  19. Radioembolization for Neuroendocrine Liver Metastases: Safety, Imaging, and Long-Term Outcomes

    SciTech Connect

    Memon, Khairuddin; Lewandowski, Robert J.; Mulcahy, Mary F.; Riaz, Ahsun; Ryu, Robert K.; Sato, Kent T.; Gupta, Ramona; Nikolaidis, Paul; Miller, Frank H.; Yaghmai, Vahid; Gates, Vanessa L.; Atassi, Bassel; Newman, Steven; Omary, Reed A.; Benson, Al B.; Salem, Riad

    2012-07-01

    Purpose: To present long-term outcomes on the safety and efficacy of Yttrium-90 radioembolization in the treatment of unresectable hepatic neuroendocrine metastases refractory to standard-of-care therapy. Methods and Materials: This study was approved by our institutional review board and was compliant with the Health Insurance Portability and Accountability Act. Forty patients with hepatic neuroendocrine metastases were treated with {sup 90}Y radioembolization at a single center. Toxicity was assessed using National Cancer Institute Common Terminology Criteria v3.0. Response to therapy was assessed by World Health Organization (WHO) guidelines for size and European Association for the Study of the Liver disease (EASL) guidelines for necrosis. Time to response and overall survival were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed. Results: The median dose was 113 Gy (29-299 Gy). Clinical toxicities included fatigue (63%), nausea/vomiting (40%), abdominal pain (18%), fever (8%), diarrhea and weight loss (5%); Grade 3 and 4 bilirubin toxicities were experienced by 2 patients and 1 patient, respectively. Different responses were noted by WHO (complete response, 1.2%; partial response, 62.7%) and EASL (complete response, 20.5%; partial response, 43.4%). Median time to response was 4 and 4.9 months by lesion and patient, respectively. The 1-, 2-, and 3-year overall survival rates were 72.5%, 62.5%, and 45%, respectively. Eastern Cooperative Oncology Group (ECOG) performance score 0 (p < 0.0001), tumor burden {<=}25% (p = 0.0019), albumin {>=}3.5 g/dL (p = 0.017), and bilirubin {<=}1.2 mg/dL (p = 0.002) prognosticated survival on univariate analysis; only ECOG performance score 0 and bilirubin {<=}1.2 mg/dL prognosticated better survival outcome on multivariate analysis (p = 0.0001 and p = 0.02). Conclusion: Yttrium-90 therapy for hepatic neuroendocrine metastases leads to satisfactory tumor response and patient survival

  20. Preclinical evaluation of multistep targeting of diasialoganglioside GD2 using a IgG-scFv bispecific antibody with high affinity for GD2 and DOTA metal complex

    PubMed Central

    Cheal, Sarah M.; Xu, Hong; Guo, Hong-fen; Zanzonico, Pat B.; Larson, Steven M.; Cheung, Nai-Kong

    2014-01-01

    Bispecific antibodies (BsAb) have proven to be useful targeting vectors for pretargeted radioimmunotherapy (PRIT). We sought to overcome key PRIT limitations such as high renal radiation exposure and immunogenicity (e.g. of streptavidin-antibody fusions), to advance clinical translation of this PRIT strategy for diasialoganglioside GD2-positive (GD2(+)) tumors. For this purpose, a IgG-scFv BsAb was engineered using the sequences for the anti-GD2 humanized monoclonal antibody hu3F8 (1) and C825, a murine scFv antibody with high affinity for the chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) complexed with beta-particle emitting radiometals such as 177Lu and 90Y (2, 3). A three-step regimen including hu3F8-C825, a dextran-based clearing agent, and p-aminobenzyl-DOTA radiolabeled with 177Lu (as 177Lu-DOTA-Bn; t1/2 = 6.71 days (d)) was optimized in immunocompromised mice carrying subcutaneous (s.c.) human GD2(+) neuroblastoma (NB) xenografts. Absorbed doses for tumor and normal tissues were ∼85 cGy/MBq and ≤3.7 cGy/MBq, respectively, with therapeutic indicies (TI) of 142 for blood and 23 for kidney. A therapy study (n = 5 per group; tumor volume: 240 ± 160 mm3) with three successive PRIT cycles (total 177Lu: ∼33 MBq; tumor dose ∼3400 cGy), revealed complete tumor response in 5/5 animals, with no recurrence up to 28 d post-treatment. Tumor ablation was confirmed histologically in 4/5 mice, and normal organs showed minimal overall toxicities. All non-treated mice required sacrifice within 12 d (>1.0 cm3 tumor volume). We conclude that this novel anti-GD2 PRIT approach has sufficient TI to successfully ablate s.c. GD2(+)–NB in mice while sparing kidney and bone marrow. PMID:24944121

  1. Conformal external beam radiation or selective internal radiation therapy—a comparison of treatment outcomes for hepatocellular carcinoma

    PubMed Central

    Oladeru, Oluwadamilola T.; Miccio, Joseph A.; Yang, Jie; Xue, Yaqi; Ryu, Samuel

    2016-01-01

    Background Non-operative treatment for hepatocellular carcinoma (HCC) has expanded significantly with the use of selective internal radiotherapy (SIRT) mostly with yttrium 90 (90Y) tagged microspheres and highly conformal external beam radiation therapy such as stereotactic body radiotherapy (SBRT) to treat unresectable liver tumors for local tumor control. SBRT is a noninvasive procedure using external radiation source under image guidance, while SIRT delivers radioactive particles by transarterial radioembolization (TARE). However, the survival benefits of SBRT versus SIRT have never been compared. The aim of the present study is to compare the outcomes of overall and disease specific survival (DSS) using SIRT versus SBRT to treat HCC. Methods The Surveillance, Epidemiology, and End Results (SEER) registry database [2004–2011] was queried for cases of unresectable HCC. Patients with missing data and those who received surgery were excluded from the study. A total of 189 patients with unresectable HCC were identified and used for statistical analysis, with 112 receiving SBRT and 77 receiving SIRT. Overall and disease-specific survival was compared using multivariable cox proportional hazard models. Results After adjusting for confounding factors (age at diagnosis, gender, race, grade, stage, AFP level and type of surgery), there were no significant difference in overall survival (OS) [hazard ratio (HR), 0.72; 95% confidence interval (CI), 0.49–1.07; P=0.1077] and DSS (HR, 0.70; 95% CI, 0.46–1.05; P=0.0880) for SIRT compared to SBRT. However, patients with elevated AFP level were associated with higher death risk (P=0.0459) and disease specific death risk (P=0.0233) than those with AFP within normal limits in both treatment groups. Conclusions The retrospective analysis serves as the first comparison of SIRT to SBRT in treatment of unresectable HCC. Our findings suggest both treatment approaches result in similar outcomes in overall and disease

  2. Biological optimization of heterogeneous dose distributions in systemic radiotherapy

    SciTech Connect

    Strigari, Lidia; D'Andrea, Marco; Maini, Carlo Ludovico; Sciuto, Rosa; Benassi, Marcello

    2006-06-15

    The standard computational method developed for internal radiation dosimetry is the MIRD (medical internal radiation dose) formalism, based on the assumption that tumor control is given by uniform dose and activity distributions. In modern systemic radiotherapy, however, the need for full 3D dose calculations that take into account the heterogeneous distribution of activity in the patient is now understood. When information on nonuniform distribution of activity becomes available from functional imaging, a more patient specific 3D dosimetry can be performed. Application of radiobiological models can be useful to correlate the calculated heterogeneous dose distributions to the current knowledge on tumor control probability of a homogeneous dose distribution. Our contribution to this field is the introduction of a parameter, the F factor, already used by our group in studying external beam radiotherapy treatments. This parameter allows one to write a simplified expression for tumor control probability (TCP) based on the standard linear quadratic (LQ) model and Poisson statistics. The LQ model was extended to include different treatment regimes involving source decay, incorporating the repair '{mu}' of sublethal radiation damage, the relative biological effectiveness and the effective 'waste' of dose delivered when repopulation occurs. The sensitivity of the F factor against radiobiological parameters ({alpha},{beta},{mu}) and the influence of the dose volume distribution was evaluated. Some test examples for {sup 131}I and {sup 90}Y labeled pharmaceuticals are described to further explain the properties of the F factor and its potential applications. To demonstrate dosimetric feasibility and advantages of the proposed F factor formalism in systemic radiotherapy, we have performed a retrospective planning study on selected patient case. F factor formalism helps to assess the total activity to be administered to the patient taking into account the heterogeneity in

  3. [VALUES OF WAIST/HIP RATIO AMONG CHILDREN AND ADOLESCENTS FROM BOGOTÁ, COLOMBIA: THE FUPRECOL STUDY].

    PubMed

    Rodríguez-Bautista, Yenni Paola; Correa-Bautista, Jorge Enrique; González-Jiménez, Emilio; Schmidt-RioValle, Jacqueline; Ramírez-Vélez, Robinson

    2015-11-01

    Objetivo: determinar los valores del índice cintura/cadera (ICC) en una población escolar de Bogotá, Colombia, pertenecientes al estudio FUPRECOL. Métodos: estudio descriptivo y transversal, realizado en 3.005 niños y 2.916 adolescentes de entre 9 y 17,9 años de edad, pertenecientes a instituciones educativas oficiales de Bogotá, Colombia. Se tomaron medidas de peso, talla, circunferencia de cintura, circunferencia de cadera y estado de maduración sexual por autorreporte. Se calcularon los percentiles (P3, P10, P25, P50, P75, P90 y P97) según sexo y edad y se realizó una comparación entre los valores del ICC observados y los estándares internacionales. Resultados: de la población general (n = 5.921), el 57,0% eran chicas (promedio de edad 12,7 ± 2,3 años). En todas las edades el ICC fue mayor en los chicos que en las chicas, observándose un descenso en la media de los valores obtenidos desde los 9 hasta los 17,9 años. En los chicos, los valores del ICC mayores del P90 (asociados a riesgo cardiovascular) estuvieron en el rango 0,87 y 0,93 y en las chicas entre 0,85 y 0,89. Al comparar los resultados de este estudio, por grupos de edad y sexo, con trabajos internacionales de niños y adolescentes de Europa, Suramérica, Asia y África, se observa que los valores del ICC fueron menores en este estudio en ambos sexos, con excepción de los escolares originarios de Grecia y Venezuela. Conclusiones: se presentan percentiles del ICC según edad y sexo que podrán ser usados como de referencia en la evaluación del estado nutricional y en la predicción del riesgo cardiovascular desde edades tempranas.

  4. Comparative analysis of 11 different radioisotopes for palliative treatment of bone metastases by computational methods

    SciTech Connect

    Guerra Liberal, Francisco D. C. E-mail: adriana-tavares@msn.com; Tavares, Adriana Alexandre S. E-mail: adriana-tavares@msn.com; Tavares, João Manuel R. S.

    2014-11-01

    Purpose: Throughout the years, the palliative treatment of bone metastases using bone seeking radiotracers has been part of the therapeutic resources used in oncology, but the choice of which bone seeking agent to use is not consensual across sites and limited data are available comparing the characteristics of each radioisotope. Computational simulation is a simple and practical method to study and to compare a variety of radioisotopes for different medical applications, including the palliative treatment of bone metastases. This study aims to evaluate and compare 11 different radioisotopes currently in use or under research for the palliative treatment of bone metastases using computational methods. Methods: Computational models were used to estimate the percentage of deoxyribonucleic acid (DNA) damage (fast Monte Carlo damage algorithm), the probability of correct DNA repair (Monte Carlo excision repair algorithm), and the radiation-induced cellular effects (virtual cell radiobiology algorithm) post-irradiation with selected particles emitted by phosphorus-32 ({sup 32}P), strontium-89 ({sup 89}Sr), yttrium-90 ({sup 90}Y ), tin-117 ({sup 117m}Sn), samarium-153 ({sup 153}Sm), holmium-166 ({sup 166}Ho), thulium-170 ({sup 170}Tm), lutetium-177 ({sup 177}Lu), rhenium-186 ({sup 186}Re), rhenium-188 ({sup 188}Re), and radium-223 ({sup 223}Ra). Results: {sup 223}Ra alpha particles, {sup 177}Lu beta minus particles, and {sup 170}Tm beta minus particles induced the highest cell death of all investigated particles and radioisotopes. The cell survival fraction measured post-irradiation with beta minus particles emitted by {sup 89}Sr and {sup 153}Sm, two of the most frequently used radionuclides in the palliative treatment of bone metastases in clinical routine practice, was higher than {sup 177}Lu beta minus particles and {sup 223}Ra alpha particles. Conclusions: {sup 223}Ra and {sup 177}Lu hold the highest potential for palliative treatment of bone metastases of all

  5. On resonance phase alternated CWFP sequences for rapid and simultaneous measurement of relaxation times.

    PubMed

    Monaretto, Tatiana; Andrade, Fabiana Diuk; Moraes, Tiago Bueno; Souza, Andre Alves; deAzevedo, Eduardo Ribeiro; Colnago, Luiz Alberto

    2015-10-01

    T1 and T2 relaxation times have been frequently used as probes for physical-chemical properties in several time-domain NMR applications (TD-NMR) such as food, polymers and petroleum industries. T2 measurements are usually achieved using the traditional Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence because it is a fast and robust method. On the other hand, the traditional methods for determining T1, i.e., inversion and saturation recovery, are time-consuming, driving several authors to develop rapid 1D and 2D methods to obtain T1 and T2 or T1/T2 ratio. However, these methods usually require sophisticated processing and/or high signal to noise ratio (SNR). This led us to develop simple methods for rapid and simultaneous determination of T1 and T2 using Continuous Wave Free Precession (CWFP) and Carr-Purcell Continuous Wave Free Precession (CP-CWFP) pulse sequences. Nevertheless, a drawback of these sequences is that they require specific adjustment of the frequency offset or the time interval between pulses (Tp). In this paper we present an alternative form of these sequences, named CWFPx-x, CP-CWFPx-x, where a train of π/2 pulses with phases alternated by π enable performing the experiments on-resonance and independently of Tp, when Tp90y-y. In these approaches, the relaxation times are determined using the magnitude of the signals after the first pulse |M0| and in the steady-state |Mss|, as well as the exponential time constant T(∗) to reach the steady-state regime, as in conventional CWFP. CP-CWFPx-x shows the highest dynamic range to measure T(∗) among CWFP sequences and, therefore, is the best technique to measure T1 and T2 since it is less susceptible to SNR and can be performed for any T1/T2 ratio. PMID:26363504

  6. Alpha Production Cross Sections for Some Target Fusion Structural Materials up to 35 MeV

    NASA Astrophysics Data System (ADS)

    Yiğit, M.; Tel, E.

    2013-08-01

    In the next century, because of the worldwide energy shortage, human life will badly be affected. Nuclear fusion energy is the remarkable solution to the rising energy challenges because it has the great potential for sustainability, economic and reliability. There have been many research and development studies to get energy from fusion. Moreover, the neutron induced reaction cross section data around 14-15 MeV are need to the design and development of nuclear fusion reactors. Thus, the working out the systematics of ( n, α) reaction cross sections is very important and necessary for the definition of the excitation curves at around 14-15 MeV energy. In this study, neutron induced reaction cross sections for structural fusion materials such as Sc ( Scandium), Co ( Cobalt), Ni ( Nickel), Cu ( Copper), Y ( Yttrium), Mo ( Molybdenum), Zr ( Zirconium) and Nb ( Niobium) have been investigated for the ( n, α) reactions. The new calculations on the excitation functions of 45 Sc( n, a) 42 K, 59 Co ( n, a) 56 Mn, 62 Ni( n, a) 59 Fe, 63 Cu( n, a) 60 Co, 65 Cu( n, a) 62 Co, 89 Y( n, a) 86 Rb, 92 Mo( n, a) 89 Zr, 98 Mo( n, a) 95 Zr, 92 Zr( n, a) 89 Sr, 94 Zr( n, a) 91 Sr and 93 Nb( n, a) 90 Y reactions have been carried out up to 35 MeV incident neutron energies. In these calculations, the pre-equilibrium and equilibrium effects have been investigated. The pre-equilibrium calculations involve the new evaluated the geometry dependent hybrid model, hybrid model and the cascade exciton model. The equilibrium effects of the excitation functions for the investigated reactions are calculated according to the Weisskopf-Ewing model. Additionaly, in the present work, the ( n, α) reaction cross sections have calculated by using evaluated empirical formulas developed by Tel et al. at 14-15 MeV energy. The calculated results have been discussed and compared with the available experimental data taken from EXFOR database.

  7. Experimental radioimmunotherapy.

    PubMed

    Buchsbaum, D J; Langmuir, V K; Wessels, B W

    1993-01-01

    Radiolabeled monoclonal antibodies have been used for radioimmunotherapy studies with human tumor spheroids and murine and human tumor xenografts in experimental animals. This paper reviews the work that has been performed in these models with different types of cancer, and highlights those papers that have presented dosimetry estimates and attempts to correlate the findings. Radioimmunotherapy studies in multicell spheroids, as a model for micrometastases, have been performed in human neuroblastoma, colon cancer, and melanoma cell lines using 131I-, 125I-, 186Re-, and 212Bi-labeled antibodies. The uniform geometry of the spheroid has allowed radiation dose estimates to be made. Up to three logs of cell kill have been achieved with 131I- and 186Re-specific antibody with minimal toxicity from labeled nonspecific antibody, but 212Bi-antibody had little effect because of its short half-life as shown by Langmuir. It appears that the two most important factors for therapeutic efficacy in this model are good penetration of the radiolabeled antibody and an adequate radionuclide half-life to allow penetration of the immunoconjugate prior to significant radionuclide decay. Radioimmunotherapy studies in animals bearing transplants of colon cancer, leukemia, lymphoma, hepatoma, renal cell carcinoma, neuroblastoma, glioma, mammary carcinoma, small cell lung carcinoma, cervical carcinoma, ovarian carcinoma, and bladder cancer have been performed with 131I, 90Y, 186Re, 153Sm, and 177Lu beta emitting, and 212Bi alpha emitting radionuclides conjugated to monoclonal antibodies. A few studies compared different radionuclides in the same model system. The approaches that have been used in these studies to estimate tumor dosimetry include the MIRD approach, thermoluminescent dosimetry, autoradiography, and comparison to external irradiation. The majority of investigators have estimated the dose to tumor and normal organs using MIRD-based calculations (time-activity curve and

  8. SU-E-CAMPUS-T-06: Radiochromic Film Analysis Based On Principal Components

    SciTech Connect

    Wendt, R

    2014-06-15

    Purpose: An algorithm to convert the color image of scanned EBT2 radiochromic film [Ashland, Covington KY] into a dose map was developed based upon a principal component analysis. The sensitive layer of the EBT2 film is colored so that the background streaks arising from variations in thickness and scanning imperfections may be distinguished by color from the dose in the exposed film. Methods: Doses of 0, 0.94, 1.9, 3.8, 7.8, 16, 32 and 64 Gy were delivered to radiochromic films by contact with a calibrated Sr-90/Y-90 source. They were digitized by a transparency scanner. Optical density images were calculated and analyzed by the method of principal components. The eigenimages of the 0.94 Gy film contained predominantly noise, predominantly background streaking, and background streaking plus the source, respectively, in order from the smallest to the largest eigenvalue. Weighting the second and third eigenimages by −0.574 and 0.819 respectively and summing them plus the constant 0.012 yielded a processed optical density image with negligible background streaking. This same weighted sum was transformed to the red, green and blue space of the scanned images and applied to all of the doses. The curve of processed density in the middle of the source versus applied dose was fit by a twophase association curve. A film was sandwiched between two polystyrene blocks and exposed edge-on to a different Y-90 source. This measurement was modeled with the GATE simulation toolkit [Version 6.2, OpenGATE Collaboration], and the on-axis depth-dose curves were compared. Results: The transformation defined using the principal component analysis of the 0.94 Gy film minimized streaking in the backgrounds of all of the films. The depth-dose curves from the film measurement and simulation are indistinguishable. Conclusion: This algorithm accurately converts EBT2 film images to dose images while reducing noise and minimizing background streaking. Supported by a sponsored research

  9. Amelioration of both early and late radiation-induced damage to pig skin by essential fatty acids

    SciTech Connect

    Hopewell, J.W.; Van den Aardweg, G.J.M.J.; Morris, G.M.

    1994-12-01

    To evaluate the possible role of essential fatty acids, specifically gamma-linolenic and eicosapentaenoic acid, in the amelioration of early and late radiation damage to the skin. Skin sites on the flank of 22-25 kg female large white pigs were irradiated with either single or fractionated doses (20 F/28 days) of {beta}-rays from 22.5 mm diameter {sup 90}Sr/{sup 90}Y plaques at a dose rate of {approximately}3 Gy/min. Essential fatty acids were administered orally in the form of two {open_quotes}active{close_quotes} oils, So-1100 and So-5407, which contained gamma-linolenic acid and a mixture of that oil with eicosapentaenoic acid, respectively. Oils (1.5-6.0 ml) were given daily for 4 weeks prior, both 4 weeks prior and 10-16 weeks after, or in the case of one single dose study, just for 10 weeks after irradiation. Control animals received a {open_quotes}placebo{close_quotes} oil, So-1129, containing no gamma linolenic acid or eicosapentaenoic acid over similar time scales before and after irradiation. Acute and late skin reactions were assessed visually and the dose-related incidence of a specific reaction used to compare the effects of different treatment schedules. A reduction in the severity of both the early and late radiation reactions in the skin was only observed when {open_quotes}active{close_quotes} oils were given over the time course of the expression of radiation damage. Prior treatment with oils did not modify the radiation reaction. A 3.0 ml daily dose of either So-1100 or So-5407 given prior to, but also after irradiation with single and fractionated doses of {beta}-rays produced the most significant modification to the radiation reactions, effects consistent with dose modification factors between 1.06-1.24 for the acute reactions of bright red erythema and/or moist desquamation, and of 1.14-1.35 for the late reactions of dusky/mauve erythema and dermal necrosis. 38 refs., 5 tabs.

  10. Possible time-dependent sensitization to xenobiotics: self-reported illness from chemical odors, foods, and opiate drugs in an older adult population.

    PubMed

    Bell, I R; Schwartz, G E; Peterson, J M; Amend, D; Stini, W A

    1993-01-01

    The present paper summarizes key features of time-dependent sensitization (TDS) in neuropharmacology (progressive amplification of behavioral, neuronal, endocrine, and/or immune responses to repeated intermittent exposures to an environmental agent or cross-sensitizing agents) as a possible model for cacosmia (subjective sense of feeling ill from low levels of environmental chemical odors) in nonindustrial and industrial populations; and extends previous cacosmia research in nonpatient populations to an elderly sample. This study examined the symptom and psychological profiles of 263 older adults (aged 60-90 y, 71% women, 29% men); 57% reported that at least one chemical and 17% reported that at least four of five chemicals (pesticide, automobile exhaust, paint, new carpet, perfume) made them feel ill. Cacosmia ratings correlated weakly and negatively with age (r = -0.19, p = .001) over the whole sample. Cacosmia correlated significantly with self-reported illness from foods that may mobilize or generate opioid peptides (wheat, dairy, eggs) (r = 0.32, p < .0001) and with illness from opiate drugs (r = 0.23, p < .0001). When the sample was divided into four cells on the basis of above-versus below-median total chemical-induced illness score (CI) and total food-induced illness score (FI), the high CI and high FI, high CI only, and high FI only groups had more frequent indigestion, and the high CI group had more frequent difficulty concentrating than the groups below median for illness from both chemicals and foods (NOILL), even after covarying for age and anxiety. The most cacosmic subjects noted higher prevalence of physician-diagnosed allergies and irritable bowel than did noncacosmic subjects. In contrast with previous young adult cohort studies, the older illness groups did not differ with regard to sex distribution, depression, shyness, or repressive defensiveness. When considered with prior surveys of young adults, the present findings are consistent with the

  11. The NUKDOS software for treatment planning in molecular radiotherapy.

    PubMed

    Kletting, Peter; Schimmel, Sebastian; Hänscheid, Heribert; Luster, Markus; Fernández, Maria; Nosske, Dietmar; Lassmann, Michael; Glatting, Gerhard

    2015-09-01

    The aim of this work was the development of a software tool for treatment planning prior to molecular radiotherapy, which comprises all functionality to objectively determine the activity to administer and the pertaining absorbed doses (including the corresponding error) based on a series of gamma camera images and one SPECT/CT or probe data. NUKDOS was developed in MATLAB. The workflow is based on the MIRD formalism For determination of the tissue or organ pharmacokinetics, gamma camera images as well as probe, urine, serum and blood activity data can be processed. To estimate the time-integrated activity coefficients (TIAC), sums of exponentials are fitted to the time activity data and integrated analytically. To obtain the TIAC on the voxel level, the voxel activity distribution from the quantitative 3D SPECT/CT (or PET/CT) is used for scaling and weighting the TIAC derived from the 2D organ data. The voxel S-values are automatically calculated based on the voxel-size of the image and the therapeutic nuclide ((90)Y, (131)I or (177)Lu). The absorbed dose coefficients are computed by convolution of the voxel TIAC and the voxel S-values. The activity to administer and the pertaining absorbed doses are determined by entering the absorbed dose for the organ at risk. The overall error of the calculated absorbed doses is determined by Gaussian error propagation. NUKDOS was tested for the operation systems Windows(®) 7 (64 Bit) and 8 (64 Bit). The results of each working step were compared to commercially available (SAAMII, OLINDA/EXM) and in-house (UlmDOS) software. The application of the software is demonstrated using examples form peptide receptor radionuclide therapy (PRRT) and from radioiodine therapy of benign thyroid diseases. For the example from PRRT, the calculated activity to administer differed by 4% comparing NUKDOS and the final result using UlmDos, SAAMII and OLINDA/EXM sequentially. The absorbed dose for the spleen and tumour differed by 7% and 8

  12. Considerations of anthropometric, tissue volume, and tissue mass scaling for improved patient specificity of skeletal S values.

    PubMed

    Bolch, W E; Patton, R W; Shah, A R; Rajon, D A; Jokisch, D W

    2002-06-01

    It is generally acknowledged that reference man (70 kg in mass and 170 cm in height) does not adequately represent the stature and physical dimensions of many patients undergoing radionuclide therapy, and thus scaling of radionuclide S values is required for patient specificity. For electron and beta sources uniformly distributed within internal organs, the mean dose from self-irradiation is noted to scale inversely with organ mass, provided no escape of electron energy occurs at the organ boundaries. In the skeleton, this same scaling approach is further assumed to be correct for marrow dosimetry; nevertheless, difficulties in quantitative assessments of marrow mass in specific skeletal regions of the patient make this approach difficult to implement clinically. Instead, scaling of marrow dose is achieved using various anthropometric parameters that presumably scale in the same proportion. In this study, recently developed three-dimensional macrostructural transport models of the femoral head and humeral epiphysis in three individuals (51-year male, 82-year female, and 86-year female) are used to test the abilities of different anthropometric parameters (total body mass, body surface area, etc.) to properly scale radionuclide S values from reference man models. The radionuclides considered are 33P, 177Lu, 153Sm, 186Re, 89Sr, 166Ho, 32P, 188Re, and 90Y localized in either the active marrow or endosteal tissues of the bone trabeculae. S value scaling is additionally conducted in which the 51-year male subject is assigned as the reference individual; scaling parameters are then expanded to include tissue volumes and masses for both active marrow and skeletal spongiosa. The study concludes that, while no single anthropometric parameter emerges as a consistent scaler of reference man S values, lean body mass is indicated as an optimal scaler when the reference S values are based on 3D transport techniques. Furthermore, very exact patient-specific scaling of

  13. Insecticidal genes of Yersinia spp.: taxonomical distribution, contribution to toxicity towards Manduca sexta and Galleria mellonella, and evolution

    PubMed Central

    Fuchs, Thilo M; Bresolin, Geraldine; Marcinowski, Lisa; Schachtner, Joachim; Scherer, Siegfried

    2008-01-01

    Background Toxin complex (Tc) proteins termed TcaABC, TcdAB, and TccABC with insecticidal activity are present in a variety of bacteria including the yersiniae. Results The tc gene sequences of thirteen Yersinia strains were compared, revealing a high degree of gene order conservation, but also remarkable differences with respect to pseudogenes, sequence variability and gene duplications. Outside the tc pathogenicity island (tc-PAIYe) of Y. enterocolitica strain W22703, a pseudogene (tccC2'/3') encoding proteins with homology to TccC and similarity to tyrosine phosphatases at its C-terminus was identified. PCR analysis revealed the presence of the tc-PAIYe and of tccC2'/3'-homologues in all biotype 2–5 strains tested, and their absence in most representatives of biotypes 1A and 1B. Phylogenetic analysis of 39 TccC sequences indicates the presence of the tc-PAIYe in an ancestor of Yersinia. Oral uptake experiments with Manduca sexta revealed a higher larvae lethality of Yersinia strains harbouring the tc-PAIYe in comparison to strains lacking this island. Following subcutaneous infection of Galleria mellonella larvae with five non-human pathogenic Yersinia spp. and four Y. enterocolitica strains, we observed a remarkable variability of their insecticidal activity ranging from 20% (Y. kristensenii) to 90% (Y. enterocolitica strain 2594) dead larvae after five days. Strain W22703 and its tcaA deletion mutant did not exhibit a significantly different toxicity towards G. mellonella. These data confirm a role of TcaA upon oral uptake only, and suggest the presence of further insecticidal determinants in Yersinia strains formerly unknown to kill insects. Conclusion This study investigated the tc gene distribution among yersiniae and the phylogenetic relationship between TccC proteins, thus contributing novel aspects to the current discussion about the evolution of insecticidal toxins in the genus Yersinia. The toxic potential of several Yersinia spp. towards M. sexta

  14. On resonance phase alternated CWFP sequences for rapid and simultaneous measurement of relaxation times

    NASA Astrophysics Data System (ADS)

    Monaretto, Tatiana; Andrade, Fabiana Diuk; Moraes, Tiago Bueno; Souza, Andre Alves; deAzevedo, Eduardo Ribeiro; Colnago, Luiz Alberto

    2015-10-01

    T1 and T2 relaxation times have been frequently used as probes for physical-chemical properties in several time-domain NMR applications (TD-NMR) such as food, polymers and petroleum industries. T2 measurements are usually achieved using the traditional Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence because it is a fast and robust method. On the other hand, the traditional methods for determining T1, i.e., inversion and saturation recovery, are time-consuming, driving several authors to develop rapid 1D and 2D methods to obtain T1 and T2 or T1/T2 ratio. However, these methods usually require sophisticated processing and/or high signal to noise ratio (SNR). This led us to develop simple methods for rapid and simultaneous determination of T1 and T2 using Continuous Wave Free Precession (CWFP) and Carr-Purcell Continuous Wave Free Precession (CP-CWFP) pulse sequences. Nevertheless, a drawback of these sequences is that they require specific adjustment of the frequency offset or the time interval between pulses (Tp). In this paper we present an alternative form of these sequences, named CWFPx-x, CP-CWFPx-x, where a train of π/2 pulses with phases alternated by π enable performing the experiments on-resonance and independently of Tp, when Tp < T2∗. Moreover, a CPMG type sequence with π/2 refocusing pulses shows similar results to CP-CWFP when the pulses are alternated between y and -y axis, CPMG90y-y. In these approaches, the relaxation times are determined using the magnitude of the signals after the first pulse |M0| and in the steady-state |Mss|, as well as the exponential time constant T∗ to reach the steady-state regime, as in conventional CWFP. CP-CWFPx-x shows the highest dynamic range to measure T∗ among CWFP sequences and, therefore, is the best technique to measure T1 and T2 since it is less susceptible to SNR and can be performed for any T1/T2 ratio.

  15. Lutetium-177 DOTATATE Production with an Automated Radiopharmaceutical Synthesis System

    PubMed Central

    Aslani, Alireza; Snowdon, Graeme M; Bailey, Dale L; Schembri, Geoffrey P; Bailey, Elizabeth A; Pavlakis, Nick; Roach, Paul J

    2015-01-01

    Objective(s): Peptide Receptor Radionuclide Therapy (PRRT) with yttrium-90 (90Y) and lutetium-177 (177Lu)-labelled SST analogues are now therapy option for patients who have failed to respond to conventional medical therapy. In-house production with automated PRRT synthesis systems have clear advantages over manual methods resulting in increasing use in hospital-based radiopharmacies. We report on our one year experience with an automated radiopharmaceutical synthesis system. Methods: All syntheses were carried out using the Eckert & Ziegler Eurotope’s Modular-Lab Pharm Tracer® automated synthesis system. All materials and methods used were followed as instructed by the manufacturer of the system (Eckert & Ziegler Eurotope, Berlin, Germany). Sterile, GMP-certified, no-carrier added (NCA) 177Lu was used with GMP-certified peptide. An audit trail was also produced and saved by the system. The quality of the final product was assessed after each synthesis by ITLC-SG and HPLC methods. Results: A total of 17 [177Lu]-DOTATATE syntheses were performed between August 2013 and December 2014. The amount of radioactive [177Lu]-DOTATATE produced by each synthesis varied between 10-40 GBq and was dependant on the number of patients being treated on a given day. Thirteen individuals received a total of 37 individual treatment administrations in this period. There were no issues and failures with the system or the synthesis cassettes. The average radiochemical purity as determined by ITLC was above 99% (99.8 ± 0.05%) and the average radiochemical purity as determined by HPLC technique was above 97% (97.3 ± 1.5%) for this period. Conclusions: The automated synthesis of [177Lu]-DOTATATE using Eckert & Ziegler Eurotope’s Modular-Lab Pharm Tracer® system is a robust, convenient and high yield approach to the radiolabelling of DOTATATE peptide benefiting from the use of NCA 177Lu and almost negligible radiation exposure of the operators. PMID:27408890

  16. Concordant 241Pu-241Am Dating of Environmental Samples: Results from Forest Fire Ash

    NASA Astrophysics Data System (ADS)

    Goldstein, S. J.; Oldham, W. J.; Murrell, M. T.; Katzman, D.

    2010-12-01

    We have measured the Pu, 237Np, 241Am, and 151Sm isotopic systematics for a set of forest fire ash samples from various locations in the western U.S. including Montana, Wyoming, Idaho, and New Mexico. The goal of this study is to develop a concordant 241Pu (t1/2 = 14.4 y)-241Am dating method for environmental collections. Environmental samples often contain mixtures of components including global fallout. There are a number of approaches for subtracting the global fallout component for such samples. One approach is to use 242Pu/239Pu as a normalizing isotope ratio in a three-isotope plot, where this ratio for the non-global fallout component can be estimated or assumed to be small. This study investigates a new, complementary method of normalization using the long-lived fission product, 151Sm (t1/2 = 90 y). We find that forest fire ash concentrates actinides and fission products with ~1E10 atoms 239Pu/g and ~1E8 atoms 151Sm/g, allowing us to measure these nuclides by mass spectrometric (MIC-TIMS) and radiometric (liquid scintillation counting) methods. The forest fire ash samples are characterized by a western U.S. regional isotopic signature representing varying mixtures of global fallout with a local component from atmospheric testing of nuclear weapons at the Nevada Test Site (NTS). Our results also show that 151Sm is well correlated with the Pu nuclides in the forest fire ash, suggesting that these nuclides have similar geochemical behavior in the environment. Results of this correlation indicate that the 151Sm/239Pu atom ratio for global fallout is ~0.164, in agreement with an independent estimate of 0.165 based on 137Cs fission yields for atmospheric weapons tests at the NTS. 241Pu-241Am dating of the non-global fallout component in the forest fire ash samples yield ages in the late 1950’s-early 1960’s, consistent with a peak in NTS weapons testing at that time. The age results for this component are in agreement using both 242Pu and 151Sm normalizations

  17. RADAR Realistic Animal Model Series for Dose Assessment

    PubMed Central

    Keenan, Mary A.; Stabin, Michael G.; Segars, William P.; Fernald, Michael J.

    2010-01-01

    these small-sized organs, and measurable cross-irradiation was observed for many organ pairs for highenergy electrons (as would be emitted by nuclides such as 32P, 90Y, or 188Re). PMID:20197451

  18. SU-E-T-264: Preliminary Results On New Optically Stimulated Luminescent Materials for Proton Therapy Dosimetry

    SciTech Connect

    Doull, B; Zheng, Y; Yukihara, E

    2014-06-01

    Purpose: The objective of this work is to test the premise that luminescence materials with less under-response to proton beams can be identified by testing their dose response to low-LET radiation. The goal is to develop new Optically Stimulated Luminescence (OSL) materials with improved response for proton therapy dosimetry. Methods: We first measured the dose response of new OSL materials, synthesized in our laboratory, to low-LET radiation (beta rays from a {sup 90}Sr/{sup 90}Y source) and selected two materials having different OSL saturation characteristics and good dosimetric properties, namely MgB4O7:Ce,Li and MgO:Li. Commercial Al2O3:C was also used for comparison. These materials were then irradiated at several depths along a pristine proton beam. The luminescence responses of the materials, relative to the entrance response, were compared with the depth dose profile measured by a multiple-layer ion chamber. Results: The OSL signals of MgB4O7:Ce,Li and MgO:Li were characterized for signal stability, dose response, and response to a clinical proton beam. The materials were also compared with the commercial Al2O3:C. The signals from both MgB4O7:Ce,Li and MgO:Li were relatively stable after a one day delay following irradiation. The low-LET dose response of the materials showed that, over the dose range investigated (up to ∼800 Gy), MgB4O7:Ce,Li did not saturate, whereas MgO:Li and Al2O3:C saturated at doses of ∼100 Gy. MgB4O7:Ce,Li showed less underresponse to proton beams than MgO:Li and Al2O3:C. Conclusion: In general the material with the highest saturation doses for low-LET radiation (MgB4O7:Ce,Li) showed the least under-response to proton beams, which suggests that it may be possible to develop better OSL materials for proton dosimetry if the dose response can be controlled during synthesis. Nevertheless, the degree in which the response to proton beams can be controlled remains to be determined. The research is funded by the Oklahoma Center for

  19. BioChroma – A New and Patented Technology for Processing Radioactive Wastewater from Nuclear Medicine Therapy Facilities in Hospitals and Clinics

    PubMed Central

    Rodríguez, José Canga

    2012-01-01

    After undergoing radionuclide therapy, patients generate wastewater with a considerable amount of radioactivity, which can reach levels of as much as 90% of the administered dose. Due to the risk of accumulation after discharge into the sewer, it is advisable to collect this effluent for its treatment prior to final discharge. Delay and decay (natural decomposition of the isotope) is the most commonly used technical method of abating radioactive iodine, but it is frequently criticized as being complex and very expensive. BioChroma is a technology that has been developed as an alternative to these complicated and expensive systems. This paper describes this new technology and presents, as an example, a system that was installed and successfully commissioned in the middle of 2008 in a nuclear medicine ward with 12 beds in Stuttgart (Germany). Based on existing legislation, the responsible authorities and the company that operated the hospital agreed on a maximum activity level of 5 Bq/l. If a typical delay and decay system would have been installed, the 180 m3 treatment plant that was already available in the hospital cellar would have to be extended by additional 150 m3. By implementing the patented BioChroma process, the space requirements were reduced by 75%. For instance, since the new system was integrated into the existing installation, tanks accounting for 120 m³ could be used as buffering volume in the new wastewater treatment plant. The operation of the referred plant is currently producing very good results with values below the specified limit of 5 Bq/l for the isotope 131I. In addition, 90Y has been reported to be eliminated at the same time. Over the past 2 years of operation, the wastewater treatment plant has been able to achieve a maximum processing capacity of more than 2,000 l/day, which equates to a nuclear medicine ward with approx. 20 beds. The highest level recorded during the test period (of 180 days after start-up) was a peak of nearly 2

  20. BioChroma - A New and Patented Technology for Processing Radioactive Wastewater from Nuclear Medicine Therapy Facilities in Hospitals and Clinics.

    PubMed

    Rodríguez, José Canga

    2012-01-01

    After undergoing radionuclide therapy, patients generate wastewater with a considerable amount of radioactivity, which can reach levels of as much as 90% of the administered dose. Due to the risk of accumulation after discharge into the sewer, it is advisable to collect this effluent for its treatment prior to final discharge. Delay and decay (natural decomposition of the isotope) is the most commonly used technical method of abating radioactive iodine, but it is frequently criticized as being complex and very expensive. BioChroma is a technology that has been developed as an alternative to these complicated and expensive systems. This paper describes this new technology and presents, as an example, a system that was installed and successfully commissioned in the middle of 2008 in a nuclear medicine ward with 12 beds in Stuttgart (Germany). Based on existing legislation, the responsible authorities and the company that operated the hospital agreed on a maximum activity level of 5 Bq/l. If a typical delay and decay system would have been installed, the 180 m(3) treatment plant that was already available in the hospital cellar would have to be extended by additional 150 m(3). By implementing the patented BioChroma process, the space requirements were reduced by 75%. For instance, since the new system was integrated into the existing installation, tanks accounting for 120 m³ could be used as buffering volume in the new wastewater treatment plant. The operation of the referred plant is currently producing very good results with values below the specified limit of 5 Bq/l for the isotope (131)I. In addition, (90)Y has been reported to be eliminated at the same time. Over the past 2 years of operation, the wastewater treatment plant has been able to achieve a maximum processing capacity of more than 2,000 l/day, which equates to a nuclear medicine ward with approx. 20 beds. The highest level recorded during the test period (of 180 days after start-up) was a peak of

  1. Skeletal dosimetry in a voxel-based rat phantom for internal exposures to photons and electrons

    SciTech Connect

    Xie Tianwu; Han Dao; Liu Yang; Sun Wenjuan; Liu Qian

    2010-05-15

    Purpose: The skeleton makes a significant contribution to the whole body absorbed dose evaluation of rats, since the bone marrow and bone surface in the skeleton express high radiosensitivity and are considered to be important dose-limiting tissues. The bone marrow can be categorized as red bone marrow (RBM) and yellow bone marrow (YBM). It is important to investigate the bone marrow in skeletal dosimetry. Methods: Cryosectional color images of the skeleton of a 156 g rat were segmented into mineral bone (including cortical bone and trabecular bone), RBM, and YBM. These three tissue types were identified at 40 different bone sites and integrated into a previously developed voxel-based rat computational phantom. Photon and electron skeletal absorbed fractions were then calculated using the MCNPX Monte Carlo code. Results: Absorbed fraction (AF) and specific absorbed fraction (SAF) for mineral bone, RBM, and YBM at the 40 different bone sites were established for monoenergetic photon and electron sources placed in 18 organs and seven bone sites. Discrete photon energy was varied from 0.01 to 5.0 MeV in 21 discrete steps, while 21 discrete electron energies were studied, from 0.1 to 10.0 MeV. The trends and values found were consistent with the results of other researchers [M. G. Stabin, T. E. Peterson, G. E. Holburn, and M. A. Emmons, ''Voxel-based mouse and rat models for internal dose calculations,'' J. Nucl. Med. 47, 655-659 (2006)]. S-factors for the radionuclides {sup 169}Er, {sup 143}Pr, {sup 89}Sr, {sup 32}P, and {sup 90}Y, located in 18 organs and seven bone sites for the skeleton, were calculated and are provided in detail. Conclusions: For internal dose calculations, the AF data reveal that the mineral bone in the rat skeletal system is responsible for significant attenuation of gamma rays, especially at low energies. The photon SAF curves of RBM show that, for photon energies greater than 0.6 MeV, there is an increase in secondary photons emitted from the

  2. Dosimetry for Radiopharmaceutical Therapy

    PubMed Central

    Sgouros, George; Hobbs, Robert F.

    2014-01-01

    Radiopharmaceutical therapy (RPT) involves the use of radionuclides that are either conjugated to tumor-targeting agents (eg, nanoscale constructs, antibodies, peptides, and small molecules) or concentrated in tissue through natural physiological mechanisms that occur predominantly in neoplastic or otherwise targeted cells (eg, Graves disease). The ability to collect pharmacokinetic data by imaging and use this to perform dosimetry calculations for treatment planning distinguishes RPT from other systemic treatment modalities. Treatment planning has not been widely adopted, in part, because early attempts to relate dosimetry to outcome were not successful. This was partially because a dosimetry methodology appropriate to risk evaluation rather than efficacy and toxicity was being applied to RPT. The weakest links in both diagnostic and therapeutic dosimetry are the accuracy of the input and the reliability of the radiobiological models used to convert dosimetric data to the relevant biologic end points. Dosimetry for RPT places a greater demand on both of these weak links. To date, most dosimetric studies have been retrospective, with a focus on tumor dose-response correlations rather than prospective treatment planning. In this regard, transarterial radioembolization also known as intra-arterial radiation therapy, which uses radiolabeled (90Y) microspheres of glass or resin to treat lesions in the liver holds much promise for more widespread dosimetric treatment planning. The recent interest in RPT with alpha-particle emitters has highlighted the need to adopt a dosimetry methodology that specifically accounts for the unique aspects of alpha particles. The short range of alpha-particle emitters means that in cases in which the distribution of activity is localized to specific functional components or cell types of an organ, the absorbed dose will be equally localized and dosimetric calculations on the scale of organs or even voxels (~5 mm) are no longer sufficient

  3. Improved dosimetry techniques for intravascular brachytherapy

    NASA Astrophysics Data System (ADS)

    Sehgal, Varun

    Coronary artery disease leads to the accumulation of atheromatous plaque leading to coronary stenosis. Coronary intervention techniques such as balloon angioplasty and atherectomy are used to address coronary stenosis and establish a stable lumen thus enhancing blood flow to the myocardium. Restenosis or re-blockage of the arteries is a major limitation of the above mentioned interventional techniques. Neointimal hyperplasia or proliferation of cells in response to the vascular injury as a result of coronary intervention is considered to be one of the major causes of restenosis. Recent studies indicated that irradiation of the coronary lesion site, with radiation doses ranging from 15 to 30 Gy, leads to diminishing neointimal hyperplasia with subsequent reduction in restenosis. The radiation dose is given by catheter-based radiation delivery systems using beta-emitters 90Sr/90Y, 32P and gamma-emitting 192Ir among others. However the dose schema used for dose prescription for these sources are relatively simplistic, and are based on calculations using uniform homogenous water or tissue media and simple cylinder geometry. Stenotic coronary vessels are invariably lined with atheromatous plaque of heterogeneous composition, the radiation dose distribution obtained from such dosimetry data can cause significant variations in the actual dose received by a given patient. Such discrepancies in dose calculation can introduce relatively large uncertainties in the limits of dose window for effective and safe application of intravascular brachytherapy, and consequently in the clinical evaluation of the efficacy of this modality. In this research study we investigated the effect of different geometrical and material heterogeneities, including residual plaque, catheter non-centering, lesion eccentricity and cardiac motion on the radiation dose delivered at the lesion site. Correction factors including dose perturbation factors and dose variation factors have been calculated

  4. SU-E-CAMPUS-I-06: Y90 PET/CT for the Instantaneous Determination of Both Target and Non-Target Absorbed Doses Following Hepatic Radioembolization

    SciTech Connect

    Pasciak, A; Kao, J

    2014-06-15

    Purpose The process of converting Yttrium-90 (Y90) PET/CT images into 3D absorbed dose maps will be explained. The simple methods presented will allow the medical physicst to analyze Y90 PET images following radioembolization and determine the absorbed dose to tumor, normal liver parenchyma and other areas of interest, without application of Monte-Carlo radiation transport or dose-point-kernel (DPK) convolution. Methods Absorbed dose can be computed from Y90 PET/CT images based on the premise that radioembolization is a permanent implant with a constant relative activity distribution after infusion. Many Y90 PET/CT publications have used DPK convolution to obtain 3D absorbed dose maps. However, this method requires specialized software limiting clinical utility. The Local Deposition method, an alternative to DPK convolution, can be used to obtain absorbed dose and requires no additional computer processing. Pixel values from regions of interest drawn on Y90 PET/CT images can be converted to absorbed dose (Gy) by multiplication with a scalar constant. Results There is evidence that suggests the Local Deposition method may actually be more accurate than DPK convolution and it has been successfully used in a recent Y90 PET/CT publication. We have analytically compared dose-volume-histograms (DVH) for phantom hot-spheres to determine the difference between the DPK and Local Deposition methods, as a function of PET scanner point-spread-function for Y90. We have found that for PET/CT systems with a FWHM greater than 3.0 mm when imaging Y90, the Local Deposition Method provides a more accurate representation of DVH, regardless of target size than DPK convolution. Conclusion Using the Local Deposition Method, post-radioembolization Y90 PET/CT images can be transformed into 3D absorbed dose maps of the liver. An interventional radiologist or a Medical Physicist can perform this transformation in a clinical setting, allowing for rapid prediction of treatment efficacy by

  5. [In Process Citation].

    PubMed

    Vivas-Díaz, José Andrés; Ramírez-Vélez, Robinson; Correa-Bautista, Jorge Enrique; Izquierdo, Mikel

    2016-03-25

    Introducción: la evaluación de la fuerza de prensión realizada comúnmente mediante dinamometría manual actualmente es considerada como un indicador del estado nutricional y como un marcador temprano en la morbimortalidad de la enfermedad cardiometabólica. Objetivos: en este estudio, se presentan valores de la fuerza prensil por dinamometría manual en una muestra de estudiantes universitarios de Colombia. Método: estudio descriptivo y transversal realizado en 5.647 estudiantes universitarios aparentemente sanos (58,5% mujeres, edad media 20,6 ± 2,7 años) pertenecientes a instituciones privadas y públicas de Bogotá y Cali (Colombia). La fuerza prensil se midió utilizando dinamómetro manual, ajustado para cada individuo según el tamaño de la mano. Se calcularon percentiles (P 3 , P 10 , P 25 , P 50 , P 75 , P 90 y P 97 ) y curvas centiles ajustado por edad y sexo. Resultados: el valor medio de fuerza prensil fue significativamente mayor en los hombres (37,1 ± 8,3 kg) en comparación con las mujeres (24.2 ± 8.1 kg) (p < 0,001). En ambos sexos, la fuerza prensil aumentó con la edad y fue significativamente mayor y homogénea en los hombres en todas las categorías de edad. Adicionalmente, se presentan tablas de referencia que pueden ser empleadas para identificar estudiantes con niveles de fuerza saludable. Conclusión: este trabajo puede ser tenido en cuenta como referencia para estudiar las tendencias seculares y las variaciones de la fuerza prensil en universitarios y para identificar puntos de corte clínicamente relevantes en el estado nutricional y como un marcador de manifestaciones tempranas asociadas a la enfermedad cardiometabólica en la población Suramericana.

  6. Discriminatory power of indicators predictors of visceral adiposity evaluated by computed tomography in adults and elderly individuals.

    PubMed

    Carneiro Roriz, Anna Karla; Santana Passos, Luiz Carlos; Cunha de Oliveira, Carolina; Eickemberg, Michaela; de Almeida Moreira, Pricilla; Ramos Sampaio, Lílian

    2014-06-01

    Introducción: La identificación de métodos antropométricos de adiposidad abdominal, los predictores de exceso del tejido adiposo visceral (TAV) permiten una evaluación rápida y de bajo costo del riesgo de enfermedades cardiovasculares en ancianos. Objetivo: Evaluar el poder discriminatorio de los indicadores antropométricos para la detección de exceso del tejido adiposo visceral. Métodos: Estudio transversal compuesto por 194 adultos y ancianos para la comparación entre ambos sexos y por grupos de edad. Las variables antropométricas: Razón cintura/estatura (RCE), Razón cintura/muslo (RCM), el Índice Diámetro Abdominal (SAD/muslo) e el Índice diámetro abdominal altura (SAD/estatura). El área TAV fue identificado por tomografía computarizada. Análisis con la curva ROC. Resultados: Se observó una alta correlación entre el área del tejido adiposo visceral y la mayoría de los indicadores antropométricos (p ≤0,001). Entre los hombres de edad avanzada, la razón cintura/estatura mostró áreas bajo la curva ROC por encima de 0,90 y puntos de corte de 0,55 (sens: 85,7%, espec: 82,4%, VPP: 99,9%). Para las mujeres de edad avanzada, el corte fue de 0,58 (sens: 81,0%, espec: 78,6%). Para SAD/estatura, las áreas bajo la curva ROC fueron ≥0,83 (p ≤0,01), con puntos de corte de 0,12 para hombres y 0,13 para las mujeres. Conclusión: Había se ha observado un fuerte poder discriminatorio de los indicadores antropométricos de obesidad abdominal visceral. La Razón cintura/altura y el diámetro abdominal estatura mostraron un mejor desempeño para predecir la área de TAV de riesgo en los ancianos, sin la necesidad de medirla por tomografía computarizada.

  7. Evaluating the purity of a {sup 57}Co flood source by PET

    SciTech Connect

    DiFilippo, Frank P.

    2014-11-01

    Purpose: Flood sources of {sup 57}Co are commonly used for quality control of gamma cameras. Flood uniformity may be affected by the contaminants {sup 56}Co and {sup 58}Co, which emit higher energy photons. Although vendors specify a maximum combined {sup 56}Co and {sup 58}Co activity, a convenient test for flood source purity that is feasible in a clinical environment would be desirable. Methods: Both {sup 56}Co and {sup 58}Co emit positrons with branching 19.6% and 14.9%, respectively. As is known from {sup 90}Y imaging, a positron emission tomography (PET) scanner is capable of quantitatively imaging very weak positron emission in a high single-photon background. To evaluate this approach, two {sup 57}Co flood sources were scanned with a clinical PET/CT multiple times over a period of months. The {sup 56}Co and {sup 58}Co activity was clearly visible in the reconstructed PET images. Total impurity activity was quantified from the PET images after background subtraction of prompt gamma coincidences. Results: Time-of-flight PET reconstruction was highly beneficial for accurate image quantification. Repeated measurements of the positron-emitting impurities showed excellent agreement with an exponential decay model. For both flood sources studied, the fit parameters indicated a zero intercept and a decay half-life consistent with a mixture of {sup 56}Co and {sup 58}Co. The total impurity activity at the reference date was estimated to be 0.06% and 0.07% for the two sources, which was consistent with the vendor’s specification of <0.12%. Conclusions: The robustness of the repeated measurements and a thorough analysis of the detector corrections and physics suggest that the accuracy is acceptable and that the technique is feasible. Further work is needed to validate the accuracy of this technique with a calibrated high resolution gamma spectrometer as a gold standard, which was not available for this study, and for other PET detector models.

  8. Radioanalytical Chemistry for Automated Nuclear Waste Process Monitoring

    SciTech Connect

    Devol, Timothy A.

    2005-06-01

    Comparison of different pulse shape discrimination methods was performed under two different experimental conditions and the best method was identified. Beta/gamma discrimination of 90Sr/90Y and 137Cs was performed using a phoswich detector made of BC400 (2.5 cm OD x 1.2 cm) and BGO (2.5 cm O.D. x 2.5 cm ) scintillators. Alpha/gamma discrimination of 210Po and 137Cs was performed using a CsI:Tl (2.8 x 1.4 x 1.4 cm3) scintillation crystal. The pulse waveforms were digitized with a DGF-4c (X-Ray Instrumentation Associates) and analyzed offline with IGOR Pro software (Wavemetrics, Inc.). The four pulse shape discrimination methods that were compared include: rise time discrimination, digital constant fraction discrimination, charge ratio, and constant time discrimination (CTD) methods. The CTD method is the ratio of the pulse height at a particular time after the beginning of the pulse to the time at the maximum pulse height. The charge comparison method resulted in a Figure of Merit (FoM) of 3.3 (9.9 % spillover) and 3.7 (0.033 % spillover) for the phoswich and the CsI:Tl scintillator setups, respectively. The CTD method resulted in a FoM of 3.9 (9.2 % spillover) and 3.2 (0.25 % spillover), respectively. Inverting the pulse shape data typically resulted in a significantly higher FoM than conventional methods, but there was no reduction in % spillover values. This outcome illustrates that the FoM may not be a good scheme for the quantification of a system to perform pulse shape discrimination. Comparison of several pulse shape discrimination (PSD) methods was performed as a means to compare traditional analog and digital PSD methods on the same scintillation pulses. The X-ray Instrumentation Associates DGF-4C (40 Msps, 14-bit) was used to digitize waveforms from a CsI:Tl crystal and BC400/BGO phoswich detector.

  9. Endovenous laser therapy for occlusion of incompetent saphenous veins using 1940nm

    NASA Astrophysics Data System (ADS)

    Sroka, Ronald; Pongratz, Thomas; Esipova, Anna; Dikic, Slobodan; Demhasaj, Sahit; Comsa, Florin; Schmedt, Claus-Georg

    2015-07-01

    Objective: Several studies indicate that ELT using wavelengths of high water absorption showed advantages compared to conventional ELT. Thulium-Lasers emit nearby the local absorption maximum of water at 1940nm. In this clinical study the effectiveness, safety and the feasibility of 1940nm-ELT is proven. Materials and Method: A single centric, prospective observational study was performed. 1940nm-laserenergy was applied using radial emitting fibres with continuous pullback (1mm/s). Treatment was performed under anesthesia (general, spinal, tumescent) thus simultaneous miniphlebectomy and ligation of perforators could be applied. Patient and technical details were systematically collected. Evaluation included: standardized questionnaire, clinical examination, color-duplex ultrasonography preoperatively, 3d, 4w, 6m postoperatively, statistic. Results: The 1940nm-ELT study include 55 patients (female/men=34/21, mean age 55y, range 23-90y) treating n=72 vessels. The mean maximum diameter of great saphenous veins (GSV, n=59) was 7.5mm (range 3.7-11.3mm) and of small saphenous veins (SSV, n=13) was 5.3mm (3.0-10.0mm). The mean applied longitudinal endovenous energy density (LEED) was 64.3J/cm (40.3-98.2J/cm) in GSVs and 51.0J/cm (37.6-72.7J/cm) in SSVs. Complete occlusion of the vein without sign of reflux was achieved in 100%. The mean length of non-occluded stump at the sapheno-femoral junction was 6.0mm (1.0-20.0mm). Postoperative reduction of the diameter of GSV was 1.6mm (21.3%) and 2.0mm (37.7%) in SSV. One (1.4%) endovenous heat induced thrombus (EHIT) was observed. Further adverse events were: paresthesia 10/72 (13.9%), ecchymosis 1/72 (1.4%), lymphocele 1/72 (1.4%), hyperpigmentation 1/72 (1.4%). The mean postoperative pain intensity was 1.3 and 1.8 single doses of analgesics were administered. Normal physical activity was reached after 3d (1-21d). Conclusion: 1940nm-ELT using radial light application effectively eliminates the reflux in insufficient saphenous

  10. [Assessment of pulmonary complications in renal transplantation through the use of radiography].

    PubMed

    Ramírez-García, Laura Elena; Juárez-Hernández, Fortunato; Tanus-Hajj, Janet; Avelar-Garnica, Francisco José

    2016-01-01

    Introducción: las infecciones del tracto respiratorio inferior son la complicación más frecuente en pacientes trasplantados de riñón en los primeros seis meses y están asociadas a alta mortalidad. Otras complicaciones pulmonares incluyen edema, embolia y hemorragia pulmonar. Se buscó evaluar las complicaciones pulmonares en los pacientes trasplantados de riñón utilizando la radiografía de tórax. Métodos: se analizaron 516 radiografías de tórax de 150 pacientes que recibieron trasplante renal en el 2014. Las radiografías se tomaron en la valoración preoperatoria, postoperatoria dentro de las 48 horas posteriores, 3 a 7, 8 a 15, 16 a 30, 31 a 90, 91 a 180 y más de 180 días. Para el estudio del parénquima pulmonar se dividió el tórax en cuatro cuadrantes asignando un valor de 1 a cada patrón radiográfico que se encontrara: reticulonodular o de ocupación alveolar, lobar o segmentario, atelectasia y vidrio deslustrado; el parénquima pulmonar obtuvo un valor mínimo de 0 y un mayor de 16 puntos. También se evaluó género, edad, comorbilidad asociada y tipo de trasplante renal. Resultados: se obtuvo la información de un total de 150 pacientes; 19 presentaron complicaciones pulmonares en las primeras 24-48 horas y 15 entre los 90 y los 180 días posteriores al trasplante renal. Las complicaciones más frecuentes fueron edema agudo pulmonar en la etapa temprana e infecciones en la etapa tardía. Conclusión: la prevalencia de complicaciones diagnosticadas por radiografía de tórax fue baja y se observó más en la etapa temprana y tardía.

  11. Accounting for beta-particle energy loss to cortical bone via paired-image radiation transport (PIRT).

    PubMed

    Shah, Amish P; Rajon, Didier A; Patton, Phillip W; Jokisch, Derek W; Bolch, Wesley E

    2005-05-01

    approximately 14% to 76% for high-energy beta emitters (32p, 188Re, and 90Y). The PIRT methodology allows for detailed modeling of the 3D macrostructure of individual marrow-containing bones within the skeleton thus permitting improved estimates of absorbed fractions and radionuclide S values for intermediate-to-high energy beta emitters.

  12. Concordant plutonium-241-americium-241 dating of environmental samples: results from forest fire ash

    SciTech Connect

    Goldstein, Steven J; Oldham, Warren J; Murrell, Michael T; Katzman, Danny

    2010-12-07

    We have measured the Pu, {sup 237}Np, {sup 241}Am, and {sup 151}Sm isotopic systematics for a set of forest fire ash samples from various locations in the western U.S. including Montana, Wyoming, Idaho, and New Mexico. The goal of this study is to develop a concordant {sup 241}Pu (t{sub 1/2} = 14.4 y)-{sup 241}Am dating method for environmental collections. Environmental samples often contain mixtures of components including global fallout. There are a number of approaches for subtracting the global fallout component for such samples. One approach is to use {sup 242}/{sup 239}Pu as a normalizing isotope ratio in a three-isotope plot, where this ratio for the nonglobal fallout component can be estimated or assumed to be small. This study investigates a new, complementary method of normalization using the long-lived fission product, {sup 151}Sm (t{sub 1/2} = 90 y). We