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Sample records for 90y ibritumomab tiuxetan

  1. 90 Y-ibritumomab tiuxetan: a nearly forgotten opportunity

    PubMed Central

    Mondello, Patrizia; Cuzzocrea, Salvatore; Navarra, Michele; Mian, Michael

    2016-01-01

    Y-ibritumomab tiuxetan (90Y-IT) combines the benefits of a monoclonal antibody with the efficacy of radiation in the treatment of B-cell non-Hodgkin lymphoma (NHL), a remarkably radiosensitive hematologic malignancy. 90Y-IT activity has been well established in the indolent setting, being approved in front-line treatment of follicular lymphoma (FL) patients as well as salvage therapy. However, no advantage in OS was observed with respect to standard treatment. Promising data are available also for aggressive B-cell lymphoma. In particular, the addition of RIT to short-course first line chemotherapy enables reduction of chemotherapy while maintaining cure rates in elderly, untreated diffuse large B-cell lymphoma (DLBCL) patients. Furthermore, 90Y-IT improves response rate and outcomes of relapsed/refractory DLBCL patients, eligible and ineligible for autologous stem cell transplantation (ASCT). Clinical results have shown a role of 90Y-IT even in mantle cell lymphoma (MCL). RIT might improve responses and treat minimal residual disease when used as consolidation after first-line chemotherapy in MCL. Moreover, 90Y-IT has demonstrated its efficacy in combination with high-dose chemotherapies as conditioning regimen for ASCT, with evidence suggesting the ability to overcome chemotherapy resistance. Herein, we review the available evidence for this approved drug and examine the recently published and ongoing trials for potential novel indication in aggressive B-cell NHL. PMID:26657116

  2. Dynamic Metabolic Changes during the First 3 Months after 90Y-Ibritumomab Tiuxetan Radioimmunotherapy

    PubMed Central

    Koyama, Keitaro; Kurokawa, Mineo; Ohtomo, Kuni

    2014-01-01

    Objective. To elucidate the time course of tumor metabolism during the first 3 months after 90Y-ibritumomab tiuxetan radioimmunotherapy (RIT) in patients with refractory malignant lymphoma. Materials and Methods. Seven patients with recurrent follicular lymphoma underwent FDG-PET imaging before and after 1-, 4-, and 12-week RIT with 90Y-ibritumomab tiuxetan. Tumor metabolic activity on FDG-PET scans was assessed as the maximum standard uptake value (SUVmax). Results. Decrease in metabolism was detected 1 week after RIT. In the most decreased lesion, SUVmax decreased to 20% of the baseline value during the first week. Most lesions continued to decrease for up to 4 weeks. Some lesions showed increased metabolism from 4 to 12 weeks, while the level of FDG accumulations at 12 weeks was still lower than the baseline. Conclusions. Tumor response to RIT could be observed as early as 1 week after the administration of RIT. After tumor activity decreases, the metabolism may increase at least between 4 and 12 weeks. It suggests that the metabolic changes should be carefully evaluated during this period. PMID:25050390

  3. Radioimmunotherapy ((90) Y-Ibritumomab Tiuxetan) for Posttransplant Lymphoproliferative Disorders After Prior Exposure to Rituximab.

    PubMed

    Rossignol, J; Terriou, L; Robu, D; Willekens, C; Hivert, B; Pascal, L; Guieze, R; Trappe, R; Baillet, C; Huglo, D; Morschhauser, F

    2015-07-01

    Posttransplantation lymphoproliferative disorders (PTLDs) are life-threatening complications after solid organ and hematopoietic stem cell transplantation. Only half of CD20-positive PTLDs respond to rituximab monotherapy, and outcomes remain poor for patients with relapsed/refractory disease, especially those who do not qualify for an anthracycline containing regimen due to frailty or comorbidities. Radioimmunotherapy (RIT) might be an option in this particular setting. We report a panel of eight patients with rituximab refractory/relapsed CD20-positive PTLDs including three ineligible for subsequent CHOP-like chemotherapy who received (90) Y-Ibritumomab tiuxetan as a single agent (n = 7) or combined to chemotherapy (n = 1). Five out of eight patients were kidney transplant recipients, while 2/8 had a liver transplant and 1/8 had a heart transplant. Patients received a median of two previous therapies. Overall response rate was 62.5%. Importantly, all responders achieved complete response. At a median follow-up of 37 months [5; 84], complete response was ongoing in four patients. Toxicity was predominantly hematological and easily manageable. No graft rejection was noticed concomitantly or following RIT administration despite immunosuppression reduction after diagnosis of PTLDs. This report emphasizes the potential efficiency of salvage RIT for early rituximab refractory PTLDs without any unexpected toxicity.

  4. Efficacy of 90Y ibritumomab-tiuxetan treatment in a case of resistant gastric MALT non-Hodgkin’s lymphoma

    PubMed Central

    Ferrucci, PF; Vanazzi, A; Crosta, C; Pruneri, G; Grana, C; Bartolomei, M; Paganelli, G; Martinelli, G

    2008-01-01

    Treatment modalities for resistant/relapsing gastric mucosa associated lymphoid tissue (MALT) non-Hodgkin’s lymphoma (NHL) are not yet well standardized. In the past, most patients were treated surgically with a gastrectomy, while, more recently, radiotherapy and systemic approaches (chemotherapy and immunotherapy) have been used with improving results. Here, we report the case of a patient affected by MALT NHL resistant to antibiotics, chemotherapy and immunotherapy, who achieved a durable complete remission after radio-immunotherapy treatment with Zevalin (90Y ibritumomab-tiuxetan), administered in a single-standard dose. This observation must be confirmed on a larger series but suggests that radio-immunotherapy may be a valid approach in treating relapsing MALT NHL patients, or those resistant to conventional therapies, so avoiding more aggressive and toxic approaches. PMID:22275968

  5. 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.

  6. Short-course R-CHOP followed by 90Y-Ibritumomab tiuxetan in previously untreated high-risk elderly diffuse large B-cell lymphoma patients: 7-year long-term results

    PubMed Central

    Stefoni, V; Casadei, B; Bottelli, C; Gaidano, G; Ciochetto, C; Cabras, M G; Ansuinelli, M; Argnani, L; Broccoli, A; Gandolfi, L; Pellegrini, C; Zinzani, P L

    2016-01-01

    An update at 7 years was conceived for our multicenter phase II study in which 55 elderly high-risk untreated diffuse large B-cell lymphoma patients were treated with 90Y-ibritumomab tiuxetan after a short course of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) as long-term follow-up analyses of this combined therapeutic modality are lacking. The overall response rate to the entire regimen was 80%, including 73% (40/55) of complete response (CR) rate and 7% (4/55) of partial response rate. At the time of writing, 24/55 (43.6%) patients experienced a progression disease and 20 of 40 (50%) patients who obtained a CR are still alive in continuous CR. With a median follow-up of 7 years, the disease-free survival was 43.3% and the progression-free survival was 36.1%. The overall survival at 7.9 years was 38.9% (27 deaths mainly because of lymphoma). Two patients developed secondary hematological malignancies, an acute myeloid leukemia and a myelodysplastic syndrome, at 4 and 3 years from radioimmunotherapy, respectively. Our data confirm the feasibility, efficacy and safety of four cycles of R-CHOP followed by radioimmunotherapy consolidation even in the long term: this combination allows dispensing less chemotherapy in a frail group of patients without invalidating response quality and duration. PMID:27176801

  7. 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

  8. 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.

  9. Early treatment intensification with R-ICE and 90Y-ibritumomab tiuxetan (Zevalin)-BEAM stem cell transplantation in patients with high-risk diffuse large B-cell lymphoma patients and positive interim PET after 4 cycles of R-CHOP-14

    PubMed Central

    Hertzberg, Mark; Gandhi, Maher K.; Trotman, Judith; Butcher, Belinda; Taper, John; Johnston, Amanda; Gill, Devinder; Ho, Shir-Jing; Cull, Gavin; Fay, Keith; Chong, Geoff; Grigg, Andrew; Lewis, Ian D.; Milliken, Sam; Renwick, William; Hahn, Uwe; Filshie, Robin; Kannourakis, George; Watson, Anne-Marie; Warburton, Pauline; Wirth, Andrew; Seymour, John F.; Hofman, Michael S.; Hicks, Rodney J.

    2017-01-01

    In the treatment of diffuse large B-cell lymphoma, a persistently positive [18F]fluorodeoxyglucose positron emission tomography (PET) scan typically carries a poor prognosis. In this prospective multi-center phase II study, we sought to establish whether treatment intensification with R-ICE (rituximab, ifosfamide, carboplatin, and etoposide) chemotherapy followed by 90Y-ibritumomab tiuxetan–BEAM (BCNU, etoposide, cytarabine, and melphalan) for high-risk diffuse large B-cell lymphoma patients who are positive on interim PET scan after 4 cycles of R-CHOP-14 (rituximab, cyclophosphamide, doxorubicin, and prednisone) can improve 2-year progression-free survival from a historically unfavorable rate of 40% to a rate of 65%. Patients received 4 cycles of R-CHOP-14, followed by a centrally-reviewed PET performed at day 17–20 of cycle 4 and assessed according to International Harmonisation Project criteria. Median age of the 151 evaluable patients was 57 years, with 79% stages 3–4, 54% bulk, and 54% International Prognostic Index 3–5. Among the 143 patients undergoing interim PET, 101 (71%) were PET-negative (96 of whom completed R-CHOP), 42 (29%) were PET-positive (32 of whom completed R-ICE and 90Y-ibritumomab tiuxetan-BEAM). At a median follow up of 35 months, the 2-year progression-free survival for PET-positive patients was 67%, a rate similar to that for PET-negative patients treated with R-CHOP-14 (74%, P=0.11); overall survival was 78% and 88% (P=0.11), respectively. In an exploratory analysis, progression-free and overall survival were markedly superior for PET-positive Deauville score 4 versus score 5 (P=0.0002 and P=0.001, respectively). Therefore, diffuse large B-cell lymphoma patients who are PET-positive after 4 cycles of R-CHOP-14 and who switched to R-ICE and 90Y-ibritumomab tiuxetan-BEAM achieved favorable survival outcomes similar to those for PET-negative R-CHOP-14-treated patients. Further studies are warranted to confirm these promising results

  10. Role of consolidation with yttrium-90 ibritumomab tiuxetan in patients with advanced-stage follicular lymphoma

    PubMed Central

    Sánchez Ruiz, Antonio C.; de la Cruz-Merino, Luis

    2014-01-01

    Non-Hodgkin’s lymphoma (NHL) accounts for 4% of all cancers diagnosed in the United States. Follicular lymphoma (FL) is the most common type of indolent NHL with a survival from 5 to 15 years. Although it is very sensitive to chemotherapy and radiotherapy, relapses are the main cause of therapeutic failure, and currently there is no consensus on the first-line treatment and optimal therapeutic strategies for patients with FL. Immediate treatment offers any survival benefit for asymptomatic and more indolent disease. In order to improve outcomes in FL, extend the remission, postpone the need for chemotherapy and improve OS, maintenance therapies with rituximab and consolidation treatments represent very attractive strategies. 90Y-ibritumomab tiuxetan (90Y-IT, Zevalin®) is approval as consolidation therapy in previously untreated FL patients who achieve response to first-line chemotherapy. Consolidation therapy with 90Y-IT after initial induction treatment has shown improved activity compared with induction chemotherapy alone, even in patients previously treated with rituximab, in one phase III and several phase II trials, improving progression-free survival (PFS) and rate of conversion from partial response (PR) to complete response (CR). The phase III international FIT trial shows an improvement in PFS that is maintained after a median follow up of 7.3 years. Several phase II trials show high rate of conversion from PR to CR and a significant improvement in PFS. Treatment is feasible and well tolerated although myelodysplastic syndrome cases has been observed in some trials. 90Y-IT should be considered for the initial treatment of FL in patients who are unable to tolerate standard chemotherapy, e.g., elderly or frail patients and otherwise in high-risk patients who achieve a PR or CR due to improvements in CR rate and PFS. PMID:24883180

  11. 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.

  12. 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

  13. Efficacy of ⁹⁰Yttrium-ibritumomab tiuxetan in relapsed/refractory extranodal marginal-zone lymphoma.

    PubMed

    Vanazzi, Anna; Grana, Chiara; Crosta, Cristiano; Pruneri, Giancarlo; Rizzo, Stefania; Radice, Davide; Pinto, Antonello; Calabrese, Liliana; Paganelli, Giovanni; Martinelli, Giovanni

    2014-03-01

    We evaluated clinical activity of ⁹⁰Yttrium-ibritumomab (⁹⁰Y-ibritumomab) tiuxetan in extranodal marginal-zone lymphoma. From May 2004 to April 2011, 30 patients affected by relapsed/refractory marginal-zone lymphoma--arisen at any extranodal site--received ⁹⁰Y-ibritumomab tiuxetan at the activity of 0.4 mCi/kg. Median age was 57 years. At time of treatment, 13 out of 30 patients had disseminated disease (stage III/IV). All patients had received a previous treatment with a maximum of 7. Overall response rate was 90%: 23 patients achieved a complete response (77%); partial response occurred in 4 patients (13%), stable disease in 2 patients (7%) and 1 progression (3%). With a median follow-up of 5.3 years, median time to relapse was not reached; 2 patients relapsed after complete response; 18 out of 23 complete responses are still responders after >3 years, 12 of them after >5 years. ⁹⁰Y-ibritumomab tiuxetan seems to be active in patients with extranodal marginal-zone lymphoma relapsed/refractory to conventional treatment including radiotherapy. These results suggest that radioimmunotherapy could represent a possible option for the treatment in this subset of patients.

  14. A phase I trial of immunostimulatory CpG 7909 oligodeoxynucleotide and 90 yttrium ibritumomab tiuxetan radioimmunotherapy for relapsed B-cell non-Hodgkin lymphoma.

    PubMed

    Witzig, Thomas E; Wiseman, Gregory A; Maurer, Matthew J; Habermann, Thomas M; Micallef, Ivana N M; Nowakowski, Grzegorz S; Ansell, Stephen M; Colgan, Joseph P; Inwards, David J; Porrata, Luis F; Link, Brian K; Zent, Clive S; Johnston, Patrick B; Shanafelt, Tait D; Allmer, Cristine; Asmann, Yan W; Gupta, Mamta; Ballas, Zuhair K; Smith, Brian J; Weiner, George J

    2013-07-01

    Radioimmunotherapy (RIT) for relapsed indolent non-Hodgkin lymphoma produces overall response rates (ORR) of 80% with mostly partial remissions. Synthetic CpG oligonucleotides change the phenotype of malignant B-cells, are immunostimulatory, and can produce responses when injected intratumorally and combined with conventional radiation. In this phase I trial, we tested systemic administration of both CpG and RIT. Eligible patients had biopsy-proven previously treated CD20+ B-cell NHL and met criteria for RIT. Patients received rituximab 250 mg/m(2) days 1,8, and 15; (111) In-ibritumomab tiuxetan days 1, 8; CpG 7909 days 6, 13, 20, 27; and 0.4 mCi/kg of (90) Y-ibritumomab tiuxetan day 15. The doses of CpG 7909 tested were 0.08, 0.16, 0.32 (six patients each) and 0.48 mg/kg (12 patients) IV over 2 hr without dose limiting toxicity. The ORR was 93% (28/30) with 63% (19/30) complete remission (CR); median progression free survival of 42.7 months (95% CI 18-NR); and median duration of response (DR) of 35 months (4.6-76+). Correlative studies demonstrated a decrease in IL10 and TNFα, and an increase in IL1β, in response to therapy. CpG 7909 at a dose of 0.48 mg/kg is safe with standard RIT and produces a high CR rate and long DR; these results warrant confirmation.

  15. A Phase I Trial of Immunostimulatory CpG 7909 Oligodeoxynucleotide and 90Yttrium Ibritumomab Tiuxetan Radioimmunotherapy for Relapsed B-cell Non-Hodgkin Lymphoma

    PubMed Central

    Witzig, Thomas E.; Wiseman, Gregory A.; Maurer, Matthew J.; Habermann, Thomas M.; Micallef, Ivana N. M.; Nowakowski, Grzegorz S.; Ansell, Stephen M.; Colgan, Joseph P.; Inwards, David J.; Porrata, Luis F.; Link, Brian K.; Zent, Clive S.; Johnston, Patrick B.; Shanafelt, Tait D.; Allmer, Cristine; Asmann, Yan W.; Gupta, Mamta; Ballas, Zuhair K.; Smith, Brian J.; Weiner, George J.

    2014-01-01

    Radioimmunotherapy (RIT) for relapsed indolent non-Hodgkin lymphoma produces overall response rates (ORR) of 80% with mostly partial remissions. Synthetic CpG oligonucleotides change the phenotype of malignant B-cells, are immunostimulatory, and can produce responses when injected intratumorally and combined with conventional radiation. In this phase I trial we tested systemic administration of both CpG and RIT. Eligible patients had biopsy-proven previously treated CD20+ B-cell NHL and met criteria for RIT. Patients received rituximab 250 mg/m2 days 1,8, and 15; 111In-ibritumomab tiuxetan days 1, 8; CpG 7909 days 6, 13, 20, 27; and 0.4 mCi/kg of 90Y-ibritumomab tiuxetan day 15. The doses of CpG 7909 tested were 0.08, 0.16, 0.32 (six patients each) and 0.48 mg/kg (12 patients) IV over 2 hours without dose limiting toxicity. The ORR was 93% (28/30) with 63% (19/30) complete remission (CR); median progression free survival of 42.7 months (95% CI 18-NR); and median duration of response (DR) of 35 months (4.6-76+). Correlative studies demonstrated a decrease in IL10 and TNFα, and an increase in IL1β, in response to therapy. CpG 7909 at a dose of 0.48 mg/kg is safe with standard RIT and produces a high CR rate and long DR; these results warrant confirmation. PMID:23619698

  16. 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

  17. FCR (Fludarabine, Cyclophosphamide, Rituximab) regimen followed by 90yttrium ibritumomab tiuxetan consolidation for the treatment of relapsed grades 1 and 2 follicular lymphoma: a report of 9 cases

    PubMed Central

    2011-01-01

    Background This retrospective analysis is focused on the efficacy and safety of radioimmunotherapy (RIT) with Zevalin® in nine patients with recurrent follicular lymphoma (FL) who were treated in a consolidation setting after having achieved complete remission or partial remission with FCR. Methods The median age was 63 yrs (range 46-77), all patients were relapsed with histologically confirmed CD20-positive (grade 1 or 2) FL, at relapse they received FCR every 28 days: F (25 mg/m2x 3 days), C (1 gr/m2 day 1) and R (375 mg/m2 day 4) for 4 cycles. Who achieved at least a partial remission, with < 25% bone marrow involvement, was treated with 90Yttrium Ibritumomab Tiuxetan 11.1 or 14.8 MBq/Kg up to a maximum dose 1184 MBq, at 3 months after the completion of FCR. The patients underwent a further restaging at 12 weeks after 90Y-RIT with total body CT scan, FDG-PET/CT and bilateral bone marrow biopsy. Results Nine patients have completed the treatment: FCR followed by 90Y-RIT (6 patients at 14.8 MBq/Kg, 3 patients at 11.1 MBq/Kg). After FCR 7 patients obtained CR and 2 PR; after 90Y-RIT two patients in PR converted to CR 12 weeks later. With median follow up of 34 months (range 13-50) the current analysis has shown that overall survival (OS) is 89% at 2 years, 76% at 3 years and 61% at 4 years. The most common grade 3 or 4 adverse events were hematologic, one patient developed herpes zoster infection after 8 months following valacyclovir discontinuation; another patient developed fungal infection. Conclusions Our experience indicate feasibility, tolerability and efficacy of FCR regimen followed by 90Y-RIT in patients relapsed with grades 1 and 2 FL with no unexpected toxicities. A longer follow up and a larger number of patients with relapsed grades 1 and 2 FL are required to determine the impact of this regimen on long-term duration of response and PFS. PMID:21303501

  18. Phase II Study of Yttrium-90 Ibritumomab Tiuxetan Plus High-Dose BCNU, Etoposide, Cytarabine, and Melphalan for Non-Hodgkin Lymphoma: The Role of Histology.

    PubMed

    Krishnan, Amrita Y; Palmer, Joycelynne; Nademanee, Auayporn P; Chen, Robert; Popplewell, Leslie L; Tsai, Ni-Chun; Sanchez, James F; Simpson, Jennifer; Spielberger, Ricardo; Yamauchi, Dave; Forman, Stephen J

    2017-03-04

    Standard-dose (90)yttrium-ibritumomab tiuxetan (.4 mci/kg) together with high-dose BEAM (BCNU, etoposide, cytarabine, and melphalan) (Z-BEAM) has been shown to be a well-tolerated autologous hematopoietic stem cell transplantation preparative regimen for non-Hodgkin lymphoma. We report the outcomes of a single-center, single-arm phase II trial of Z-BEAM conditioning in high-risk CD20(+) non-Hodgkin lymphoma histologic strata: diffuse large B cell (DLBCL), mantle cell, follicular, and transformed. Robust overall survival and notably low nonrelapse mortality rates (.9% at day +100 for the entire cohort), with few short- and long-term toxicities, confirm the safety and tolerability of the regimen. In addition, despite a high proportion of induction failure patients (46%), the promising response and progression-free survival (PFS) rates seen in DLBCL (3-year PFS: 71%; 95% confidence interval, 55 to 82%), support the premise that the Z-BEAM regimen is particularly effective in this histologic subtype. The role of Z-BEAM in other strata is less clear in the context of the emergence of novel agents.

  19. Phase II Study of Yttrium-90-Ibritumomab Tiuxetan as Part of Reduced-Intensity Conditioning (with Melphalan, Fludarabine ± Thiotepa) for Allogeneic Transplantation in Relapsed or Refractory Aggressive B Cell Lymphoma: A GELTAMO Trial.

    PubMed

    Cabrero, Monica; Martin, Alejandro; Briones, Javier; Gayoso, Jorge; Jarque, Isidro; López, Javier; Grande, Carlos; Heras, Inmaculada; Arranz, Reyes; Bernal, Teresa; Perez-Lopez, Estefania; López-Godino, Oriana; Conde, Eulogio; Caballero, Dolores

    2017-01-01

    We designed a phase II clinical trial including Y-90 ibritumomab-tiuxetan as part of a reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (AlloSCT) in high-risk non-Hodgkin lymphoma (Clinical Trials Identifier: NCT00644371). Eligible patients had high-risk relapsed/refractory aggressive lymphoma. The conditioning regimen consisted of rituximab 250 mg (days -21 and -14), Y-90 ibritumomab IV (.4 m Ci/kg, day -14), fludarabine 30 mg/m(2) i.v. (days -3 and -2) plus melphalan 70 mg/m(2) i.v. (days -3 and -2) or 1 dose of melphalan and thiotepa 5 mg/kg (day -8). Donors were related. Eighteen patients were evaluable. At the time of transplantation, responses were complete remission (CR) (n = 7, 39%), partial remission (n = 6, 33%) or refractory disease (n = 4, 28%). Y-90-ibritumomab infusions were well tolerated, with no adverse reactions. Nonrelapse mortality at 1 year was 28%. Median follow-up was 46 (range, 39 to 55) months. Estimated 1-year progression-free survival (PFS) was 50%, and 4-year overall survival (OS) and PFS were both 44.4%. CR at the moment of AlloSCT had significant impact on PFS (71% versus 27%, P = .046) and OS (71% versus 27%, P = .047). Our results show that Y-90-ibritumomab-tiuxetan as a component of RIC for AlloSCT is feasible in patients with high-risk B cell lymphoma. Development of phase III clinical trials is needed to clarify the contribution of radioimmunotherapy to RIC AlloSCT.

  20. 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.

  1. 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.

  2. 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 ...

  3. 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

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

    ClinicalTrials.gov

    2016-12-20

    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

  5. Patient dosimetry for 90Y selective internal radiation treatment based on 90Y PET imaging.

    PubMed

    Ng, Sherry C; Lee, Victor H; Law, Martin W; Liu, Rico K; Ma, Vivian W; Tso, Wai Kuen; Leung, To Wai

    2013-09-06

    Until recently, the radiation dose to patients undergoing the 90Y selective internal radiation treatment (SIRT) procedure is determined by applying the partition model to 99mTc MAA pretreatment scan. There can be great uncertainty in radiation dose calculated from this approach and we presented a method to compute the 3D dose distributions resulting from 90Y SIRT based on 90Y positron emission tomography (PET) imaging. Five 90Y SIRT treatments were retrospectively analyzed. After 90Y SIRT, patients had 90Y PET/CT imaging within 6 hours of the procedure. To obtain the 3D dose distribution of the patients, their respective 90Y PET images were convolved with a Monte Carlo generated voxel dose kernel. The sensitivity of the PET/CT scanner for 90Y was determined through phantom studies. The 3D dose distributions were then presented in DICOM RT dose format. By applying the linear quadratic model to the dose data, we derived the biologically effective dose and dose equivalent to 2 Gy/fraction delivery, taking into account the spatial and temporal dose rate variations specific for SIRT. Based on this data, we intend to infer tumor control probability and risk of radiation induced liver injury from SIRT by comparison with established dose limits. For the five cases, the mean dose to target ranged from 51.7 ± 28.6 Gy to 163 ± 53.7 Gy. Due to the inhomogeneous nature of the dose distribution, the GTVs were not covered adequately, leading to very low values of tumor control probability. The mean dose to the normal liver ranged from 21.4 ± 30.7 to 36.7 ± 25.9 Gy. According to QUANTEC recommendation, a patient with primary liver cancer and a patient with metastatic liver cancer has more than 5% risk of radiotherapy-induced liver disease (RILD).

  6. 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

  7. 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

  8. Purification and uses of /sup 90/Y for medical research

    SciTech Connect

    Wike, J.S.; Haff, K.W.; Phillips, B.P.

    1985-11-01

    Medical researchers are utilizing two new products recently developed for a new attack on some forms of human cancer. One development in the early 1980s was the monoclonal antibody. A second product for liver cancer therapy is being developed. A radioactive isotope must meet rigid criteria to be used for labeling of these products. It must have a short half-life (days), be free of other long-lived radionuclides, and emit rays with energy that have a short path length in flesh. One isotope that meets these criteria is /sup 90/Y, which is the decay daughter of /sup 90/Sr. It has a 63.4-h half-life, a 2.25-MeV beta energy with no gamma energy, and decays to stable /sup 90/Zr. When /sup 90/Y is to be used with human patients, it is necessary to remove the /sup 90/Sr precursor to the lowest possible levels. A 50-Ci strontium cow was prepared at the Oak Ridge National Laboratory (ORNL) for the production of ultra-pure /sup 90/Y chloride. This cow was placed in a remote cell with master/slave manipulators for processing the /sup 90/Y. No other radionuclides are processed in this cell, thus eliminating the possibility of contamination of the finished product with alpha- and gamma-emitting nuclides. The 50-Ci source of /sup 90/Sr was selected for the production of /sup 90/Y in multicurie quantities. Large quantities of /sup 90/Y will be needed if research programs demonstrate that it is effective in the treatment of cancer.

  9. 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

  10. Beta spectra of /sup 90/Sr and /sup 90/Y

    SciTech Connect

    Devaney, J.J.

    1985-08-01

    Using as a base the beta energy spectra provided by T.R. England, the number spectra of /sup 90/Sr and /sup 90/Y were corrected for the Coulomb effects on the first forbidden shape factor using the tables of M.E. Rose, and for higher order effects using the experimentally determined corrections of H. Daniel et al. We, therefore, present a fully corrected beta number spectrum of /sup 90/Sr and its daughter /sup 90/Y. The half-lives and end-point energies are also listed.

  11. Testis dosimetry in individual patients by combining a small-scale dosimetry model and pharmacokinetic modeling-application of 111In-Ibritumomab Tiuxetan (Zevalin®)

    NASA Astrophysics Data System (ADS)

    Meerkhan, Suaad A.; Sjögreen-Gleisner, Katarina; Larsson, Erik; Strand, Sven-Erik; Jönsson, Bo-Anders

    2014-12-01

    A heterogeneous distribution of radionuclides emitting low-energy electrons in the testicles may result in a significant difference between an absorbed dose to the radiosensitive spermatogonia and the mean absorbed dose to the whole testis. This study focused on absorbed dose distribution in patients at a finer scale than normally available in clinical dosimetry, which was accomplished by combining a small-scale dosimetry model with patient pharmacokinetic data. The activity in the testes was measured and blood sampling was performed for patients that underwent pre-therapy imaging with 111In-Zevalin®. Using compartment modeling, testicular activity was separated into two components: vascular and extravascular. The uncertainty of absorbed dose due to geometry variations between testicles was explored by an assumed activity micro-distribution and by varying the radius of the interstitial tubule. Results showed that the absorbed dose to germ cells might be strongly dependent on the location of the radioactive source, and may exceed the absorbed dose to the whole testis by as much as a factor of two. Small-scale dosimetry combined with compartmental analysis of clinical data proved useful for gauging tissue dosimetry and interpreting how intrinsic geometric variation influences the absorbed dose.

  12. 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

    2017-01-04

    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

  13. 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

  14. 90Y-Edotreotide for Metastatic Carcinoid Refractory to Octreotide

    PubMed Central

    Bushnell, David L.; O'Dorisio, Thomas M.; O'Dorisio, M. Sue; Menda, Yusuf; Hicks, Rodney J.; Van Cutsem, Eric; Baulieu, Jean-Louis; Borson-Chazot, Francoise; Anthony, Lowell; Benson, Al B.; Oberg, Kjell; Grossman, Ashley B.; Connolly, Mary; Bouterfa, Hakim; Li, Yong; Kacena, Katherine A.; LaFrance, Norman; Pauwels, Stanislas A.

    2010-01-01

    Purpose Metastatic carcinoid is an incurable malignancy whose symptoms, such as diarrhea and flushing, can be debilitating and occasionally life-threatening. Although symptom relief is available with octreotide, the disease eventually becomes refractory to octreotide, leaving no proven treatment options. The goal of this study was to evaluate the clinical effect of using 90Y-edotreotide to treat symptomatic patients with carcinoid tumors. Patients and Methods Patients enrolled had metastatic carcinoid, at least one sign/symptom refractory to octreotide, and at least one measurable lesion. Study treatment consisted of three cycles of 4.4 GBq (120 mCi) 90Y-edotreotide each, once every 6 weeks. Results Ninety patients were enrolled in the study. Using Southwest Oncology Group tumor response criteria, 67 (74.%) of 90 patients (95% CI, 65.4% to 83.4%) were objectively stable or responded. A statistically significant linear trend toward improvement was demonstrated across all 12 symptoms assessed. Median progression-free survival was significantly greater (P = .03) for the 38 patients who had durable diarrhea improvement than the 18 patients who did not (18.2 v 7.9 months, respectively). Adverse events (AEs) were reported in 96.7% (87 of 90) of patients. These AEs consisted primarily of reversible GI events (76 of 90), which could be caused in part by concomitant administration of amino acid solution given to reduce radiation exposure to the kidneys. There was one case each of grade 3 oliguria and grade 4 renal failure, each lasting 6 days. Conclusion 90Y-edotreotide treatment improved symptoms associated with malignant carcinoid among subjects with no treatment alternatives. Treatment was well-tolerated and had an acceptable expected AE profile. PMID:20194865

  15. Determination of 90Sr traces in medical 90Y after separation on DGA column.

    PubMed

    Pawlak, Dariusz W; Parus, Jozef L; Dziel, Tomasz; Muklanowicz, Anna; Mikolajczak, Renata

    2013-09-30

    A new analytical procedure for (90)Sr determination in freshly milked (90)Y from a (90)Sr/(90)Y generator is described. To a solution containing 125 mg of Sr a 200 to 400 MBq sample of (90)Y is added and strontium is separated from (90)Y using DGA column of 1 mL volume. (90)Sr is recovered in a yield close to 100% and counted in a liquid scintillation spectrometer (LSC). The separated strontium is slightly contaminated with (90)Y in the range from 7 to 19% of (90)Sr activity. The separation and counting can be completed within 30 min. The detection limit in 900 s counting time is equal to about 0.2 Bq. This corresponds to (90)Sr/(90)Y activity ratio of 10(-8) level.

  16. Dosimetry of yttrium-labelled radiopharmaceuticals for internal therapy: 86Y or 90Y imaging?

    PubMed

    Walrand, Stephan; Flux, Glenn D; Konijnenberg, Mark W; Valkema, Roelf; Krenning, Eric P; Lhommel, Renaud; Pauwels, Stanislas; Jamar, Francois

    2011-05-01

    This paper reviews issues concerning (86)Y positron emission tomography (PET), (90)Y PET and (90)Y bremsstrahlung imaging. Specific methods and corrections developed for quantitative imaging, for application in preclinical and clinical studies, and to assess (90)Y dosimetry are discussed. The potential imaging capabilities with the radioisotopes (87)Y and (88)Y are also considered. Additional studies required to assess specific unaddressed issues are also identified.

  17. 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.

  18. Recurrent villonodular synovitis of the knee. Successful treatment with /sup 90/Y

    SciTech Connect

    Wiss, D.A.

    1982-09-01

    A 40-year-old woman with recurrent pigmented villonodular synovitis of the knee was treated with /sup 90/Y radiocolloid. The advantages of /sup 90/Y include effectiveness, low cost, simplicity, and low morbidity. The radiophysical properties of /sup 90/Y that make it a useful therapeutic agent are short half-life, pure beta emission and good penetration of the soft tissues. Side effects are few, predictable, and for the most part, avoidable. Radionecrosis of soft tissue, needle tract pigmentation, injection site tenderness, pyrexia, and lymphocyte chromosomal abnormalities have been reported. The indications for intra-articular radiocolloid therapy are the same as for surgical synovectomy, except that it is reserved for patients older than 35 years of age. The pathologic events following /sup 90/Y therapy in experimental animals show coagulation necrosis of the synovium, followed by an intense inflammatory reaction, leading ultimately to fibrosis. /sup 90/Y is a useful adjuvant in the treatment of recurrent pigmented villonodular synovitis.

  19. 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.

  20. 90Y. B72. 3 against pancreatic cancer: Dosimetric and biological analysis

    SciTech Connect

    Mehta, M.P.; Kubsad, S.S.; Fowler, J.F.; Verma, A.K.; Hsieh, J.T.; Kinsella, T.J. )

    1990-09-01

    Nude mice xenografted with a human pancreatic carcinoma cell line were injected with yttrium-90 (90Y) conjugated to diethylene triaminepenta acetic acid (DTPA) alone, and DTPA covalently linked to a monoclonal antibody, B72.3. The animals were sacrificed in temporal sequence to evaluate isotope distribution. Dosimetry was carried out using the principles outlined in MIRD and ICRU Report 32. Results are expressed as percent uptake per unit mass in organs and tumor and as relative absorbed dose normalized to 90Y uptake in liver at 7 hr. When conjugated to B72.3, an 8-fold increase in isotope localization in the tumor was noted by 24 hr. When the relative absorbed dose is calculated for 90Y and 90Y.B72.3, a 26-fold increase in tumor dose is noted for the 90Y conjugate. Normal tissues show no to modest (less than 5x) enhanced dose with 90Y.B72.3. B72.3, therefore, deserves further investigation as a potential monoclonal antibody for targeting therapeutic radioisotopes and possibly diagnostic radioisotopes to pancreatic cancer. Radiobiological aspects of the low dose rates from radioimmunotherapy are discussed.

  1. Preliminary evaluation of indigenous 90Y-labelled microspheres for therapy of hepatocellular carcinoma

    PubMed Central

    Subramanian, Suresh; Pandey, Usha; Chaudhari, Pradip; Tyagi, Monica; Gupta, Sanjay; Singh, Geetanjali; Dash, Ashutosh; Samuel, Grace; Venkatesh, Meera

    2016-01-01

    Background & objectives: Yttrium-90 (90Y)-based radioembolization has been employed to treat hepatocellular carcinoma (HCC) as commercial radioactive glass and polymeric resin microspheres. However, in India and other Asian countries, these preparations must be imported and are expensive, validating the need for development of indigenous alternatives. This work was aimed to develop an economically and logistically favourable indigenous alternative to imported radioembolizing agents for HCC therapy. Methods: The preparation of 90Y-labelled Biorex 70 microspheres was optimized and in vitro stability was assessed. Hepatic tumour model was generated in Sprague-Dawley rats by orthotopic implantation of N1S1 rat HCC cell line. In vivo localization and retention of the 90Y-labelled Biorex 70 microspheres was assessed for seven days, and impact on N1S1 tumour growth was studied by histological examination and biochemical assays. Results: Under optimal conditions, >95% 90Y-labelling yield of Biorex70 resin microspheres was obtained, and these showed excellent in vitro stability of labelling (>95%) at seven days. In animal studies, 90Y-labelled Biorex 70 microspheres were retained (87.72±1.56% retained in liver at 7 days). Rats administered with 90Y-labelled Biorex 70 microspheres exhibited lower tumour to liver weight ratio, reduced serum alpha-foetoprotein level and greater damage to tumour tissue as compared to controls. Interpretation & conclusions: 90Y-labelled Biorex 70 microspheres showed stable retention in the liver and therapeutic effect on tumour tissue, indicating the potential for further study towards clinical use. PMID:27748281

  2. 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

  3. 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

  4. Determination of 90Sr-90Y activity in urine samples by using Cherenkov counting.

    PubMed

    Tsroya, S; German, U; Pelled, O; Katorza, E; Alfassi, Z B

    2013-03-01

    Cherenkov counting of the (90)Sr-(90)Y pure beta emitters in aqueous samples is an attractive method; but color quenching correction is needed, this being especially significant for urine which is characterized by a strong coloration. A quench correction method based on the external source of some liquid scintillation systems (named ESAR-External Source Area Ratio) was proposed for aqueous solutions. In the present work, the application of the ESAR method for determination of (90)Sr-(90)Y in human urine samples is described.

  5. (90)Y Radioembolization: Multimodality Imaging Pattern Approach with Angiographic Correlation for Optimized Target Therapy Delivery.

    PubMed

    Camacho, Juan C; Moncayo, Valeria; Kokabi, Nima; Reavey, Hamilton E; Galt, James R; Yamada, Kei; Kies, Darren D; Williams, Roger S; Kim, Hyun S; Schuster, David M

    2015-01-01

    Primary and metastatic liver cancers are responsible for considerable morbidity and mortality, and many patients are not curable at presentation. Therefore, new therapies such as radioembolization with yttrium 90 ((90)Y)-labeled microspheres are an alternative method to treat patients with unresectable primary or secondary liver tumors. Patient selection, treatment technique, and early recognition of potential complications are the keys for successful patient outcomes. The activity of administered (90)Y microspheres depends on multiple variables, including the tumor burden, the volume of the liver lobe to be treated, the type of (90)Y microspheres, and the hepatopulmonary shunt fraction. Preprocedural planning relies on the results of cross-sectional imaging to determine the extent of disease, tumoral and nontumoral liver volumes, patency of the portal vein, and the degree of extrahepatic disease. A multidisciplinary approach that combines expertise in cross-sectional imaging, nuclear medicine, and flow dynamics is critical to adequately target malignant tissue. Preprocedural multimodality imaging, particularly combined single photon emission computed tomography (SPECT) and computed tomography (CT) imaging (SPECT/CT), may be used to identify nontarget imaging patterns that, if recognized, can potentially be corrected with either branch vessel embolization or catheter repositioning. Postprocedural multimodality imaging is also useful to confirm the appropriate delivery of (90)Y microspheres, enabling early identification of potential complications and the adequacy of microsphere distribution, thereby optimizing planning for subsequent therapies.

  6. 90Y radioembolization versus chemoembolization in the treatment of hepatocellular carcinoma: an analysis of comparative effectiveness.

    PubMed

    Xing, Minzhi; Kokabi, Nima; Camacho, Juan C; Kooby, David A; El-Rayes, Bassel F; Kim, Hyun S

    2013-07-01

    Locoregional catheter-based therapies for unresectable hepatocellular carcinoma (HCC) include conventional transarterial chemoembolization (cTACE), drug-eluting bead chemoembolization and yttrium-90 ((90)Y) radioembolization. Although current guidelines recommend cTACE for inoperable HCC, comparative effectiveness of drug-eluting bead chemoembolization and (90)Y radioembolization in the management of HCC remains undefined due to the lack of data evaluating safety and effectiveness among these therapies. A comprehensive search of the literature was carried out for studies examining comparative effectiveness of cTACE and (90)Y based on objective tumor response and overall patient survival. Further data on efficacy, safety, toxicity and cost-effectiveness was also examined. The National Cancer Institute Levels of Evidence for Cancer Treatment Studies provided a useful framework for the critical understanding and stratification of current evidence on locoregional therapy for unresectable HCC. Based on current retrospective cohort studies, evidence for similar efficacy and safety between cTACE and (90)Y radioembolization was demonstrated. Further prospective, randomized studies are required to validate these observations and to analyze cost-effectiveness of these interventions in unresectable HCC patients for definitive recommendations to be made.

  7. Posttherapy radiation safety considerations in radiomicrosphere treatment with 90Y-microspheres.

    PubMed

    Gulec, Seza A; Siegel, Jeffry A

    2007-12-01

    Radiomicrosphere treatment involves the intrahepatic arterial administration of (90)Y-resin or (90)Y-glass microspheres. The microspheres are biocompatible, but not biodegradable, and little to no (90)Y leaches from the microspheres. Without any bioelimination, the beta-dose delivery is generally confined to the liver. Although U.S. Nuclear Regulatory Commission requirements permit patients treated with these microspheres to be released without the need for dose determination or patient instructions, there are important radiation safety issues that need scientific clarification. We carefully evaluated the radiation exposure mechanisms, including the bremsstrahlung radiation doses to others, for a variety of lifestyle behaviors. Dose estimates were also made for several practical and theoretic situations involving the patient's gonads, an embryo or fetus, and a nursing infant. For the infant, we evaluated the potential beta-dose that might be introduced via breast milk ingestion. The bremsstrahlung component of the decay scheme of the pure beta-emitter (90)Y has traditionally been ignored in internal and external dose calculations. Because the production of in vivo bremsstrahlung with the high-energy pure beta-particle-emitting radionuclides used for therapeutic purposes is sufficient to permit external detection and imaging, we believe that the contribution of such radiation should be considered with regard to patient release; we therefore chose to evaluate this potential external radiation hazard. In all cases, the estimated doses were very small, indicating that no patient restrictions are required for radiation safety purposes after the release of a patient who has been treated with (90)Y-microspheres.

  8. 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

  9. Radiopharmaceutical development based on human blood albumin microspheres and 90Y

    NASA Astrophysics Data System (ADS)

    Petriev, V. M.; Vlasova, O. P.; Postnov, A. A.; Epstein, N. B.

    2017-01-01

    New radiopharmaceutial (RP) based on human serum albumin microspheres (MSA) and 90Y was developed for treatment of liver cancer. The optimized synthesis using chelation resulted in approximately 80% yield with high specific activity. The RP developed was tested in mice with inoculated sarcoma-37. In two weeks the tumor size reduced by 43% after the treatment with the dose of 500 μCi injected into the tumor site.

  10. 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.

  11. Standardisation of (90)Y and determination of calibration factors for (90)Y microspheres (resin) for the NPL secondary ionisation chamber and a Capintec CRC-25R.

    PubMed

    Ferreira, Kelley M; Fenwick, Andrew J; Arinc, Arzu; Johansson, Lena C

    2016-03-01

    The use of (90)Y resin microspheres (SIR-Spheres® microspheres) in Nuclear Medicine has dramatically increased in recent years due to its favourable outcome in the treatment of liver cancer and liver metastases (Rajekar et al., 2011). The measurement of administered activity before and residual activity after treatment in radionuclide calibrators is required to determine total activity delivered to the patient. In comparison with External Beam Radiotherapy (EBRT) where administered doses are often know to within ±5%, the actual administered activity in nuclear medicine procedures may only be known to within ±20% and subsequent dose calculations can result in even larger uncertainties (Fenwick et al., 2009). It is a well-recognised issue that ion chambers are instruments that are sensitive to the measurement geometry and matrix of a source, in particular for pure beta or low energy (<100keV) x-ray emitters (Gadd et al., 2006). This paper presents new calibration factors for NPL secondary standard ionisation chamber system (Vinten 671) and a Capintec CRC-25R radionuclide calibrator along with a discussion of the measurement problems associated with this radionuclide and matrix. Calibration of the NPL secondary standard system for this measurement matrix will enable NPL to provide standards for the Nuclear Medicine community and consequently increase the measurement capability.

  12. 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.

  13. Gastrectomy for the treatment of refractory gastric ulceration after radioembolization with 90Y microspheres

    PubMed Central

    Yim, Sun Young; Jung, Jin Yong; Kim, Chang Ha; Seo, Yeon Seok; Yim, Hyung Joon; Um, Soon Ho; Ryu, Ho Sang; Kim, Yun Hwan; Kim, Chong Suk; Shin, Eun

    2014-01-01

    Transcatheter arterial radioembolization (TARE) with Yttrium-90 (90Y)-labeled microspheres has an emerging role in treatment of patients with unresectable hepatocellular carcinoma. Although complication of TARE can be minimized by aggressive pre-evaluation angiography and preventive coiling of aberrant vessels, radioembolization-induced gastroduodenal ulcer can be irreversible and can be life-threatening. Treatment of radioembolization-induced gastric ulcer is challenging because there is a few reported cases and no consensus for management. We report a case of severe gastric ulceration with bleeding that eventually required surgery due to aberrant deposition of microspheres after TARE. PMID:25320734

  14. 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.

  15. 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

  16. 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.

  17. Synthesis and Comparative Biological Evalution of Bifunctional Ligands for Radiotherapy Applications of 90Y and 177Lu

    PubMed Central

    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

    2015-01-01

    Zevalin® is an antibody-drug conjugate radiolabeled with a cytotoxic radioisotope (90Y) 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 90Y and 177Lu. The bifunctional ligands were evaluated for radiolabeling kinetics with 90Y and 177Lu, and the corresponding 90Y or 177Lu-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 90Y and 177Lu, and the corresponding 90Y- and 177Lu-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 90Y and 177Lu. PMID:25648683

  18. 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.

  19. Intra-arterial {sup 90}Y brachytherapy: Preliminary dosimetric study using a specially modified angioplasty balloon

    SciTech Connect

    Popowski, Y.; Nouet, P.; Rouzaud, M.

    1995-10-15

    Irradiation has been shown to be effective in preventing restenosis after dilatation in human peripheral arteries. We have developed a dedicated system for coronary intraarterial irradiation using a {sup 90}Y pure beta-emitting source inside a specially modified angioplasty balloon. This paper presents a preliminary dosimetric evaluation of this system. Thermoluminescent dosimetric measurements using the standard balloons filled with contrast medium were plotted semilogarithmically as a function of distance from the balloon surface. The logarithms of the measured doses fit a straight line as a function of depth. The doses at 1 mm and 3 mm are approximately 50 and 10% of the surface dose, respectively. Due to the poor centering of the source in the conventional balloons, the dispersion and standard deviations (SDs) of the measured surface doses increased proportionally to the balloon diameter (SDs are 1.89, 5.52, 5.79, and 6.46 Gy for 2.5, 3, 3.5, and 4 mm balloon diameters, respectively). For the 3.5 mm centering and conventional balloons the respective mean, minimum, and maximum surface doses were 8.41 Gy (min.7.26; max. 9.46) and 7.89 Gy (min. 2.18; max. 16.06) and their standard deviations were 0.66 and 5.79 Gy, respectively. Conventional angioplasty balloons cannot ensure a homogeneous dose delivery to an arterial wall with an intralumenal {sup 90}Y beta source. Preliminary dosimetric results using a modified centering balloon show that it permits improved surface dose distribution (axial and circumferential homogeneity), making it suitable for clinical applications. 9 refs., 5 figs.

  20. 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

  1. 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.; ...

    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

  2. Inflammation-induced synergetic enhancement of nanoparticle treatments with DOXIL® and 90Y-Lactosome for orthotopic mammary tumor

    NASA Astrophysics Data System (ADS)

    Kurihara, Kensuke; Ueda, Motoki; Hara, Isao; Hara, Eri; Sano, Kohei; Makino, Akira; Ozeki, Eiichi; Yamamoto, Fumihiko; Saji, Hideo; Togashi, Kaori; Kimura, Shunsaku

    2016-05-01

    Polymeric micelles (Lactosome) in the size of 20-30 nm were labeled with radionuclides of 111In (111In-DOTA-Lactosome) for SPECT imaging and 90Y (90Y-DOTA-Lactosome) for β-ray irradiation for mammary tumor in mice. The tumor site at the femoral right leg grafted with 4T1 cells was clearly imaged at 24 h after the intravenous injection. Biodistribution revealed that the half-life time of 111In-DOTA-Lactosome was 11 h, which enabled the nanoparticle selectively accumulated in tumor site due to the enhanced permeability and retention (EPR) effect. The anti-tumor therapeutic effect of 90Y-DOTA-Lactosome was observed depending on the dose frequency and amount. Under the condition of the percutaneous ethanol injection treatment, the therapeutic effect of 90Y-DOTA-Lactosome was enhanced due to the super EPR effect. Owing to the super EPR effect, co-administration of 90Y-DOTA-Lactosome and DOXIL® inhibited the tumor growth during 15 days with their administrations.

  3. 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.

  4. 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.

  5. Detection of bremsstrahlung radiation of 90Sr-90Y for emergency lung counting.

    PubMed

    Ho, A; Hakmana Witharana, S S; Jonkmans, G; Li, L; Surette, R A; Dubeau, J; Dai, X

    2012-09-01

    This study explores the possibility of developing a field-deployable (90)Sr detector for rapid lung counting in emergency situations. The detection of beta-emitters (90)Sr and its daughter (90)Y inside the human lung via bremsstrahlung radiation was performed using a 3″ × 3″ NaI(Tl) crystal detector and a polyethylene-encapsulated source to emulate human lung tissue. The simulation results show that this method is a viable technique for detecting (90)Sr with a minimum detectable activity (MDA) of 1.07 × 10(4) Bq, using a realistic dual-shielded detector system in a 0.25-µGy h(-1) background field for a 100-s scan. The MDA is sufficiently sensitive to meet the requirement for emergency lung counting of Type S (90)Sr intake. The experimental data were verified using Monte Carlo calculations, including an estimate for internal bremsstrahlung, and an optimisation of the detector geometry was performed. Optimisations in background reduction techniques and in the electronic acquisition systems are suggested.

  6. Verification and uniformity control of doses for 90Sr/90Y intravascular brachytherapy sources using radiochromic film dosimetry

    PubMed Central

    Demir, Bayram; Ahmed, Asm Sabbir; Babalik, Erhan; Demir, Mustafa; Gürmen, Tevfik

    2008-01-01

    Intravascular brachytherapy (IVBT) is a useful treatment modality for the recurrence of in-stent restenosis following drug-eluting stents (DES) or IVBT failure. The objective of this study was to measure the dose rate of 90Sr/90Y IVBT sources for comparison with that given by the manufacturer and to control the dose uniformities of these sources along the source axis. The dose rates of 90Sr/90Y beta sources were measured with a radiochromic film in a custom-made phantom. The films for calibration were irradiated using 60Co photon beams. The results for the three sources were 4.5%, 2.3%, and 3.5% higher than the corresponding certificate values. Maximum and minimum of the dose rates varied within ±10% of those at source center; and maximum dose discrepancy for the first 90Sr/90Y source train was 8.2%; for the second source train, 7.1%; and for the third source train, 5.1%. Our study showed that the dose rates given by the manufacturer for the three 90Sr/90Y IVBT sources were reliable and dose uniformities were within ±10% along two thirds of the treatment length. PMID:19893691

  7. (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.

  8. Simulation of a 32P Sourcewire and a 90Sr/90Y Sourcetrain Using MCNP4b and EGS4

    NASA Astrophysics Data System (ADS)

    Todorovic, M.; Cremers, F.; Albers, D.; Schmidt, R.

    The two simulated sources, the 32P sourcewire and the 90Sr/90Y sourcetrain, are parts of catheter-based systems developed for vascular brachytherapy. Percutaneous transluminal coronary angioplasty (PTCA) is a widely accepted therapy for symptomatic coronary disease, but within the first 6 months often restenosis occur. The intracoronary brachytherapy is a new method to help avoiding restenosis [1].

  9. 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.

  10. 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.

  11. Synthesis and Evaluation of a New Bifunctional NETA Chelate for Molecular Targeted Radiotherapy Using 90Y or 177Lu

    PubMed Central

    Kang, Chi Soo; Chen, Yunwei; Lee, Hyunbeom; Liu, Dijie; Sun, Xiang; Kweon, Junghun; Lewis, Michael R.; Chong, Hyun-Soon

    2015-01-01

    Introduction Therapeutic potential of β-emitting cytotoxic radionuclides 90Y and 177Lu have been demonstrated in numerous preclinical and clinical trials. A bifunctional chelate that can effectively complex with the radioisotopes is a critical component for molecular targeted radiotherapy 90Y and 177Lu. A new bifunctional chelate 5p-C-NETA with a relatively long alkyl spacer between the chelating backbone and the functional unit for conjugation to a tumor targeting moiety was synthesized. 5p-C-NETA was conjugated to a model targeting moiety, a cyclic Arg-Gly-Asp-D-Tyr-Lys (RGDyK) peptide binding integrin αvβ3 protein overexpressed on various cancers. 5p-C-NETA was conjugated to c(RGDyK) peptide and evaluated for potential use in molecular targeted radiotherapy of 90Y and 177Lu. Methods 5p-C-NETA conjugated with c(RGDyK) was evaluated in vitro for radiolabeling, serum stability, binding affinity, and the result of the in vitro studies of 5p-C-NETA-c(RGDyK) was compared to that of 3p-CNETA-c(RGDyK). 177Lu-5p-C-NETA-c(RGDyK) was further evaluated for in vivo biodistribution using gliobastoma bearing mice. Result The new chelate rapidly and tightly bound to a cytotoxic radioisotope for cancer therapy, 90Y or 177Lu with excellent radiolabeling efficiency and maximum specific activity under mild condition (>99%, RT, <1 min). 90Y- and 177Lu-radiolabeled complexes of the new chelator remained stable in human serum without any loss of the radiolanthanide for 14 days. Introduction of the tumor targeting RGD moiety to the new chelator made little impact on complexation kinetics and stability with 90Y or 177Lu. 177Lu-radiolabeled 5p-C-NETA-c(RGDyK) conjugate was shown to target tumors in mice and produced a favorable in vivo stability profile. Conclusion The results of in vitro and in vivo evaluation suggest that 5p-C-NETA is an effective bifunctional chelate of 90Y and 177Lu that can be applied for generation of versatile molecular targeted radiopharmaceuticals. PMID

  12. Activity measurements of 18F and 90Y with commercial radionuclide calibrators for nuclear medicine in Switzerland.

    PubMed

    Caffari, Yvan; Spring, Philippe; Bailat, Claude; Nedjadi, Youcef; Bochud, François

    2010-01-01

    The activity of radiopharmaceuticals in nuclear medicine is measured before patient injection with radionuclide calibrators. In Switzerland, the general requirements for quality controls are defined in a federal ordinance and a directive of the Federal Office of Metrology (METAS) which require each instrument to be verified. A set of three gamma sources (Co-57, Cs-137 and Co-60) is used to verify the response of radionuclide calibrators in the gamma energy range of their use. A beta source, a mixture of (90)Sr and (90)Y in secular equilibrium, is used as well. Manufacturers are responsible for the calibration factors. The main goal of the study was to monitor the validity of the calibration factors by using two sources: a (90)Sr/(90)Y source and a (18)F source. The three types of commercial radionuclide calibrators tested do not have a calibration factor for the mixture but only for (90)Y. Activity measurements of a (90)Sr/(90)Y source with the (90)Y calibration factor are performed in order to correct for the extra-contribution of (90)Sr. The value of the correction factor was found to be 1.113 whereas Monte Carlo simulations of the radionuclide calibrators estimate the correction factor to be 1.117. Measurements with (18)F sources in a specific geometry are also performed. Since this radionuclide is widely used in Swiss hospitals equipped with PET and PET-CT, the metrology of the (18)F is very important. The (18)F response normalized to the (137)Cs response shows that the difference with a reference value does not exceed 3% for the three types of radionuclide calibrators.

  13. 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

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. Fractionated Radioimmunotherapy With 90Y-Clivatuzumab Tetraxetan and Low-Dose Gemcitabine Is Active in Advanced Pancreatic Cancer

    PubMed Central

    Ocean, Allyson J.; Pennington, Kenneth L.; Guarino, Michael J.; Sheikh, Arif; Bekaii-Saab, Tanios; Serafini, Aldo N.; Lee, Daniel; Sung, Max W.; Gulec, Seza A.; Goldsmith, Stanley J.; Manzone, Timothy; Holt, Michael; O’Neil, Bert H.; Hall, Nathan; Montero, Alberto J.; Kauh, John; Gold, David V.; Horne, Heather; Wegener, William A.; Goldenberg, David M.

    2014-01-01

    BACKGROUND It has been demonstrated that the humanized clivatuzumab tetraxetan (hPAM4) antibody targets pancreatic ductal carcinoma selectively. After a trial of radioimmunotherapy that determined the maximum tolerated dose of single-dose yttrium-90-labeled hPAM4 (90Y-hPAM4) and produced objective responses in patients with advanced pancreatic ductal carcinoma, the authors studied fractionated radioimmunotherapy combined with low-dose gemcitabine in this disease. METHODS Thirty-eight previously untreated patients (33 patients with stage IV disease and 5 patients with stage III disease) received gemcitabine 200 mg/m2 weekly for 4 weeks with 90Y-hPAM4 given weekly in Weeks 2, 3, and 4 (cycle 1), and the same cycle was repeated in 13 patients (cycles 2–4). In the first part of the study, 19 patients received escalating weekly 90Y doses of 6.5 mCi/m2, 9.0 mCi/m2, 12.0 mCi/m2, and 15.0 mCi/m2. In the second portion, 19 additional patients received weekly doses of 9.0 mCi/m2 or 12.0 mCi/m2. RESULTS Grade 3/4 thrombocytopenia or neutropenia (according to version 3.0 of the National Cancer Institute’s Common Terminology Criteria for Adverse Events) developed in 28 of 38 patients after cycle 1 and in all retreated patients; no grade >3 nonhematologic toxicities occurred. Fractionated dosing of cycle 1 allowed almost twice the radiation dose compared with single-dose radioimmunotherapy. The maximum tolerated dose of 90Y-hPAM4 was 12.0 mCi/m2 weekly for 3 weeks for cycle 1, with ≤9.0 mCi/m2 weekly for 3 weeks for subsequent cycles, and that dose will be used in future trials. Six patients (16%) had partial responses according to computed tomography-based Response Evaluation Criteria in Solid Tumors, and 16 patients (42%) had stabilization as their best response (58% disease control). The median overall survival was 7.7 months for all 38 patients, including 11.8 months for those who received repeated cycles (46% [6 of 13 patients] ≥1 year), with improved efficacy at

  1. 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.

  2. WE-AB-204-01: Performance Characterization of Regularized-Reconstruction Algorithm for 90Y PET/CT Images

    SciTech Connect

    Siman, W; Kappadath, S; Mawlawi, O

    2015-06-15

    Purpose: {sup 90}Y PET/CT imaging and quantification have recently been suggested as an approach of treatment verification. However, due to low positron yield (32ppm), the {sup 90}Y-PET/CT images are very noisy. Iterative reconstruction techniques that employ regularization, e.g. block sequential regularized expectation maximization (BSREM) algorithm (recently implemented on GE scanners – QClear™), has the potential to increase quantitative accuracy with lower noise penalty compared to OSEM. Our aim is to investigate the performance of RR algorithms in {sup 90}Y PET/CT studies. Methods: A NEMA IEC phantom filled with 3GBq {sup 90}YCl{sub 2} (to simulate patient treatment) was imaged on GE-D690 for 1800s/bed. The sphere-to-background ratio of 7. The data were reconstructed using OSEM and BSREM with PSF modeling and TOF correction while varying the iterations (IT) from 1–6 with fixed 24subsets. For BSREM, the edge-preservation parameter (γ ) was 2 and the penalty-parameters (β) was varied 350–950. In all cases a post-reconstruction filter of 5.2mm (2pixel) transaxial and standard z-axis were used. Sphere average activity concentration (AC) and background standard deviation (SD) were then calculated from VOIs drawn in the spheres and background. Results: Increasing IT from 1to6, the %SD in OSEM increased from 30% to 80%, whereas %SD in BSREM images increased by <5% for all βs. BSREM with β=350 didn’t offer any improvement over OSEM (convergence of mean achieved at 2 IT, in this study). Increasing β from 350 to 950 reduced the AC accuracy of small spheres (<20mm) by 10% and noise from 40% to 20%, which resulted in CNR increase from 11 to 17. Conclusion: In count-limited studies such as {sup 90}Y PET/CT, BSREM can be used to suppress image noise and increase CNR at the expense of a relatively small decrease of quantitative accuracy. The BSREM parameters need to be optimized for each study depending on the radionuclides and count densities. Research

  3. 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

  4. The effect of heat treatment on amorphous Fe74Zr19Ta7 and Fe90Y10 alloys

    NASA Astrophysics Data System (ADS)

    Prater, J. T.; Merz, M. D.

    1981-03-01

    Magnetic measurements are reported for two iron-based amorphous alloys: Fe90Y10 and Fe74Zr19Ta7. Each is prepared by sputter deposition. X-tay diffraction is used to established the amorphous structure and X-ray fluorescence analysis to confirm the composition. Fe74Zr19Ta7 has a Curie temperature of 195 K and a crystallization temperature of 733 K (460 °C). Annealing studies on Fe74Zr19Ta7 indicate that this alloy does not show the dramatic increases in Curie temperature that are commonly observed in amorphous alloys that contain metalloid elements. Rather, this alloy exhibits small irreversible decreases in the Curie temperature following heat treatments up to 733 K (460 °C), the crystallization temperature. The amorphous Fe90Y10 alloy shows only short range order and has a large anisotropy field that prevents the saturation of the magnetic moment in a 10 kOe field at 78 K. The anisotropy decreases upon crystallization to a bcc iron structure, but ferromagnetism is observed only after annealing the alloy at elevated temperatures.

  5. Dosimetry of a (90)Y-hydroxide liquid brachytherapy treatment approach to canine osteosarcoma using PET/CT.

    PubMed

    Zhou, Jien Jie; Gonzalez, Arnulfo; Lenox, Mark W; Fossum, Theresa W; Frank, R Keith; Simon, Jaime; Stearns, Stan; Ruoff, Catherine M; Wendt, Richard E; Akabani, Gamal

    2015-03-01

    A new treatment strategy based on direct injections of (90)Y-hydroxide into the tumor bed in dogs with osteosarcoma was studied. Direct injections of the radiopharmaceutical into the tumor bed were made according to a pretreatment plan established using (18)F-FDG images. Using a special drill, cannulas were inserted going through tissue, tumor and bone. Using these cannulas, direct injections of the radiopharmaceutical were made. The in vivo biodistribution of (90)Y-hydroxide and the anatomical tumor bed were imaged using a time-of-flight (TOF) PET/CT scanner. The material properties of the tissues were estimated from corresponding CT numbers using an electron-density calibration. Radiation absorbed dose estimates were calculated using Monte Carlo methods where the biodistribution of the pharmaceutical from PET images was sampled using a collapsing 3-D rejection technique. Dose distributions in the tumor bed and surrounding tissues were calculated, showing significant heterogeneity with multiple hot spots at injection sites. Dose volume histograms showed that approximately 33.9% of bone and tumor and 70.2% of bone marrow and trabecular bone received an absorbed dose over 200Gy; approximately 3.2% of bone and tumor and 31.0% of bone marrow and trabecular bone received a total dose of over 1000Gy.

  6. 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.

  7. 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.

  8. 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.

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

    PubMed

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

    2015-01-01

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

  10. Absorbed dose assessment of cardiac and other tissues around the cardiovascular system in brachytherapy with 90Sr/90Y source by Monte Carlo simulation.

    PubMed

    Saghamanesh, S; Karimian, A; Abdi, M

    2011-09-01

    Cardiac disease is one of the most important causes of death in the world. Coronary artery stenosis is a very common cardiac disease. Intravascular brachytherapy (IVBT) is one of the radiotherapy methods which have been used recently in coronary artery radiation therapy for the treatment of restenosis. (90)Sr/(90)Y, a beta-emitting source, is a proper option for cardiovascular brachytherapy. In this research, a Monte Carlo simulation was done to calculate dosimetry parameters and effective equivalent doses to the heart and its surrounding tissues during IVBT. The results of this study were compared with the published experimental data and other simulations performed by different programs but with the same source of radiation. A very good agreement was found between results of this work and the published data. An assessment of the risk for cardiac and other sensitive soft tissues surrounding the treated vessel during (90)Sr/(90)Y IVBT was also performed in the study.

  11. 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

  12. Genotoxic and cytotoxic effects of 60Co gamma-rays and 90Sr/90Y beta-rays on Chinese hamster ovary cells (CHO-K1).

    PubMed

    Murakami, Daniella; Suzuki, Miriam Fussae; da Silva Dias, Mauro; Okazaki, Kayo

    2004-07-01

    Among various types of ionizing radiation, the beta emitter radionuclides are involved in many sectors of human activity, such as nuclear medicine, nuclear industries and biomedicine, with a consequently increased risk of accidental, occupational or therapeutic exposure. Despite their recognized importance, there is little information about the effect of beta particles at the cellular level when compared to other types of ionizing radiation. Thus, the objective of the present study was to evaluate the genotoxic and cytotoxic effects of (90)Sr/(90)Y-a pure, highly energetic beta source-on Chinese hamster ovary (CHO) cells and to compare them with data obtained with (60)Co. CHO cells irradiated with different doses of (60)Co (0.34 Gy min(-1)) and (90)Sr/(90)Y (0.23 Gy min(-1)) were processed for analysis of clonogenic death, induction of micronuclei (MN) and interphase death. The survival curves obtained for both types of radiation were fitted by the exponential quadratic model and were found to be similar. Also, the cytogenetic results showed similar frequencies of radio-induced MN between gamma and beta radiations and the MN distribution pattern among cells did not follow the expected Poisson probability pattern. The relative variance values were significantly higher in cells irradiated with (90)Sr/(90)Y than with (60)Co in all exposure doses. The irradiated cells showed more necrotic cells 72 h and 96 h after exposure to beta than to gamma radiation. In general, the (90)Sr/(90)Y beta-radiation was more damaging than (60)Co gamma-rays. The data obtained also demonstrated the need to use several parameters for a better estimate of cellular sensitivity to the action of genotoxic agents, which would be important in terms of radiobiology, oncology and therapeutics.

  13. 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.

  14. 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.

  15. 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.

  16. Radioembolization with 90Y glass microspheres for the treatment of unresectable metastatic liver disease from chemotherapy-refractory gastrointestinal cancers: final report of a prospective pilot study

    PubMed Central

    Kerlan, Robert K.; Hawkins, Randall A.; Pampaloni, Miguel; Taylor, Andrew G.; Kohi, Maureen P.; Kolli, K. Pallav; Atreya, Chloe E.; Bergsland, Emily K.; Kelley, R. Kate; Ko, Andrew H.; Korn, W. Michael; Van Loon, Katherine; McWhirter, Ryan M.; Luan, Jennifer; Johanson, Curt; Venook, Alan P.

    2016-01-01

    Background This prospective pilot single-institution study was undertaken to document the feasibility, safety, and efficacy of radioembolization of liver-dominant metastatic gastrointestinal cancer using 90Y glass microspheres. Methods Between June 2010 and October 2013, 42 adult patients (26 men, 16 women; median age 60 years) with metastatic chemotherapy-refractory unresectable colorectal (n=21), neuroendocrine (n=11), intrahepatic bile duct (n=7), pancreas (n=2), and esophageal (n=1) carcinomas underwent 60 lobar or segmental administrations of 90Y glass microspheres. Data regarding clinical and laboratory adverse events (AE) were collected prospectively for up to 5.5 years after radioembolization. Radiographic responses were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Time to maximum response, response duration, progression-free survival (PFS) (hepatic and extrahepatic), and overall survival (OS) were measured. Results Median target dose and activity were 109.4 Gy and 2.6 GBq per treatment session, respectively. Majority of clinical AE were grade 1 or 2 in severity. Patients with colorectal cancer had hepatic objective response rate (ORR) of 25% and a hepatic disease control rate (DCR) of 80%. Median PFS and OS were 1.0 and 4.4 months, respectively. Patients with neuroendocrine tumors (NET) had hepatic ORR and DCR of 73% and 100%, respectively. Median PFS was 8.9 months for this cohort. DCR and median PFS and OS for patients with cholangiocarcinoma were 86%, 1.1 months, and 6.7 months, respectively. Conclusions 90Y glass microspheres device has a favorable safety profile, and achieved prolonged disease control of hepatic tumor burden in a subset of patients, including all patients enrolled in the neuroendocrine cohort. PMID:28078110

  17. A 90Y-labelled anti-ROBO1 monoclonal antibody exhibits antitumour activity against hepatocellular carcinoma xenografts during ROBO1-targeted radioimmunotherapy

    PubMed Central

    2014-01-01

    Background ROBO1 is a membrane protein that functions in axon guidance. ROBO1 contributes to tumour metastasis and angiogenesis and may have potential as a target protein of immunotherapy because ROBO1 is specifically expressed at high levels in hepatocellular carcinoma. In this study, we examined biodistribution and radioimmunotherapy (RIT) using a radioisotope-labelled anti-ROBO1 monoclonal antibody (MAb) against hepatocellular carcinoma models. Methods ROBO1-positive HepG2 human hepatocellular carcinoma xenograft nude mice were used in this study. We conjugated anti-ROBO1 MAb with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), and the conjugates were labelled with 111In and 90Y. To study biodistribution, the 111In-DOTA-anti-ROBO1 MAb was injected into HepG2 xenograft mice via the tail vein. To evaluate any antitumour effect, a RIT study was performed, and the 90Y-DOTA-anti-ROBO1 MAb was injected via the tail vein. Tumour volume, mouse weight, and blood cell count were periodically measured throughout the experiments. The tumours and organs of mice were collected, and a histopathological analysis was carried out. Results The tumour uptake of 111In-anti-ROBO1 MAb in HepG2 xenograft mice was 15.0% ± 0.69% injected dose per gram at 48 h after injection. Immunotherapy with cold-anti-ROBO1 MAb (70 μg) did not cause a significant antitumour effect. RIT with 6.7 MBq of 90Y-anti-ROBO1 MAb caused significant tumour growth suppression. Transient body weight loss and bone-marrow suppression were observed. Histopathological analyses of tumours revealed the fatal degeneration of tumour cells, significant reduction of the Ki-67 index, and an increase of the apoptosis index. Normal organs showed no significant injury, but a transient reduction of hematopoietic cells was observed in the spleen and in the sternal bone marrow. Conclusions These results suggest that RIT with 90Y-anti-ROBO1 MAb is a promising treatment for ROBO1-positive hepatocellular

  18. (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.

  19. 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.

  20. Partition Model-Based 99mTc-MAA SPECT/CT Predictive Dosimetry Compared with 90Y TOF PET/CT Posttreatment Dosimetry in Radioembolization of Hepatocellular Carcinoma: A Quantitative Agreement Comparison.

    PubMed

    Gnesin, Silvano; Canetti, Laurent; Adib, Salim; Cherbuin, Nicolas; Silva Monteiro, Marina; Bize, Pierre; Denys, Alban; Prior, John O; Baechler, Sebastien; Boubaker, Ariane

    2016-11-01

    (90)Y-microsphere selective internal radiation therapy (SIRT) is a valuable treatment in unresectable hepatocellular carcinoma (HCC). Partition-model predictive dosimetry relies on differential tumor-to-nontumor perfusion evaluated on pretreatment (99m)Tc-macroaggregated albumin (MAA) SPECT/CT. The aim of this study was to evaluate agreement between the predictive dosimetry of (99m)Tc-MAA SPECT/CT and posttreatment dosimetry based on (90)Y time-of-flight (TOF) PET/CT.

  1. Local injection of the 90Y-labelled peptidic vector DOTATOC to control gliomas of WHO grades II and III: an extended pilot study.

    PubMed

    Schumacher, T; Hofer, S; Eichhorn, K; Wasner, M; Zimmerer, S; Freitag, P; Probst, A; Gratzl, O; Reubi, J-C; Maecke, R; Mueller-Brand, J; Merlo, A

    2002-04-01

    We have previously presented preliminary observations on targeting somatostatin receptor-positive malignant gliomas of all grades by local injection of the radiolabelled peptidic vector 90Y-DOTATOC. We now report on our more thorough clinical experience with this novel compound, focussing on low-grade and anaplastic gliomas. Small peptidic vectors have the potential to target invisible infiltrative disease within normal surrounding brain tissue, thereby opening a window of opportunity for early intervention. Five progressive gliomas of WHO grades II and III and five extensively debulked low-grade gliomas were treated with varying fractions of 90Y-DOTATOC. The vectors were locally injected into the resection cavity or into solid tumour. The activity per single injection ranged from 555 to 1,875 MBq, and the cumulative activity from 555 to 7,030 MBq, according to tumour volumes and eloquence of the affected brain area, yielding dose estimates from 76+/-15 to 312+/-62 Gy. Response was assessed by the clinical status, by steroid dependence and, every 4-6 months, by magnetic resonance imaging and fluorine-18 fluorodeoxyglucose positron emission tomography. In the five progressive gliomas, lasting responses were obtained for at least 13-45 months without the need for steroids. Radiopeptide brachytherapy had been the only modality applied to counter tumour progression. Interestingly, we observed the slow transformation of a solid, primarily inoperable anaplastic astrocytoma into a resectable multi-cystic lesion 2 years after radiopeptide brachytherapy. Based on these observations, we also assessed the feasibility of local radiotherapy following extensive debulking, which was well tolerated. Targeted beta-particle irradiation based on diffusible small peptidic vectors appears to be a promising modality for the treatment of malignant gliomas.

  2. 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

  3. 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.

  4. Targeted cancer therapy with a novel low-dose rate alpha-emitting radioimmunoconjugate.

    PubMed

    Dahle, Jostein; Borrebaek, Jørgen; Jonasdottir, Thora J; Hjelmerud, Anne Kristine; Melhus, Katrine B; Bruland, Øyvind S; Press, Oliver W; Larsen, Roy H

    2007-09-15

    Alpha-emitting radionuclides are highly cytotoxic and are of considerable interest in the treatment of cancer. A particularly interesting approach is in radioimmunotherapy. However, alpha-emitting antibody conjugates have been difficult to exploit clinically due to the short half-life of the radionuclides, low production capability, or limited source materials. We have developed a novel technology based on the low-dose rate alpha-particle-emitting nuclide (227)Th, exemplified here using the monoclonal antibody rituximab. In vitro, this radioimmunoconjugate killed lymphoma cells at Becquerel per milliliter (Bq/mL) levels. A single injection of (227)Th-rituximab induced complete tumor regression in up to 60% of nude mice bearing macroscopic (32-256 mm(3)) human B-lymphoma xenografts at Becquerel per gram (Bq/g) levels without apparent toxicity. Therapy with (227)Th-rituximab was significantly more effective than the control radioimmunoconjugate (227)Th-trastuzumab and the standard beta-emitting radioimmunoconjugate for CD20(+) lymphoma(90)Y-tiuxetan-ibritumomab. Thorium-227 based constructs may provide a novel approach for targeted therapy against a wide variety of cancers.

  5. 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

  6. 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.

  7. Yttrium-90 (90Y) in the principal radionuclide therapies: an efficacy correlation between peptide receptor radionuclide therapy, radioimmunotherapy and transarterial radioembolization therapy. Ten years of experience (1999-2009).

    PubMed

    Goffredo, Veronica; Paradiso, Angelo; Ranieri, Girolamo; Gadaleta, Cosmo Damiano

    2011-12-01

    The clinical application of the pure beta emitter (90)Y constitutes a fundamental advancement in non-invasive medicine. Nowadays, mainly three oncological therapies exploit the intrinsic emissive characteristic of (90)Y. Radionuclide therapies include peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumour (NET) treatment, radioimmunotherapy (RIT) in non-Hodgkin's lymphoma (NHL) treatment and transarterial radioembolization therapy (TARET) in unresectable hepatocellular carcinoma (HCC) and liver metastatic colorectal cancer (mCRC) treatment. The last ten years of clinical experience from E-PubMed research have been reviewed and an efficacy correlation between (90)Y-therapies has shown a better objective response rate for RIT (ORR 80±15%; range 53-100) compared to PRRT (ORR 23.5±14%; range 9-50), and TARET (ORR for mCRC, 40±25%; range 19-91, and ORR for HCC, 42±20%; range 20-82). This review reports on the state of the art of the efficacy of (90)Y-therapies from the last decade and discusses new perspectives of therapeutic development.

  8. The use of gel dosimetry to measure the 3D dose distribution of a 90Sr/90Y intravascular brachytherapy seed.

    PubMed

    Massillon-Jl, G; Minniti, R; Mitch, M G; Maryanski, M J; Soares, C G

    2009-03-21

    Absorbed dose distributions in 3D imparted by a single (90)Sr/(90)Y beta particle seed source of the type used for intravascular brachytherapy were investigated. A polymer gel dosimetry medium was used as a dosemeter and phantom, while a special high-resolution laser CT scanner with a spatial resolution of 100 microm in all dimensions was used to quantify the data. We have measured the radial dose function, g(L)(r), observing that g(L)(r) increases to a maximum value and then decreases as the distance from the seed increases. This is in good agreement with previous data obtained with radiochromic film and thermoluminescent dosemeters (TLDs), even if the TLDs underestimate the dose at distances very close to the seed. Contrary to the measurements, g(L)(r) calculated through Monte Carlo simulations and reported previously steadily decreases without a local maximum as a function of the distance from the seed. At distances less than 1.5 mm, differences of more than 20% are observed between the measurements and the Monte Carlo calculations. This difference could be due to a possible underestimation of the energy absorbed into the seed core and encapsulation in the Monte Carlo simulation, as a consequence of the unknown precise chemical composition of the core and its respective density for this seed. The results suggest that g(L)(r) can be measured very close to the seed with a relative uncertainty of about 1% to 2%. The dose distribution is isotropic only at distances greater than or equal to 2 mm from the seed and is almost symmetric, independent of the depth. This study indicates that polymer gel coupled with the special small format laser CT scanner are valid and accurate methods for measuring the dose distribution at distances close to an intravascular brachytherapy seed.

  9. 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.

  10. SU-E-T-02: 90Y Microspheres Dosimetry Calculation with Voxel-S-Value Method: A Simple Use in the Clinic

    SciTech Connect

    Maneru, F; Gracia, M; Gallardo, N; Olasolo, J; Fuentemilla, N; Bragado, L; Martin-Albina, M; Lozares, S; Pellejero, S; Miquelez, S; Rubio, A; Otal, A

    2015-06-15

    Purpose: To present a simple and feasible method of voxel-S-value (VSV) dosimetry calculation for daily clinical use in radioembolization (RE) with {sup 90}Y microspheres. Dose distributions are obtained and visualized over CT images. Methods: Spatial dose distributions and dose in liver and tumor are calculated for RE patients treated with Sirtex Medical miscrospheres at our center. Data obtained from the previous simulation of treatment were the basis for calculations: Tc-99m maggregated albumin SPECT-CT study in a gammacamera (Infinia, General Electric Healthcare.). Attenuation correction and ordered-subsets expectation maximization (OSEM) algorithm were applied.For VSV calculations, both SPECT and CT were exported from the gammacamera workstation and registered with the radiotherapy treatment planning system (Eclipse, Varian Medical systems). Convolution of activity matrix and local dose deposition kernel (S values) was implemented with an in-house developed software based on Python code. The kernel was downloaded from www.medphys.it. Final dose distribution was evaluated with the free software Dicompyler. Results: Liver mean dose is consistent with Partition method calculations (accepted as a good standard). Tumor dose has not been evaluated due to the high dependence on its contouring. Small lesion size, hot spots in health tissue and blurred limits can affect a lot the dose distribution in tumors. Extra work includes: export and import of images and other dicom files, create and calculate a dummy plan of external radiotherapy, convolution calculation and evaluation of the dose distribution with dicompyler. Total time spent is less than 2 hours. Conclusion: VSV calculations do not require any extra appointment or any uncomfortable process for patient. The total process is short enough to carry it out the same day of simulation and to contribute to prescription decisions prior to treatment. Three-dimensional dose knowledge provides much more information than

  11. Clinical impact of (99m)Tc-MAA SPECT/CT-based dosimetry in the radioembolization of liver malignancies with (90)Y-loaded microspheres.

    PubMed

    Garin, Etienne; Rolland, Yan; Laffont, Sophie; Edeline, Julien

    2016-03-01

    Radioembolization with (90)Y-loaded microspheres is increasingly used in the treatment of primary and secondary liver cancer. Technetium-99 m macroaggregated albumin (MAA) scintigraphy is used as a surrogate of microsphere distribution to assess lung or digestive shunting prior to therapy, based on tumoral targeting and dosimetry. To date, this has been the sole pre-therapeutic tool available for such evaluation. Several dosimetric approaches have been described using both glass and resin microspheres in hepatocellular carcinoma (HCC) and liver metastasis. Given that each product offers different specific activities and numbers of spheres injected, their radiobiological properties are believed to lightly differ. This paper summarizes and discusses the available studies focused on MAA-based dosimetry, particularly concentrating on potential confounding factors like clinical context, tumor size, cirrhosis, previous or concomitant therapy, and product used. In terms of the impact of tumoral dose in HCC, the results were concordant and a response relationship and tumoral threshold dose was clearly identified, especially in studies using glass microspheres. Tumoral dose has also been found to influence survival. The concept of treatment intensification has recently been introduced, yet despite several studies publishing interesting findings on the tumor dose-metastasis relationship, no consensus has been reached, and further clarification is thus required. Nor has the maximal tolerated dose to the liver been well documented, requiring more accurate evaluation. Lung dose was well described, despite recently identified factors influencing its evaluation, requiring further assessment. Conclusion: MAA SPECT/CT dosimetry is accurate in HCC and can now be used in order to achieve a fully customized approach, including treatment intensification. Yet further studies are warranted for the metastasis setting and evaluating the maximal tolerated liver dose.

  12. Late and very late catch-up after 90Sr/90Y beta-irradiation for the treatment of coronary in-stent restenosis.

    PubMed

    Schiele, Thomas M; Herbst, Jan; Pöllinger, Barbara; Rieber, Johannes; König, Andreas; Sohn, Hae-Young; Krötz, Florian; Leibig, Marcus; Belka, Claus; Klauss, Volker

    2011-03-01

    Since late vessel failure has been speculated as a significant limitation of vascular brachytherapy (VBT), we conducted a prospective clinical evaluation at 6, 12, 24, 36 and 60 months follow-up after irradiation with (90)Sr/(90)Y for in-stent restenosis (ISR) regardless of the patient's symptomatic status. Complete five-year follow-up is reported for 104 consecutive patients. The cumulative rate of death was 13.5% (6 months: 0.96%; 12 months: 2.88%; 24 months: 4.81%; 36 months: 7.69%), of acute myocardial infarction 4.81% (2.88%; 4.81%; 4.81%; 4.81%), of late thrombotic occlusion 4.81% (3.85%; 4.81%; 4.81%; 4.81%), of target lesion revascularization (TLR) 27.9% (8.65%; 12.5%; 17.3%; 21.2%), of target vessel revascularization (TVR) 43.3% (12.5%; 19.2%; 22.1%; 29.8%), and of all major adverse cardiovascular events (MACE) 61.5% (16.3%; 26.9%; 31.7%; 42.3%), respectively. Considered that the annual incidence of TVR after the first year following drug-eluting stenting for in-stent restenosis has been reported as approximately 3% per year, an incidence of 5.8% per year following VBT of our study population clearly indicates a more pronounced, delayed and, even in the fifth year after the index procedure, ongoing restenotic process following beta-irradiation of in-stent restenotic lesions associated with clinically relevant adverse cardiovascular events.

  13. Complementary approaches for the evaluation of biocompatibility of 90Y-labeled superparamagnetic citric acid (Fe,Er)3O4 coated nanoparticles

    DOE PAGES

    Antic, Bratislav; Boskovic, Marko; Nikodinovic-Runic, Jasmina; ...

    2017-02-10

    Magnetic nanoparticles (MNPs) are of immense interest for diagnostic and therapeutic applications in medicine. Design and development of new iron oxide-based MNPs for such applications is of rather limited breadth without reliable and sensitive methods to determine their levels in body tissues. Commonly used methods, such as ICP, are quite problematic, due to the inability to decipher the origin of the detected iron, i.e. whether it originates from the MNPs or endogenous from tissues and bodily fluids. One of the approaches to overcome this problem and to increase reliability of tracing MNPs is to partially substitute iron ions in themore » MNPs with Er. Here, we report on the development of citric acid coated (Fe,Er)3O4 nanoparticles and characterization of their physico-chemical and biological properties by utilization of various complementary approaches. The synthesized MNPs had a narrow (6–7 nm) size distribution, as consistently seen in atomic pair distribution function, transmission electron microscopy, and DC magnetization measurements. The particles were found to be superparamagnetic, with a pronounced maximum in measured zero-field cooled magnetization at around 90 K. Reduction in saturation magnetization due to incorporation of 1.7% Er3+ into the Fe3O4 matrix was clearly observed. From the biological standpoint, citric acid coated (Fe,Er)3O4 NPs were found to induce low toxicity both in human cell fibroblasts and in zebrafish (Danio rerio) embryos. Biodistribution pattern of the MNPs after intravenous administration in healthy Wistar rats was followed by the radiotracer method, revealing that 90Y-labeled MNPs were predominantly found in liver (75.33% ID), followed by lungs (16.70% ID) and spleen (2.83% ID). Quantitative agreement with these observations was obtained by ICP-MS elemental analysis using Er as the detected tracer. Based on the favorable physical, chemical and biological characteristics, citric acid coated (Fe,Er)3O4 MNPs could be further

  14. 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

  15. Ultra-Violet Light Emission from HPV-G Cells Irradiated with Low Let Radiation From (90)Y; Consequences for Radiation Induced Bystander Effects.

    PubMed

    Ahmad, Syed Bilal; McNeill, Fiona E; Byun, Soo Hyun; Prestwich, William V; Mothersill, Carmel; Seymour, Colin; Armstrong, Andrea; Fernandez, Cristian

    2013-01-01

    In this study, we aimed to establish the emission of UV photons when HPV-G cells and associated materials (such as the cell substrate and cell growth media) are exposed to low LET radiation. The potential role of UV photons in the secondary triggering of biological processes led us to hypothesize that the emission and absorption of photons at this wavelength explain some radiation induced "bystander effects" that have previously been thought to be chemically mediated. Cells were plated in Petri-dishes of two different sizes, having different thicknesses of polystyrene (PS) substrate, and were exposed to β-radiation from (90)Y produced by the McMaster Nuclear Reactor. UV measurements were performed using a single photon counting system employing an interference-type filter for selection of a narrow wavelength range, 340±5 nm, of photons. Exposure of the cell substrates (which were made of polystyrene) determined that UV photons were being emitted as a consequence of β particle irradiation of the Petri-dishes. For a tightly collimated β-particle beam exposure, we observed 167 photons in the detector per unit μCi in the shielded source for a 1.76 mm thick substrate and 158 photons/μCi for a 0.878 mm thick substrate. A unit μCi source activity was equivalent to an exposure to the substrate of 18 β-particles/cm(2) in this case. The presence of cells and medium in a Petri-dish was found to significantly increase (up to a maximum of 250%) the measured number of photons in a narrow band of wavelengths of 340±5 nm (i.e. UVA) as compared to the signal from an empty control Petri-dish. When coloured growth medium was added to the cells, it reduced the measured count rate, while the addition of transparent medium in equal volume increased the count rate, compared to cells alone. We attribute this to the fact that emission, scattering and absorption of light by cells and media are all variables in the experiment. Under collimated irradiation conditions, it was observed

  16. Ultra-Violet Light Emission from HPV-G Cells Irradiated with Low Let Radiation From 90Y; Consequences for Radiation Induced Bystander Effects

    PubMed Central

    Ahmad, Syed Bilal; McNeill, Fiona E.; Byun, Soo Hyun; Prestwich, William V.; Mothersill, Carmel; Seymour, Colin; Armstrong, Andrea; Fernandez, Cristian

    2013-01-01

    In this study, we aimed to establish the emission of UV photons when HPV-G cells and associated materials (such as the cell substrate and cell growth media) are exposed to low LET radiation. The potential role of UV photons in the secondary triggering of biological processes led us to hypothesize that the emission and absorption of photons at this wavelength explain some radiation induced “bystander effects” that have previously been thought to be chemically mediated. Cells were plated in Petri-dishes of two different sizes, having different thicknesses of polystyrene (PS) substrate, and were exposed to β-radiation from 90Y produced by the McMaster Nuclear Reactor. UV measurements were performed using a single photon counting system employing an interference-type filter for selection of a narrow wavelength range, 340±5 nm, of photons. Exposure of the cell substrates (which were made of polystyrene) determined that UV photons were being emitted as a consequence of β particle irradiation of the Petri-dishes. For a tightly collimated β-particle beam exposure, we observed 167 photons in the detector per unit μCi in the shielded source for a 1.76 mm thick substrate and 158 photons/μCi for a 0.878 mm thick substrate. A unit μCi source activity was equivalent to an exposure to the substrate of 18 β-particles/cm2 in this case. The presence of cells and medium in a Petri-dish was found to significantly increase (up to a maximum of 250%) the measured number of photons in a narrow band of wavelengths of 340±5 nm (i.e. UVA) as compared to the signal from an empty control Petri-dish. When coloured growth medium was added to the cells, it reduced the measured count rate, while the addition of transparent medium in equal volume increased the count rate, compared to cells alone. We attribute this to the fact that emission, scattering and absorption of light by cells and media are all variables in the experiment. Under collimated irradiation conditions, it was observed

  17. 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.

  18. 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

  19. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-03-01

    phosphate; Vandetanib, VIA-2291, Vinflunine, Vorinostat; XL-019; Yttrium 90 (90Y) ibritumomab tiuxetan.

  20. [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.

  1. Gateways to clinical trials.

    PubMed

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

    2004-01-01

    , testosterone gel, tezosentan disodium, tipifarnib, tolvaptan, trabectedin, travoprost, travoprost/timolol, treprostinil sodium; Vardenafil hydrochloride hydrate; Xcellerated T cells, XR-5944; Yttrium 90 (90Y) ibritumomab tiuxetan; Ziconotide.

  2. 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.

  3. 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

  4. Study of influence of plastic scintillators thicknesses to detect Beta particles and Gamma radiation by means of spectral analysis of {sup 90}Sr, {sup 90}Y and {sup 137}Cs sources

    SciTech Connect

    Cardenas, Jose Patricio Nahuel; Filho, Tufic Madi; Pereira, Maria da Conceicao Costa; Santos, Brianna B. dos; Correa, Eduardo de L.; Santos, Lucas Rodrigues dos; Lopes, Anderson Figueredo; Silva, Alexandre F.P. da; Santos, Diogo F. dos; Camilo, Douglas de S.; Purgato, Rafael T.; Aredes, Vitor O.G.

    2015-07-01

    The Nuclear and Energy Research Institute - IPEN, offers post-graduate programs, namely: Nuclear Technology - Applications (TNA), Nuclear Technology - Materials (TNM), Nuclear Technology - Reactors (TNR). The Institute programs mission is to form expert technicians, physicists and engineers with a strong knowledge in their discipline to work in the nuclear area. The course: 'Theoretical Fundamentals and Practices of the Instrumentation used in Nuclear Data Acquisition' covers the use of laboratory nuclear instrumentation and the accomplishment of experiments to obtain nuclear parameters. One of these experimental exercises is object of this work: 'Study of influence of plastic scintillators to detect Beta particles and Gamma radiation by means of spectral analysis of {sup 90}Sr, {sup 90}Y and {sup 137}Cs sources'. The use of scintillators plastic for the detection has the advantage of low cost, high mechanical strength, is not hygroscopic and can be manufactured in large volumes. This work aims to present the analysis of relative efficiency of detection of plastic scintillators of various thicknesses for beta particles and gamma radiation by the spectrum of {sup 137}Cs and {sup 90}Sr. Due to lack of resolution of the detectors plastic scintillators we worked with relative efficiency. The evaluation was done by reading deposited energy, using the software MAESTRO, for each detector thickness. For beta particles was observed an ideal thickness around 3 mm and the better photon efficiency was observed with increasing the thickness of the detector. The present experiment does not intend to establish a new technique for this subject: it solely aims student's practical exercises in nuclear properties of elements and detectors being part of the nuclear experimental course. (authors)

  5. 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.

  6. 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

  7. Ongoing investigations and new uses of radioimmunotherapy in the treatment of non-Hodgkin's lymphoma

    SciTech Connect

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

    2006-10-01

    Studies in radiation oncology are focusing on the optimal use of systemic targeted radionuclide therapy (STaRT) in the treatment of patients with cancer. The two approved radioimmunotherapy agents, yttrium-90 ibritumomab tiuxetan and iodine-131 tositumomab, are being studied in a range of lymphoid malignancies, from low-grade to aggressive B-cell non-Hodgkin's lymphomas. Studies of standard- and escalated-dose radioimmunotherapy with or without stem cell support are reviewed, as are radioimmunotherapy with other therapeutic modalities in these settings. The results of these trials have important implications for clinical practice, and it is hoped that they will further clarify the optimal timing and dosing of these agents.

  8. Basic treatment planning parameters for a 90Sr / 90Y source train used in endovascular brachytherapy.

    PubMed

    Kirisits, Christian; Berger, Daniel; Schmid, Rainer; Syeda, Bonni; Pokrajac, Boris; Glogar, Dietmar; Pötter, Richard; Georg, Dietmar

    2004-01-01

    Working groups of the AAPM, DGMP, and ESTRO have published recommendations for endovascular brachytherapy, introducing concepts of relevant parameters for dose specification and treatment planning. However, the procedures for this treatment remain often mainly based on trial protocols and manufacturer instructions. Treatment planning requires the essential knowledge of the radial and longitudinal dose distribution, as well as information about geometrical uncertainties. The present study includes a whole data set for daily clinical practice using a commercially available device for endovascular brachytherapy (Novoste Betacath). The dose distribution around the 90Sr seed train was calculated with Monte-Carlo algorithms and verified by film dosimetry. The radial dose profile was determined starting from the surface of the delivery catheter Calculated dose profiles were in good agreement to measured values. The geometrical uncertainties were estimated with a retrospective analysis of 51 patient treatments. This shows the importance of using a safety margin of at least 10 mm between Intervention Length and Reference Isodose Length. Based on the longitudinal dose profile and the necessary safety margins, the maximum treatable intervention length is 25 mm and 45 mm for a 40 mm and 60 mm source train, respectively.

  9. 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.

  10. 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)

  11. Gamma camera scans and pretreatment tumor volumes as predictors of response and progression after Y-90 anti-CD20 radioimmunotherapy

    SciTech Connect

    Gokhale, Abhay S.; Mayadev, Jyoti; Pohlman, Brad . E-mail: macklir@ccf.org

    2005-09-01

    Purpose: To evaluate two potential approaches to predicting site-specific patterns of recurrence after yttrium-90 ibritumomab tiuxetan radioimmunotherapy (RIT) for CD20+ B-cell Non-Hodgkin's lymphoma. These predictive methods may be useful in evaluating the utility of local intensification of individual nodal or extranodal sites using external beam radiotherapy. Methods and Materials: Records and images were evaluated for 20 patients previously treated with yttrium-90 ibritumomab RIT. Intensity of isotope uptake on the pretreatment two-dimensional antibody scans and maximal extent of tumor deposits found on computed tomography images of each anatomic site were correlated with response and subsequent patterns of recurrence or progression. Results: Our data failed to suggest a significant correlation between the site-by-site two-dimensional image intensity on the pre-RIT scan and the likelihood of response at those sites. In contrast, an analysis of pretreatment target volumes did correlate significantly with progression. A collective analysis of disease sites from all 20 patients found that 83% (10/12) sites of 'bulky' (maximal diameter {>=}5 cm) disease displayed evidence of progression vs. 28% (26/93) of 'nonbulky' disease sites containing gross disease but no area measuring >5 cm (p < 0.001). All patients with at least one site of bulky disease had initial disease progression occur at a bulky site, with a bulky site being the sole first site of progression in approximately 50%. In patients with only nonbulky disease sites, approximately one third progressed initially at an entirely new site of disease. Conclusion: We conclude that we can use tumor bulk to establish a statistical hierarchy of likely tumor progression sites and use this pattern to direct the use of additional external beam radiotherapy to augment treatment.

  12. Zevalin and BEAM (Z-BEAM) versus rituximab and BEAM (R-BEAM) conditioning chemotherapy prior to autologous stem cell transplantation in patients with mantle cell lymphoma.

    PubMed

    Berger, Martin D; Branger, Giacomo; Klaeser, Bernd; Taleghani, Behrouz Mansouri; Novak, Urban; Banz, Yara; Mueller, Beatrice U; Pabst, Thomas

    2016-09-01

    Early relapse is common in patients with mantle cell lymphoma (MCL) highlighting the unmet need for further improvement of therapeutic options for these patients. CD20 inhibition combined with induction chemotherapy as well as consolidation with high-dose chemotherapy (HDCT) is increasingly considered cornerstones within current therapy algorithms of MCL whereas the role of radioimmunotherapy is unclear. This retrospective single center study compared 46 consecutive MCL patients receiving HDCT in first or second remission. Thirty-five patients had rituximab and BEAM (R-BEAM), and 11 patients received ibritumomab tiuxetan (Zevalin®), an Yttrium-90 labeled CD20 targeting antibody, prior to BEAM (Z-BEAM) followed by autologous stem cell transplantation (ASCT). We observed that the 5-year overall survival (OS) in the R-BEAM and Z-BEAM groups was 55% and 71% (p = 0.288), and the 4-year progression free survival (PFS) was 32% and 41%, respectively (p = 0.300). There were no treatment related deaths in both groups, and we observed no differences in toxicities, infection rates or engraftment. Our data suggest that the Z-BEAM conditioning regimen followed by ASCT is well tolerated, but was not associated with significantly improved survival compared to R-BEAM. Copyright © 2015 John Wiley & Sons, Ltd.

  13. Radioimmunotherapy in a radiation oncology environment: Building a multi-specialty team

    SciTech Connect

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

    2006-10-01

    Radioimmunotherapy (RIT) is a new branch of radiation medicine in which antibodies specific for tumor-associated antigens are linked to radioactive atoms to provide biologically targeted short-range molecular radiotherapy. Two such biologically targeted radiopharmaceuticals have been approved for commercial use in the last few years. Y-90 ibritumomab tiuxetan (Zevalin) and I-131 tositumomab (Bexxar) both recognize the CD-20 surface antigen found on normal and malignant B cells. Both of these compounds produce impressive clinical results when used in the management of indolent, refractory, and transformed CD-20+ B-cell non-Hodgkin's lymphoma, but the unsealed sources involved in this class of compounds also require new types of patient care coordination and patient/environmental safety procedures. Because these multifunctional compounds are ideally administered through a multi-departmental team approach, the planning process to initiate and direct such a team is quite important. This article reviews some of the key processes that may be necessary to establish a successful clinical RIT team. The manuscript highlights the important roles that Radiation oncology team members may play in this multi-department enterprise.

  14. 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.

  15. 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.

  16. 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.

  17. Long-lived impurities of 90Y-labeled microspheres, TheraSphere and SIR-spheres, and the impact on patient dose and waste management.

    PubMed

    Metyko, John; Williford, John M; Erwin, William; Poston, John; Jimenez, Sandra

    2012-11-01

    Yittrium-90 microsphere brachytherapy procedures have increased in number due to their efficacy in treating some unresectable metastatic liver tumors. The discovery of long-lived impurities in two microsphere products, first reported between 2006 and 2007, has resulted in some radiation safety concerns. Since then, microsphere production processes have been refined, which reportedly lead to a reduction in detectable by-products. In this study unused vials of TheraSphere and SIR-Spheres, manufactured in early January 2011, were analyzed to identify and quantify the low-level radioactive impurities. Absorbed dose calculations were performed to assess the potential increased dose to the patient due to long-lived impurities. Results showed that while the SIR-Spheres vials contained no detectable impurities (contrary to other published results in the literature), the TheraSphere vials contained 17 radionuclides in one sample and 15 in the other. The dominant impurities were Y and Y, with specific activities ranging from 0.99 ± 3.40 × 10 kBq mg to 6.30 ± 0.40 kBq mg at vendor assay date. Other impurities were on the order of Bq mg. Based on Medical Internal Radiation Dose (MIRD) liver and lung dose estimates, the long-lived impurities would be expected to increase an administered dose by less than 0.1% from the prescribed dose.

  18. 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.

  19. 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.

  20. A Monte Carlo and physical phantom evaluation of quantitative In-111 SPECT

    NASA Astrophysics Data System (ADS)

    He, Bin; Du, Yong; Song, Xiyun; Segars, W. Paul; Frey, Eric C.

    2005-09-01

    Accurate estimation of the 3D in vivo activity distribution is important for dose estimation in targeted radionuclide therapy (TRT). Although SPECT can potentially provide such estimates, SPECT without compensation for image degrading factors is not quantitatively accurate. In this work, we evaluated quantitative SPECT (QSPECT) reconstruction methods that include compensation for various physical effects. Experimental projection data were obtained using a GE VH/Hawkeye system and an RSD torso phantom. Known activities of In-111 chloride were placed in the lungs, liver, heart, background and two spherical compartments with inner diameters of 22 mm and 34 mm. The 3D NCAT phantom with organ activities based on clinically derived In-111 ibritumomab tiuxetan data was used for the Monte Carlo (MC) simulation studies. Low-noise projection data were simulated using previously validated MC simulation methods. Fifty sets of noisy projections with realistic count levels were generated. Reconstructions were performed using the OS-EM algorithm with various combinations of attenuation (A), scatter (S), geometric response (G), collimator-detector response (D) and partial volume compensation (PVC). The QSPECT images from the various combinations of compensations were evaluated in terms of the accuracy and precision of the estimates of the total activity in each organ. For experimental data, the errors in organ activities for ADS and PVC compensation were less than 6.5% except the smaller sphere (-11.9%). For the noisy simulated data, the errors in organ activity for ADS compensation were less than 5.5% except the lungs (20.9%) and blood vessels (15.2%). Errors for other combinations of compensations were significantly (A, AS) or somewhat (AGS) larger. With added PVC, the error in the organ activities improved slightly except for the lungs (11.5%) and blood vessels (3.6%) where the improvement was more substantial. The standard deviation/mean ratios were all less than 1.5%. We

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

    PubMed

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

    2015-06-01

    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 (99m)Tc-MAA scan and SPECT/CT. Twenty-three patients with liver malignancy were included in the study. (99m)Tc-MAA was injected during planning angiography and whole body (99m)Tc-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 (99m)Tc-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 (99m)Tc-MAA SPECT/CT and ⁹⁰Y-microsphere PET/CT results. Lung shunt fraction was overestimated on (99m)Tc-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 (99m)Tc-MAA SPECT/CT and ⁹⁰Y-microsphere PET/CT (r = 0.64, P < 0.01), although the result from (99m)Tc-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 (99m)Tc-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 (99m)Tc-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)Tc-MAA SPECT/CT was not a significant predictor for PFS. Activity planning based on (99m)Tc-MAA scan and SPECT/CT can be effectively used as a conservative method. Post-SIRT dosimetry based on ⁹⁰Y-microsphere PET/CT is an effective method to predict treatment efficacy.

  2. Lutetium-177-labeled gastrin releasing peptide receptor binding analogs: a novel approach to radionuclide therapy.

    PubMed

    Panigone, S; Nunn, A D

    2006-12-01

    Optimization of therapy for individual patients remains a goal of clinical practice. Radionuclide imaging can identify those patients who may benefit from subsequent targeted therapy by providing regional information on the distribution of the target. An ideal situation may be when the imaging and the therapeutic compounds are the same agent. Two antibodies ([ [90Y]ibritumomab, [131I]tositumomab) are now approved for the systemic radiotherapy of non-Hodgkin's lymphoma. The main hurdle is to deliver higher absorbed doses to the more refractory solid tumors paying particular regard to the bone marrow toxicity. The low dose is thought to be a result of the large size of antibodies slowing delivery to the target. Peptides having high affinity to receptors expressed on cancer cells are a promising alternative. They are usually rapidly excreted from the body through renal and/or hepatobiliary excretion thus creating a prolonged accumulation of the radioactivity in the kidneys, which represents a recognized issue for systemic radiotherapy. The first radiopeptide developed was a somatostatin analogue, which led to a major breakthrough in the field. Beside the kidney issue, somatostatin use remains limited to few cancers that express receptors in sufficiently large quantities, mainly neuroendocrine tumors. The gastrin releasing peptide (GRP) receptor is an attractive target for development of new radiopeptides with diagnostic and therapeutic potential. This is based upon the functional expression of GRP receptors in several of the more prevalent cancers including prostate, breast, and small cell lung cancer. This review covers the efforts currently underway to develop new and clinically promising GRP-receptor specific molecules labeled with imageable and therapeutic radionuclides.

  3. 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

  4. 14 CFR Appendix B to Part 420 - Method for Defining a Flight Corridor

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION LICENSING LICENSE TO OPERATE A LAUNCH SITE Pt. 420, App. B Appendix... transformation from the X90, Y90, Z90, X 90, Y 90, Z 90, components to E, N, U, E, N, U. The...

  5. 14 CFR Appendix B to Part 420 - Method for Defining a Flight Corridor

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION LICENSING LICENSE TO OPERATE A LAUNCH SITE Pt. 420, App. B Appendix... transformation from the X90, Y90, Z90, X 90, Y 90, Z 90, components to E, N, U, E, N, U. The...

  6. 14 CFR Appendix B to Part 420 - Method for Defining a Flight Corridor

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION LICENSING LICENSE TO OPERATE A LAUNCH SITE Pt. 420, App. B Appendix... transformation from the X90, Y90, Z90, X 90, Y 90, Z 90, components to E, N, U, E, N, U. The...

  7. 14 CFR Appendix B to Part 420 - Method for Defining a Flight Corridor

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION LICENSING LICENSE TO OPERATE A LAUNCH SITE Pt. 420, App. B Appendix... transformation from the X90, Y90, Z90, X 90, Y 90, Z 90, components to E, N, U, E, N, U. The...

  8. Intraprocedural yttrium-90 positron emission tomography/CT for treatment optimization of yttrium-90 radioembolization.

    PubMed

    Bourgeois, Austin C; Chang, Ted T; Bradley, Yong C; Acuff, Shelley N; Pasciak, Alexander S

    2014-02-01

    Radioembolization with yttrium-90 ((90)Y) microspheres relies on delivery of appropriate treatment activity to ensure patient safety and optimize treatment efficacy. We report a case in which (90)Y positron emission tomography (PET)/computed tomography (CT) was performed to optimize treatment planning during a same-day, three-part treatment session. This treatment consisted of (i) an initial (90)Y infusion with a dosage determined using an empiric treatment planning model, (ii) quantitative (90)Y PET/CT imaging, and (iii) a secondary infusion with treatment planning based on quantitative imaging data with the goal of delivering a specific total tumor absorbed dose.

  9. Possible novel agents in marginal zone lymphoma.

    PubMed

    Zinzani, Pier Luigi; Broccoli, Alessandro

    Efficacy, safety and mechanisms of action of novel agents in marginal zone lymphoma patients, both with a nodal and extranodal presentation, are reviewed. Data on lenalidomide, bortezomib and (90)yttrium-ibrutumomab tiuxetan are obtained from trials specifically designed for patients affected by marginal zone lymphoma and with various disease presentations. The role of targeted agents, such as obinutuzumab, ibrutinib and idelalisib, and of some very new drugs (venetoclax, copanlisib, ublituximab and TGR-1202) is also discussed, taking into account the most relevant experiences in patients with indolent non-Hodgkin's lymphomas. A glance to some possible drug combinations will also be provided, along with an update of the most relevant ongoing trials.

  10. Chemistry for commercial scale production of yttrium-90 for medical research.

    PubMed

    Wike, J S; Guyer, C E; Ramey, D W; Phillips, B P

    1990-01-01

    Studies were initiated at Oak Ridge National Laboratory (ORNL) in 1982 for the radiolabeling of resin microspheres with yttrium-90 (90Y) for liver cancer therapy. Yttrium-90 is the decay product of strontium-90 (90Sr). Subsequently, 90Y became a major radioisotope of choice for labeling antibodies for therapeutic trials in the treatment of other forms of cancer. A 25-Ci 90Y 90Y generator or 90Sr cow was placed in service to supply the anticipated needs of customers. In vivo use of 90Y required that the 90Sr contamination levels be kept below 10 muCi/Ci 90Y (corrected to preparation time). Also, it was necessary to remove trace metals that interfered in the 90Y antibody radiolabeling process, giving low radiolabeling yields. Di-(2-ethylhexyl) phosphoric acid (HDEHP) in dodecane has been used routinely at ORNL to extract 90Y and thereby give a product that meets the radiochemical purity required with respect to 90Sr. Methods were also developed to remove interfering trace elements to provide acceptable labeling yields.

  11. Yttrium-90 microspheres (TheraSphere and SIR-Spheres) for the treatment of unresectable hepatocellular carcinoma.

    PubMed

    Allison, C

    2007-09-01

    (1) Microspheres containing radioactive yttrium-90 (90Y) are infused into the hepatic artery. These deliver high doses of ionizing radiation to inoperable hepatocellular carcinoma, the most common type of primary liver cancer. (2) Limited evidence from several case series indicates that palliative therapy with 90Y microspheres may reduce tumour size and increase survival time. (3) In some patients, 90Y treatment may result in enough tumour reduction to permit liver resection or transplantation. (4) While 90Y microsphere therapy is generally well tolerated, major complications and several treatment-related deaths have occurred. Improved patient selection criteria and technical changes to microsphere delivery have reduced the risks of complications and death. (5) Patient selection and the technical aspects of 90Y microsphere treatment are complex and require the coordinated expertise of a multidisciplinary team.

  12. 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.

  13. 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.

  14. Case Report of Cirrhosis following Yttrium-90 Radioembolization for Pancreatic Neuroendocrine Liver Metastases

    PubMed Central

    Loree, Jonathan M.; Hiruki, Tadaaki; Kennecke, Hagen F.

    2016-01-01

    Background Management options for pancreatic neuroendocrine tumors (pNETs) metastatic to the liver include surgical, ablative, cytotoxic, and radioisotope approaches. One potential local treatment option includes selective internal radiotherapy utilizing yttrium-90 (90Y) microspheres. 90Y has also been used in the treatment of hepatocellular carcinoma and tumors metastatic to the liver. It appears to be well tolerated; however, there is no randomized controlled trial reporting long-term toxicities. Previous retrospective reports have described biliary damage as a potential complication of therapy with 90Y and chemoembolization; however, the long-term sequelae of 90Y treatment are poorly understood. Case Presentation We present the case of a 65-year-old Caucasian woman who suffered biliary damage following 90Y administration for metastatic pNETs and subsequently developed cirrhosis. Given the timeline of her various treatments and the lack of any other identifiable etiology for her cirrhosis, we believe this to be a potential long-term complication of 90Y therapy. Conclusion This case provides pathologic confirmation of cirrhosis as a potential long-term sequela of 90Y treatment. This long-term risk needs to be considered when sequencing therapy for patients with neuroendocrine tumors who have a good prognosis. There are now several other systemic and ablative treatment options available to these patients, and long-term complications must be considered during treatment. PMID:26933423

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. Yttrium-90 Radioembolization for Hepatocellular Carcinoma.

    PubMed

    Hickey, Ryan M; Lewandowski, Robert J; Salem, Riad

    2016-03-01

    (90)Y radioembolization refers to the selective, transcatheter, and intra-arterial injection of micrometer-sized particles loaded with the radioisotope yttrium-90 for the treatment of primary and metastatic hepatic malignancies. In the treatment of intermediate- and advanced-stage hepatocellular carcinoma, (90)Y radioembolization provides favorable outcomes with minimal side effects, offering an alternative treatment option to other transarterial therapies, such as bland embolization and chemoembolization. This review provides an overview of the use of (90)Y radioembolization in the treatment of hepatocellular carcinoma, including patient selection criteria, dosimetry, and clinical outcomes.

  2. 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.

  3. Resin versus Glass Microspheres for Yttrium-90 Transarterial Radioembolization: Comparing Survival in Unresectable Hepatocellular Carcinoma using Pretreatment Partition Model Dosimetry.

    PubMed

    VAN DER Gucht, Axel; Jreige, Mario; Denys, Alban; Blanc-Durand, Paul; Boubaker, Ariane; Pomoni, Anastasia; Mitsakis, Periklis; Silva-Monteiro, Marina; Gnesin, Silvano; Nicod-Lalonde, Marie; Duran, Rafael; Prior, John; Schaefer, Niklaus

    2017-01-12

    The aim of this study was to compare survival of patients treated for unresectable hepatocellular carcinoma (uHCC) with Yttrium-90 ((90)Y) transarterial radioembolization (TARE) using pretreatment partition model dosimetry (PMD).

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

    PubMed Central

    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.

    2013-01-01

    High resolution yttrium-90 (90Y) 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 90Y 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 90Y 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 90Y bremsstrahlung single-photon emission computed tomography with integrated computed tomography (SPECT/CT) or technetium-99m macroaggregated albumin SPECT/CT. PMID:24551594

  5. Chemoembolic hepatopulmonary shunt reduction to allow safe yttrium-90 radioembolization lobectomy of hepatocellular carcinoma.

    PubMed

    Gaba, Ron C; Vanmiddlesworth, Kyle A

    2012-12-01

    Yttrium-90 ((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 (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 (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 (90)Y radioembolization in patients with extensive tumor-related hepatopulmonary shunting.

  6. Methods to assess the biodistribution of radiolabelled somatostatin analogues and treatment response of neuroendocrine tumours

    NASA Astrophysics Data System (ADS)

    Gnanasegaran, Gopinath

    Introduction: During the past decade, proof of the principle that somatostatin receptors can be successfully used for in vivo targeting of neuroendocrine tumours (NETs) has been provided. These tumours are imaged with 111Indium-pentetreotide and treated with 90Yttrium labeled somatostatin analogues. The aim of this study was to assess (a) the biodistribution and residency of 90Y labelled agents using the brehmsstrahlung imaging technique (b) the tumour response to various treatment modalities using a simplified scintigraphic method [Functional SPECT tumour volume (STV)]. Material and methods: 1) 19 patients with NETs were imaged with 111In-pentetreotide and 14 of them underwent treatment with 90Y-lanreotide. The rest underwent treatment with 90Y-SMT. All the patients were imaged 24 hours post-therapy. Brehmsstrahlung images obtained post therapies were used to assess the 90Y-lanreotide biodistribution in 14 patients and the 5 patients treated with 90Y-SMT, comparing them with 111In-pentetreotide. 2) In 42 patients with NETs a retrospective analysis was performed of the 111In-pentetreotide imaging and CT scan in patients treated with different therapies. A simplified scintigraphic method using 111In-pentetreotide SPECT liver imaging was used to monitor changes in tumour response and to determine how this correlates with CT scan and clinical response. Results: 1) 90Y-lanreotide and 90Y-SMT (with amino acids) have much lower uptake in the kidney (p 0.000 and 0.041 respectively) than 111In-pentetreotide. G Gnanasegaran MD 2 2) 22/42 patients had a good clinical response. A mean fall in total functional STV of 37% was seen in patients with symptomatic relief and a mean increase of 72 % was seen in patients with no symptomatic relief STV predicted the clinical outcome in 34 patients (81%) and CT predicted the outcome in 21 (50%) patients. Conclusion: There was a difference in biodistribution between 111In-pentetreotide and 90Y-lanreotide/ 90Y-SMT, especially in the

  7. 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.

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

    PubMed Central

    Molvar, Christopher; Lewandowski, Robert

    2015-01-01

    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 (90Y) radioembolization. This review will showcase the performance of 90Y 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. PMID:26622103

  9. Comparison of yttrium-90 quantitative imaging by TOF and non-TOF PET in a phantom of liver selective internal radiotherapy

    NASA Astrophysics Data System (ADS)

    van Elmbt, Larry; Vandenberghe, Stefaan; Walrand, Stephan; Pauwels, Stanislas; Jamar, François

    2011-11-01

    The aim of this study is to determine the feasibility of achieving quantitative measurement in 90Y-microspheres liver selective internal radiotherapy (SIRT) by imaging 90Y with a conventional non-time of flight (TOF) PET device. Instead of the bremsstrahlung x-rays of the β-decay, the low branch of e-- e+ pair production in the 90Y-decay was used. The activity distribution in a phantom-simulated liver SIRT was obtained by direct 90Y-PET imaging. We tested a LYSO TOF PET and two GSO and BGO non-TOF PET scanners using a 3.6-l cylindrical phantom filled with the 90Y solution containing two sets of hot and cold spheres. The best hot contrast was obtained with the LYSO TOF. It was close to the expected value and remained constant, even for short acquisition times. The LYSO non-TOF was about 10% lower. The GSO performed similarly but degraded for shorter times whilst the BGO was the worst with 40% loss. For the cold spheres, the LYSO TOF and the GSO provided the best results, while the LYSO non-TOF and the BGO were the worst. 90Y PET imaging in liver SIRT is achievable with LYSO TOF. Conventional LYSO and GSO show a loss of contrast and require longer acquisition times. BGO imaging is not feasible for dosimetry calculation.

  10. SIRT of liver metastases: physiological and pathophysiological considerations.

    PubMed

    Van de Wiele, Christophe; Maes, Alex; Brugman, Eddy; D'Asseler, Yves; De Spiegeleer, Bart; Mees, Gilles; Stellamans, Karin

    2012-10-01

    Available literature on the differences in circulation and microcirculation of normal liver and liver metastases as well as in rheology of the different radiolabelled microspheres [(99m)Tc-labelled macroaggregates of albumin (MAA), (90)Y-TheraSpheres and (90)Y-SIR-spheres] used in selective internal radiation therapy (SIRT) are reviewed and implications thereof on the practice of SIRT discussed. As a result of axial accumulation and skimming, large microspheres are preferentially deposited in regions of high flow, whereas smaller microspheres are preferentially diverted to regions of low flow. As flow to normal liver tissue is considerably variable between segments and also within one segment, microspheres will be delivered heterogeneously within the microvasculature of normal liver tissue. This non-uniformity in microsphere distribution in normal liver tissue has a significant "liver-sparing" effect on the dose distribution of (90)Y-labelled microspheres. Arterial flow to liver metastases is most pronounced in the hypervascular rim of metastases, followed by the smaller metastases and finally by the central hypoperfused region of the larger metastases. Because of the wide variability in size of labelled MAAs and because of the skimming effect, existing differences in flow between metastatic lesions of variable size are likely exaggerated on (99m)Tc-MAA scintigraphy when compared to (90)Y-TheraSpheres and (90)Y-SIR-spheres (smaller variability in size and probably also in specific activity). Ideally, labelled MAAs would contain a size range similar to that of (90)Y-SIR-spheres or (90)Y-TheraSpheres. Furthermore, the optimal number of MAA particles to inject for the pretreatment planning scintigraphy warrants further exploration as it was shown that concentrated suspensions of microspheres produce more optimal tumour to normal liver distribution ratios. Finally, available data suggest that the flow-based heterogeneous distribution of microspheres to metastatic

  11. Preparation and in vivo evaluation of multifunctional ⁹⁰Y-labeled magnetic nanoparticles designed for cancer therapy.

    PubMed

    Radović, Magdalena; Calatayud, María Pilar; Goya, Gerardo Fabián; Ibarra, Manuel Ricardo; Antić, Bratislav; Spasojević, Vojislav; Nikolić, Nadežda; Janković, Drina; Mirković, Marija; Vranješ-Đurić, Sanja

    2015-01-01

    Two different types of magnetic nanoparticles (MNPs) were synthesized in order to compare their efficiency as radioactive vectors, Fe₃O₄-Naked (80 ± 5 nm) and polyethylene glycol 600 diacid functionalized Fe₃O₄(Fe₃O₄-PEG600) MNPs (46 ± 0.6 nm). They were characterized based on the external morphology, size distribution, and colloidal and magnetic properties. The obtained specific power absorption value for Fe₃O₄-PEG600 MNPs was 200 W/g, indicated their potential in hyperthermia based cancer treatments. The labeling yield, in vitro stability and in vivo biodistribution profile of (90) Y-MNPs were compared. Both types of MNPs were (90)Y-labeled in reproducible high yield (>97%). The stability of the obtained radioactive nanoparticles was evaluated in saline and human serum media in order to optimize the formulations for in vivo use. The biodistribution in Wistar rats showed different pharmacokinetic behaviors of nanoparticles: a large fraction of both injected MNPs ended in the liver (14.58%ID/g for (90)Y-Fe₃O₄-Naked MNPs and 19.61%ID/g for (90)Y-Fe₃O₄-PEG600 MNPs) whereas minor fractions attained in other organs. The main difference between the two types of MNPs was the higher accumulation of (90)Y-Fe₃O₄-Naked MNPs in the lungs (12.14%ID/g vs. 2.00%ID/g for (90)Y-Fe₃O₄-PEG600 MNPs) due to their in vivo agglomeration. The studied radiolabeled magnetic complexes such as (90)Y-Fe₃O₄-PEG600 MNPs constitute a great promise for multiple diagnostic-therapeutic uses combining, for example, MRI-magnetic hyperthermia and regional radiotherapy.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Optimization of image reconstruction for yttrium-90 SIRT on a LYSO PET/CT system using a Bayesian penalized likelihood reconstruction algorithm.

    PubMed

    Rowley, Lisa M; Bradley, Kevin M; Boardman, Philip; Hallam, Aida; McGowan, Daniel R

    2016-09-29

    Imaging on a gamma camera with Yttrium-90 ((90)Y) following selective internal radiotherapy (SIRT) may allow for verification of treatment delivery but suffers relatively poor spatial resolution and imprecise dosimetry calculation. (90)Y Positron Emission Tomography (PET) / Computed Tomography (CT) imaging is possible on 3D, time-of-flight machines however images are usually poor due to low count statistics and noise. A new PET reconstruction software using a Bayesian penalized likelihood (BPL) reconstruction algorithm (termed Q.Clear) released by GE was investigated using phantom and patient scans to optimize the reconstruction for post-SIRT imaging and clarify if this leads to an improvement in clinical image quality using (90)Y.

  17. [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.

  18. 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.

  19. 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.

  20. 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…

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

    PubMed

    Lubberink, Mark; Lundqvist, Hans; Tolmachev, Vladimir

    2002-02-21

    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.

  2. 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.

  3. 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.

  4. 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.

  5. Histological study of effects of colloidal 90 yttrium on knee joint tissues of rabbits.

    PubMed

    Pavelka, K; Meier-Ruge, W; Müller, W; Fridrich, R

    1975-02-01

    The administration of 0-2-0-4 mCi 90 yttrium (90Y) into a normal rabbit knee joint fails to induce medical synovectomy and results in the proliferation of the synovialis. The synovial mesothelium shows early radiation damage but subsequently follows a restitution of the whole. Later (within 4 to 16 weeks) an extensive fibrosis of the stratum synovialis develops, as well as an occlusion and sclerosis of smaller synovial vessels and capillaries. These changes explain the beneficial therapeutic effect of 90Y in a chronic inflammatory joint effusion. After irradiation that joint cartilage shows an increased cellular proliferation of the superficial tangential cells and in the vicinity of the cruciate ligaments small foci of degenerated cartilage are present. The overall pattern of a joint treated with intra-articular 90Y corresponds to the histological pattern encountered regularly in joints of older people. Changes of the cartilage after the 90Y radiation could represent a factor predisposing the treated joint to a subsequent development of osteoarthrosis.

  6. Yttrium 90 microspheres for the treatment of hepatocellular carcinoma.

    PubMed

    Memon, Khairuddin; Lewandowski, Robert J; Riaz, Ahsun; Salem, Riad

    2013-01-01

    Yttrium-90 microspheres are radioactive particles which are increasingly being employed for treating patients with unresectable hepatocellular carcinoma (HCC). The procedure is called radioembolization. It involves the injection of micron-sized embolic particles loaded with a radioisotope by use of transarterial techniques. Because of the sensitivity of liver parenchyma and relative insensitivity of tumor, external radiation has played a limited role in treating HCC. (90)Y administered via arterial route directs the highly concentrated radiation to the tumor while healthy liver parenchyma is relatively spared due to its preferential blood supply from portal venous blood. This technique has proven useful for the majority of patients with HCC as most of them present in advanced stage, beyond potentially curative options (resection/liver transplantation). (90)Y microspheres can be used in downstaging large tumors to bring within transplantable criteria, in patients with portal venous thrombosis due to tumor invasion and as palliative therapy. There are two available devices for (90)Y administration; TheraSphere® (glass based) and SIR-Spheres® (resin based). The procedure is performed on an outpatient basis. The incidence of complications is comparatively less and may include nausea, fatigue, abdominal pain, hepatic dysfunction, biliary injury, fibrosis, radiation pneumonitis, GI ulcers, and vascular injury; however, these can be avoided by meticulous pretreatment assessment, careful patient selection, and adequate dosimetry. This article explores the technical and clinical aspects of (90)Y radioembolization with keeping emphasis on patient selection, uses, and complications.

  7. Yttrium-90 radioembolization for hepatocellular carcinoma: what we know and what we need to know.

    PubMed

    Kim, Yun Hwan; Kim, Do Young

    2013-01-01

    In spite of substantial progress in the management of hepatocellular carcinoma (HCC), suboptimal treatment results are frequently seen in the intermediate and advanced stages of HCC. The current staging system indicates that multinodular HCC without vascular invasion needs to be treated by transarterial chemoembolization (TACE) and HCC with vascular nvasion or distant metastasis is linked to sorafenib, an an-tiangiogenic therapy. Radioembolization with yttrium-90 ((90)Y) is a recently introduced liver-directed therapy employing a catheter-based approach. Growing data suggest that (90)Y radioembolization has a potent anticancer effect with negligible adverse events if appropriate pretreatment evaluations including dosimetry, calculation of lung shunt fraction and assessment of vascular anatomy are performed. Retrospective and small prospective studies have shown response rates and survival after (90)Y therapy which are comparable to TACE and sorafenib in the intermediate and advanced stages, respectively. Although a large sample size is necessary to compare the outcome between TACE and radioembolization in intermediate-stage HCC, selected populations, for whom TACE would not be effective, are candidates for testing the role of (90)Y radioembolization. A multidisciplinary, combined approach in advanced HCC using loco-regional therapy such as radioembolization and systemic therapy including sorafenib also has to be investigated.

  8. Image-based dosimetry for selective internal radiation therapy (SIRT) using yttrium-90 microspheres

    NASA Astrophysics Data System (ADS)

    Selwyn, Reed G.

    90Y-loaded microspheres are currently used as a palliative treatment for patients with primary and metastatic solid liver tumors. These microspheres contain radioactive 90Y, which decays via beta-minus transition to 90Zr. While the normal liver receives about 75% of its blood supply from the portal vein, hepatic tumors receive their blood supply almost exclusively from the hepatic artery. Taking advantage of this unique blood flow, radioactive microspheres are injected into the hepatic artery resulting in a preferential distribution to tumor sites within the liver. Studies show that the single best prognostic indicator for patient response is the tumor-to-normal tissue (T:N) activity uptake ratio. However, 90Y emits very few photons its broad bremsstrahlung spectrum leads to diffuse, low resolution images, which are insufficient for accurate T:N quantification. Thus, the first objective was to develop a PET-labeled microsphere as a surrogate for the therapeutic microsphere to provide accurate biodistribution information. Furthermore, patient outcome is also suspected to be linked to the mean tumor dose and tumor dose volume histogram. Therefore, a second objective was to develop and validate a method to calculate the dose distribution within the tumor and normal liver tissue. Computer software that generates three-dimensional (3D) dose distributions was validated by comparing results to experimental measurements. The novel development of a 3D gel dosimeter will be discussed as well as a new protocol for 2D film dosimetry. Both dosimetry methods were validated but only film provided the desired accuracy. The overall accuracy of the dose distribution depends on the uncertainty of the 90Y assay, which can extend to 15% at 1sigma. Therefore, the third objective was to develop an accurate non-destructive assay of 90Y. To this end, a new 90Y positron branching ratio was measured and a clinically relevant transfer standard was developed. In summation, this thesis will

  9. Preparation, characterisation and tumour targeting of cross-linked divalent and trivalent anti-tumour Fab' fragments.

    PubMed Central

    Casey, J. L.; King, D. J.; Chaplin, L. C.; Haines, A. M.; Pedley, R. B.; Mountain, A.; Yarranton, G. T.; Begent, R. H.

    1996-01-01

    The monoclonal anti-CEA antibody, A5B7, has previously been administered to patients for radioimmunotherapy (RIT). Long circulation time and the formation of an immune response have limited therapeutic success in the clinic. Antibody fragments can be used to reduce the in vivo circulation time, but the best combination of fragment and radioisotope to use for therapy is far from clear. In this study we have compared the biodistribution of A5B7 IgG and F(ab')2 with chemically cross-linked divalent (DFM) and trivalent (TFM) A5B7 Fab' fragments in nude mice bearing human colorectal tumour xenografts. The cross-linkers were designed to allow site-specific labelling using yttrium 90 (90Y), a high-energy beta-emitter. We have also compared the above antibody forms conjugated to both 131I and 90Y. Both DFM and TFM were fully immunoreactive and remained intact after radiolabelling and incubation in serum at 37 degrees C for 24 h. Biodistribution results showed similar tumour uptake levels and an identical blood clearance pattern for F(ab')2 and DFM with high tumour-blood ratios generated in each case. However, unacceptably high kidney accumulation for both F(ab')2 and DFM and elevated splenic uptake of DFM labelled with 90Y was observed. Kinetic analysis of antigen binding revealed that DFM had the fastest association rate (kass = 1.6 x 10(5) Ms-1) of the antibody forms, perhaps owing to increased flexibility of the cross-linker. This advantage implies that DFM may be more suitable than F(ab')2 radiolabelled with 131I for RIT. TFM cleared from the blood significantly faster than A5B7 IgG when labelled with both 131I and 90Y, producing an improved therapeutic tumour-blood ratio. Kidney accumulation was not observed for [90Y]TFM, but a slightly higher splenic uptake was observed that may indicate reticuloendothelial system (RES) uptake. Overall, tumour uptake was higher for 90Y-labelled antibodies than for 131I-labelled antibodies. Because of the faster clearance, it should

  10. Quantitative Comparison of PET and Bremsstrahlung SPECT for Imaging the In Vivo Yttrium-90 Microsphere Distribution after Liver Radioembolization

    PubMed Central

    Elschot, Mattijs; Vermolen, Bart J.; Lam, Marnix G. E. H.; de Keizer, Bart; van den Bosch, Maurice A. A. J.; de Jong, Hugo W. A. M.

    2013-01-01

    Background After yttrium-90 (90Y) microsphere radioembolization (RE), evaluation of extrahepatic activity and liver dosimetry is typically performed on 90Y Bremsstrahlung SPECT images. Since these images demonstrate a low quantitative accuracy, 90Y PET has been suggested as an alternative. The aim of this study is to quantitatively compare SPECT and state-of-the-art PET on the ability to detect small accumulations of 90Y and on the accuracy of liver dosimetry. Methodology/Principal Findings SPECT/CT and PET/CT phantom data were acquired using several acquisition and reconstruction protocols, including resolution recovery and Time-Of-Flight (TOF) PET. Image contrast and noise were compared using a torso-shaped phantom containing six hot spheres of various sizes. The ability to detect extra- and intrahepatic accumulations of activity was tested by quantitative evaluation of the visibility and unique detectability of the phantom hot spheres. Image-based dose estimates of the phantom were compared to the true dose. For clinical illustration, the SPECT and PET-based estimated liver dose distributions of five RE patients were compared. At equal noise level, PET showed higher contrast recovery coefficients than SPECT. The highest contrast recovery coefficients were obtained with TOF PET reconstruction including resolution recovery. All six spheres were consistently visible on SPECT and PET images, but PET was able to uniquely detect smaller spheres than SPECT. TOF PET-based estimates of the dose in the phantom spheres were more accurate than SPECT-based dose estimates, with underestimations ranging from 45% (10-mm sphere) to 11% (37-mm sphere) for PET, and 75% to 58% for SPECT, respectively. The differences between TOF PET and SPECT dose-estimates were supported by the patient data. Conclusions/Significance In this study we quantitatively demonstrated that the image quality of state-of-the-art PET is superior over Bremsstrahlung SPECT for the assessment of the 90Y

  11. Quantitative Evaluation of Scintillation Camera Imaging Characteristics of Isotopes Used in Liver Radioembolization

    PubMed Central

    Elschot, Mattijs; Nijsen, Johannes Franciscus Wilhelmus; Dam, Alida Johanna; de Jong, Hugo Wilhelmus Antonius Maria

    2011-01-01

    Background Scintillation camera imaging is used for treatment planning and post-treatment dosimetry in liver radioembolization (RE). In yttrium-90 (90Y) RE, scintigraphic images of technetium-99m (99mTc) are used for treatment planning, while 90Y Bremsstrahlung images are used for post-treatment dosimetry. In holmium-166 (166Ho) RE, scintigraphic images of 166Ho can be used for both treatment planning and post-treatment dosimetry. The aim of this study is to quantitatively evaluate and compare the imaging characteristics of these three isotopes, in order that imaging protocols can be optimized and RE studies with varying isotopes can be compared. Methodology/Principal Findings Phantom experiments were performed in line with NEMA guidelines to assess the spatial resolution, sensitivity, count rate linearity, and contrast recovery of 99mTc, 90Y and 166Ho. In addition, Monte Carlo simulations were performed to obtain detailed information about the history of detected photons. The results showed that the use of a broad energy window and the high-energy collimator gave optimal combination of sensitivity, spatial resolution, and primary photon fraction for 90Y Bremsstrahlung imaging, although differences with the medium-energy collimator were small. For 166Ho, the high-energy collimator also slightly outperformed the medium-energy collimator. In comparison with 99mTc, the image quality of both 90Y and 166Ho is degraded by a lower spatial resolution, a lower sensitivity, and larger scatter and collimator penetration fractions. Conclusions/Significance The quantitative evaluation of the scintillation camera characteristics presented in this study helps to optimize acquisition parameters and supports future analysis of clinical comparisons between RE studies. PMID:22073149

  12. 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

  13. WE-AB-204-02: Molecular-Imaging Based Assessment of Liver Complications for Yttrium-90 Microsphere Treatments: Can Existing NTCP Models Explain Clinical Outcomes?

    SciTech Connect

    Lin, M; Choi, E; Chuong, M; Saboury, B; Moeslein, F; D’Souza, W; Guerrero, M

    2015-06-15

    Purpose: To evaluate weather the current radiobiological models can predict the normal liver complications of radioactive Yttrium-90 ({sup 90}Y) selective-internal-radiation-treatment (SIRT) for metastatic liver lesions based on the post-infusion {sup 90}Y PET images. Methods: A total of 20 patients with metastatic liver tumors treated with SIRT that received a post-infusion {sup 90}Y-PET/CT scan were analyzed in this work. The 3D activity distribution of the PET images was converted into a 3D dose distribution via a kernel convolution process. The physical dose distribution was converted into the equivalent dose (EQ2) delivered at 2 Gy based on the linear-quadratic (LQ) model considering the dose rate effect. The biological endpoint of this work was radiation-induce liver disease (RILD). The NTCPs were calculated with four different repair-times (T1/2-Liver-Repair= 0,0.5,1.0,2.0 hr) and three published NTCP models (Lyman-external-RT, Lyman 90Y-HCC-SIRT, parallel model) were compared to the incidence of RILD of the recruited patients to evaluate their ability of outcome prediction. Results: The mean normal liver physical dose (avg. 51.9 Gy, range 31.9–69.8 Gy) is higher than the suggested liver dose constraint for external beam treatment (∼30 Gy). However, none of the patients in our study developed RILD after the SIRT. The estimated probability of ‘no patient developing RILD’ obtained from the two Lyman models are 46.3% to 48.3% (T1/2-Liver-Repair= 0hr) and <1% for all other repair times. For the parallel model, the estimated probability is 97.3% (0hr), 51.7% (0.5hr), 2.0% (1.0hr) and <1% (2.0hr). Conclusion: Molecular-images providing the distribution of {sup 90}Y enable the dose-volume based dose/outcome analysis for SIRT. Current NTCP models fail to predict RILD complications in our patient population, unless a very short repair-time for the liver is assumed. The discrepancy between the Lyman {sup 90}Y-HCC-SIRT model predicted and the clinically

  14. Radioimmunotherapy of colorectal carcinoma xenografts in nude mice with yttrium-90 A33 IgG and Tri-Fab (TFM).

    PubMed Central

    Antoniw, P.; Farnsworth, A. P.; Turner, A.; Haines, A. M.; Mountain, A.; Mackintosh, J.; Shochat, D.; Humm, J.; Welt, S.; Old, L. J.; Yarranton, G. T.; King, D. J.

    1996-01-01

    The monoclonal antibody A33 recognises a tumour-associated antigen on human colorectal carcinoma, and has undergone preliminary evaluation in the clinic where selective localisation to hepatic metastases has been demonstrated [Welt et al. (1994) J. Clin. Oncol. 12, 1561-1571]. A33 and an A33 tri-fab fragment (TFM) were labelled with 90Y via a stable macrocyclic ligand for biodistribution and therapy studies in nude mice bearing SW1222 colon carcinoma xenografts. Biodistribution studies demonstrated tumour localisation for both A33 IgG and TFM with low bone, liver and kidney levels. Clearance of TFM from the blood was much faster than IgG and this led to lower tumour accumulation for TFM but superior tumour-blood ratios. The maximum per cent injected dose per g localised to tumour was 35.9% +/- 5.3% for A33 IgG and 12.9% +/- 4.6% for A33 TFM with tumour-blood ratios at 48 h after administration of 5.6 +/- 1.8 and 29.2 +/- 9.8 respectively. Autoradiography studies with 125I-labelled A33 IgG and TFM demonstrated a homogeneous distribution within tumour tissue which was not observed with other anti-colorectal tumour antibodies. TFM penetrated into the tumour tissue more rapidly than IgG. In therapy studies, a single dose of 90Y-A33 IgG (250 microCi per mouse) or 90Y-A33 TFM (300 microCi per mouse) led to complete regression of 2-week-old tumour xenografts with long-term tumour-free survivors. A transient drop in white blood cell count was observed with both IgG and TFM but was significantly more pronounced with IgG. The cell count fell to 8.4% of control for IgG, whereas with TFM cell counts fell to 51% of control before recovery. These results indicate that the more rapid blood clearance of 90Y-TFM confers reduced toxicity compared with 90Y-IgG although similar therapeutic effects are achieved. When the dose of 90Y-IgG was adjusted to give the same dose to tumour achieved with 300 microCi 90Y-TFM, a lesser therapeutic effect was observed. This may be owing to more

  15. 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

  16. 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

  17. Color quench correction for low level Cherenkov counting.

    PubMed

    Tsroya, S; Pelled, O; German, U; Marco, R; Katorza, E; Alfassi, Z B

    2009-05-01

    The Cherenkov counting efficiency varies strongly with color quenching, thus correction curves must be used to obtain correct results. The external (152)Eu source of a Quantulus 1220 liquid scintillation counting (LSC) system was used to obtain a quench indicative parameter based on spectra area ratio. A color quench correction curve for aqueous samples containing (90)Sr/(90)Y was prepared. The main advantage of this method over the common spectra indicators is its usefulness also for low level Cherenkov counting.

  18. 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.

  19. Hepatic Abscess After Yttrium-90 Radioembolization for Islet-Cell Tumor Hepatic Metastasis

    SciTech Connect

    Mascarenhas, Neil B.; Mulcahy, Mary F.; Lewandowski, Robert J.; Salem, Riad; Ryu, Robert K.

    2010-06-15

    Infectious complications after yttrium-90 (y-90) radioembolization of hepatic tumors are rare. Most reports describe hepatic abscesses as complications of other locoregional therapies, such as transcatheter arterial embolization or chemoembolization. These usually occur in patients with a history of biliary intervention and present several weeks after treatment. We report a case of hepatic abscess formed immediately after y-90 radioembolization of a hepatic metastasis in a patient who had no history of previous biliary instrumentation.

  20. 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.

  1. Review of five consecutive studies of radiolabeled immunoglobulin therapy in Hodgkin's disease.

    PubMed

    Vriesendorp, H M; Morton, J D; Quadri, S M

    1995-12-01

    Recurrent Hodgkin's Disease (HD) provides unique opportunities to improve radiolabeled immunoglobulin therapy (RIT). Normal tissue toxicity after RIT is limited to bone marrow damage and is well documented and quantified in HD patients. Anti-antibody formation is rare in patients with HD, allowing for multiple RIT cycles. Overall, 134 patients with recurrent HD were treated on five different studies with i.v. antiferritin, labeled with 131I or with 111In for diagnostic purposes and 90Y for therapeutic purposes. Patients with recurrent, end-stage HD obtain a 60% response rate following 90Y-labeled antiferritin. One-half of the therapy responses are complete. Responses are more common in patients with longer disease histories (> 3 years) and smaller tumor volumes (< 30 cm3) and in patients receiving at least 0.4 mCi 90Y-labeled antiferritin/kg body weight. Complete responders survive significantly longer than partial responders (2 years versus 1 year). Partial responders survive longer than patients with progressive disease (1 year versus 4 months). HD in one-third of the patients recurs in new areas. A low protein dose (2-5 mg) and a moderate specific activity (10 mCi/mg) are recommended. Results obtained with 90Y-labeled antiferritin are significantly better than results with 131I-labeled antiferritin. Further translational research in vitro in the radio pharmacy and in vivo with experimental animals is ongoing to improve the therapeutic results of RIT in HD. Obviously, many permutations of RIT cannot be explored in HD patients for ethical, financial, or logistic reasons, and predictive preclinical research is required to achieve further progress. Currently, RIT is a low-toxicity, low-cost outpatient procedure for recurrent HD with a high response rate in a patient population with an unfavorable prognosis.

  2. Cerenkov luminescence endoscopy: Improved molecular sensitivity with β--emitting radiotracers

    DOE PAGES

    Carpenter, Colin M.; Ma, Xiaowei; Liu, Hongguang; ...

    2014-10-09

    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. Here,more » 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. As a result, 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. In conclusion, the use of 90Y for Cerenkov endoscopic imaging enabled superior results compared with an 18F radiotracer.« less

  3. Targeting Phosphatidylserine for Radioimmunotherapy of Breast Cancer Brain Metastasis

    DTIC Science & Technology

    2014-10-01

    care for these patients is whole brain radiotherapy (WBRT). WBRT, however, is often associated with neurological complications that preclude...offers an opportunity to selectively radiate tumor cells while sparing normal tissues. The high energy β- emitter, Yttrium-90 (90Y), a FDA approved...11. Penetrate the syringe needle into intercoastal space promptly through skin and muscle layers into the left ventricle under the guidance of

  4. Analysis of Prognostic Factors After Yttrium-90 Radioembolization of Advanced Hepatocellular Carcinoma

    SciTech Connect

    Inarrairaegui, Mercedes; Martinez-Cuesta, Antonio; Rodriguez, Macarena; Bilbao, J. Ignacio

    2010-08-01

    Purpose: To analyze which patient-, tumor-, and treatment-related factors may influence outcome after {sup 90}Y radioembolization ({sup 90}Y-RE) for hepatocellular carcinoma (HCC). Patients and Methods: Seventy-two consecutive patients with advanced HCC treated with {sup 90}Y-RE were studied to detect which factors may have influenced response to treatment and survival. Results: Median overall survival was 13 months (95% confidence interval, 9.6-16.3 months). In univariate analysis, survival was significantly better in patients with one to five lesions (19 vs. 8 months, p = 0.001) and in patients with alpha-fetoprotein <52 UI/mL (24 vs. 11 months, p = 0.002). The variation in target tumor size and the appearance of new lesions were analyzed among 50 patients with measurable tumors. A decrease in target tumor size was observed in most patients, and the intensity of such decrease was not associated with any of the factors under study. Patients who developed new lesions in the treated liver (and also in the nontargeted liver) at month 3 more frequently had more than five nodules, bilobar disease, and alpha-fetoprotein >52 UI/mL, and their survival in the multivariate analysis was significantly worse (hazard ratio, 4.7; 95% confidence interval, 13-1.73) (p = 0.002). Conclusions: Yttrium-90 radioembolization results in control of target lesions in the majority of patients with HCC but does not prevent the development of new lesions. Survival of patients treated with {sup 90}Y-RE seems to depend largely on factors related to the aggressiveness of the disease (number of nodules, levels of alpha-fetoprotein, and presence of microscopic disease).

  5. 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.

  6. 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

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

    PubMed Central

    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.

    2016-01-01

    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 90Y-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 × 107 haploidentical donor bone marrow cells (day 0). Haploidentical bone marrow transplantation (BMT) with 300 μCi 90Y-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 90Y-DOTA-30F11, CY, and haploidentical BMT were cured and lived >200 days. Mice treated with 200 μCi 90Y-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

  8. Hepatocellular carcinoma with intra-atrial tumor extension identified on 99mTc-labeled macroaggregated albumin single photon emission computed tomography/computed tomography

    PubMed Central

    Chandra, Piyush; Shah, Sneha; Purandare, Nilendu; Agrawal, Archi; Rangarajan, Venkatesh

    2016-01-01

    99mTc macroaggregated albumin (MAA) scintigraphy is always performed before administration of 90Y--microspheres for the treatment of liver tumors for hepatopulmonary shunt calculation. Tumor thrombus visualization in the hepatic vasculature is an infrequent finding on the 99m Tc--MAA single photon emission computed tomography. We present a rare case of a hepatocellular carcinoma extending as a tumor thrombus through hepatic vein, inferior vena cava into the right atrium. PMID:27833324

  9. 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.

  10. 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.

  11. Early Dose Response to Yttrium-90 Microsphere Treatment of Metastatic Liver Cancer by a Patient-Specific Method Using Single Photon Emission Computed Tomography and Positron Emission Tomography

    SciTech Connect

    Campbell, Janice M. Wong, C. Oliver; Muzik, Otto; Marples, Brian; Joiner, Michael; Burmeister, Jay

    2009-05-01

    Purpose: To evaluate a patient-specific single photon emission computed tomography (SPECT)-based method of dose calculation for treatment planning of yttrium-90 ({sup 90}Y) microsphere selective internal radiotherapy (SIRT). Methods and Materials: Fourteen consecutive {sup 90}Y SIRTs for colorectal liver metastasis were retrospectively analyzed. Absorbed dose to tumor and normal liver tissue was calculated by partition methods with two different tumor/normal liver vascularity ratios: an average 3:1 and a patient-specific ratio derived from pretreatment technetium-99m macroaggregated albumin SPECT. Tumor response was quantitatively evaluated from fluorine-18 fluoro-2-deoxy-D-glucose positron emission tomography scans. Results: Positron emission tomography showed a significant decrease in total tumor standardized uptake value (average, 52%). There was a significant difference in the tumor absorbed dose between the average and specific methods (p = 0.009). Response vs. dose curves fit by linear and linear-quadratic modeling showed similar results. Linear fit r values increased for all tumor response parameters with the specific method (+0.20 for mean standardized uptake value). Conclusion: Tumor dose calculated with the patient-specific method was more predictive of response in liver-directed {sup 90}Y SIRT.

  12. Phosphorus-32, a Clinically Available Drug, Inhibits Cancer Growth by Inducing DNA Double-Strand Breakage

    PubMed Central

    Cheng, Yulan; Kiess, Ana P.; Herman, Joseph M.; Pomper, Martin G.; Meltzer, Stephen J.; Abraham, John M.

    2015-01-01

    Radioisotopes that emit electrons (beta particles), such as radioiodine, can effectively kill target cells, including cancer cells. Aqueous 32P[PO4] is a pure beta-emitter that has been used for several decades to treat non-malignant human myeloproliferative diseases. 32P[PO4] was directly compared to a more powerful pure beta-emitter, the clinically important 90Y isotope. In vitro, 32P[PO4] was more effective at killing cells than was the more powerful isotope 90Y (P ≤ 0.001) and also caused substantially more double-stranded DNA breaks than did 90Y. In vivo, a single low-dose intravenous dose of aqueous elemental 32P significantly inhibited tumor growth in the syngeneic murine cancer model (P ≤ 0.001). This effect is exerted by direct incorporation into nascent DNA chains, resulting in double-stranded breakage, a unique mechanism not duplicatable by other, more powerful electron-emitting radioisotopes. 32P[PO4] should be considered for human clinical trials as a potential novel anti-cancer drug. PMID:26030880

  13. A comparative study of the safety and efficacy of dysprosium-165 hydroxide macro-aggregate and yttrium-90 silicate colloid in radiation synovectomy--a multicentre double blind clinical trial. Australian Dysprosium Trial Group.

    PubMed

    Edmonds, J; Smart, R; Laurent, R; Butler, P; Brooks, P; Hoschl, R; Wiseman, J; George, S; Lovegrove, F; Warwick, A

    1994-10-01

    The aim of our study was to compare the safety and efficacy of a new preparation, Dysprosium-165 Hydroxide Macroaggregate (165Dy) with Yttrium-90 Silicate (90Y) for radiation synovectomy of the knee in patients with RA and OA. A multicentre double blind clinical trial with subjects randomized to receive 165Dy or 90Y was undertaken in Sydney, Melbourne and Perth. Seventy knees of 59 patients were studied, using as clinical end point measurements, pain in the knee on walking, pain in the knee at rest and stiffness in the knee after rest. Cytogenetic damage, knee retention and extra-articular spread of the radionuclide to regional lymph nodes, liver, urine and blood were evaluated. There was no significant difference in clinical response in the two treatment groups for either RA or OA. Chromosomal changes occurred with equal frequency and the knee retention and extra-articular leakage of radiocolloids to regional lymph nodes and liver were comparable in the two groups. For radiation synovectomy of the knee, 165Dy is at least as safe and as effective as 90Y and has the advantage of a short half-life (2.334 h) and hence requires a shorter period of post-injection immobilization and hospitalization.

  14. 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.

  15. 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.

  16. Beta Bremsstrahlung dose in concrete shielding

    NASA Astrophysics Data System (ADS)

    Manjunatha, H. C.; Chandrika, B. M.; Rudraswamy, B.; Sankarshan, B. M.

    2012-05-01

    In a nuclear reactor, beta nuclides are released during nuclear reactions. These betas interact with shielding concrete and produces external Bremsstrahlung (EB) radiation. To estimate Bremsstrahlung dose and shield efficiency in concrete, it is essential to know Bremsstrahlung distribution or spectra. The present work formulated a new method to evaluate the EB spectrum and hence Bremsstrahlung dose of beta nuclides (32P, 89Sr, 90Sr-90Y, 90Y, 91Y, 208Tl, 210Bi, 234Pa and 40K) in concrete. The Bremsstrahlung yield of these beta nuclides in concrete is also estimated. The Bremsstrahlung yield in concrete due to 90Sr-90Y is higher than those of other given nuclides. This estimated spectrum is accurate because it is based on more accurate modified atomic number (Zmod) and Seltzer's data, where an electron-electron interaction is also included. Presented data in concrete provide a quick and convenient reference for radiation protection. The present methodology can be used to calculate the Bremsstrahlung dose in nuclear shielding materials. It can be quickly employed to give a first pass dose estimate prior to a more detailed experimental study.

  17. 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.

  18. 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

  19. 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.

  20. Targeting of human glioma xenografts in vivo utilizing radiolabeled antibodies

    SciTech Connect

    Williams, J.A.; Wessels, B.W.; Wharam, M.D.; Order, S.E.; Wanek, P.M.; Poggenburg, J.K.; Klein, J.L. )

    1990-06-01

    Radiolabeled antibodies provide a potential basis for selective radiotherapy of human gliomas. We have measured tumor targeting by radiolabeled monoclonal and polyclonal antibodies directed against neuroectodermal and tumor-associated antigens in nude mice bearing human glioma xenografts. Monoclonal P96.5, a mouse IgG2a immunoglobulin, defines an epitope of a human melanoma cell surface protein, and specifically binds the U-251 human glioma as measured by immunoperoxidase histochemistry. 111In-radiolabeled P96.5 specifically targets the U-251 human glioma xenograft and yields 87.0 microCuries (microCi) of tumor activity per gram per 100 microCi injected activity compared to 4.5 microCi following administration of radiolabeled irrelevant monoclonal antibody. Calculations of targeting ratios demonstrate deposited dose to be 11.6 times greater with radiolabeled P96.5 administration compared to irrelevant monoclonal antibody. The proportion of tumor dose found in normal organs is less than 10%, further supporting specific targeting of the human glioma xenograft by this antibody. Monoclonal antibody ZME018, which defines a second melanoma-associated antigen, and polyclonal rabbit antiferritin, which defines a tumor-associated antigen, demonstrate positive immunoperoxidase staining of the tumor, but comparatively decreased targeting. When compared to the 111In-radiolabeled antibody, 90Y-radiolabeled P96.5 demonstrates comparable tumor targeting and percentages of tumor dose found in normal organs. To test the therapeutic potential of 90Y-radiolabeled P96.5, tumors and normal sites were implanted with miniature thermoluminescent dosimeters (TLD). Seven days following administration of 100 microCi 90Y-radiolabeled P96.5, average absorbed doses of 3770, 980, 353, and 274 cGy were observed in tumor, liver, contralateral control site, and total body, respectively.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Surgical synovectomy combined with yttrium 90 in patients with recurrent joint synovitis.

    PubMed

    Oztemür, Zekeriya; Bulut, Okay; Korkmaz, Murat; Gölge, Umut Hatay; Oztürk, Hayati; Tezeren, Gündüz; Günaydın, Ilhan

    2013-05-01

    Radiation synovectomy (RS) is one of many therapeutic options used for recurrent joint synovitis. Our aim was to analyze the effect of the surgical synovectomy combined with yttrium 90 ((90)Y) in the treatment for recurrent joint synovitis. A surgical combined RS procedure was used on 32 knees of 30 patients. They were divided into two groups. Group 1 consisted of 7 knees of 7 patients (5 women and 2 men) with a mean age of 40.7 years in whom RS was combined with the open synovectomy. Group 2 consisted of 25 knees of 23 patients (21 men and 2 women) with a mean age of 45.5 years in whom RS was combined with the arthroscopic synovectomy. Arthroscopic synovectomy or open surgery biopsy was carried out for all cases who diagnosed of having synovitis. A scintigraphic examination was conducted within 24 h after the RS procedure to investigate the systemic leakage of (90)Y in all patients. The outcome of treatment was assessed based on self-reporting using the visual analogue scale (VAS) of night pain, rest pain, activity pain, effusion, and satisfactory scores. The average follow-up period was 4.15 years. There was a significant difference between before and after treatment in terms of outcome parameters' VAS scores in both groups (p < 0.05). But there was no statistically significant difference between open and arthroscopic synovectomy groups in terms of outcome parameters (p > 0.05). Satisfactory outcome was excellent in 3 patients (42.8 %) in group 1 and 8 patients (32 %) in group 2. Surgical synovectomy with combined (90)Y could treat recurrent joint synovitis successfully. There was no statistically significant difference between open and arthroscopic synovectomy techniques combined with RS procedure.

  6. 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

  7. Factors associated with increased incidence of severe toxicities following yttrium-90 resin microspheres in the treatment of hepatic malignancies

    PubMed Central

    Roberson II, John D; McDonald, Andrew M; Baden, Craig J; Lin, Chee Paul; Jacob, Rojymon; Burnett III, Omer L

    2016-01-01

    AIM: To further define variables associated with increased incidences of severe toxicities following administration of yttrium-90 (90Y) microspheres. METHODS: Fifty-eight patients undergoing 79 treatments were retrospectively assessed for development of clinical and laboratory toxicity incidence following 90Y administration. Severe toxicity events were defined using Common Terminology Criteria for Adverse Events version 4.03 and defined as grade ≥ 3. Univariate logistic regression analyses were used to evaluate the effect of different factors on the incidence of severe toxicity events. Multicollinearity was assessed for all factors with P < 0.1 using Pearson correlation matrices. All factors not excluded due to multicollinearity were included in a multivariate logistic regression model for each measurement of severe toxicity. RESULTS: Severe (grade ≥ 3) toxicities occurred following 21.5% of the 79 treatments included in our analysis. The most common severe laboratory toxicities were severe alkaline phosphatase (17.7%), albumin (12.7%), and total bilirubin (10.1%) toxicities. Decreased pre-treatment albumin (OR = 26.2, P = 0.010) and increased pre-treatment international normalized ratio (INR) (OR = 17.7, P = 0.048) were associated with development of severe hepatic toxicity. Increased pre-treatment aspartate aminotransferase (AST; OR = 7.4, P = 0.025) and decreased pre-treatment hemoglobin (OR = 12.5, P = 0.025) were associated with severe albumin toxicity. Increasing pre-treatment model for end-stage liver disease (MELD) score (OR = 1.8, P = 0.033) was associated with severe total bilirubin toxicity. Colorectal adenocarcinoma histology was associated with severe alkaline phosphatase toxicity (OR = 5.4, P = 0.043). CONCLUSION: Clinicians should carefully consider pre-treatment albumin, INR, AST, hemoglobin, MELD, and colorectal histology when choosing appropriate candidates for 90Y microsphere therapy. PMID:26973396

  8. 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

  9. Ophthalmic applicators: an overview of calibrations following the change to SI units.

    PubMed

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

    2009-05-01

    Since the NIST dose to water standard for 90Sr/90Y 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%.

  10. Analysis of radioactive strontium-90 in food by Čerenkov liquid scintillation counting.

    PubMed

    Pan, Jingjing; Emanuele, Kathryn; Maher, Eileen; Lin, Zhichao; Healey, Stephanie; Regan, Patrick

    2017-01-27

    A simple liquid scintillation counting method using DGA/TRU resins for removal of matrix/radiometric interferences, Čerenkov counting for measuring (90)Y, and EDXRF for quantifying Y recovery was validated for analyzing (90)Sr in various foods. Analysis of samples containing energetic β emitters required using TRU resin to avoid false detection and positive bias. Additional 34% increase in Y recovery was obtained by stirring the resin while eluting Y with H2C2O4. The method showed acceptable accuracy (±10%), precision (10%), and detectability (~0.09Bqkg(-1)).

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. Medical Isotope Production using High Intensity Accelerator Neutrons

    NASA Astrophysics Data System (ADS)

    Nagai, Yasuki

    We proposed aprototype facility for the generation of radioisotopes with accelerator neutrons by deuterons. The neutrons are producedbynatC(d,n) with 40MeV 2 mA deuteron beams, and about 8.1 TBq/week of 99Mois produced by irradiating an enriched 100Mo sample with the neutrons.High-quality 99mTc can be separatedfrom an irradiated 100MoO3 sample by thermo-chromatographic separation.In this contribution we present the system to produce medical radioisotopes, such as 99Mo, 90Y, and 67Cu, and experimental studies on 99Mo and 67Cu produced by using accelerator neutrons.

  17. 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.

  18. Numerical modeling of large-area beta sources constructed from anodized-aluminum foils.

    PubMed

    Stanga, D

    2012-09-01

    The numerical modeling of large-area beta sources constructed from anodized-aluminum foils is described in this paper. Based on a realistic model for the activity depth distribution, theoretical lower and upper bounds for the efficiency and the transmission coefficient were calculated and used to analyze the comparison method recommended by ISO 8769 for measuring the surface emission rate. The analysis shows that this method can provide measurement results with relative standard uncertainties smaller than 3% for high energy beta emitters such as (90)Sr-(90)Y, (36)Cl and (204)Tl.

  19. 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.

  20. Verification of absorbed dose rates in reference beta radiation fields: Measurements with an extrapolation chamber and radiochromic film.

    PubMed

    Reynaldo, S R; Benavente, J A; Da Silva, T A

    2016-11-01

    Beta Secondary Standard 2 (BSS 2) provides beta radiation fields with certified values of absorbed dose to tissue and the derived operational radiation protection quantities. As part of the quality assurance, the reliability of the CDTN BSS2 system was verified through measurements in the (90)Sr/(90)Y and (85)Kr beta radiation fields. Absorbed dose rates and their angular variation were measured with a 23392 model PTW extrapolation chamber and with Gafchromic radiochromic films on a PMMA slab phantom. The feasibility of using both methods was analyzed.

  1. Radiation dermatitis following radioembolization for hepatocellular carcinoma: a case for prophylactic embolization of a patent falciform artery.

    PubMed

    Leong, Quor M; Lai, Hee K; Lo, Richard G H; Teo, Terence K B; Goh, Anthony; Chow, Pierce K H

    2009-06-01

    The most common use of radioembolization is in the treatment of primary and secondary liver tumors, and the most common radioisotope used is yttrium-90. This form of therapy has been proven to be successful in achieving tumor reduction and prolonging survival. Adverse events, although uncommon and usually self-limiting, have been reported. The present report describes a case of radiation dermatitis caused by shunting of (90)Y microspheres to the anterior abdominal wall via a patent falciform artery. When identified, prophylactic embolization of this patent artery may prevent the potential adverse event of radiation-induced dermatitis after radioembolization.

  2. Dramatic Response of a Large, 10 Cm Hepatocellular Carcinoma to Monotherapy with Yttrium-90 Based Selective Internal Radiation Therapy.

    PubMed

    Diwanji, Tejan; Dong, Tuo; Moeslein, Fred; Chuong, Michael

    2015-12-22

    Hepatocellular carcinoma (HCC) is predominantly diagnosed in advanced stages and not amenable to surgical resection and transplantation. Systemic therapies have had a limited efficacy in treating HCC. Although HCC is a radiosensitive tumor, treatments with external-beam radiation are limited by radiosensitivity of normal liver tissue and surrounding organs-at-risk, i.e. bowel, stomach, and kidney. Several large retrospective series have demonstrated a modest effect of selective internal radiation therapy (SIRT) with Yttrium-90 ((90)Y) microspheres in unresectable HCC, both in terms of tumor response and survival. The authors present a patient with an extremely large, multifocal, unresectable HCC who achieved a dramatic response with SIRT treatment.

  3. Radiolabeling and biological evaluation of DOTA-Ph-Al derivative conjugated to anti-EGFR antibody ior egf/r3 for targeted tumor imaging and therapy.

    PubMed

    Pnwar, Puja; Iznaga-Escobar, Normando; Mishra, Pushpa; Srivastava, Vibha; Sharma, Rakesh Kumar; Chandra, Ramesh; Mishra, Anil K

    2005-08-01

    An appropriate bifunctional chelating agent namely DOTA-Ph-Al was developed for the conjugation with biological vectors (anti EGFr antibody). We hereby report the synthesis of p-bromoacetamidobenzyl derivative of DOTA and its conjugation to monoclonal antibody anti-EGFR ior egf/r3. Immunoconjugate was prepared by conjugation of p-bromoacetamidobenzyl derivative of DOTA with ior egf/r3. Modified antibody was purified by size exclusion chromatography. DOTA-Ph-Al-ior egf/r3 exhibited quantitative 99mTc-labeling (>96%) with specific activity 10-20 mCi/mg of protein and 90Y-labeling with specific activity 2-5 mCi/mg. Immunoreactivity was determined by flow cytometry. Receptor ligand assay on murine cell line EAT and human tumor cell line U-87MG showed Kd = 2.87 nM and 4.86 nM respectively. The stability in serum indicated that 99mTc remained bound to antibodies up to 24h and 98% 90Y was associated with the mAb for five days. Biodistribution characteristics of Ab-conjugate radiolabeled to 99mTc and 90Y radionuclide was examined in BALB/c mice grafted with EAT and athymic mice with U-87MG cell line demonstrated high tumor uptake with 5.5 +/- 1.3 and 7.85 +/- 1.2%ID/g at four and 24 h for 99mTc- DOTA-Ph-AI-ior egf/r3 in EAT tumors after post injection respectively. Maximal radiotracer uptake peaked 17.6 +/- 2.5%ID/g in EAT tumor and 12.89 +/- 0.66% ID/g in U-87MG tumor at 48h for 90Y. The drug excreted through renal routes as the activity in the kidneys was 13.42 +/- 0.33%ID/g at 1 h and 4.51 +/- 1.2%ID/g at 4 h for 99mTc- DOTA-Ph-Al-ior egf/r3.

  4. 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.

  5. Estimation of doses to personnel and patients during endovascular brachytherapy applications.

    PubMed

    Kirisits, Christian; Hefner, Alfred; Wexberg, Paul; Pokrajac, Boris; Glogar, Dietmar; Pötter, Richard; Georg, Dietmar

    2004-01-01

    In the last few years coronary endovascular brachytherapy using gamma- and beta-emitting radionuclides has been established as a standard treatment procedure to prevent restenosis after percutaneous coronary interventions. Direct measurements and calculations were made to determine personnel doses and organ doses of patients due to gamma rays of 192Ir and beta rays of 90Sr/90Y and 32P sources. In general, our results show that the dose levels are low compared with the X-ray exposure from angiography. The dose rate from bremsstrahlung at 1 m distance from a device containing a 90Sr/90Y source of 2.3 GBq is 4 micro Sv h(-1). The skin dose from beta rays during source transfer into and from the patient was estimated with the directional dose equivalent H'(0.07) of 10 micro Sv at 1 m distance from the catheter. By maintaining safe distances, the dose levels can be kept well within annual dose limits.

  6. 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.

  7. 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.

  8. 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.

  9. Beta camera for static and dynamic imaging of charged-particle emitting radionuclides in biologic samples.

    PubMed

    Ljunggren, K; Strand, S E

    1990-12-01

    A detection system based on microchannel plates has been constructed to image charged particles emitted by radionuclides in biomedical samples. This technique has significant advantages over conventional film autoradiography for investigating the distribution of radiolabeled compounds: shorter acquisition times due to the high sensitivity, easier sample handling, direct quantification and the ability to perform dynamic studies. The detector performance shows a spatial resolution of 0.9 mm for carbon-14 (14C) (0.156 MeV), good linearity and homogeneity. The noise level is below 50/(cm2.sec). Successful imaging with this system has been performed with beta-emitters 14C, sulfur-35 (35S), iodine-131 (131I), yttrium-90 (90Y), and positron emitters gallium-68 (68Ga), and fluorine-18 (18F). Dynamic studies of axonal transport of 35S-methionine in a nerve, and static images of 90Y-labeled monoclonal antibodies in slices of tumors are presented. The system shows promise for rapid quantitative imaging of charged-particle emitting radionuclides in small biologic samples.

  10. 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.

  11. 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.

  12. 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.

  13. Lobar hepatocellular carcinoma with ipsilateral portal vein tumor thrombosis treated with yttrium-90 glass microsphere radioembolization: preliminary results.

    PubMed

    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 (90)Y-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 (90)Y-microS with sorafenib, taking into account not only survival but also the possibility of secondary surgery for putative curative intention after downstaging.

  14. 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.

  15. In vivo comparative study of hydroxyapatite labeled with different radioisotopes: evaluation of the scintigraphic images.

    PubMed

    Couto, R M; De Barboza, M F; De Souza, A A; Muramoto, E; Mengatti, J; De Araújo, E B

    2010-05-10

    Radyosinovectomy (RSV) is a radiotherapeutic modality where a beta-emitting radionuclide is administered locally by intra-articular injection on the form of a colloid or radiolabeled particulate. RSV is a well-accepted therapeutic procedure in inflammatory joint diseases and has been successfully employed for more than 50 years as a viable alternative to surgical and chemical synovectomy. The aim of this work is to compare the in vivo stability of hydroxyapatite labelled with (177)Lu, (90)Y and (153)Sm. All radionuclides were labelled with high yield and were retained in the joint for 7 days, showing stability and usefulness as tools in the RSV treatment. A similar retention of the products in the muscle was observed when the particles were administrated in the muscle. However, the pure form of the radionuclides were rapidly cleared from the blood and accumulated in the liver when injected i.v.. Although (153)Sm-HA is already available for nuclear medicine procedures and clinical studies with (90)Y-HA have been developed, (177)Lu-labeled RSV agents will be economically more viable and has not been studied yet. Its favorable characteristics contribute to follow, to predict and asses the success of RSV by bone scintigraphy studies.

  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.; ...

    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. APMP supplementary comparison report of absorbed dose rate in tissue for beta radiation (BIPM KCDB: APMP.RI(I)-S2)

    NASA Astrophysics Data System (ADS)

    Kato, M.; Kurosawa, T.; Saito, N.; Kadni, T. B.; Kim, I. J.; Kim, B. C.; Yi, C.-Y.; Pungkun, V.; Chu, C.-H.

    2017-01-01

    The supplementary comparison of absorbed dose rate in tissue for beta radiation (APMP.RI(I)-S2) was performed with five national metrology institutes in 2013 and 2014. Two commercial thin window ionization chambers were used as transfer instruments and circulated among the participants. Two of the NMIs measured the calibration coefficients of the chambers in reference fields produced from Pm-147, Kr-85 and Sr-90/Y-90, while the other three measured those only in Sr-90/Y-90 beta-particle field. The degree of equivalence for the participants was determined and this comparison verifies the calibration capabilities of the participating laboratories. In addition, most of the results of this comparison are consistent with another international comparison (EUROMET.RI(I)-S2) reported before this work. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  19. 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.

  20. Patient-specific dosimetry in peptide receptor radionuclide therapy: a clinical review.

    PubMed

    Chalkia, M T; Stefanoyiannis, A P; Chatziioannou, S N; Round, W H; Efstathopoulos, E P; Nikiforidis, G C

    2015-03-01

    Neuroendocrine tumours (NETs) belong to a relatively rare class of neoplasms. Nonetheless, their prevalence has increased significantly during the last decades. Peptide receptor radionuclide therapy (PRRT) is a relatively new treatment approach for inoperable or metastasised NETs. The therapeutic effect is based on the binding of radiolabelled somatostatin analogue peptides with NETs' somatostatin receptors, resulting in internal irradiation of tumours. Pre-therapeutic patient-specific dosimetry is essential to ensure that a treatment course has high levels of safety and efficacy. This paper reviews the methods applied for PRRT dosimetry, as well as the dosimetric results presented in the literature. Focus is given on data concerning the therapeutic somatostatin analogue radiopeptides (111)In-[DTPA(0),D-Phe(1)]-octreotide ((111)In-DTPA-octreotide), (90)Y-[DOTA(0),Tyr(3)]-octreotide ((90)Y-DOTATOC) and (177)Lu-[DOTA(0),Tyr(3),Thr(8)]-octreotide ((177)Lu-DOTATATE). Following the Medical Internal Radiation Dose (MIRD) Committee formalism, dosimetric analysis demonstrates large interpatient variability in tumour and organ uptake, with kidneys and bone marrow being the critical organs. The results are dependent on the image acquisition and processing protocol, as well as the dosimetric imaging radiopharmaceutical.

  1. 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.

  2. 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.

  3. 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

  4. Characteristics of a 85Kr beta-particle source applied in Series 1 reference irradiations of DIS-1 direct ion storage dosemeters.

    PubMed

    Hakanen, A T; Sipilä, P M; Sahla, T T

    2007-01-01

    Characteristics necessary to specify an ISO 6980 Series 1 reference radiation field were determined for a commercially available 85Kr beta-particle source, using a BEAM EGS4 Monte Carlo code. The characteristics include residual maximum beta energy, E(res), and the uniformity of the dose rate over the calibration area. The E(res) and the uniformity were also determined experimentally, using an extrapolation ionization chamber (EC) and a 0.2 cm3 parallel plate ionization chamber, respectively. The depth-dose curve measured with the EC gave a value 0.62 MeV for the E(res). Series 2 90Sr + 90Y and Series 1(85) Kr beta-particle sources calibrated for H(p)(0.07) at the secondary standard dosimetry laboratory (SSDL) of STUK were used to determine the energy and angular responses of DIS-1 direct ion storage dosemeters. The averaged zero angle H(p)(0.07) responses to the 90Sr + 90Y and 85Kr reference radiations were 135 and 80%, respectively. The responses were normalized to 100%, H(p)(0.07) response to 137Cs photon radiation.

  5. Prevention and treatment of complications of selective internal radiation therapy: Expert guidance and systematic review.

    PubMed

    Sangro, Bruno; Martínez-Urbistondo, Diego; Bester, Lourens; Bilbao, Jose I; Coldwell, Douglas M; Flamen, Patrick; Kennedy, Andrew; Ricke, Jens; Sharma, Ricky A

    2017-04-13

    Selective internal radiation therapy (SIRT or radioembolisation) by intraarterial injection of radioactive yttrium-90 ((90) Y)-loaded microspheres is increasingly used for the treatment of patients with liver metastases or primary liver cancer. The high-dose beta-radiation penetrates an average of only 2.5 mm from the source so that its effects are limited to the site of delivery. However the off-target diversion of (90) Y microspheres to tissues other than the tumor may lead to complications. The most prominent ones include: radiation gastritis and gastrointestinal (GI) ulcers, cholecystitis, radiation pneumonitis, and radioembolisation-induced liver disease (REILD). Complications may occur despite careful pre-treatment planning and SIRT demands an expert multidisciplinary team (MDT) approach in order to provide comprehensive care for patients. This review provides recommendations to MDTs on the optimal medical processes in order to ensure the safe delivery of SIRT. Based on the best available published evidence and expert opinion, we recommend the most appropriate strategies for the prevention, early diagnosis and management of potential radiation injury to the liver and to other organs. This article is protected by copyright. All rights reserved.

  6. 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.; ...

    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

  7. Adsorption and separation behavior of yttrium and strontium in nitric acid solution by extraction chromatography using a macroporous silica-based adsorbent.

    PubMed

    Xu, Yuanlai; Kim, Seong-Yun; Ito, Tatsuya; Nakazawa, Kasane; Funaki, Yoshihito; Tada, Tsutomu; Hitomi, Keitaro; Ishii, Keizo

    2012-11-09

    To separate (90)Y from the fission product (90)Sr-(90)Y group, a silica-based TODGA/SiO(2)-P adsorbent was prepared by impregnating N,N,N',N'-tetraoctyl-3-oxapentane-1,5-diamide (TODGA) extractant into the macroporous SiO(2)-P support with a mean diameter of 60 μm. The adsorption behavior of Sr(II) and Y(III) onto TODGA/SiO(2)-P adsorbent from HNO(3) solution and their mutual separation were investigated. Under the experimental conditions, this adsorbent showed high adsorption affinity to Y(III) and weak adsorption to Sr(II). It was found that the adsorption process of Y(III) could be expressed by both of Langmuir monomolecular layer adsorption mode and the pseudo-second order model. From the results of stability experiments, it became clear that TODGA/SiO(2)-P adsorbent is stable in 3M HNO(3) solution for 1 month contact time at 298 K. Using a column packed with TODGA/SiO(2)-P adsorbent, Sr(II) and Y(III) were eluted by distilled water and diethylenetriamine pentaacetic acid (DTPA) solution, respectively. The separation of Y(III) from Sr(II)-Y(III) group was achieved successfully.

  8. 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

  9. Holmium-166 radioembolization for the treatment of patients with liver metastases: design of the phase I HEPAR trial

    PubMed Central

    2010-01-01

    Background Intra-arterial radioembolization with yttrium-90 microspheres ( 90Y-RE) is an increasingly used therapy for patients with unresectable liver malignancies. Over the last decade, radioactive holmium-166 poly(L-lactic acid) microspheres ( 166Ho-PLLA-MS) have been developed as a possible alternative to 90Y-RE. Next to high-energy beta-radiation, 166Ho also emits gamma-radiation, which allows for imaging by gamma scintigraphy. In addition, Ho is a highly paramagnetic element and can therefore be visualized by MRI. These imaging modalities are useful for assessment of the biodistribution, and allow dosimetry through quantitative analysis of the scintigraphic and MR images. Previous studies have demonstrated the safety of 166Ho-PLLA-MS radioembolization ( 166Ho-RE) in animals. The aim of this phase I trial is to assess the safety and toxicity profile of 166Ho-RE in patients with liver metastases. Methods The HEPAR study (Holmium Embolization Particles for Arterial Radiotherapy) is a non-randomized, open label, safety study. We aim to include 15 to 24 patients with liver metastases of any origin, who have chemotherapy-refractory disease and who are not amenable to surgical resection. Prior to treatment, in addition to the standard technetium-99m labelled macroaggregated albumin ( 99mTc-MAA) dose, a low radioactive safety dose of 60-mg 166Ho-PLLA-MS will be administered. Patients are treated in 4 cohorts of 3-6 patients, according to a standard dose escalation protocol (20 Gy, 40 Gy, 60 Gy, and 80 Gy, respectively). The primary objective will be to establish the maximum tolerated radiation dose of 166Ho-PLLA-MS. Secondary objectives are to assess tumour response, biodistribution, performance status, quality of life, and to compare the 166Ho-PLLA-MS safety dose and the 99mTc-MAA dose distributions with respect to the ability to accurately predict microsphere distribution. Discussion This will be the first clinical study on 166Ho-RE. Based on preclinical studies

  10. Discrete beta dose kernel matrices for nuclides applied in targeted radionuclide therapy (TRT) calculated with MCNP5

    SciTech Connect

    Reiner, Dora; Blaickner, Matthias; Rattay, Frank

    2009-11-15

    Purpose: Radiopharmaceuticals administered in targeted radionuclide therapy (TRT) rely to a great extent not only on beta-emitting nuclides but also on emitters of monoenergetic electrons. Recent advances like combined PET/CT devices, the consequential coregistration of both data, the concept of using beta couples for diagnosis and therapy, respectively, as well as the development of voxel models offer a great potential for developing TRT dose calculation systems similar to those available for external beam treatment planning. The deterministic algorithms in question for this task are based on the convolution of three-dimensional matrices, one representing the activity distribution and the other the dose point kernel. This study aims to report on three-dimensional kernel matrices for various nuclides used in TRT. Methods: The Monte Carlo code MCNP5 was used to calculate discrete dose kernels of beta particles including the contributions from their respective secondary radiation in soft tissue for the following nuclides: {sup 32}P, {sup 33}P, {sup 67}Cu, {sup 89}Sr, {sup 90}Y, {sup 103}Rh{sup m}, {sup 131}I, {sup 177}Lu, {sup 186}Re, and {sup 188}Re. For each nuclide a kernel cube of 10x10x10 mm{sup 3} was calculated, the dimensions of a voxel being 1 mm{sup 3}. Additional kernels with voxel sizes of 3x3x3 mm{sup 3} were simulated. Results: Comparison with the S-value data regarding {sup 32}P, {sup 89}Sr, {sup 90}Y, and {sup 131}I of the MIRD committee which were calculated with the EGS4 code showed a very good agreement, the secondary particle transport of {sup 90}Y being the only exception. Documented analytical kernels on the other side show deviations very close and very far to the source. Conclusions: The good accordance with the only discrete dose kernels published up to date justifies the method chosen. Together with the additional six nuclides, this report provides a considerable database for three-dimensional kernel matrices with regard to beta

  11. Effects of image noise, respiratory motion, and motion compensation on 3D activity quantification in count-limited PET images

    NASA Astrophysics Data System (ADS)

    Siman, W.; Mawlawi, O. R.; Mikell, J. K.; Mourtada, F.; Kappadath, S. C.

    2017-01-01

    The aims of this study were to evaluate the effects of noise, motion blur, and motion compensation using quiescent-period gating (QPG) on the activity concentration (AC) distribution—quantified using the cumulative AC volume histogram (ACVH)—in count-limited studies such as 90Y-PET/CT. An International Electrotechnical Commission phantom filled with low 18F activity was used to simulate clinical 90Y-PET images. PET data were acquired using a GE-D690 when the phantom was static and subject to 1-4 cm periodic 1D motion. The static data were down-sampled into shorter durations to determine the effect of noise on ACVH. Motion-degraded PET data were sorted into multiple gates to assess the effect of motion and QPG on ACVH. Errors in ACVH at AC90 (minimum AC that covers 90% of the volume of interest (VOI)), AC80, and ACmean (average AC in the VOI) were characterized as a function of noise and amplitude before and after QPG. Scan-time reduction increased the apparent non-uniformity of sphere doses and the dispersion of ACVH. These effects were more pronounced in smaller spheres. Noise-related errors in ACVH at AC20 to AC70 were smaller (<15%) compared to the errors between AC80 to AC90 (>15%). The accuracy of ACmean was largely independent of the total count. Motion decreased the observed AC and skewed the ACVH toward lower values; the severity of this effect depended on motion amplitude and tumor diameter. The errors in AC20 to AC80 for the 17 mm sphere were  -25% and  -55% for motion amplitudes of 2 cm and 4 cm, respectively. With QPG, the errors in AC20 to AC80 of the 17 mm sphere were reduced to  -15% for motion amplitudes  <4 cm. For spheres with motion amplitude to diameter ratio  >0.5, QPG was effective at reducing errors in ACVH despite increases in image non-uniformity due to increased noise. ACVH is believed to be more relevant than mean or maximum AC to calculate tumor control and normal tissue complication probability

  12. 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

  13. Complete eradication of hepatic metastasis from colorectal cancer by Yttrium-90 SIRT.

    PubMed

    Garrean, Sean; Muhs, Amanda; Bui, James T; Blend, Michael J; Owens, Charles; Helton, William S; Espat, N Joseph

    2007-06-07

    Yttrium-90 (Y-90) radioembolization, also known as selective internal radiation therapy (SIRT), is a regional hepatic therapy used in the treatment of unresectable colorectal cancer (CRC) liver metastases. In SIRT, Y-90 impregnated microspheres are injected into the VASCULAR SUPPLY of hepatic tumor, leading to selective irradiation and necrosis of tumor TISSUE. While several studies demonstrate improved local control and survival with SIRT, the specific indications for this therapy have yet to be defined. Typically, SIRT is given in combination with chemotherapy as multimodal treatment for unresectable hepatic CRC. However, it has also found increasing use as a salvage therapy in chemo-refractory patients. Herein, the authors describe their experience with SIRT as "stand alone" therapy in a surgically-prohibitive, chemotherapy naive patient with hepatic CRC metastasis. The results suggest that Y-90 SIRT may have potential applications beyond its usual role as a palliative or salvage therapy for unresectable hepatic CRC.

  14. 90Yttrium PET/MR-based dosimetry after liver radioembolization (SIRT).

    PubMed

    Wissmeyer, Michael; Delattre, Bénédicte M A; Zaidi, Habib; Terraz, Sylvain; Ratib, Osman

    2015-04-01

    Biodistribution and dosimetric aspects are important issues in the preparation realization of radionuclide therapies and thus play an emerging role in radioembolization of liver malignancies. Biodistribution assessment of liver selective internal radiotherapy (SIRT) has been shown feasible using PET/CT PET/magnetic resonance (MR). Whereas prospective dosimetry using 99mTc macroaggregated albumin SPECT/CT is discussed controversially, retrospective 90Y PET/CT has been shown feasible for dosimetry of SIRT in recent studies. Considering the advantages of PET/MR with regard to lesion detection radiation dose reduction compared to PET/CT, especially when repeated scanning is intended, we investigated the use of PET/MR for dosimetry of liver SIRT.

  15. 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.

  16. Rapid screening of 90Sr activity in water and milk samples using Cherenkov radiation.

    PubMed

    Stamoulis, K C; Ioannides, K G; Karamanis, D T; Patiris, D C

    2007-01-01

    A method for screening 90Sr in milk samples is proposed. This method is based on a liquid scintillation technique taking advantage of Cherenkov radiation, which is produced in a liquid medium and then detected by the photomultipliers of a Liquid Scintillation Counter (LSC). Twenty millilitres of water and milk samples spiked with various concentrations of 90Sr/90Y in equilibrium were added in plastic vials and then were measured with an LSC (TriCarb 3170 TR/SL). The derived efficiencies were 49% for water samples and 14% for milk samples. The detection limit was 470 mBq L(-1)(90)Sr for water, without any pretreatment. Milk contains potassium, which also produces Cherenkov radiation due to the presence of 40K. For this reason, the interference of 40K in the measurements of 90Sr in milk samples was also investigated. The detection limit for milk was 1.7 Bq L(-1)90Sr.

  17. 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).

  18. 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.

  19. 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.

  20. 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.

  1. Alcohol misuse Y91 coding in ICD-11: rational terminology and logical coding specifically to encourage early identification and advice.

    PubMed

    Touquet, Robin; Harris, Dan

    2012-01-01

    Alcohol misuse is a common presentation to the Emergency Department (ED). The International Classification of Diseases ICD-10 for alcohol misuse, both under F10 and Y90/Y91, is not straightforward. The practicalities of coding ED attendances reveal an increasing detachment from ICD-10 (currently under review). Early identification [sometimes using blood alcohol concentrations (BACs)] and brief advice (IBA) can reduce unscheduled alcohol-related ED re-attendance. The UK Government Department of Health has implemented use of the terms 'Hazardous Drinking', 'Harmful Drinking' and 'Dependent Drinking' in its Public Service Agreements aimed at reducing harm by alcohol. Simplifying coding might increase IBA usage. We suggest that coding improvements in ICD-11 should update Y91 (currently 'clinical assessment')-with ICD-10 Y90 remaining for BAC to classify a patient's 'alcohol status'. Y90 and Y91 together would indicate the urgency for early IBA and/or speciality referral, aiming to reduce the prevalence of 'Dependent Drinking'.

  2. 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.

  3. Radioisotope therapy of cystic craniopharyngeomas

    SciTech Connect

    Strauss, L.; Sturm, V.; Georgi, P.; Schlegel, W.; Ostertag, H.; Clorius, J.H.; Van Kaick, G.

    1982-09-01

    Eighteen patients suffering from cystic craniopharyngeoma were treated with intracavitary irradiation. The beta-emitting radioisotope /sup 90/y (2.25 MeV) was instilled into the cyst following stereotactic puncture of the space-occupying lesion. The surgical approach was planned using angiograms and reconstructed transmission computer tomography (TCT) coronal and saggital sections. Therapy was devised to deliver 20,000 rad to the cyst's wall. Eleven patients received follow-up TCT examinations after four months. Eight of 11 patients had a significant volume decrease in the craniopharyngeoma cyst. In two patients, the cystic volume remained unchanged; one had progression of disease. It is concluded that the intracavitary treatment of cystic craniopharyngeoma will result in a reduction of the size of the space-occupying lesion.

  4. 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.

  5. Analysis of the distribution of intra-arterial microspheres in human liver following hepatic yttrium-90 microsphere therapy

    NASA Astrophysics Data System (ADS)

    Campbell, Andrew M.; Bailey, Ian H.; Burton, Mark A.

    2000-04-01

    The microscopic distribution of microspheres in human liver following hepatic infusion of 32 µm diameter resin microspheres labelled with 90 Y as treatment for an 80 millimetre diameter liver cancer has been investigated. Microspheres were found to deposit inhomogeneously in tissues, preferentially lodging in a region approximately 6 mm wide around the periphery of the tumour. A relative concentration of microspheres of 50 to 70 times that of normal hepatic parenchyma and 65 to 94 times that in the tumour centre was measured in this region. The deposition of spheres in the tumour periphery was not uniform, and cluster analysis showed that the spheres could be classified into clusters. The number of microspheres in a cluster was skewed towards low numbers and cluster sizes varied from 20 to 1500 µm. The observed deposition patterns indicate that the vascular tumour periphery will receive much greater radiation doses from radioactive microspheres than both normal tissue and the avascular tumour centre.

  6. Yttrium-90 microsphere radioembolization for hepatocellular carcinoma.

    PubMed

    Edeline, Julien; Gilabert, Marine; Garin, Etienne; Boucher, Eveline; Raoul, Jean-Luc

    2015-03-01

    Yttrium-90 (Y90) radioembolization is an emerging strategy to treat liver malignancies, and clinical data supporting its use have accumulated in recent years. Y90-radioembolization has shown clinical effectiveness in intermediate and advanced hepatocellular carcinoma, with a favorable safety profile. Retrospective data show similar levels of effectiveness to transarterial chemoembolization in intermediate hepatocellular carcinoma, with some evidence of better tolerance. While phase 3 studies comparing Y90-radioembolization to chemoembolization in intermediate hepatocellular carcinoma would be difficult to conduct, studies comparing or combining Y90-radioembolization with sorafenib are under way. Questions also remain about the most suitable modalities for defining the dose to administer. Phase 3 studies are under way to clarify the place of Y90-radioembolization in the algorithm of HCC treatment.

  7. 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.

  8. Distribution pattern of 90Sr and 137Cs in the Nile delta and the adjacent regions after Chernobyl accident.

    PubMed

    Shawky, S; el-Tahawy, M

    1999-02-01

    Strontium and cesium contents in surface soil samples across the Nile Delta and the north coast of Egypt after the Chernobyl accident have been investigated. The concentration of 137Cs and 90Sr was determined using a high resolution gamma spectrometer based on hyperpure germanium detector (HPGe) and a liquid scintillation counter (LSC) respectively. 90Sr was determined through its decay product 90Y using Cerenkov counting. The determination of 90Sr was based on tributylphosphate (TBP) extraction of yttrium from nitric acid extract of ashed samples. The radioactivity of soils ranged between 18.5 and 2175 Bq/m2 with a mean of 652 Bq/m2 and 234 and 3129 Bq/m2 with a mean of 760 Bq/m2 for 137Cs and 90Sr respectively. An estimated absorbed dose equivalent due to the measured deposit of 137Cs was found to be 0.062 murem/h.

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

    PubMed

    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 our own experiments involving attempted asymmetric radiolysis of DL-amino acids using quantitative gas chromotography as a probe for optical activity. Our radiation sources included 90Sr-90Y, 14C and 32P 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% gross radiolysis. We thus find no unambiguous support for the Vester-Ulbricht hypothesis in any of the attempted asymmetric radiolyses performed to date. Radioracemization, a possible reason for these failures, is discussed.

  10. Radiochemical Separations:. Useful Methods for the Preparation of No-Carrier Solutions of Different Radionuclides for Metabolic Radiotherapy

    NASA Astrophysics Data System (ADS)

    Zona, C.; Groppi, F.; Persico, E.; Canella, L.; Bonardi, M. L.; Chinol, M.; Abbas, K.; Holzwarth, U.; Gibson, N.

    2008-06-01

    In Nuclear Medicine, radionuclides are used in the detection and the treatment for cancers and others diseases. We must obtain, for therapeutic purposes, solutions of radionuclides in the required chemical form, with an high specific activity (AS). To reach our goal we must, first, obtain no-carrier-added (NCA) solutions. In this work we present different methods for the production of NCA radionuclides, based on either wet-chemistry, or thermc- and radio-chromatography. We set up four different methods: two for the preparation of the alpha emitter 211At, and two for the beta emitters 186gRe and 90Y. These radionuclides had been chosen because of their chemical and nuclear properties as their half-life, type, abundance and energy of emissions, that make them among the most promising radionuclides to label compounds for the metabolic radionuclide therapy.

  11. Investigation of the diamond based detectors characteristics with different thickness of the sensor element

    NASA Astrophysics Data System (ADS)

    Gladchenkov, E. V.; Ibragimov, R. F.; Kolyubin, V. A.; Nedosekin, P. G.; Tyurin, E. M.; Zaharchenko, K. V.

    2017-01-01

    This work is devoted to study of the diamond based radiation detectors. Experiments were carried out with two types of detectors: based on a thin diamond film and on a composite diamond plate. The following types of ionizing radiation has been used in experiments: beta radiation of 90Sr - 90Y, fission fragments and alpha particles of 252Cf, and Kr ions obtained at the particle accelerator. It is shown that the developed thin-film diamond based detector effectively registers heavy charged particles, whereas beta, neutron and gamma radiation does not give a significant contribution to the detector signals. Those type of detectors are proposed for measurement of heavy charged particles linear energy transfer in diamond. The multilayer diamond based detector (detector with a composite diamond plate) showed improved charge collection efficiency values in compare with the detection with a single diamond plate.

  12. The NIST radioactivity measurement assurance program for the radiopharmaceutical industry.

    PubMed

    Cessna, Jeffrey T; Golas, Daniel B

    2012-09-01

    The National Institute of Standards and Technology (NIST) maintains a program for the establishment and dissemination of activity measurement standards in nuclear medicine. These standards are disseminated through Standard Reference Materials (SRMs), Calibration Services, radionuclide calibrator settings, and the NIST Radioactivity Measurement Assurance Program (NRMAP, formerly the NEI/NIST MAP). The MAP for the radiopharmaceutical industry is described here. Consolidated results show that, for over 3600 comparisons, 96% of the participants' results differed from that of NIST by less than 10%, with 98% being less than 20%. Individual radionuclide results are presented from 214 to 439 comparisons, per radionuclide, for (67)Ga, (90)Y, (99m)Tc, (99)Mo, (111)In, (125)I, (131)I, and (201)Tl. The percentage of participants results within 10% of NIST ranges from 88% to 98%.

  13. 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.

  14. Hepatic falciform ligament Tc-99m-macroaggregated albumin activity on SPECT/CT prior to Yttrium-90 microsphere radioembolization: prophylactic measures to prevent non-target microsphere localization via patent hepatic falciform arteries.

    PubMed

    Kao, Yung Hsiang; Tan, Andrew E H; Khoo, Li Ser; Lo, Richard H G; Chow, Pierce K H; Goh, Anthony S W

    2011-06-01

    Yttrium-90 (Y-90) selective internal radiation therapy (SIRT) is increasingly used to treat inoperable hepatocellular carcinoma. We describe two patients where hepatic falciform ligament Technetium-99m-macroaggregated albumin (Tc-99m-MAA) activity was identified on single photon emission computed tomography with integrated low-dose CT (SPECT/CT) scan during pre-therapy planning, and the steps taken to prevent radiation dermatitis. The first patient underwent prophylactic coil embolization of the patent hepatic falciform artery; the second patient underwent super-selective infusion of Y-90 resin microspheres to avoid the patent hepatic falciform artery. The incidence of falciform ligament Tc-99m-MAA activity detected on SPECT/CT at our institution is 10%. Tc-99m-MAA SPECT/CT scan provides valuable diagnostic information for treatment planning prior to Y-90 SIRT.

  15. Radiation-Damage Resistance in Phyllosilicate Minerals From First Principles and Implications for Radiocesium and Strontium Retention in Soils

    SciTech Connect

    Sassi, Michel; Rosso, Kevin M.; Okumura, Masahiko; Machida, Masahiko

    2016-04-01

    Accidental discharges of the hazardous nuclear fission products 137Cs+ and 90Sr2+ into the environment, such as during the Fukushima Dai-ichi nuclear accident, have repeatedly occurred throughout the nuclear age. Numerous studies of their fate and transport in soils and sediments have demonstrated their strong and selective binding to phyllosilicates such as clay minerals, primarily via cation exchange into interlayer sites. The locally concentrated amounts of these radioactive beta-emitters that can be found in these host minerals raises important questions regarding the long-term interplay and durability of radioisotope-clay association, which is not well known. This study goes beyond the usual short-term focus to address the permanence of radioisotope retention in clay minerals, by developing a general theoretical understanding of their resistance to defect creation. We report ab initio molecular dynamics (AIMD) calculations of the threshold displacement energy (TDE) of each symmetry-unique atomic specie comprising the unit cell of model vermiculite. The determined TDE values are material specific and radiation independent. We use them to estimate the probability of Frenkel pair creation via direct electron-ion collision, as could be induced by the passage of a high energy electron emitted during the beta-decay of 137Cs, 90Sr and daughter 90Y. For 137Cs and 90Sr, we found that the probability is about 36%, while for 90Y the probability is much higher with about 89%. The long-term retention picture that emerges is that decay will progressively alter the clay interlayer structure and charge, likely leading to delamination of the clay and re-release of residual parent isotopes. Future work examining the effect of Frenkel defect accumulation on the binding energy of parent and daughter radionuclides in the interlayer is thus justifiable, and potentially important for accurate long-term forecasting of radionuclide transport in the environment.

  16. Targeting and therapy of human glioma xenografts in vivo utilizing radiolabeled antibodies

    SciTech Connect

    Williams, J.A.; Wessels, B.W.; Edwards, J.A.; Kopher, K.A.; Wanek, P.M.; Wharam, M.D.; Order, S.E.; Klein, J.L. )

    1990-02-01

    Radiolabeled antibodies provide a potential basis for selective radiotherapy of human gliomas. We have measured tumor targeting by radiolabeled monoclonal antibodies directed against neuroectodermal and tumor-associated antigens in nude mice bearing human glioma xenografts. Monoclonal P96.5, a mouse IgG2a immunoglobulin, defines an epitope of a human melanoma cell surface protein and specifically binds the U-251 human glioma as measured by immunoperoxidase histochemistry. IIIIn-radiolabeled P96.5 specifically targets the U-251 human glioma xenograft and yields 87.0 microCi of tumor activity/g/100 microCi injected activity compared to 4.5 microCi following administration of 100 microCi radiolabeled irrelevant monoclonal antibody. Calculations of targeting ratios demonstrate the deposited dose to be 11.6 times greater with radiolabeled P96.5 administration compared to irrelevant monoclonal antibody. The dose found in normal organs is less than 20% of that in the tumor, further supporting specific targeting of the human glioma xenograft by this antibody. Monoclonal antibody ZME018, which defines a second melanoma-associated antigen, demonstrates positive immunoperoxidase staining of the tumor, but comparatively decreased targeting. To test the therapeutic potential of 90Y-radiolabeled P96.5 and ZME018, tumors and normal sites were implanted with miniature thermoluminescent dosimeters. Average absorbed doses of 3770 +/- 445 (SEM) and 645 +/- 48 cGy in tumor, 353 +/- 41 and 222 +/- 13 cGy in a contralateral control i.m. site, 980 +/- 127 and 651 +/- 63 cGy in liver, and 275 +/- 14 and 256 +/- 18 cGy in total body were observed 7 days following administration of 100 microCi 90Y-radiolabeled P96.5 and ZME018, respectively. Calculations of absorbed dose by the medical internal radiation dose method confirmed thermoluminescent dosimeter absorbed dose measurements.

  17. Novel "Add-On" Molecule Based on Evans Blue Confers Superior Pharmacokinetics and Transforms Drugs to Theranostic Agents.

    PubMed

    Chen, Haojun; Jacobson, Orit; Niu, Gang; Weiss, Ido D; Kiesewetter, Dale O; Liu, Yi; Ma, Ying; Wu, Hua; Chen, Xiaoyuan

    2017-04-01

    One of the major design considerations for a drug is its pharmacokinetics in the blood. A drug with a short half-life in the blood is less available at a target organ. Such a limitation dictates treatment with either high doses or more frequent doses, both of which may increase the likelihood of undesirable side effects. To address the need for additional methods to improve the blood half-life of drugs and molecular imaging agents, we developed an "add-on" molecule that contains 3 groups: a truncated Evans blue dye molecule that binds to albumin with a low micromolar affinity and provides a prolonged half-life in the blood; a metal chelate that allows radiolabeling for imaging and radiotherapy; and maleimide for easy conjugation to drug molecules. Methods: The truncated Evans blue molecule was conjugated with the chelator NOTA or DOTA, and the resulting conjugate was denoted as NMEB or DMEB, respectively. As a proof of concept, we coupled NMEB and DMEB to c(RGDfK), which is a small cyclic arginine-glycine-aspartic acid (RGD) peptide, for targeting integrin αvβ3 NMEB and DMEB were radiolabeled with (64)Cu and (90)Y, respectively, and tested in xenograft models. Results: The resulting radiolabeled conjugates showed a prolonged circulation half-life and enhanced tumor accumulation in integrin αvβ3-expressing tumors. Tumor uptake was markedly improved over that with NOTA- or DOTA-conjugated c(RGDfK). Tumor radiotherapy experiments in mice with (90)Y-DMEB-RGD showed promising results; existing tumors were eliminated. Conclusion: Conjugation of our novel add-on molecule, NMEB or DMEB, to potential tracers or therapeutic agents improved blood half-life and tumor uptake and could transform such agents into theranostic entities.

  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. 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.

  20. Strontium-90 concentration measurements in human bones and teeth in Greece.

    PubMed

    Stamoulis, K C; Assimakopoulos, P A; Ioannides, K G; Johnson, E; Soucacos, P N

    1999-05-19

    Strontium-90 concentration was measured in human bones and teeth collected in Greece during the period 1992-1996. One hundred and five bone samples, mainly cancellous bone, and 108 samples, taken from a total of 896 individual teeth were processed. Samples were classified according to the age and sex of the donors. Samples were chemically pre-treated according to a specially devised method to enable extraction of 90Y, at equilibrium with 90Sr in the original sample. Subsequently, 90Y beta activity was measured with a gas proportional counter. Radiostrontium concentration in bone samples showed small variations with respect to age or sex, with an average value of 30 mBq 90Sr/g Ca. However, 90Sr concentration measurements in teeth demonstrated a pronounced structure, which clearly reflects contamination from the 1960s atmospheric nuclear weapons tests and the more recent Chernobyl accident. This difference is attributed to the different histological structure of skeletal bones and teeth, the later consisting mainly of compact bone. An age-dependent model for radiostrontium concentration in human bones and teeth is developed which is able to successfully reproduce the experimental data. Through a fitting process, the model also yielded calcium turnover rates for compact bone, as a function of age, as well as an estimate of radiostrontium contamination of foodstuffs in Greece for the past four decades. The results obtained in this study indicate that radiostrontium environmental contamination which resulted from the atmospheric nuclear weapons tests in the 1960s, exceed by far that caused by the Chernobyl accident.

  1. Zeta potential response of human erythrocyte membranes to the modulators of Gardos channel activity under low rate β-radiation.

    PubMed

    Zhirnov, V V; Iakovenko, I N; Voitsitskiy, V M; Khyzhnyak, S V; Zubrikova-Chugainova, O G; Gorobetz, V A

    2015-12-01

    Tsel' raboty. Izuchenie reaktsii dzeta potentsiala (DP) membran éritrotsitov cheloveka pri modifikatsii aktivatorami i blokatorami funktsional'nogo sostoianiia Ca2+-zavisimykh kalievykh kanalov v pole radioizotopnogo izlucheniia 90Sr/90Y maloi moshchnosti.Materialy i metody. Éritrotsity poluchali iz donorskoi krovi. DP vychisliali po poluchennomu znacheniiu élektroforeticheskoi podvizhnosti kletok. V kletochnye suspenzii predvaritel'no vnosili issleduemye veshchestva, a zatem alikvoty rastvora 90Sr(NO3)2, chtoby poluchit' konechnuiu kontsentratsiiu 44,4⋅kBk⋅l-1.Rezul'taty. Radioizotopnoe izluchenie 90Sr/90Y (RI, 15 mkGr/ch) povyshaet absoliutnoe znachenie DP (DPab) membran éritrotsitov i ego deistvie iavliaetsia obratimym. Éto ukazyvaet na to, chto éffekt oposreduetsia neioniziruiushchei komponentoi RI. Dibutiril-tsAMF v diapazone kontsentratsii 1–100 mkM dozonezavisimo povyshaet DPab membran éritrotsitov, no RI ne usilivaet ego éffekt. Anaprilin v kontsentratsiiakh 10 i 100 mkM dozonezavisimo povyshaet DPab. Éffekt maksimal'noi kontsentratsii anaprilina (100 mkM) – snizhaetsia RI. Klotrimazol v diapazone kontsentratsii 0,1–10 mkM povyshaet DPab membran éritrotsitov otnositel'no kontrolia, togda kak ego maksimal'naia kontsentratsiia – snizhet, a minimal'naia – dostoverno ne vliiaet na étot pokazatel'. Deistvie klotrimazola na DP pri kontsentratsiiakh 10–100 mkM otmeniaetsia RI, no ne izmeniaetsia pri 0,1–1 mkM. Nitrendipin vo vsem diapazone kontsentratsii dozonezavisimo povyshaet DPab membran éritrotsitov, a RI usilivaet ego deistvie. Vyvody. 1. Dlia ioniziruiushchei komponenty radionuklidnogo izlucheniia sushchestvuet porog biologicheskogo deistviia na kletki, opredeliaemyi éffektivnost'iu ikh antioksidantnoi sistemy.2. Pri moshchnosti doz nizhe porogovoi deistvie radioizotopnogo izlucheniia oposreduetsia ego neioniziruiushchei komponentoi i iavliaetsia obratimym, a poétomu opredeliaetsia tol'ko v pole izlucheniia.

  2. 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.

  3. Transarterial Hepatic Yttrium-90 Radioembolization in Patients with Unresectable Intrahepatic Cholangiocarcinoma: Factors Associated with Prolonged Survival

    SciTech Connect

    Hoffmann, Ralf-T. Paprottka, Philipp M.; Schoen, Agnes; Bamberg, Fabian; Haug, Alexander; Duerr, Eva-Maria; Rauch, Barbara; Trumm, Christoph T.; Jakobs, Tobias F.; Helmberger, Thomas K.; Reiser, Maximilian F.; Kolligs, Frank T.

    2012-02-15

    Introduction: In unresectable intrahepatic cholangiocarcinoma (ICC), systemic chemotherapy often is viewed as the only option, although efficacy is limited. Radioembolization (RE) using yttrium-90 ({sup 90}Y) microspheres is an accepted therapy for patients with hepatocellular-carcinoma or metastatic liver tumors. However, there are limited data on the value of RE in patients with ICC and few data on factors influencing prognosis. The purpose of our retrospective analysis was to establish which factors influenced time-to-progression (TTP) and overall survival (OS). Methods: Patients with unresectable ICC were treated with {sup 90}Y resin-microspheres and assessed at 3-monthly intervals. Radiologic response was evaluated by using Response Criteria in Solid Tumors (RECIST). Baseline characteristics, biochemical/clinical toxicities, and response were examined for impact on TTP and OS. Results: Thirty-four treatments were administered to 33 patients without major complications. By RECIST, 12 patients had a partial response, 17 had stable disease, and 5 had progressive disease after 3 months. The median OS was 22 months posttreatment and 43.7 months postdiagnosis. Median TTP was 9.8 months. Survival and TTP were significantly prolonged in patients with ECOG 0 (vs. ECOG 1 or 2; median OS: 29.4, 10, and 5.1 months; TTP: 17.5, 6.9, and 2.4 months), tumor burden {<=}25% (OS: 26.7 vs. 6 months; TTP: 17.5 vs. 2.3 months), or tumor response (PR or SD vs. PD; OS: 35.5, 17.7 vs. 5.7 months; TTP: 31.9, 9.8 vs. 2.5 months), respectively (P < 0.001). Conclusions: Radioembolization is an effective and safe option for patients with unresectable ICC. Predictors for prolonged survival are performance status, tumor burden, and RECIST response.

  4. Peptide receptor radionuclide therapy in the management of gastrointestinal neuroendocrine tumors: efficacy profile, safety, and quality of life

    PubMed Central

    Severi, Stefano; Grassi, Ilaria; Nicolini, Silvia; Sansovini, Maddalena; Bongiovanni, Alberto; Paganelli, Giovanni

    2017-01-01

    Peptide receptor radionuclide therapy (PRRT), developed over the last two decades, is carried out using radiopharmaceuticals such as 90Y-DOTA-Tyr3-octreotide and 177Lu-DOTA-Tyr3-octreotate (177Lu-Dotatate). These radiocompounds are obtained by labeling a synthetic somatostatin analog with a β-emitting radioisotope. The compounds differ from each other in terms of their energetic features (due to the radionuclide) and peptide receptor affinity (due to the analog) but share the common characteristic of binding specific membrane somatostatin receptors that are (generally) overexpressed in neuroendocrine neoplasms (NENs) and their metastases. NENs are tumors arising from diffuse neuroendocrine system cells that are classified according to grading based on Ki67 percentage values (Grades 1 and 2 are classed as neuroendocrine tumors [NETs]) and to the anatomical site of occurrence (in this paper, we only deal with gastroenteropancreatic [GEP]-NETs, which account for 60%–70% of all NENs). They are also characterized by specific symptoms such as diarrhea and flushing (30% of cases). Despite substantial experience gained in the area of PRRT and its demonstrable effects in terms of efficacy, safety, and improvement in quality of life, these compounds are still not registered (registration of 177Lu-Dotatate for the treatment of midgut NETs is expected soon). Thus, PRRT can only be used in experimental protocols. We provide an overview of the work of leading groups with wide-ranging experience and continuity in data publication in the area of GEP-NET PRRT and report our own personal experience of using different dosage schedules based on the presence of kidney and bone marrow risk factors. Our results on the retreatment of patients previously administered 90Y-DOTA-Tyr3-octreotide with a low dosage of 177Lu-Dotatate are also included. A comment on potential future developments of PRRT in GEP-NETs is provided. PMID:28203088

  5. 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.

  6. 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.

  7. Influence of voxel S factors on three-dimensional internal dosimetry calculations.

    PubMed

    Berenato, Salvatore; Amato, Ernesto; Fischer, Alexander; Baldari, Sergio

    2016-10-01

    Internal dosimetry is a fundamental instrument for the personalization of nuclear medicine therapies, to maximize the therapeutic effect while minimizing the radiation burden to other organs. Three-dimensional (3D) dosimetry can quantify the impact of heterogeneous radiopharmaceutical distributions in organs, lesions and tissues. We analysed the influence of radionuclide voxel S factors in 3D dosimetry of (111)In, (177)Lu and (90)Y, the most used radionuclides in Peptide Receptor Radionuclide Therapy (PRRT). Calculations were carried out for kidneys on a workstation equipped with a software for 3D dosimetry (Imalytics STRATOS, Philips AG), adopting a computational anthropomorphic phantom and, retrospectively, the SPECT-CT image series of a clinical case of PRRT. Two sets of voxel S factors were adopted: the pre-loaded Philips kernels, calculated by direct Monte Carlo simulation, and the ones calculated through a previously proposed analytical approach. Philips (111)In kernel did not account for mono-energetic Auger or Conversion electrons. Results indicate a difference of about -32% in voxel S factors for (111)In in 4.42mm voxel size and around -35% in 4.80mm voxel size, particularly self-dose values; this lead to significant shift in dose histograms and average doses. For (177)Lu and (90)Y, differences are about 2% and 12% for 4.42mm voxels and about -8% and 9% for 4.80mm voxels, respectively, attributable to the different calculation methods of the voxel S factors; this does not lead to significant discrepancies between the two dose histograms. Consequently, voxel S factors must account accurately for all radiations emitted by the nuclide.

  8. Use of the GEANT4 Monte Carlo to determine three-dimensional dose factors for radionuclide dosimetry

    NASA Astrophysics Data System (ADS)

    Amato, Ernesto; Italiano, Antonio; Minutoli, Fabio; Baldari, Sergio

    2013-04-01

    The voxel-level dosimetry is the most simple and common approach to internal dosimetry of nonuniform distributions of activity within the human body. Aim of this work was to obtain the dose "S" factors (mGy/MBqs) at the voxel level for eight beta and beta-gamma emitting radionuclides commonly used in nuclear medicine diagnostic and therapeutic procedures. We developed a Monte Carlo simulation in GEANT4 of a region of soft tissue as defined by the ICRP, divided into 11×11×11 cubic voxels, 3 mm in side. The simulation used the parameterizations of the electromagnetic interaction optimized for low energy (EEDL, EPDL). The decay of each radionuclide (32P, 90Y, 99mTc, 177Lu, 131I, 153Sm, 186Re, 188Re) were simulated homogeneously distributed within the central voxel (0,0,0), and the energy deposited in the surrounding voxels was mediated on the 8 octants of the three dimensional space, for reasons of symmetry. The results obtained were compared with those available in the literature. While the iodine deviations remain within 16%, for phosphorus, a pure beta emitter, the agreement is very good for self-dose (0,0,0) and good for the dose to first neighbors, while differences are observed ranging from -60% to +100% for voxels far distant from the source. The existence of significant differences in the percentage calculation of the voxel S factors, especially for pure beta emitters such as 32P or 90Y, has already been highlighted by other authors. These data can usefully extend the dosimetric approach based on the voxel to other radionuclides not covered in the available literature.

  9. SU-E-T-154: Calculation of Tissue Dose Point Kernels Using GATE Monte Carlo Simulation Toolkit to Compare with Water Dose Point Kernel

    SciTech Connect

    Khazaee, M; Asl, A Kamali; Geramifar, P

    2015-06-15

    Purpose: the objective of this study was to assess utilizing water dose point kernel (DPK)instead of tissue dose point kernels in convolution algorithms.to the best of our knowledge, in providing 3D distribution of absorbed dose from a 3D distribution of the activity, the human body is considered equivalent to water. as a Result tissue variations are not considered in patient specific dosimetry. Methods: In this study Gate v7.0 was used to calculate tissue dose point kernel. the beta emitter radionuclides which have taken into consideration in this simulation include Y-90, Lu-177 and P-32 which are commonly used in nuclear medicine. the comparison has been performed for dose point kernels of adipose, bone, breast, heart, intestine, kidney, liver, lung and spleen versus water dose point kernel. Results: In order to validate the simulation the Result of 90Y DPK in water were compared with published results of Papadimitroulas et al (Med. Phys., 2012). The results represented that the mean differences between water DPK and other soft tissues DPKs range between 0.6 % and 1.96% for 90Y, except for lung and bone, where the observed discrepancies are 6.3% and 12.19% respectively. The range of DPK difference for 32P is between 1.74% for breast and 18.85% for bone. For 177Lu, the highest difference belongs to bone which is equal to 16.91%. For other soft tissues the least discrepancy is observed in kidney with 1.68%. Conclusion: In all tissues except for lung and bone, the results of GATE for dose point kernel were comparable to water dose point kernel which demonstrates the appropriateness of applying water dose point kernel instead of soft tissues in the field of nuclear medicine.

  10. 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.

  11. 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.

  12. Radiolabeled peptides in oncology: role in diagnosis and treatment.

    PubMed

    Weiner, Ronald E; Thakur, Mathew L

    2005-01-01

    results in clinical trials in humans. Radiolabelled peptide therapy is usually indicated for patients with widespread disease that is not amenable to focused radiation therapy or is refractory to chemotherapy. Phase I/II studies using various radiolabelled peptides (including (111)In-pentetreotide, Yttrium-90 [90Y]-DOTA-Phe1-Tyr3-octreotide, 90Y-DOTA-lanreotide, and Lutetium-177 [177Lu]-DOTA-octreotate) for the treatment of patients with neuroendocrine malignancy are in progress. Over 400 patients have been treated, and the response rate has ranged from 60% to 75%, although few patients have had a complete response. Patients have been given individual doses ranging from 2 to 11 GBq with a slow infusion every 4-8 weeks (up to 12 times). The kidney is the dose-limiting organ and most patients experience a transient decline in blood cell counts. A concomitant infusion of an amino acid mixture can reduce kidney toxicity and increase the effective tumor dose. Other peptides currently under investigation, some of which have shown promising results, include Rhenium-188 (188Re)-P2045 and 90Y-alpha(v)beta3 antagonist.

  13. 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

  14. 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

  15. 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.

  16. Pretargeted Radioimmunotherapy Using Anti-CD45 Monoclonal Antibodies to Deliver Radiation to Murine Hematolymphoid Tissues and Human Myeloid Leukemia

    SciTech Connect

    Pagel, John M.; Matthews, Dana C.; Kenoyer, Aimee L.; Hamlin, Donald K.; Wilbur, D. Scott; Fisher, Darrell R.; Gopal, Ajay K.; Lin, Yukang; Saganic, Laura; Appelbaum, Frederick R.; Press, Oliver W.

    2009-01-01

    The efficacy of radioimmunotherapy (RIT) for treatment of patients with hematological malignancies frequently fails because of disease recurrence. We therefore conducted pretargeted RIT studies to augment the efficacy in mice of therapy using a pretargeted anti-human (h)CD45 antibody (Ab)-streptavidin (SA) conjugate followed by delivery of a biotinylated clearing agent and radiolabeled-DOTA-biotin. Tumor-to-blood ratios at 24 hours were 20:1 using pretargeted anti-hCD45 RIT and <1:1 with conventional RIT. In vivo imaging studies confirmed that the pretargeted RIT approach provided high-contrast tumor images with minimal blood-pool activity, whereas directly-labeled anti-hCD45 Ab produced distinct tumor images but the blood pool retained a large amount of labeled antibody for a prolonged time. Therapy experiments demonstrated that 90Y-DOTA-biotin significantly prolonged survival of mice treated pretargeted with anti-hCD45 Ab-SA compared to mice treated with conventional RIT using 90Y-labeled anti-hCD45 Ab at the maximally tolerated dose (400 µCi). Since human CD45 antigens are confined to xenograft tumor cells in this model, and all murine tissues are devoid of hCD45 and will not bind anti-hCD45 Ab, we also compared one-step and pretargeted RIT using an anti-murine (m)CD45 Ab (A20 ) in a model where the target antigen is present on normal hematopoietic tissues. After 24 hours, 27.3 ± 2.8% of the injected dose of radionuclide was delivered per gram (% ID/g) of lymph node using 131I-A20-Ab compared with 40.0 ± 5.4% ID/g for pretargeted 111In-DOTA-biotin (p value). These data suggest that multi-step pretargeted methods for delivering RIT are superior to conventional RIT when targeting CD45 for the treatment of leukemia and may allow for the intensification of therapy, while minimizing toxicities.

  17. Thermoluminescence solid-state nanodosimetry--the peak 5A/5 dosemeter.

    PubMed

    Fuks, E; Horowitz, Y S; Horowitz, A; Oster, L; Marino, S; Rainer, M; Rosenfeld, A; Datz, H

    2011-02-01

    The shape of composite peak 5 in the glow curve of LiF:Mg,Ti (TLD-100) following (90)Sr/(90)Y beta irradiation, previously demonstrated to be dependent on the cooling rate used in the 400°C pre-irradiation anneal, is shown to be dependent on ionisation density in both naturally cooled and slow-cooled samples. Following heavy-charged particle high-ionisation density (HID) irradiation, the temperature of composite peak 5 decreases by ∼5°C and the peak becomes broader. This behaviour is attributed to an increase in the relative intensity of peak 5a (a low-temperature satellite of peak 5). The relative intensity of peak 5a is estimated using a computerised glow curve deconvolution code based on first-order kinetics. The analysis uses kinetic parameters for peaks 4 and 5 determined from ancillary measurements resulting in nearly 'single-glow peak' curves for both the peaks. In the slow-cooled samples, owing to the increased relative intensity of peak 5a compared with the naturally cooled samples, the precision of the measurement of the 5a/5 intensity ratio is found to be ∼15% (1 SD) compared with ∼25% for the naturally cooled samples. The ratio of peak 5a/5 in the slow-cooled samples is found to increase systematically and gradually through a variety of radiation fields from a minimum value of 0.13±0.02 for (90)Sr/(90)Y low-ionisation density irradiations to a maximum value of ∼0.8 for 20 MeV Cu and I ion HID irradiations. Irradiation by low-energy electrons of energy 0.1-1.5 keV results in values between 1.27 and 0.95, respectively. The increasing values of the ratio of peak 5a/5 with increasing ionisation density demonstrate the viability of the concept of the peak 5a/5 nanodosemeter and its potential in the measurement of average ionisation density in a 'nanoscopic' mass containing the trapping centre/luminescent centre spatially correlated molecule giving rise to composite peak 5.

  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. Identification of 90Sr/40K Based on Cherenkov Detector for Recovery from the Fukushima Nuclear Accident

    NASA Astrophysics Data System (ADS)

    Ito, Hiroshi; Han, Soorim; Kobayashi, Atsushi; Kaneko, Naomi; Kawai, Hideyuki; Tabata, Makoto

    Although five years have passed since the Fukushima nuclear accident of 2011, the local fisheries have yet to recover from its effects. One reason for this situation is the difficulty of measuring the radioactivity owing to 90Sr in seafood. After the accident, the radioactivity due to Cs isotopes in samples was measured with precision, which facilitated the enforcement of the maximum concentration of Cs radioisotopes in food at 100 Bq/kg, as defined by the Ministry of Health, Labour and Welfare in Japan. However, 90Sr is more dangerous than Cs isotopes because it has an effective half-life of 18 years and accumulates in the bone. The radioactivity owing to 90Sr in a sample is difficult to measure because the beta rays from 137Cs or 40K also contribute to the signal. When measured based on the endpoint pulse height as determined by a conventional survey meter, the beta ray signal from 90Y (daughter of 90Sr) cannot be differentiated from the beta rays from other sources. To overcome this difficulty, in this study, we develop a Cherenkov detector based on a silica aerogel with a refractive index of 1.034 that can identify beta rays from 90Y within a background of beta rays from 137Cs and 40K. This instrument involves a detector that is sensitive to beta rays from 90Sr but less sensitive to radiation from other sources. This detector comprises a trigger counter that uses scintillating fibers, an aerogel Cherenkov counter with wavelength-shifting fibers, and a veto counter to suppress cosmic rays. We characterize the detector using a 90Sr source, 137Cs source, and pure potassium chloride reagent of 16.6 Bq/g, where the radioactivity of natural 40K is estimated to be 31.7 Bq/g. The following results are obtained: the absolute detection efficiency for 90Sr, 137Cs, and 40K is [2.24 ± 0.01 (stat) ± 0.44 (sys)] × 10-3 Bq-1 s-1, [1.27 ± 0.08 (stat) ± 0.25 (sys)] × 10-6 Bq-1 s-1, and [5.05 ± 2.40 (stat) ± 0.15 (sys)] × 10-5 Bq-1 s-1, respectively. To aid in the

  20. The prognostic value of functional and anatomical parameters for the selection of patients receiving yttrium-90 microspheres for the treatment of liver cancer

    NASA Astrophysics Data System (ADS)

    Mesoloras, Geraldine

    Yttrium-90 (90Y) microsphere therapy is being utilized as a treatment option for patients with primary and metastatic liver cancer due to its ability to target tumors within the liver. The success of this treatment is dependent on many factors, including the extent and type of disease and the nature of prior treatments received. Metabolic activity, as determined by PET imaging, may correlate with the number of viable cancer cells and reflect changes in viable cancer cell volume. However, contouring of PET images by hand is labor intensive and introduces an element of irreproducibility into the determination of functional target/tumor volume (FTV). A computer-assisted method to aid in the automatic contouring of FTV has the potential to substantially improve treatment individualization and outcome assessment. Commercial software to determine FTV in FDG-avid primary and metastatic liver tumors has been evaluated and optimized. Volumes determined using the automated technique were compared to those from manually drawn contours identified using the same cutoff in the standard uptake value (SUV). The reproducibility of FTV is improved through the introduction of an optimal threshold value determined from phantom experiments. Application of the optimal threshold value from the phantom experiments to patient scans was in good agreement with hand-drawn determinations of the FTV. It is concluded that computer-assisted contouring of the FTV for primary and metastatic liver tumors improves reproducibility and increases accuracy, especially when combined with the selection of an optimal SUV threshold determined from phantom experiments. A method to link the pre-treatment assessment of functional (PET based) and anatomical (CT based) parameters to post-treatment survival and time to progression was evaluated in 22 patients with colorectal cancer liver metastases treated using 90Y microspheres and chemotherapy. The values for pre-treatment parameters that were the best

  1. 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

  2. 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

  3. Baseline hemoglobin and liver function predict tolerability and overall survival of patients receiving radioembolization for chemotherapy-refractory metastatic colorectal cancer

    PubMed Central

    Ball, David; Cohen, Steven J.; Cohn, Michael; Coldwell, Douglas M.; Drooz, Alain; Ehrenwald, Edward; Kanani, Samir; Moeslein, Fred M.; Nutting, Charles W.; Putnam, Samuel G.; Rose, Steven C.; Savin, Michael; Schirm, Sabine; Sharma, Navesh K.; Wang, Eric

    2017-01-01

    Background Patients with liver metastatic colorectal cancer (mCRC) often benefit from receiving 90Y-microsphere radioembolization (RE) administered via the hepatic arteries. Prior to delivery of liver-directed radiation, standard laboratory tests may assist in improving outcome by identifying correctable pre-radiation abnormalities. Methods A database containing retrospective review of consecutively treated patients of mCRC from July 2002 to December 2011 at 11 US institutions was used. Data collected included background characteristics, prior chemotherapy, surgery/ablation, radiotherapy, vascular procedures, 90Y treatment, subsequent adverse events and survival. Kaplan-Meier estimates compared the survival of patients across lines of chemotherapy. The following values were obtained within 10 days prior to each RE treatment: haemoglobin (HGB), albumin, alkaline phosphatase (Alk phosph), aspartate aminotransferase (AST), alanine transaminase (ALT), total bilirubin and creatinine. Common Terminology Criteria Adverse Events (CTCAEs) 3.0 grade was assigned to each parameter and analysed for impact on survival by line of chemotherapy. Consensus Guidelines were used to categorize the parameter grades as either within or outside guidelines for treatment. Results A total of 606 patients (370 male; 236 female) were studied with a median follow-up was 8.5 mo. (IQR 4.3–15.6) after RE. Fewer than 11% of patients were treated outside recommended RE guidelines, with albumin being the most common, 10.5% grade 2 (<3–2.0 g/dL) at time of RE. All seven parameters showed statistically significant decreased median survivals with any grade >0 (P<0.001) across all lines of prior chemotherapy. Compared to grade 0, grade 2 albumin decreased overall survival 67%; for grade 2 total bilirubin a 63% drop occurred, and grade 1 HGB resulted in 66% lower median survival. Conclusions Review of pre-RE laboratory parameters may aid in improving median survivals if correctable grade >0 values

  4. Anti-tax interacting protein-1 (TIP-1) monoclonal antibody targets human cancers.

    PubMed

    Yan, Heping; Kapoor, Vaishali; Nguyen, Kim; Akers, Walter J; Li, Hua; Scott, Jalen; Laforest, Richard; Rogers, Buck; Thotala, Dinesh; Hallahan, Dennis

    2016-07-12

    Radiation-inducible neo-antigens are proteins expressed on cancer cell surface after exposure to ionizing radiation (IR). These neo-antigens provide opportunities to specifically target cancers while sparing normal tissues. Tax interacting protein-1 (TIP-1) is induced by irradiation and is translocated to the surface of cancer cells. We have developed a monoclonal antibody, 2C6F3, against TIP-1.Epitope mapping revealed that 2C6F3 binds to the QPVTAVVQRV epitope of the TIP-1 protein. 2C6F3 binds to the surface of lung cancer (A549, LLC) and glioma (D54, GL261) cell lines. 2C6F3 binds specifically to TIP-1 and ELISA analysis showed that unconjugated 2C6F3 efficiently blocked binding of radiolabeled 2C6F3 to purified TIP-1 protein. To study in vivo tumor binding, we injected near infrared (NIR) fluorochrome-conjugated 2C6F3 via tail vein in mice bearing subcutaneous LLC and GL261 heterotopic tumors. The NIR images indicated that 2C6F3 bound specifically to irradiated LLC and GL261 tumors, with little or no binding in un-irradiated tumors.We also determined the specificity of 2C6F3 to bind tumors in vivo using SPECT/CT imaging. 2C6F3 was conjugated with diethylene triamine penta acetic acid (DTPA) chelator and radiolabeled with 111Indium (111In). SPECT/CT imaging revealed that 111In-2C6F3 bound more to the irradiated LLC tumors compared to un-irradiated tumors. Furthermore, injection of DTPA-2C6F3 labeled with the therapeutic radioisotope, 90Y, (90Y-DTPA-2C6F3) significantly delayed LLC tumor growth. 2C6F3 mediated antibody dependent cell-mediated cytotoxicity (ADCC) and antibody dependent cell-mediated phagocytosis (ADCP) in vitro.In conclusion, the monoclonal antibody 2C6F3 binds specifically to TIP-1 on cancer and radio-immunoconjugated 2C6F3 improves tumor control.

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

    PubMed Central

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

    2010-01-01

    Bevacizumab is a humanized monoclonal antibody that binds to tumor-secreted VEGF-A and inhibits tumor angiogenesis. In 2004, the antibody was approved by the United States FDA for the treatment of metastatic colorectal carcinoma in combination with chemotherapy. This report describes the preclinical evaluation of a radioimmunoconjugate, 86Y-CHX-A″-DTPA-bevacizumab, for potential use in PET imaging of VEGF-A tumor angiogenesis and as a surrogate marker for 90Y based radioimmunotherapy. Bevacizumab was conjugated to CHX-A″-DTPA and radiolabeled with 86Y. 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 high 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 d post-injection (p.i) was 13.6 ± 1.5, 17.4 ± 1.7 and 6.8 ± 0.7 % ID/g, respectively. The corresponding tumor uptake in mice co-injected 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 86Y-CHX-A″-DTPA-bevacizumab. Organ uptake quantified by PET closely correlated (r2=0.87, p=0.64, n=18) to values determined by biodistribution studies. This preclinical study demonstrates the potential of the radioimmunoconjugate, 86Y-CHX-A″-DTPA-bevacizumab, for non-invasive assessment of the VEGF-A tumor angiogenesis status and as a surrogate marker for 90Y-CHX-A″-DTPA-bevacizumab radioimmunotherapy. PMID:20473899

  6. Long-lived positron emitters zirconium-89 and iodine-124 for scouting of therapeutic radioimmunoconjugates with PET.

    PubMed

    Verel, Iris; Visser, Gerard W M; Boerman, Otto C; van Eerd, Julliette E M; Finn, Ron; Boellaard, Ronald; Vosjan, Maria J W D; Stigter-van Walsum, Marijke; Snow, Gordon B; van Dongen, Guus A M S

    2003-08-01

    Antibody-PET imaging might be of value for the selection of radioimmunotherapy (RIT) candidates to confirm tumor targeting and to estimate radiation doses to tumor and normal tissues. One of the requirements to be set for such a scouting procedure is that the biodistributions of the diagnostic and therapeutic radioimmunoconjugates should be similar. In the present study we evaluated the potential of the positron emitters zirconium-89 ((89)Zr) and iodine-124 ((124)I) for this approach, as these radionuclides have a relatively long half-life that matches with the kinetics of MAbs in vivo (t(1/2) 3.27 and 4.18 days, respectively). After radiolabeling of the head and neck squamous cell carcinoma (HNSCC)-selective chimeric antibody (cMAb) U36, the biodistribution of two diagnostic (cMAb U36-N-sucDf-(89)Zr and cMAb U36-(124)I) and three therapeutic radioimmunoconjugates (cMAb U36-p-SCN-Bz-DOTA-(88)Y-with (88)Y being substitute for (90)Y, cMAb U36-(131)I, and cMAb U36-MAG3-(186)Re) was assessed in mice with HNSCC-xenografts, at 24, 48, and 72 hours after injection. Two patterns of biodistribution were observed, one pattern matching for (89)Zr- and (88)Y-labeled cMAb U36 and one pattern matching for (124)I-, (131)I-, and (186)Re-cMAb U36. The most remarkable differences between both patterns were observed for uptake in tumor and liver. Tumor uptake levels were 23.2 +/- 0.5 and 24.1 +/- 0.7%ID/g for the (89)Zr- and (88)Y-cMAb U36 and 16.0 +/- 0.8, 15.7 +/- 0.79 and 17.1 +/- 1.6%ID/g for (124)I-, (131)I-, and (186)Re-cMAb U36-conjugates, respectively, at 72 hours after injection. For liver these values were 6.9 +/- 0.8 ((89)Zr), 6.2 +/- 0.8 ((88)Y), 1.7 +/- 0.1 ((124)I), 1.6 +/- 0.1 ((131)I), and 2.3 +/- 0.1 ((186)Re), respectively. These preliminary data justify the further development of antibody-PET with (89)Zr-labeled MAbs for scouting of therapeutic doses of (90)Y-labeled MAbs. In such approach (124)I-labeled MAbs are most suitable for scouting of (131)I- and (186)Re

  7. A dose point kernel database using GATE Monte Carlo simulation toolkit for nuclear medicine applications: Comparison with other Monte Carlo codes

    SciTech Connect

    Papadimitroulas, Panagiotis; Loudos, George; Nikiforidis, George C.; Kagadis, George C.

    2012-08-15

    Purpose: GATE is a Monte Carlo simulation toolkit based on the Geant4 package, widely used for many medical physics applications, including SPECT and PET image simulation and more recently CT image simulation and patient dosimetry. The purpose of the current study was to calculate dose point kernels (DPKs) using GATE, compare them against reference data, and finally produce a complete dataset of the total DPKs for the most commonly used radionuclides in nuclear medicine. Methods: Patient-specific absorbed dose calculations can be carried out using Monte Carlo simulations. The latest version of GATE extends its applications to Radiotherapy and Dosimetry. Comparison of the proposed method for the generation of DPKs was performed for (a) monoenergetic electron sources, with energies ranging from 10 keV to 10 MeV, (b) beta emitting isotopes, e.g., {sup 177}Lu, {sup 90}Y, and {sup 32}P, and (c) gamma emitting isotopes, e.g., {sup 111}In, {sup 131}I, {sup 125}I, and {sup 99m}Tc. Point isotropic sources were simulated at the center of a sphere phantom, and the absorbed dose was stored in concentric spherical shells around the source. Evaluation was performed with already published studies for different Monte Carlo codes namely MCNP, EGS, FLUKA, ETRAN, GEPTS, and PENELOPE. A complete dataset of total DPKs was generated for water (equivalent to soft tissue), bone, and lung. This dataset takes into account all the major components of radiation interactions for the selected isotopes, including the absorbed dose from emitted electrons, photons, and all secondary particles generated from the electromagnetic interactions. Results: GATE comparison provided reliable results in all cases (monoenergetic electrons, beta emitting isotopes, and photon emitting isotopes). The observed differences between GATE and other codes are less than 10% and comparable to the discrepancies observed among other packages. The produced DPKs are in very good agreement with the already published data

  8. Y-90-DOTA-hLL2: An Agent for Radioimmunotherapy of Non-Hodgkin's Lymphoma

    SciTech Connect

    Griffiths, Gary L.; Govindan, Serengulam V.; Sharkey, Robert M.; Fisher, Darrell R. ); Goldenberg, David M.

    2003-01-01

    The goal of this work was to determine an optimal radioimmunotherapy agent for non-Hodgkin's lymphoma. We established the stability profile of yttrium-90-labeled humanized LL2 (hLL2) monoclonal antibody prepared with different chelating agents, and from these data estimated the improvement using the most stable yttrium-90 chelate-hLL2 complex. Methods: The complementary-determining region- (cdr)-grafted (humanized) anti-CD22 mAb, hLL2 (epratuzumab), was conjugated to derivatives of DTPA and 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA). The conjugates were labeled with Y-90 and tested against a 10,000-fold molar excess of free DTPA and against human serum. The conjugates were also labeled with Y-88 and compared for biodistribution in normal and lymphoma xenograft-bearing athymic mice. In vivo data were analyzed for uptake of yttrium in bone and washed bone when either the DOTA or the Mx-DTPA chelates were used, and dosimetry calculations were made for each. Results: Y-90-DOTA -mAb were stable to either DTPA or serum challenge. DTPA complexes of hLL2 lost 3-4% of Y-90 (days 1-4) and 10-15% thereafter. In vivo, stability differences showed lower Y-90 uptake in bone using DOTA. Absorbed doses per 37 MBq (1 mCi) Y-90-mAb were 3555 and 5405 cGy for bone, and 2664 and 4524 cGy for washed-bone for 90Y-DOTA-hLL2 and 90Y-MxDTPA-hLL2, respectively, amounting to 52% and 69.8% increases in absorbed radiation doses for bone and washed-bone when switching from a DOTA to a Mx-DTPA chelate. Conclusion: Y-90-hLL2 prepared with the DOTA chelate represents a preferred agent for RAIT of non-Hodgkin's lymphoma, with an in vivo model demonstrating a large reduction in bone-deposited yttrium, as compared to yttrium-90-hLL2 agents prepared with open-chain DTPA-type chelating agents. Dosimetry suggests that this will result in a substantial toxicological advantage for a DOTA-based hLL2 conjugate.

  9. Anti-tax interacting protein-1 (TIP-1) monoclonal antibody targets human cancers

    PubMed Central

    Yan, Heping; Kapoor, Vaishali; Nguyen, Kim; Akers, Walter J.; Li, Hua; Scott, Jalen; Laforest, Richard; Rogers, Buck; Thotala, Dinesh; Hallahan, Dennis

    2016-01-01

    Radiation-inducible neo-antigens are proteins expressed on cancer cell surface after exposure to ionizing radiation (IR). These neo-antigens provide opportunities to specifically target cancers while sparing normal tissues. Tax interacting protein-1 (TIP-1) is induced by irradiation and is translocated to the surface of cancer cells. We have developed a monoclonal antibody, 2C6F3, against TIP-1. Epitope mapping revealed that 2C6F3 binds to the QPVTAVVQRV epitope of the TIP-1 protein. 2C6F3 binds to the surface of lung cancer (A549, LLC) and glioma (D54, GL261) cell lines. 2C6F3 binds specifically to TIP-1 and ELISA analysis showed that unconjugated 2C6F3 efficiently blocked binding of radiolabeled 2C6F3 to purified TIP-1 protein. To study in vivo tumor binding, we injected near infrared (NIR) fluorochrome-conjugated 2C6F3 via tail vein in mice bearing subcutaneous LLC and GL261 heterotopic tumors. The NIR images indicated that 2C6F3 bound specifically to irradiated LLC and GL261 tumors, with little or no binding in un-irradiated tumors. We also determined the specificity of 2C6F3 to bind tumors in vivo using SPECT/CT imaging. 2C6F3 was conjugated with diethylene triamine penta acetic acid (DTPA) chelator and radiolabeled with 111Indium (111In). SPECT/CT imaging revealed that 111In-2C6F3 bound more to the irradiated LLC tumors compared to un-irradiated tumors. Furthermore, injection of DTPA-2C6F3 labeled with the therapeutic radioisotope, 90Y, (90Y-DTPA-2C6F3) significantly delayed LLC tumor growth. 2C6F3 mediated antibody dependent cell-mediated cytotoxicity (ADCC) and antibody dependent cell-mediated phagocytosis (ADCP) in vitro. In conclusion, the monoclonal antibody 2C6F3 binds specifically to TIP-1 on cancer and radio-immunoconjugated 2C6F3 improves tumor control. PMID:27270318

  10. 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

  11. Development of a primary standard for absorbed dose from unsealed radionuclide solutions

    NASA Astrophysics Data System (ADS)

    Billas, I.; Shipley, D.; Galer, S.; Bass, G.; Sander, T.; Fenwick, A.; Smyth, V.

    2016-12-01

    Currently, the determination of the internal absorbed dose to tissue from an administered radionuclide solution relies on Monte Carlo (MC) calculations based on published nuclear decay data, such as emission probabilities and energies. In order to validate these methods with measurements, it is necessary to achieve the required traceability of the internal absorbed dose measurements of a radionuclide solution to a primary standard of absorbed dose. The purpose of this work was to develop a suitable primary standard. A comparison between measurements and calculations of absorbed dose allows the validation of the internal radiation dose assessment methods. The absorbed dose from an yttrium-90 chloride (90YCl) solution was measured with an extrapolation chamber. A phantom was developed at the National Physical Laboratory (NPL), the UK’s National Measurement Institute, to position the extrapolation chamber as closely as possible to the surface of the solution. The performance of the extrapolation chamber was characterised and a full uncertainty budget for the absorbed dose determination was obtained. Absorbed dose to air in the collecting volume of the chamber was converted to absorbed dose at the centre of the radionuclide solution by applying a MC calculated correction factor. This allowed a direct comparison of the analytically calculated and experimentally determined absorbed dose of an 90YCl solution. The relative standard uncertainty in the measurement of absorbed dose at the centre of an 90YCl solution with the extrapolation chamber was found to be 1.6% (k  =  1). The calculated 90Y absorbed doses from published medical internal radiation dose (MIRD) and radiation dose assessment resource (RADAR) data agreed with measurements to within 1.5% and 1.4%, respectively. This study has shown that it is feasible to use an extrapolation chamber for performing primary standard absorbed dose measurements of an unsealed radionuclide solution. Internal radiation

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

    PubMed

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

    2015-03-07

    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 (131)I, (177)Lu, (188)Re or (90)Y. 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 (90)Y 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 (177)Lu 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

  13. External dose reconstruction in tooth enamel of Techa riverside residents.

    PubMed

    Shishkina, E A; Volchkova, A Yu; Timofeev, Y S; Fattibene, P; Wieser, A; Ivanov, D V; Krivoschapov, V A; Zalyapin, V I; Della Monaca, S; De Coste, V; Degteva, M O; Anspaugh, L R

    2016-11-01

    This study summarizes the 20-year efforts for dose reconstruction in tooth enamel of the Techa riverside residents exposed to ionizing radiation as a result of radionuclide releases into the river in 1949-1956. It represents the first combined analysis of all the data available on EPR dosimetry with teeth of permanent residents of the Techa riverside territory. Results of electron paramagnetic resonance (EPR) measurements of 302 teeth donated by 173 individuals living permanently in Techa riverside settlements over the period of 1950-1952 were analyzed. These people were residents of villages located at the free-flowing river stream or at the banks of stagnant reservoirs such as ponds or blind river forks. Cumulative absorbed doses measured using EPR are from several sources of exposure, viz., background radiation, internal exposure due to bone-seeking radionuclides ((89)Sr, (90)Sr/(90)Y), internal exposure due to (137)Cs/(137m)Ba incorporated in soft tissues, and anthropogenic external exposure. The purpose of the present study was to evaluate the contribution of different sources of enamel exposure and to deduce external doses to be used for validation of the Techa River Dosimetry System (TRDS). Since various EPR methods were used, harmonization of these methods was critical. Overall, the mean cumulative background dose was found to be 63 ± 47 mGy; cumulative internal doses due to (89)Sr and (90)Sr/(90)Y were within the range of 10-110 mGy; cumulative internal doses due to (137)Cs/(137m)Ba depend on the distance from the site of releases and varied from 1 mGy up to 90 mGy; mean external doses were maximum for settlements located at the banks of stagnant reservoirs (~500 mGy); in contrast, external doses for settlements located along the free-flowing river stream did not exceed 160 mGy and decreased downstream with increasing distance from the site of release. External enamel doses calculated using the TRDS code and derived from the EPR measurements were

  14. Radiolabeled Somatostatin Analogues Therapy in Advanced Neuroendocrine Tumors: A Single Centre Experience

    PubMed Central

    Filice, A.; Fraternali, A.; Frasoldati, A.; Asti, M.; Grassi, E.; Massi, L.; Sollini, M.; Froio, A.; Erba, P. A.; Versari, A.

    2012-01-01

    The aim of this study was to assess the efficacy of PRRT in patients with advanced neuroendocrine tumors (NETs). Patients and Methods. From January 2007 to August 2011, we enrolled 65 patients (m/f 38/27; mean age 65 years, range 33–83) with advanced NETs having enhanced SSTR expression, treated with PRRT. The enhanced expression of SSTR was assessed using 68Ga-DOTATOC/DOTATATE PET/CT. Among all the enrolled patients, 6 of them were excluded from the present analysis since they voluntarily interrupted treatment. Mean activity/cycle of 2.6 GBq (90Y-DOTATOC/DOTATATE) or 6.0 GBq (177Lu-DOTATOC/DOTATATE) was administrated intravenously (max 9 cycles). Results. Complete response (CR) was found in 1/59 (2%) patients, partial remission (PR) in 24/59 (40.5%) patients, stable disease (SD) in 24/59 (40.5%), and progression (PD) in 10/59 (17%) patients. The overall tumor response rate (CR + PR) was 42.5%. In 40.5% of patients, the disease could be stabilized. Overall, 49 out of 59 patients had no tumor progression (83%). Twelve patients out of 59 (20%) had grade 2-3 hematological side effects including anemia, thrombocytopenia, and leukopenia. Long-term nephrotoxicity was observed in 3 patients (2 moderate, 1 severe). Conclusions. PRRT is a promising perspective for patients with advanced NETs. PMID:22934111

  15. Redshifted Cherenkov Radiation for in vivo Imaging: Coupling Cherenkov Radiation Energy Transfer to multiple Förster Resonance Energy Transfers

    PubMed Central

    Bernhard, Yann; Collin, Bertrand; Decréau, Richard A.

    2017-01-01

    Cherenkov Radiation (CR), this blue glow seen in nuclear reactors, is an optical light originating from energetic β-emitter radionuclides. CR emitter 90Y triggers a cascade of energy transfers in the presence of a mixed population of fluorophores (which each other match their respective absorption and emission maxima): Cherenkov Radiation Energy Transfer (CRET) first, followed by multiple Förster Resonance Energy transfers (FRET): CRET ratios were calculated to give a rough estimate of the transfer efficiency. While CR is blue-weighted (300–500 nm), such cascades of Energy Transfers allowed to get a) fluorescence emission up to 710 nm, which is beyond the main CR window and within the near-infrared (NIR) window where biological tissues are most transparent, b) to amplify this emission and boost the radiance on that window: EMT6-tumor bearing mice injected with both a radionuclide and a mixture of fluorophores having a good spectral overlap, were shown to have nearly a two-fold radiance boost (measured on a NIR window centered on the emission wavelength of the last fluorophore in the Energy Transfer cascade) compared to a tumor injected with the radionuclide only. Some CR embarked light source could be converted into a near-infrared radiation, where biological tissues are most transparent. PMID:28338043

  16. Redshifted Cherenkov Radiation for in vivo Imaging: Coupling Cherenkov Radiation Energy Transfer to multiple Förster Resonance Energy Transfers.

    PubMed

    Bernhard, Yann; Collin, Bertrand; Decréau, Richard A

    2017-03-24

    Cherenkov Radiation (CR), this blue glow seen in nuclear reactors, is an optical light originating from energetic β-emitter radionuclides. CR emitter (90)Y triggers a cascade of energy transfers in the presence of a mixed population of fluorophores (which each other match their respective absorption and emission maxima): Cherenkov Radiation Energy Transfer (CRET) first, followed by multiple Förster Resonance Energy transfers (FRET): CRET ratios were calculated to give a rough estimate of the transfer efficiency. While CR is blue-weighted (300-500 nm), such cascades of Energy Transfers allowed to get a) fluorescence emission up to 710 nm, which is beyond the main CR window and within the near-infrared (NIR) window where biological tissues are most transparent, b) to amplify this emission and boost the radiance on that window: EMT6-tumor bearing mice injected with both a radionuclide and a mixture of fluorophores having a good spectral overlap, were shown to have nearly a two-fold radiance boost (measured on a NIR window centered on the emission wavelength of the last fluorophore in the Energy Transfer cascade) compared to a tumor injected with the radionuclide only. Some CR embarked light source could be converted into a near-infrared radiation, where biological tissues are most transparent.

  17. Age-related decrease in TCR repertoire diversity measured with deep and normalized sequence profiling.

    PubMed

    Britanova, Olga V; Putintseva, Ekaterina V; Shugay, Mikhail; Merzlyak, Ekaterina M; Turchaninova, Maria A; Staroverov, Dmitriy B; Bolotin, Dmitriy A; Lukyanov, Sergey; Bogdanova, Ekaterina A; Mamedov, Ilgar Z; Lebedev, Yuriy B; Chudakov, Dmitriy M

    2014-03-15

    The decrease of TCR diversity with aging has never been studied by direct methods. In this study, we combined high-throughput Illumina sequencing with unique cDNA molecular identifier technology to achieve deep and precisely normalized profiling of TCR β repertoires in 39 healthy donors aged 6-90 y. We demonstrate that TCR β diversity per 10(6) T cells decreases roughly linearly with age, with significant reduction already apparent by age 40. The percentage of naive T cells showed a strong correlation with measured TCR diversity and decreased linearly up to age 70. Remarkably, the oldest group (average age 82 y) was characterized by a higher percentage of naive CD4(+) T cells, lower abundance of expanded clones, and increased TCR diversity compared with the previous age group (average age 62 y), suggesting the influence of age selection and association of these three related parameters with longevity. Interestingly, cross-analysis of individual TCR β repertoires revealed a set >10,000 of the most representative public TCR β clonotypes, whose abundance among the top 100,000 clones correlated with TCR diversity and decreased with aging.

  18. 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.

  19. Beta measurements at Department of Energy facilities

    SciTech Connect

    Rathbun, L.A.; Swinth, K.L.; Haggard, D.L.

    1987-08-01

    Pacific Northwest Laboratory performed a two-step process to characterize the current beta measurement practices at DOE facilities. PNL issued a survey questionnaire on beta measurement practices to DOE facilities and reported the results. PNL measured beta doses and spectra at seven selected DOE facilities and compared selected measurement techniques in the facility environment. This report documents the results of the radiation field measurements and the comparison of measurement techniques at the seven facilities. Data collected included beta dose and spectral measurements at seven DOE facilities that had high beta-to-gamma ratios (using a silicon surface barrier spectrometer, a plastic scintillator spectrometer, and a multielement beta dosimeter). Other dosimeters and survey meters representative of those used at DOE facilities or under development were also used for comparison. Field spectra were obtained under two distinct conditions. Silicon- and scintillation-based spectrometer systems were used under laboratory conditions where high beta-to-gamma dose ratios made the beta spectra easier to observe and analyze. In the second case, beta spectrometers were taken into actual production and maintenance areas of DOE facilities. Analyses of beta and gamma spectra showed that /sup 234/Th- /sup 234m/Pa, /sup 231/Th, /sup 137/Cs, and /sup 90/Sr//sup 90/Y were the major nuclides contributing to beta doses at the facilities visited. Beta doses from other fission products and /sup 60/Co were also measured, but the potential for exposure was less significant. 21 refs., 64 figs., 18 tabs.

  20. Determination of photon conversion factors relating exposure and dose for several extremity phantom designs

    SciTech Connect

    Roberson, P.L.; Eichner, F.N.; Reece, W.D.

    1986-09-01

    This report presents the results of measurements of dosimetric properties of simple extremity phantoms suitable for use in extremity dosimeter performance testing. Two sizes of phantoms were used in this study. One size represented the forearm or lower leg and the other size represented the finger or toe. For both phantom sizes, measurements were performed on solid plastic phantoms and on phantoms containing simulated bone material to determine the effect of backscattered radiations from the bone on the surface dose. Exposure-to-dose conversion factors (C/sub x/ factors) were determined for photon energies ranging from 16 to 1250 keV (average for /sup 60/Co). The effect of the presence of a phantom was also measured for a /sup 90/Sr//sup 90/Y source. Significant differences in the measured C/sub x/ factors were found among the phantoms investigated. The factors for the finger-sized phantoms were uniformly less than for the arm-sized phantoms.

  1. A small-scale anatomical dosimetry model of the liver

    NASA Astrophysics Data System (ADS)

    Stenvall, Anna; Larsson, Erik; Strand, Sven-Erik; Jönsson, Bo-Anders

    2014-07-01

    Radionuclide therapy is a growing and promising approach for treating and prolonging the lives of patients with cancer. For therapies where high activities are administered, the liver can become a dose-limiting organ; often with a complex, non-uniform activity distribution and resulting non-uniform absorbed-dose distribution. This paper therefore presents a small-scale dosimetry model for various source-target combinations within the human liver microarchitecture. Using Monte Carlo simulations, Medical Internal Radiation Dose formalism-compatible specific absorbed fractions were calculated for monoenergetic electrons; photons; alpha particles; and 125I, 90Y, 211At, 99mTc, 111In, 177Lu, 131I and 18F. S values and the ratio of local absorbed dose to the whole-organ average absorbed dose was calculated, enabling a transformation of dosimetry calculations from macro- to microstructure level. For heterogeneous activity distributions, for example uptake in Kupffer cells of radionuclides emitting low-energy electrons (125I) or high-LET alpha particles (211At) the target absorbed dose for the part of the space of Disse, closest to the source, was more than eight- and five-fold the average absorbed dose to the liver, respectively. With the increasing interest in radionuclide therapy of the liver, the presented model is an applicable tool for small-scale liver dosimetry in order to study detailed dose-effect relationships in the liver.

  2. 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.

  3. 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.

  4. Suppression of glycosaminoglycan synthesis by articular cartilage, but not of hyaluronic acid synthesis by synovium, after exposure to radiation

    SciTech Connect

    Hugenberg, S.T.; Myers, S.L.; Brandt, K.D.

    1989-04-01

    We recently found that injection of 2 mCi of yttrium 90 (90Y; approximately 23,000 rads) into normal canine knees stimulated glycosaminoglycan (GAG) synthesis by femoral condylar cartilage. The present investigation was conducted to determine whether radiation affects cartilage metabolism directly. Rates of GAG synthesis and degradation in normal canine articular cartilage were studied following irradiation. Cultured synovium from the same knees was treated similarly, to determine the effects of irradiation on hyaluronic acid synthesis. Twenty-four hours after exposure to 1,000 rads, 10,000 rads, or 50,000 rads, 35S-GAG synthesis by the cartilage was 93%, 69%, and 37%, respectively, of that in control, nonirradiated cartilage. The effect was not rapidly reversible: 120 hours after exposure to 50,000 rads, GAG synthesis remained at only 28% of the control level. Autoradiography showed marked suppression of 35S uptake by chondrocytes after irradiation. Cartilage GAG degradation was also increased following irradiation: 4 hours and 8 hours after exposure to 50,000 rads, the cartilage GAG concentration was only 66% and 54%, respectively, of that at time 0, while corresponding values for control, nonirradiated cartilage were 90% and 87%. In contrast to its effects on cartilage GAG metabolism, radiation at these levels had no effect on synovial hyaluronic acid synthesis.

  5. 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.

  6. Development of modern approach to absorbed dose assessment in radionuclide therapy, based on Monte Carlo method simulation of patient scintigraphy

    NASA Astrophysics Data System (ADS)

    Lysak, Y. V.; Klimanov, V. A.; Narkevich, B. Ya

    2017-01-01

    One of the most difficult problems of modern radionuclide therapy (RNT) is control of the absorbed dose in pathological volume. This research presents new approach based on estimation of radiopharmaceutical (RP) accumulated activity value in tumor volume, based on planar scintigraphic images of the patient and calculated radiation transport using Monte Carlo method, including absorption and scattering in biological tissues of the patient, and elements of gamma camera itself. In our research, to obtain the data, we performed modeling scintigraphy of the vial with administered to the patient activity of RP in gamma camera, the vial was placed at the certain distance from the collimator, and the similar study was performed in identical geometry, with the same values of activity of radiopharmaceuticals in the pathological target in the body of the patient. For correct calculation results, adapted Fisher-Snyder human phantom was simulated in MCNP program. In the context of our technique, calculations were performed for different sizes of pathological targets and various tumors deeps inside patient’s body, using radiopharmaceuticals based on a mixed β-γ-radiating (131I, 177Lu), and clear β- emitting (89Sr, 90Y) therapeutic radionuclides. Presented method can be used for adequate implementing in clinical practice estimation of absorbed doses in the regions of interest on the basis of planar scintigraphy of the patient with sufficient accuracy.

  7. 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.

  8. Like cognitive function, decision making across the life span shows profound age-related changes

    PubMed Central

    Tymula, Agnieszka; Rosenberg Belmaker, Lior A.; Ruderman, Lital; Glimcher, Paul W.; Levy, Ifat

    2013-01-01

    It has long been known that human cognitive function improves through young adulthood and then declines across the later life span. Here we examined how decision-making function changes across the life span by measuring risk and ambiguity attitudes in the gain and loss domains, as well as choice consistency, in an urban cohort ranging in age from 12 to 90 y. We identified several important age-related patterns in decision making under uncertainty: First, we found that healthy elders between the ages of 65 and 90 were strikingly inconsistent in their choices compared with younger subjects. Just as elders show profound declines in cognitive function, they also show profound declines in choice rationality compared with their younger peers. Second, we found that the widely documented phenomenon of ambiguity aversion is specific to the gain domain and does not occur in the loss domain, except for a slight effect in older adults. Finally, extending an earlier report by our group, we found that risk attitudes across the life span show an inverted U-shaped function; both elders and adolescents are more risk-averse than their midlife counterparts. Taken together, these characterizations of decision-making function across the life span in this urban cohort strengthen the conclusions of previous reports suggesting a profound impact of aging on cognitive function in this domain. PMID:24082105

  9. 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

    2015-04-08

    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.

  10. 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.

  11. Experimental verification of AI decomposition-based source optimization for M1 two-bar building blocks in 0.33NA EUVL

    NASA Astrophysics Data System (ADS)

    Last, T.; Wang, Z.; van Adrichem, P.; de Winter, L.; Finders, J.

    2016-10-01

    Traditional pupil optimization for horizontal dark field two-bar building blocks yields a dipole matching its local pitch. This classical "rule" guides the placement for the illumination into a pupil area of high contrast and exposure latitude. However under these illumination conditions the feature exhibits an extremely large relative CD Bossung separation limiting its overlapping process window. Here we show experimentally that contrast-aware source optimization is necessary to lift this relative separation. The Tachyon-generated pupil applied is a very close replica of a rigorously obtained asymmetric illumination solution. The latter has emerged out of a study which evidenced that the formation of this rigorous pupil can be traced back to the interdependency of CD Bossung formation and symmetry of the intensity spectrum across the diffraction orders. Compared to standard D90Y and leaf shape illumination, the optimized pupil provides the highest simulated contrast, and experimentally obtained highest depth-of-focus and lowest pattern shift range. Finally we compare the consequences of intensity balancing versus phase aberration minimization across the diffraction orders and conclude that the balancing of the intensity spectrum is the main responsible factor for lifting the feature's CD Bossung asymmetry and separation.

  12. 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.

  13. [Retroperitoneal fibrosis and arthritis--a manifestation of the same illness].

    PubMed

    Thiele, A; Störkel, S; Stierle, H E

    1998-10-01

    Retroperitoneal fibrosis is a disorder in which the retroperitoneal fat is the site of a subacute and chronic inflammatory reaction and is subsequently replaced by dense fibrotic tissue. Rheumatoid nodules are chronic granulomata occurring at sites of pressure and movement, both near the body surface and internally. A 55-year-old sales-manager was admitted to radiation synovectomy after a 5 year history of excessive right and left knee effusions. There were no other clinical or laboratory abnormalities. The patient did not respond to either radioisotope synoviorthesis using radioactive Yttrium (90 Y), or to open synovectomy and prostetic surgery of the right knee. One year later, surgery of left ureter was necessary. Histological findings revealed the diagnosis of Ormond's disease. Comparative histological studies of synovial membrane of knee and retroperitoneal tissues showed local necrosis, fibrin deposition, lining cell proliferation, and infiltration by lymphocytes. Diagnosis of arthritis complicated by retroperitoneal rheumatoid nodules and retroperitoneal fibrosis was made. Serum rheumatoid factor has been negative. For the last 3 years, the patient has been on successful therapy with azathioprine. Rheumatoid nodules of the retroperitoneum have vanished completely and frequency of knee effusions decreased.

  14. 90Sr in deciduous teeth from 1950 to 2002: the Swiss experience.

    PubMed

    Froidevaux, P; Geering, Jean-Jacques; Valley, J-F

    2006-08-31

    Switzerland has recorded the level of activity of 90Sr in the milk teeth of children from different regions of the country since the first atomic explosions in the atmosphere. Activity peaked at 0.421 Bq g-1 Ca at the beginning of the sixties, coinciding with the detonation of many large nuclear devices. Following the Nuclear Test Ban Treaty that ended atmospheric nuclear weapon tests, a steady and significant decrease in 90Sr activity in milk teeth has been observed-down to a value of 0.03 Bq g-1 Ca for children born in 1994. The apparent half-life of 90Sr in milk teeth is 9.8+/-3 years. With the exception of the period from 1962 to 1964, there is no correlation between the activity in the teeth of children born in a given year and the year of extraction. Between 1953 and 1992, the milk teeth of children born in Zürich county showed 16% less activity than teeth from children born in Vaud county. Dairy consumption habits might be responsible for this trend. The effect of the 90Sr deposition from Chernobyl is barely measurable in milk teeth, and no effect is seen from the five Swiss nuclear reactors. This paper emphasizes the necessity of a very high purity chemical separation of 90Sr or 90Y to determine 90Sr activity in milk teeth or other samples.

  15. Magnetic field effects on the solute luminescence of alkane solutions irradiated with heavy ions

    SciTech Connect

    LaVerne, J.A.; Brocklehurst, B.

    1996-02-01

    The effects of track structure on the luminescence decays in cyclohexane and in 2,2,4-trimethylpentane (isoocatane) solutions of 2,5-diphenyloxazole (PPO) have been determined in the presence and in the absence of an external magnetic field. Irradiations were performed with protons of 1-15 MeV and with helium ions of 2-20 MeV energy. Companion studies were performed with {sup 90}Sr-{sup 90}Y {Beta}-radiolysis. The magnetic field effect is due to the hyperfine interaction of nuclear spins in the geminate pair of solvent radical ions produced. In both solvents, the effect of the magnetic field on luminescence decreases with increasing linear energy transfer (LET) from about 40% for {Beta}-particles to only a few percent with helium ions. Magnetic field effects with protons decrease in time whereas they are constant with {Beta}-particles. This result is attributed to the overlap of initially isolated spurs during the evolution of the proton track; the probability of nongeminate recombination increases with the number of neighboring ion pairs. The total luminescence intensity per incident particle remains constant with proton energy but increases slightly with increasing helium ion energy. At a given particle energy, the intensity is greater in cyclohexane than in isoocatane. The pulse shapes of the luminescence decays reflect the distributions in ion recombination times, and very little variation in luminescence decay rates is observed with increasing LET. 37 refs., 7 figs., 1 tab.

  16. Redshifted Cherenkov Radiation for in vivo Imaging: Coupling Cherenkov Radiation Energy Transfer to multiple Förster Resonance Energy Transfers

    NASA Astrophysics Data System (ADS)

    Bernhard, Yann; Collin, Bertrand; Decréau, Richard A.

    2017-03-01

    Cherenkov Radiation (CR), this blue glow seen in nuclear reactors, is an optical light originating from energetic β-emitter radionuclides. CR emitter 90Y triggers a cascade of energy transfers in the presence of a mixed population of fluorophores (which each other match their respective absorption and emission maxima): Cherenkov Radiation Energy Transfer (CRET) first, followed by multiple Förster Resonance Energy transfers (FRET): CRET ratios were calculated to give a rough estimate of the transfer efficiency. While CR is blue-weighted (300–500 nm), such cascades of Energy Transfers allowed to get a) fluorescence emission up to 710 nm, which is beyond the main CR window and within the near-infrared (NIR) window where biological tissues are most transparent, b) to amplify this emission and boost the radiance on that window: EMT6-tumor bearing mice injected with both a radionuclide and a mixture of fluorophores having a good spectral overlap, were shown to have nearly a two-fold radiance boost (measured on a NIR window centered on the emission wavelength of the last fluorophore in the Energy Transfer cascade) compared to a tumor injected with the radionuclide only. Some CR embarked light source could be converted into a near-infrared radiation, where biological tissues are most transparent.

  17. Internal dosimetry for radioembolization therapy with Yttrium-90 microspheres.

    PubMed

    Fallahpoor, Maryam; Abbasi, Mehrshad; Parach, Ali Asghar; Kalantari, Faraz

    2017-03-01

    The absorbed doses in the liver and adjacent viscera in Yttrium-90 radioembolization therapy for metastatic liver lesions are not well-documented. We sought for a clinically practical way to determine the dosimetry of this advent treatment. Six different female XCAT BMIs and seven different male XCAT BMIs were generated. Using Monte Carlo GATE code simulation, the total of 100MBq (90) Y was deposited uniformly in the source organ, liver. Self-irradiation and absorbed doses in lung, kidney and bone marrow were calculated. The mean energy of Yittrium-90 (i.e., 0.937 MeV) was used. The S-values and equivalent doses in target organs were estimated. The dose absorbed in the liver was between 84 and 53 Gy and below the target of 80 to 150 Gy. The absorbed dose in the bone marrow, lungs, and kidneys are very low and below 0.1 , 0.4, and 0.5 Gy respectively. Our study indicates that larger activities than the conventional dose of 3 GBq may be both required and safe. Further confirmations in clinical settings are needed.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. Dosimetric model for antibody targeted radionuclide therapy of tumor cells in cerebrospinal fluid

    SciTech Connect

    Millar, W.T.; Barrett, A. )

    1990-02-01

    Although encouraging results have been obtained using systemic radioimmunotherapy in the treatment of cancer, it is likely that regional applications may prove more effective. One such strategy is the treatment of central nervous system leukemia in children by intrathecal instillation of targeting or nontargeting beta particle emitting radionuclide carriers. The beta particle dosimetry of the spine is assessed, assuming that the spinal cord and the cerebrospinal fluid compartment can be adequately represented by a cylindrical annulus. The radionuclides investigated were {sup 90}Y, {sup 131}I, {sup 67}Cu, and {sup 199}Au. It is shown that the radiation dose to the cord can be significantly reduced using short range beta particle emitters and that there is little advantage in using targeting carriers with these radionuclides. {sup 199}Au and {sup 67}Cu also have the advantage of having a suitable gamma emission for imaging, permitting pretherapy imaging and dosimetric calculations to be undertaken prior to therapy. If these methods prove successful, it may be possible to replace the external beam component used in the treatment of central nervous system leukemia in children by intrathecal radionuclide therapy, thus reducing or avoiding side effects such as growth and intellectual impairment.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. Orally disintegrating tablet of novel salt of antiepileptic drug: formulation strategy and evaluation.

    PubMed

    Rahman, Ziyaur; Siddiqui, Akhtar; Khan, Mansoor A

    2013-11-01

    The aim of present research was to design and evaluate orally disintegrating tablet (ODT) of novel lamotrigine-cyclamate salt. Box-Behnken response surface methodology was selected to design the optimized formulation. The independent factors selected were tablet hardness (X1), disintegrant (X2) and lubricant (X3) levels, and responses chosen were disintegration time (DT, Y1), friability (Y2), T50 (Y3), and T90 (Y4). The tablets were also characterized for drug uniformity by near infrared chemical imaging (NIR-CI) and taste masking evaluation by electronic tongue. All the selected independent variables were statistically (p<0.05) effect the Y1 while Y2, Y3, and Y4 affected only by X2. The optimized ODT was found to meet the regulatory requirement of DT and friability specification. The NIR-CI images indicated uniform distribution of active and inactive ingredients within the tablets. The electronic tongue results were analyzed by principle component analysis (PCA). It indicated that novel salt of lamotrigine and its ODT formulation have a taste similar to cyclamic acid which is indicated by close proximity on PCA score plot, lower Euclidean distance, and high discrimination index values. Furthermore, these parameters were very close to ODT placebo formulation. On the other hand, lamotrigine, its ODT, and placebo formulation were far from each other. In summary, lamotrigine salt provides another avenue for pediatric friendly formulation for children and will enhance patience compliance.

  8. High coercivity in mechanically milled ThMn12-type Nd-Fe-Mo nitrides

    NASA Astrophysics Data System (ADS)

    Zhang, Xiao-dong; Cheng, Ben-pei; Yang, Ying-chang

    2000-12-01

    Starting from carefully homogenized Nd10Fe90-yMoy (y=12, 10, 7) alloys and by appropriate mechanical milling, the as-milled microstructure consisting of a nanoscale mixture of severely distorted 1:12 phase and substitutional α-Fe-based solid solution was obtained. This kind of as-milled microstructure was thought to have a critical effect on the formation of iron-free nanocrystalline 1:12 phase during subsequent annealing. Upon nitrogenation, the sample of Nd10Fe78Mo12Nx exhibited a record-high coercivity of 13.1 kOe at 293 K. Measurements of initial magnetization curve and a family of demagnetization curves engendered under different maximum applied fields Hm were carried out, and the results revealed the domain-wall pinning at grain boundaries as the coercivity mechanism. A low Mo-content sample of Nd10Fe83Mo7Nx with iHc˜5.8 kOe, Br˜6.8 kG, and (BH)max˜7.0 MG Oe was made by optimizing the preparation conditions.

  9. Transarterial radioembolization with Yttrium-90 for regional management of hepatocellular cancer: the early results of a nontransplant center.

    PubMed

    Holt, Alicia; Wagman, Lawrence D; Senthil, Maheswari; McKenzie, Shaun; Marx, Howard; Chen, Yi-Jen; Vora, Nayana; Kim, Joseph

    2010-10-01

    Selective arterial radioembolization with Yttrium-90 (Y-90) microspheres has shown promise for regional management of hepatocellular cancer (HCC). Our objective was to report our early experience with this treatment modality from a nontransplant center. Treatment of patients with HCC was discussed in a multidisciplinary tumor board. Patients with unresectable disease resulting from high lesion number, ill location of the tumor, poor hepatic reserve, or medical comorbidities were offered Y-90 treatment. Liver treatment was either lobar or tumor-targeted. Response to therapy was assessed by CT scan obtained within 3 months using Response Evaluation Criteria in Solid Tumors criteria. During 2007 to 2009, 40 Y-90 radioembolizations were performed in 20 patients with age that ranged from 16 to 87 years; four patients were 80 years old or older. After the first therapy, CT assessment of the treated area showed stable disease (n=15), partial response (n=3), and progression (n=2). Of the two patients who progressed, one was retreated with a subsequent complete response. The other patient died of progressive disease. The most common side effects were mild fatigue, anorexia, and nausea. In summary, our nontransplant center experience shows that Y-90 radioembolization is a well-tolerated treatment in select patients with unresectable HCC with an associated high rate of local tumor control.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. Illumination pupil optimization in 0.33NA EUVL by intensity balancing for semi-iso dark field two-bar M1 building blocks

    NASA Astrophysics Data System (ADS)

    Last, T.; de Winter, L.; van Adrichem, P.; Finders, J.

    2016-10-01

    We will shed light on the optimization of lithographic metrics for the semi-isolated dark field two-bar logic building block. Under standard D90Y illumination this building block suffers from large mask 3D induced relative focus dependent CD asymmetries. Such behavior limits its overlapping process window and gives rise to untenable full wafer CDU and intra-field pattern shifts. We have found that besides a Ta absorber thickness reduction an illumination pupil optimization is necessary to fully remove these CD asymmetries. The pupil optimization is achieved by relating the aerial image decomposition (here: symmetrization and balancing of intensities across the diffracted orders) with lithographic metrics per pupil plane location. The resulting pupil allows us (i) to lift the focus-dependent CD asymmetries and (ii) to co-optimize a number of lithographic metrics such as overlapping process window, contrast, non-telecentricity and pattern shift. The importance of subsidiary conditions (e.g. symmetry of the pupil, required DOF) will be discussed.

  17. The effect of the beta-emitting yttrium-90 citrate on the dose-response of dicentric chromosomes in human lymphocytes: a basis for biological dosimetry after radiosynoviorthesis.

    PubMed

    Schmid, E; Selbach, H-J; Voth, M; Pinkert, J; Gildehaus, F J; Klett, R; Haney, M

    2006-07-01

    The production of dicentric chromosomes in human lymphocytes by beta-particles of yttrium-90 (Y-90) was studied in vitro to provide a basis of biological dosimetry after radiosynoviorthesis (RSO) of persistent synovitis by intra-articular administration of yttrium-90 citrate colloid. Since the injected colloid may leak into the lymphatic drainage exposing other parts of the body to radiation, the measurement of biological damage induced by beta-particles of Y-90 is important for the assessment of radiation risk to the patients. A linear dose-response relationship (alpha = 0.0229 +/- 0.0028 dicentric chromosomes per cell per gray) was found over the dose range of 0.2176-2.176 Gy. The absorbed doses were calculated for exposure of blood samples to Y-90 activities from 40 to 400 kBq using both Monte Carlo simulation and an analytical model. The maximum low-dose RBE, the RBE(M) which is equivalent to the ratio of the alpha coefficients of the dose-response curves, is well in line with published results obtained earlier for irradiation of blood of the same donor with heavily filtered 220 kV X-rays (3.35 mm copper), but half of the RBE(M) relative to weakly filtered 220 kV X-rays. Therefore, it can be concluded that for estimating an absorbed dose during RSO by the technique of biological dosimetry, in vitro and in vivo data for the same radiation quality are necessary.

  18. 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.

  19. A novel approach for preferential recovery of Sr from (Sr, Th)O2.

    PubMed

    Vyas, Chirag K; Joshirao, Pranav M; Shukla, Rakesh; Tyagi, Avesh K; Manchanda, Vijay K

    2012-11-30

    Quantitative leaching of Sr from homogeneous and calcined (Th,Sr) O(2) in dilute perchloric acid medium suggests the possibility of reducing the hazardousness of discharged nuclear fuel by separation of (90)Sr, a prominent fission product at dissolution stage itself rather than the conventional approach of its recovery from high level nuclear waste. Apart from mitigating the radiotoxicity of the nuclear waste, recovered (90)Sr can be employed as a compact heat source and as parent radionuclide for (90)Y (used in therapy radiopharmaceuticals), provided it can be made available at desired high purity. Leaching behavior of few other fission products was also investigated to quantify their contamination in leached Sr. Feasibility of employing extraction chromatography using Sr selective resin was explored in perchloric acid medium. In this context, the distribution coefficients of (85)Sr(II), Th (IV), Zr(IV), Y(III), Pd(II) as well as (152)Eu(III) and (137)Cs (I) were determined under varying nitric acid/perchloric acid concentration and under varying loading conditions of metal ions. Perchloric acid medium appears better than nitric acid medium for preferential leaching of Sr from (Th,Sr)O(2) as well as for uptake of Sr by Sr selective chromatographic resin.

  20. [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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. A small-scale anatomical dosimetry model of the liver.

    PubMed

    Stenvall, Anna; Larsson, Erik; Strand, Sven-Erik; Jönsson, Bo-Anders

    2014-07-07

    Radionuclide therapy is a growing and promising approach for treating and prolonging the lives of patients with cancer. For therapies where high activities are administered, the liver can become a dose-limiting organ; often with a complex, non-uniform activity distribution and resulting non-uniform absorbed-dose distribution. This paper therefore presents a small-scale dosimetry model for various source-target combinations within the human liver microarchitecture. Using Monte Carlo simulations, Medical Internal Radiation Dose formalism-compatible specific absorbed fractions were calculated for monoenergetic electrons; photons; alpha particles; and (125)I, (90)Y, (211)At, (99m)Tc, (111)In, (177)Lu, (131)I and (18)F. S values and the ratio of local absorbed dose to the whole-organ average absorbed dose was calculated, enabling a transformation of dosimetry calculations from macro- to microstructure level. For heterogeneous activity distributions, for example uptake in Kupffer cells of radionuclides emitting low-energy electrons ((125)I) or high-LET alpha particles ((211)At) the target absorbed dose for the part of the space of Disse, closest to the source, was more than eight- and five-fold the average absorbed dose to the liver, respectively. With the increasing interest in radionuclide therapy of the liver, the presented model is an applicable tool for small-scale liver dosimetry in order to study detailed dose-effect relationships in the liver.

  8. Estimates of dose to intraperitoneal micrometastases from alpha and beta emitters in radioimmunotherapy

    SciTech Connect

    Rotmensch, J.; Roeske, J.; Chen, G.; Pelizzari, C.; Montag, A.; Weichselbaum, R.; Herbst, A.L. )

    1990-09-01

    Intraperitoneal metastases from ovarian and other gynecologic tumors are a significant source of treatment failure. In recent years, investigators have used radiolabeled monoclonal antibodies to treat this disease with encouraging results. We have developed a dose calculational technique which generates isodose distributions from intraperitoneally administered alpha and beta particle emitters. In this study we apply the calculations to tissue biopsy samples to determine the adequacy of dose to ovarian micrometastases. Tissue samples from staging biopsies at the time of surgical debulking are scanned to identify small metastases. The patient population studied comprised those with ovarian disease who based on clinical criteria would be considered good candidates for intraperitoneal radioimmunotherapy. The regions of interest (which include the tumor and surface of the peritoneum) are digitized and tumor volumes are contoured. Dose calculations based on the modeling of intraperitoneally administered antibodies radiolabeled with various isotopes is performed and the minimum dose to tumor and normal tissue is assessed. For example, with tumor uptake of 0.1% injected dose per gram of tissue, the surface tumor dose from alpha emitters is up to 45,000 rads. The dose falls to 6000 rads at approximately 40 microns from the peritoneal surface. The surface dose from 20 mCi 90Y administered in 1500 ml saline is up to 10,000 rads, and at a 2-mm depth, approximately 2000 rads. From our calculation dose distribution from radioimmunotherapy varies as a function of physical characteristics of the isotope, absorption of activity, and amount of disease being treated.

  9. MO-A-BRD-02: Physics Perspective

    SciTech Connect

    Kappadath, S.

    2015-06-15

    Yttrium-90 (Y90) microsphere therapy, a form of radiation therapy, is an increasingly popular option for care of patients with liver metastases or unresectable hepatocellular carcinoma. The therapy directly delivers Y90 microspheres via the hepatic artery to disease sites. Following delivery, a vast majority of microspheres preferentially lodge in the capillary vessels due to their embolic size and targeted trans-arterial delivery – depositing up to 90% of its energy in the first 5 mm of tissue. There have been a number of advances in tomographic imaging within both interventional radiology and nuclear medicine that has advanced therapy planning techniques. Quantitative imaging of Y90 microsphere distribution post-therapy has also seen innovations that have led to improvements in tumor dosimetry and characterization of tumor response. A review of current trends and recent innovation in Y90 microsphere therapies will be presented. Learning Objectives: To present the imaging requirements for Y90 microsphere therapy planning To explain the standard dosimetry models used in Y90 microsphere therapy planning To report on advances in imaging for therapy planning and posttherapy assessment of tumor dosimetry and response.

  10. 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.

  11. MO-A-BRD-00: Current Trends in Y90-Microsphere Therapy: Delivery and Dosimetry

    SciTech Connect

    2015-06-15

    Yttrium-90 (Y90) microsphere therapy, a form of radiation therapy, is an increasingly popular option for care of patients with liver metastases or unresectable hepatocellular carcinoma. The therapy directly delivers Y90 microspheres via the hepatic artery to disease sites. Following delivery, a vast majority of microspheres preferentially lodge in the capillary vessels due to their embolic size and targeted trans-arterial delivery – depositing up to 90% of its energy in the first 5 mm of tissue. There have been a number of advances in tomographic imaging within both interventional radiology and nuclear medicine that has advanced therapy planning techniques. Quantitative imaging of Y90 microsphere distribution post-therapy has also seen innovations that have led to improvements in tumor dosimetry and characterization of tumor response. A review of current trends and recent innovation in Y90 microsphere therapies will be presented. Learning Objectives: To present the imaging requirements for Y90 microsphere therapy planning To explain the standard dosimetry models used in Y90 microsphere therapy planning To report on advances in imaging for therapy planning and posttherapy assessment of tumor dosimetry and response.

  12. MO-A-BRD-01: Clinical Perspective

    SciTech Connect

    Mahvash, A.

    2015-06-15

    Yttrium-90 (Y90) microsphere therapy, a form of radiation therapy, is an increasingly popular option for care of patients with liver metastases or unresectable hepatocellular carcinoma. The therapy directly delivers Y90 microspheres via the hepatic artery to disease sites. Following delivery, a vast majority of microspheres preferentially lodge in the capillary vessels due to their embolic size and targeted trans-arterial delivery – depositing up to 90% of its energy in the first 5 mm of tissue. There have been a number of advances in tomographic imaging within both interventional radiology and nuclear medicine that has advanced therapy planning techniques. Quantitative imaging of Y90 microsphere distribution post-therapy has also seen innovations that have led to improvements in tumor dosimetry and characterization of tumor response. A review of current trends and recent innovation in Y90 microsphere therapies will be presented. Learning Objectives: To present the imaging requirements for Y90 microsphere therapy planning To explain the standard dosimetry models used in Y90 microsphere therapy planning To report on advances in imaging for therapy planning and posttherapy assessment of tumor dosimetry and response.

  13. 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.

  14. Investigation of the ionisation density dependence of the glow curve characteristics of LIF:MG,TI (TLD-100)

    PubMed Central

    Horowitz, Y. S.; Horowitz, A.; Oster, L.; Marino, S.; Datz, H.; Margaliot, M.

    2008-01-01

    The dependence of the shape of the glow curve of LiF:Mg,Ti (TLD-100) on ionisation density was investigated using irradiation with 90Sr/90Y beta rays, 60 and 250 kVp X rays, various heavy-charged particles and 0.2 and 14 MeV neutrons. Special attention is focused on the properties of high-temperature thermoluminescence; specifically, the behaviour of the high-temperature ratio (HTR) of Peaks 7 and 8 as a function of batch and annealing protocol. The correlation of Peaks 7 and 8 with average linear-energy-transfer (LET) is also investigated. The HTR of Peak 7 is found to be independent of LET for values of LET approximately >30 keV µm−1. The behaviour of the HTR of Peak 8 with LET is observed to be erratic, which suggests that applications using the HTR should separate the contributions of Peaks 7 and 8 using computerised glow curve deconvolution. The behaviour of the HTR following neutron irradiation is complex and not fully understood. The shape of composite Peak 5 is observed to be broader following high ionisation alpha particle irradiation, suggesting that the combined use of the HTR and the shape of Peak 5 could lead to improved ionisation density discrimination for particles of high LET. PMID:18667402

  15. 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.

  16. Low Dose Rate Radiosensitization of Hepatocellular Carcinoma In Vitro and in Patients1

    PubMed Central

    Cuneo, Kyle C.; Davis, Mary A.; Feng, Mary U.; Novelli, Paula M.; Ensminger, William D.; Lawrence, Theodore S.

    2014-01-01

    Transarterial radioembolization (TARE) with 90Y microspheres delivers low dose rate radiation (LDR) to intrahepatic tumors. In the current study, we examined clonogenic survival, DNA damage, and cell cycle distribution in hepatocellular carcinoma (HCC) cell lines treated with LDR in combination with varying doses and schedules of 5-fluorouracil (5-FU), gemcitabine, and sorafenib. Radiosensitization was seen with 1 to 3 μM 5-FU (enhancement ratio 2.2–13.9) and 30 to 100 nM gemcitabine (enhancement ratio 1.9–2.9) administered 24 hours before LDR (0.26 Gy/h to 4.2 Gy). Sorafenib radiosensitized only at high concentrations (3–10 μM) when administered after LDR. For a given radiation dose, greater enhancement was seen with LDR compared to standard dose rate therapy. Summarizing our clinical experience with low dose rate radiosensitization, 13 patients (5 with HCC, 8 with liver metastases) were treated a total of 16 times with TARE and concurrent gemcitabine. Six partial responses and one complete response were observed with a median time to local failure of 7.1 months for all patients and 9.9 months for patients with HCC. In summary, HCC is sensitized to LDR with clinically achievable concentrations of gemcitabine and 5-FU in vitro. Encouraging responses were seen in a small cohort of patients treated with TARE and concurrent gemcitabine. Future studies are needed to validate the safety and efficacy of this approach. PMID:24956939

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. Pretreatment tumor volume as a prognostic factor in metastatic colorectal cancer treated with selective internal radiation to the liver using yttrium-90 resin microspheres

    PubMed Central

    Bhooshan, Neha; Sharma, Navesh K.; Badiyan, Shahed; Kaiser, Adeel; Moeslein, Fred M.; Kwok, Young; Amin, Pradip P.; Kudryasheva, Svetlana

    2016-01-01

    Background Yttrium-90 (90Y)—resin microspheres can prolong intrahepatic disease control and improve overall survival (OS) in patients with metastatic colorectal cancer (CRC). Prognostic factors for improved outcomes in patients undergoing selective internal radiation therapy (SIRT) have been studied, but the relationship between pre-SIRT liver tumor volume and outcomes has not well described. Methods We retrospectively reviewed the records of patients with metastatic CRC who were treated at our institution with 90Y-resin microspheres. Each patient underwent either MR or CT imaging of the liver with intravenous (IV) contrast before and within ~2–3 months after SIRT. Imaging data were transferred into our treatment planning system. Each metastatic liver lesion was contoured, and the volume of each lesion was summed to determine the total liver tumor volume at a given time point. We evaluated whether pretreatment liver tumor volume was related to OS. We also evaluated the relationship between pre-SIRT tumor volume and radiographic treatment response by either unidimensional Response Evaluation Criteria in Solid Tumors (RECIST) or three-dimensional volumetric criteria. Results We included 60 patients with a median age of 59 years (range, 38–97 years); 60% of patients received sequential lobar treatment. The median number of chemotherapy cycles received prior to SIRT was 2. Median follow-up from first SIRT was 8.9 months. Pre- and post-SIRT tumor volumes were primarily calculated on CT (87%). The median pre-SIRT tumor volume was 77 cc (range, 4.5–2,170.4 cc). The median intervals between the first SIRT and the first, second, and third follow-up scans were 2.2, 4.4, and 7.7 months, respectively. No patient experienced a radiographic complete response. Pretreatment volume was a significant predictor for estimating the odds of a patient having stable disease or partial response using volumetric response criteria at first (P=0.016), second (P=0.023), and third (P=0

  2. 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

  3. 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.

  4. 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

  5. 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

  6. Evidence for an Association Between Tako-Tsubo Cardiomyopathy and Bronchial Asthma: Retrospective Analysis in a Primary Care Hospital

    PubMed Central

    von Blotzheim, Leonardo Glutz; Christen, Stefan; Wieser, Stephan; Ulrich, Silvia; Huber, Lars C

    2015-01-01

    Objective: We investigated the prevalence of bronchial asthma in patients with Tako-Tsubo Syndrome (TTS). Design: This retrospective case-series study was conducted in a primary care hospital in Zurich, Switzerland. Data of all patients with newly diagnosed TTS (2002 - 2012) were assessed electronically by the use of ICD-10. Asthma prevalence was compared to published epidemiologic data. Setting: Bronchial asthma is characterized by airway inflammation and, during attack, release of endogenous catecholamines. Sympathomimetic drugs are the mainstay of treatment for asthma patients. Likewise, catecholamine mediated diffuse microvascular myocardial dysfunction seems to be of critical importance for the development of TTS. Results: 20 cases of TTS were identified. 90% were female, showed a median age of 70±13y [25y - 90y], an apical and/or midventricular ballooning pattern with preserved basal function and a median initial LVEF of 34±9% [25% - 55%]. 65% of patients underwent coronary angiography to rule out significant coronary artery disease. Hypertension was present in 45% of patients, 35% were smokers, none was suffering from diabetes. Prevalence of asthma in patients with TTS was significantly higher compared to the normal population (25% vs. 7%, p=0.012). In 30% of the TTS patients an iatrogenic cause for development of TTS was identified. Conclusion: Prevalence of asthma was significantly higher in patients with TTS compared to epidemiologic data from an age-matched population. Phenotypes of patients developing obstructive ventilatory disease and TTS might share common pathogenic mechanisms beyond the use of bronchodilatators. In addition, we identified other iatrogenic etiologies in patients with TTS. PMID:25767631

  7. 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.

  8. 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.

  9. 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.

  10. Monte Carlo modeling of cascade gamma rays in (86)Y PET imaging: preliminary results.

    PubMed

    Zhu, Xuping; El Fakhri, Georges

    2009-07-07

    (86)Y is a PET agent that could be used as an ideal surrogate to allow personalized dosimetry in (90)Y radionuclide therapy. However, (86)Y also emits cascade gamma rays. We have developed a Monte Carlo program based on SimSET (Simulation System for Emission Tomography) to model cascade gamma rays in PET imaging. The new simulation was validated with the GATE simulation package. Agreements within 15% were found in spatial resolution, apparent scatter fraction (ratio of coincidences outside peak regions in line source sinograms), single and coincidence statistics and detected photons energy distribution within the PET energy window. A discrepancy of 20% was observed in the absolute scatter fraction, likely caused by differences in the tracking of higher energy cascade gamma photons. On average, the new simulation is 6 times faster than GATE, and the computing time can be further improved by using variance reduction techniques currently available in SimSET. Comparison with phantom acquisitions showed agreements in spatial resolutions and the general shape of projection profiles; however, the standard scatter correction method on the scanner is not directly applicable to (86)Y PET as it leads to incorrect scatter fractions. The new simulation was used to characterize (86)Y PET. Compared with conventional (18)F PET, in which major contamination at low count rates comes from scattered events, cascade gamma-involved events are more important in (86)Y PET. The two types of contaminations have completely different distribution patterns, which should be considered for the corrections of their effects. Our approach will be further improved in the future in the modeling of random coincidences and tracking of high-energy photons, and simulation results will be used for the development of correction methods in (86)Y PET.

  11. Performance comparisons of selected personnel-dosimetry systems in use at Department of Energy facilities

    SciTech Connect

    Roberson, P.L; Holbrook, K.L.; Yoder, R.C.; Fox, R.A.; Hadley, R.T.; Hogan, B.T.; Hooker, C.D.

    1983-10-01

    Dosimeter performance data were collected to help develop a uniform approach to the calibration and use of personnel dosimetry systems for Department of Energy (DOE) laboratories. Eleven DOE laboratories participated in six months of testing using the American National Draft Standard, Criteria for Testing Personnel Dosimetry Performance, ANSI N13.11, and additional testing categories. The tests described in ANSI N13.11 used a pass/fail system to determine compliance with the draft standard. Recalculation to PNL irradiations showed that the /sup 137/Cs, /sup 90/Sr//sup 90/Y, and /sup 252/Cf categories can be recalibrated to have acceptable performance for nearly all participant systems. Deficient dosimeter design or handling techniques caused poor performance in the x-ray category for nearly half of the participants. Too little filtration for the deep-dose element caused poor performance in the beta/photon mixture category for one participant. Two participants had excessively high standard deviations in the neutron category due to dosimeter design or handling deficiencies. The participating dosimetry systems were separated into three categories on their dose evaluation procedure for low-energy photons. These were film dosimeters, fixed-calibration thermoluminescent (TL) dosimeters, and variable-calibration TL dosimeters. The performance of the variable-calibration design was best while the film dosimeters performed considerably worse than either TL dosimeter design. Beta energy dependence studies confirmed a strong correlation between sensitive element thickness, shallow element filtration and low-energy beta response. Studies of neutron calibration conditions for each participant suggested a relationship between response and calibration facility design.

  12. Targeted alpha particle immunotherapy for myeloid leukemia.

    PubMed

    Jurcic, Joseph G; Larson, Steven M; Sgouros, George; McDevitt, Michael R; Finn, Ronald D; Divgi, Chaitanya R; Ballangrud, Ase M; Hamacher, Klaus A; Ma, Dangshe; Humm, John L; Brechbiel, Martin W; Molinet, Roger; Scheinberg, David A

    2002-08-15

    Unlike beta particle-emitting isotopes, alpha emitters can selectively kill individual cancer cells with a single atomic decay. HuM195, a humanized anti-CD33 monoclonal antibody, specifically targets myeloid leukemia cells and has activity against minimal disease. When labeled with the beta-emitters (131)I and (90)Y, HuM195 can eliminate large leukemic burdens in patients, but it produces prolonged myelosuppression requiring hematopoietic stem cell transplantation at high doses. To enhance the potency of native HuM195 yet avoid the nonspecific cytotoxicity of beta-emitting constructs, the alpha-emitting isotope (213)Bi was conjugated to HuM195. Eighteen patients with relapsed and refractory acute myelogenous leukemia or chronic myelomonocytic leukemia were treated with 10.36 to 37.0 MBq/kg (213)Bi-HuM195. No significant extramedullary toxicity was seen. All 17 evaluable patients developed myelosuppression, with a median time to recovery of 22 days. Nearly all the (213)Bi-HuM195 rapidly localized to and was retained in areas of leukemic involvement, including the bone marrow, liver, and spleen. Absorbed dose ratios between these sites and the whole body were 1000-fold greater than those seen with beta-emitting constructs in this antigen system and patient population. Fourteen (93%) of 15 evaluable patients had reductions in circulating blasts, and 14 (78%) of 18 patients had reductions in the percentage of bone marrow blasts. This study demonstrates the safety, feasibility, and antileukemic effects of (213)Bi-HuM195, and it is the first proof-of-concept for systemic targeted alpha particle immunotherapy in humans.

  13. Handling interferences in ⁸⁹Sr and ⁹⁰Sr measurements of reactor coolant water: a method based on strontium separation chemistry.

    PubMed

    Holmgren, S; Tovedal, A; Jonsson, S; Nygren, U; Ramebäck, H

    2014-08-01

    Measurements for determining the activity of (89)Sr and (90)Sr in reactor coolant water are associated with limitations due to interferences from radionuclides with similar chemical properties and β(-)-energies. From a measurement bias point-of-view these interferences would result mainly in an overestimated activity concentration of (90)Sr. In order to address the interference problem, a common and well-known method was used in order to show the need for sufficient decontamination. An improvement was achieved by taking the sample through two initial strontium separations in order to increase the decontamination factor. This method determines the activity concentration of (89)Sr and (90)Sr, via its daughter nuclide (90)Y, by Cherenkov counting. This work is primarily based on theoretical calculations of strontium-, yttrium- and other potential interfering radionuclide ratios after instant fission. The work done to confirm the theoretical calculations were carried through on spiked strontium standard solutions and fresh reactor coolant water. The reactor coolant water was known to contain interferences at a composition resembling that of instant fission. The detection limit for double separation was calculated to 0.17 Bq/kg for (90)Sr and 0.38 Bq/kg for (89)Sr. When using methods that solely rely on strontium resins, this paper shows that the decontamination factor (DF) is significantly higher when using double separation than that of a single separation. The paper also shows that the DF of an initial double strontium separation is as effective when it comes to removing high ratio interferences as separations done with both Sr- and Ln-resin (EiChrom Technologies, Inc., 2003; Tovedal et al., 2009b). However, 'old' samples, where e.g. (140)Ba and (89)Sr has decayed, does not benefit from double separation. Furthermore, samples with low ratios of interfering radionuclides does not benefit from using this method either, seeing as this is a more time consuming method

  14. 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.

  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. 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.

  17. Radioembolization of Hepatic Lesions from a Radiobiology and Dosimetric Perspective

    PubMed Central

    Cremonesi, Marta; Chiesa, Carlo; Strigari, Lidia; Ferrari, Mahila; Botta, Francesca; Guerriero, Francesco; De Cicco, Concetta; Bonomo, Guido; Orsi, Franco; Bodei, Lisa; Di Dia, Amalia; Grana, Chiara Maria; Orecchia, Roberto

    2014-01-01

    Radioembolization (RE) of liver cancer with 90Y-microspheres has been applied in the last two decades with notable responses and acceptable toxicity. Two types of microspheres are available, glass and resin, the main difference being the activity/sphere. Generally, administered activities are established by empirical methods and differ for the two types. Treatment planning based on dosimetry is a prerogative of few centers, but has notably gained interest, with evidence of predictive power of dosimetry on toxicity, lesion response, and overall survival (OS). Radiobiological correlations between absorbed doses and toxicity to organs at risk, and tumor response, have been obtained in many clinical studies. Dosimetry methods have evolved from the macroscopic approach at the organ level to voxel analysis, providing absorbed dose spatial distributions and dose–volume histograms (DVH). The well-known effects of the external beam radiation therapy (EBRT), such as the volume effect, underlying disease influence, cumulative damage in parallel organs, and different tolerability of re-treatment, have been observed also in RE, identifying in EBRT a foremost reference to compare with. The radiobiological models – normal tissue complication probability and tumor control probability – and/or the style (DVH concepts) used in EBRT are introduced in RE. Moreover, attention has been paid to the intrinsic different activity distribution of resin and glass spheres at the microscopic scale, with dosimetric and radiobiological consequences. Dedicated studies and mathematical models have developed this issue and explain some clinical evidences, e.g., the shift of dose to higher toxicity thresholds using glass as compared to resin spheres. This paper offers a comprehensive review of the literature incident to dosimetry and radiobiological issues in RE, with the aim to summarize the results and to identify the most useful methods and information that should accompany future studies

  18. 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.

  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. 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

  1. 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.

  2. 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).

  3. [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.

  4. Genetic variants influencing biomarkers of nutrition are not associated with cognitive capability in middle-aged and older adults.

    PubMed

    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

    2013-05-01

    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.

  5. 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.

  6. 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.

  7. Intraperitoneal immunoconjugates

    SciTech Connect

    Griffin, T.W.; Collins, J.; Bokhari, F.; Stochl, M.; Brill, A.B.; Ito, T.; Emond, G.; Sands, H. )

    1990-02-01

    Intracavitary instillation of radioantibodies has been proposed as therapy for anatomically confined malignant disease. To evaluate this therapeutic strategy, a monoclonal antibody reactive with human transferrin receptor (7D3) was evaluated for localization in a human malignant mesothelioma transplanted i.p. in athymic nude mice. This antibody was purified and labeled with 131I, 125I, or 111In. Radiolabeled antibody was administered i.p. or i.v. to tumor-bearing mice. Three h after injection, the percentage of injected dose/g (ID/g) of tumor was higher in free-floating ascites tumor cells (31.0%/g tumor cell pellet) after i.p. injection than after i.v. injection (12.0%). However, localization of radiolabel in i.p. solid tumors was similar (5.37% ID/g i.p. versus 4.73% of ID/g i.v.), and by 24 h both routes of administration produced similar localization of radiolabel in both free-floating ascites cells and solid tumors. In contrast, uptake of radiolabel into liver, kidney, and to a lesser extent bone and bone marrow, was less with i.p. than with i.v. administration. In clinical studies with 111In and 90Y antibodies administered i.p. to patients with ovarian cancer, confined biodistribution of the radioantibody was again seen, although interpatient variability of rate of egress of the radiolabel was documented. Therefore, both preclinical and clinical data indicate that i.p. therapy with immunoconjugates may be advantageous for cancer confined to the peritoneal cavity. This advantage stems primarily from reduced localization of isotope in organs of catabolism or toxicity (liver, kidney, bone, and bone marrow), rather than greatly increased levels of isotope in tumor. Unresolved problems include degree of antibody penetration into solid tumors, microdosimetry, and radioantibody effectiveness for tumor killing.

  8. 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.

  9. Radiation Segmentectomy: A Novel Approach to Increase Safety and Efficacy of Radioembolization

    SciTech Connect

    Riaz, Ahsun; Gates, Vanessa L.; Atassi, Bassel; Lewandowski, Robert J.; Mulcahy, Mary F.; Ryu, Robert K.; Sato, Kent T.; Baker, Talia; Kulik, Laura; Gupta, Ramona; Abecassis, Michael; Benson, Al B.; Omary, Reed; Millender, Laura; Kennedy, Andrew; Salem, Riad

    2011-01-01

    Purpose: To describe a technique of segmental radioembolization for the treatment of patients with unresectable hepatocellular carcinoma (HCC). Radiation segmentectomy was defined as radioembolization of two or fewer hepatic segments. We sought to (1) calculate dose when activity is delivered segmentally assuming uniform and nonuniform distribution and, (2) determine safety and efficacy of this novel technique. Methods and Materials: A total of 84 patients with HCC who were treated with {sup 90}Y radioembolization using a segmental approach were included in this analysis. The dose delivered to the segment was calculated assuming uniform and nonuniform microsphere distribution within the treatment volume. To calculate dose assuming nonuniform distribution, a tumor hypervascularity ratio was assigned. Posttreatment response (using size and necrosis guidelines), toxicity, time to progression, and survival were determined. Results: The median treatment volume was 110 cm{sup 3}. The median radiation-naive liver volume was 1403 cm{sup 3}. The median dose delivered to the segment(s) assuming uniform distribution was 521 Gy. Taking into account tumor hypervascularity (nonuniform distribution), the median dose delivered to the tumor and normal infused hepatic volume was 1214 Gy and 210 Gy, respectively. Response by size and necrosis guidelines was seen in 59% and 81% of patients. Grade 3/4 biochemical toxicities were observed in 8 patients (9%). Median time to progression was 13.6 months (95% confidence interval, 9.3-18.7 months); median survival was 26.9 months (95% confidence interval, 20.5-30.2 months). Conclusions: Radiation segmentectomy is a safe and efficacious method of selectively delivering high dose to the tumor with minimal exposure of normal parenchyma.

  10. 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.

  11. 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.

  12. 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.

  13. Five percent dextrose maximizes dose delivery of Yttrium-90 resin microspheres and reduces rates of premature stasis compared to sterile water

    PubMed Central

    Koran, Mary Ellen; Stewart, Samantha; Baker, Jennifer C.; Lipnik, Andrew J.; Banovac, Fil; Omary, Reed A.; Brown, Daniel B.

    2016-01-01

    Resin Yttrium-90 (Y90) microspheres have historically been infused using sterile water (H2O). In 2013, recommendations expanded to allow delivery with 5% dextrose in water (D5W). In this retrospective study, we hypothesized that D5W would improve Y90 delivery with a lower incidence of stasis. We reviewed 190 resin Y90 infusions using H2O (n=137) or D5W (n=53). Y90 dosimetry was calculated using the body surface area method. Infusion was halted if intra-arterial stasis was fluoroscopically identified prior to clearing the vial. Differences between H2O and D5W groups were calculated for activity prescription, percentage of cases reaching stasis, and percentage delivery of prescribed activity using z- and t-test comparisons, with α=0.05. Thirty-one of 137 H2O infusions developed stasis compared to 2 of 53 with D5W (z=3.07, p=1.05E-03). D5W also had a significantly higher prescribed activity than H2O [28.2 millicuries (mCi) vs. 20.4 mCi, respectively; t=5.0, p=1.1E-6]. D5W had a higher delivery percentage of the prescribed dose compared to H2O (101.5 vs. 92.7%, respectively; t=3.8, p=1.92E-4). In conclusion, resin microsphere infusion utilizing D5W has a significantly lower rate of stasis than H2O and results in more complete dose delivery. D5W is preferable to H2O for resin microsphere infusion. PMID:28105342

  14. 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

  15. Study of thermoluminescence response of purple to violet amethyst quartz from Balikesir, Turkey

    NASA Astrophysics Data System (ADS)

    Nur, N.; Yeğingil, Z.; Topaksu, M.; Kurt, K.; Doğan, T.; Sarıgül, N.; Yüksel, M.; Altunal, V.; Özdemir, A.; Güçkan, V.; Günay, I.

    2015-09-01

    In thermoluminescence (TL) dosimetry, the phosphor amethyst quartz as a thermoluminescent, appears to be one of the materials arousing the highest interest. In this study the dosimetric characteristics of natural amethyst quartz crystals collected from Balikesir-Dursunbey (Turkey) were investigated for the purpose of determination of the general properties that phosphors should have in order to be useful for thermoluminescence dosimetry. The natural thermoluminescence was drained by annealing the powder samples at 450 °C for 1.5 h. The effects of high temperature annealing, dose response curves, glow curves after a postirradiation annealing, reusability of the samples and storage of trapped electrons in dark at room temperature were clarified through irradiating the samples with the desired exposures by 90Sr/90Y beta particles. Isothermal annealing before and after irradiation was found to have a definite effect upon the TL glow curve of amethyst crystal powder. The same sample varied in sensitivity depending upon its previous thermal and radiation history. The peak heights of the glow peaks were examined with respect to dose response at dose levels between 1 Gy and 5 kGy. The intermediate temperature (IT) and high temperature (HT) peaks of 230 °C and 300 °C, respectively, exhibit dose-response curves as superlinear when dose is on the logarithmic scale except the dose response of 300 °C peak for the dose values of 1 < D < 20 Gy in which linear dose response was acquired. At the end of the storage time between exposure and readout which was about one month at room temperature, the emitted light reduction was 14% comparing to the initial state. Repeating the measurements of the same sample, exposed with 0.1, 0.5, 0.8 and 1 kGy beta exposures, resulted in between 4% and 11% increase in the TL sensitivity of the material.

  16. Voxel-based dose calculation in radiocolloid therapy of cystic craniopharyngiomas

    NASA Astrophysics Data System (ADS)

    Treuer, H.; Hoevels, M.; Luyken, K.; Gierich, A.; Hellerbach, A.; Lachtermann, B.; Visser-Vandewalle, V.; Ruge, M.; Wirths, J.

    2015-02-01

    Very high doses are administered in radiocolloid therapy of cystic craniopharyngiomas. However individual dose planning is not common yet mainly due to insufficient image resolution. Our aim was to investigate whether currently available high-resolution image data can be used for voxel-based dose calculation for short-ranged β-emitters (32P,90Y,186Re) and to assess the achievable accuracy. We developed a convolution algorithm based on voxelized dose activity distributions and dose-spread kernels. Results for targets with 5-40 mm diameter were compared with high-resolution Monte Carlo calculations in spherical phantoms. Voxel size was 0.35 mm. Homogeneous volume and surface activity distributions were used. Dose-volume histograms of targets and shell structures were compared and γ index (dose tolerance 5%, distance to agreement 0.35 mm) was calculated for dose profiles along the principal axes. For volumetric activity distributions 89.3% ± 11.9% of all points passed the γ test (mean γ 0.53  ±  0.16). For surface distributions 33.6% ± 14.8% of all points passed the γ test (mean γ 2.01  ±  0.60). The shift of curves in dose-volume histograms was -1.7 Gy ± 7.6 Gy (-4.4 Gy ± 24.1 Gy for 186Re) in volumetric distributions and 46.3% ± 32.8% in surface distributions. The results show that individual dose planning for radiocolloid therapy of cystic craniopharyngiomas based on high-resolution voxelized image data is feasible and yields highly accurate results for volumetric activity distributions and reasonable dose estimates for surface distributions.

  17. Matching chelators to radiometals for radiopharmaceuticals.

    PubMed

    Price, Eric W; Orvig, Chris

    2014-01-07

    Radiometals comprise many useful radioactive isotopes of various metallic elements. When properly harnessed, these have valuable emission properties that can be used for diagnostic imaging techniques, such as single photon emission computed tomography (SPECT, e.g.(67)Ga, (99m)Tc, (111)In, (177)Lu) and positron emission tomography (PET, e.g.(68)Ga, (64)Cu, (44)Sc, (86)Y, (89)Zr), as well as therapeutic applications (e.g.(47)Sc, (114m)In, (177)Lu, (90)Y, (212/213)Bi, (212)Pb, (225)Ac, (186/188)Re). A fundamental critical component of a radiometal-based radiopharmaceutical is the chelator, the ligand system that binds the radiometal ion in a tight stable coordination complex so that it can be properly directed to a desirable molecular target in vivo. This article is a guide for selecting the optimal match between chelator and radiometal for use in these systems. The article briefly introduces a selection of relevant and high impact radiometals, and their potential utility to the fields of radiochemistry, nuclear medicine, and molecular imaging. A description of radiometal-based radiopharmaceuticals is provided, and several key design considerations are discussed. The experimental methods by which chelators are assessed for their suitability with a variety of radiometal ions is explained, and a large selection of the most common and most promising chelators are evaluated and discussed for their potential use with a variety of radiometals. Comprehensive tables have been assembled to provide a convenient and accessible overview of the field of radiometal chelating agents.

  18. 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.

  19. 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.

  20. 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.

  1. The response of thermally and optically stimulated luminescence from Al2O3:C to high-energy heavy charged particles.

    PubMed

    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.

  2. 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.

  3. 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.

  4. Radiopharmacokinetic and dosimetric parameters of 188Re-lanreotide in athymic mice with induced human cancer tumors.

    PubMed

    Molina-Trinidad, Eva M; de Murphy, Consuelo Arteaga; Ferro-Flores, Guillermina; Murphy-Stack, Eduardo; Jung-Cook, Helgi

    2006-03-09

    Radiolabeled peptides, like the somatostatin analogs, have been used for peptide receptor-mediated radionuclide therapy (PRMRT) in metastatic neuroendocrine tumors. The eight amino acid peptide 3-(2-naphthalenyl)-D-alanyl-L-cysteinyl-L-tyrosyl-D-tryptophyl-L-lysyl-L-valyl-L-cysteinyl-L-threoninamide,cyclic(2-->7)-disulfide (9Cl) (lanreotide) was found to bind to the five somatostatin tumor receptors. Lanreotide has been labeled via the bifunctional chelating agent, DOTA, to (111)In, and (90)Y. A direct labeling method was used to label lanreotide with (188)Re. Athymic mice with implanted human cancer tumors (uterine-cervix, renal, and neuroblastoma) were injected with radiochemically pure (188)Re-lanreotide (1.11 MBq). The percent injected activity (%IA/g) from serial blood samples was the input data for the WinNonlin computer program to obtain radiopharmacokinetic parameters. The organs' percent injected activity per gram of tissue (%IA/g) was extrapolated to the weights of a 70 kg male model organs and the number of nuclear transitions (N) were the input for the OLINDA/EXM program to obtain dosimetry estimates. Induced uterine-cervix tumors (HeLa cells) show a mean 2.4 %IA/g uptake up to 24 h and the tumor/blood ratio was over 1.85 (1.5-24 h post-injection) confirming (188)Re-lanreotide remains bound to the tumor. The estimated tumor absorbed dose was 460 mGy/MBq. Human effective dose was 0.0182 mSv/MBq. Therefore, (188)Re-lanreotide is a good candidate for PRMRT and a clinical trial is being planned in order to acquire individual dosimetric data.

  5. 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

  6. 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.

  7. 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.

  8. Intra-arterial embolotherapy for intrahepatic cholangiocarcinoma: update and future prospects

    PubMed Central

    Savic, Lynn Jeanette; Chapiro, Julius

    2017-01-01

    Intrahepatic cholangiocarcinoma (ICC) is a rare disease and carries a poor prognosis with surgery remaining the only curative treatment option. However, due to the late presentation of symptoms and close proximity of the tumors to central hepatic structures, only about 30% of patients are classified eligible to resection. As for palliative approaches, ICC constitutes a possible indication for loco-regional therapies (LRT). As such, intra-arterial therapies (IAT) are reported to be feasible, safe and effective in inducing tumor response in unresectable ICC. The paradigm of IAT is premised on the selective delivery of embolic, chemotherapeutic agents to the tumor via its feeding arteries, thus allowing dose escalation within the carcinoma and reduction of systemic toxicity. Conventional transcatheter arterial chemoembolization (cTACE) so far remains the most commonly used IAT modality. However, drug-eluting beads (DEB)-TACE was initiated with the idea of more selective targeting of the tumor owing to the combined embolizing as well as drug-eluting properties of the microspheres used in this setting. Moreover, radioembolization is performed by intra-arterial administration of very small spheres containing β-emitting yttrium-90 (Y90-RE) to the site of the tumor. Clinical evidence exists in support of survival benefits for IAT in the palliative treatment of ICC compared to surgery and systemic chemotherapy. As for combination regimens, cTACE, DEB-TACE and Y90-RE are reported to achieve conversion of patients to surgery in a sequential treatment planning and simultaneous IAT combinations may provide a therapeutic option for treatment escalation. Regarding the current status of literature, controlled randomized prospective trials to compare different IAT techniques and combination therapies as well as treatment recommendations for different IAT modalities are needed. PMID:28261591

  9. 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.

  10. 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.

  11. Floor Probe/Contamination Monitor (NE Model FLP3D) Test and Evaluation Report

    SciTech Connect

    Shourbaji, A.A.

    2003-06-27

    A floor contamination monitor model FLP3D manufactured by Saint-Gobain Crystals and Detectors UK Ltd. was tested at Oak Ridge National Laboratory. The purpose of the test is to evaluate the monitor's performance as a mobile instrument capable of detecting alpha and/or beta contamination that may exist on a flat surface such as a floor. The monitor consists of a large area scintillation probe (600 cm{sup 2}) and a rate meter mounted on heavy-duty wheels with a 22 mm separation between the monitored surface and the probe. Performance was evaluated under normal and severe environmental conditions in terms of temperature and humidity variations, and exposure to RF and magnetic fields. Sensitivity measurements were also made to determine the probe's efficiency for detecting alpha and beta contamination. The overall performance of the floor monitor is considered satisfactory under the various environmental conditions with no major problems observed. The monitor is approximately 50% efficiency for {sup 90}Sr/{sup 90}Y with the source placed in contact with the detector's protective grille (0 mm) and at a distance of 22 mm. However, in its present physical configuration, the floor monitor is inefficient in detecting alpha contamination due to the 22 mm separation between the surface to be monitored and the detector's surface. The alpha detection efficiency can be enhanced to a reasonable vale by redesigning the brackets holding the heavy-duty wheels to reduce the height between the surface to be monitored and the surface of the probe to a few millimeters. For use at ORNL, this change is recommended.

  12. 100y Search for Large Amplitude Variables in DASCH Scans Near M44

    NASA Astrophysics Data System (ADS)

    Tang, Sumin; Grindlay, J.; Los, E.; Laycock, S.

    2009-01-01

    Astronomical source variability is poorly explored on 1-100y timescales, where large scale systematic surveys are generally lacking. The Digital Access to a Sky Century at Harvard (DASCH) Collaboration has developed an ultra-high speed digital plate scanner which will ultimately enable the digitizing of the 500,000 Harvard plates from the 1880s to the 1980s with limiting magnitudes ranging from B=14-19. Every point on the sky has been observed typically 300-1000 times with typical error 0.1 mag. For several science demonstration projects, we have scanned more than 3000 plates in several different fields. Here we present our search for large amplitude variables (> 1 mag) over 600 plates which covered a 20deg x 20deg field (with radially decreasing coverage) centered on the open cluster M44. Preliminary detection rate of known variables in this field is 30% , but expected to improve when over-rejection and other issues are optimized. Among the new variables we found there are 77 RR Lyr, Mira, Pulsating stars, DNe or irregular variable candidates, 116 eclipsing binaries (most of them are Algol systems), 37 flare stars, 5 red R Coronae Borealis (RCB) candidates, and most interestingly, 3 very unusual variables that do not match any of the common classes and might be captured during extremely short-lived stellar evolutionary stages: one blue variable with a 1 mag flare on a 10y timescale, one red variable with unusual long-term variability which became 1 mag fainter in 90y, one 'mini-FU Orionis' red variables with a 1.5 mag flare with decay time 8y and otherwise constant for decades before and after the flare. Based on the fairly well defined sample of different classes found in the search, we also estimate the likely event rate for each class.

  13. Time domain para hydrogen induced polarization.

    PubMed

    Ratajczyk, Tomasz; Gutmann, Torsten; Dillenberger, Sonja; Abdulhussaein, Safaa; Frydel, Jaroslaw; Breitzke, Hergen; Bommerich, Ute; Trantzschel, Thomas; Bernarding, Johannes; Magusin, Pieter C M M; Buntkowsky, Gerd

    2012-01-01

    Para hydrogen induced polarization (PHIP) is a powerful hyperpolarization technique, which increases the NMR sensitivity by several orders of magnitude. However the hyperpolarized signal is created as an anti-phase signal, which necessitates high magnetic field homogeneity and spectral resolution in the conventional PHIP schemes. This hampers the application of PHIP enhancement in many fields, as for example in food science, materials science or MRI, where low B(0)-fields or low B(0)-homogeneity do decrease spectral resolution, leading to potential extinction if in-phase and anti-phase hyperpolarization signals cannot be resolved. Herein, we demonstrate that the echo sequence (45°-τ-180°-τ) enables the acquisition of low resolution PHIP enhanced liquid state NMR signals of phenylpropiolic acid derivatives and phenylacetylene at a low cost low-resolution 0.54 T spectrometer. As low field TD-spectrometers are commonly used in industry or biomedicine for the relaxometry of oil-water mixtures, food, nano-particles, or other systems, we compare two variants of para-hydrogen induced polarization with data-evaluation in the time domain (TD-PHIP). In both TD-ALTADENA and the TD-PASADENA strong spin echoes could be detected under conditions when usually no anti-phase signals can be measured due to the lack of resolution. The results suggest that the time-domain detection of PHIP-enhanced signals opens up new application areas for low-field PHIP-hyperpolarization, such as non-invasive compound detection or new contrast agents and biomarkers in low-field Magnetic Resonance Imaging (MRI). Finally, solid-state NMR calculations are presented, which show that the solid echo (90y-τ-90x-τ) version of the TD-ALTADENA experiment is able to convert up to 10% of the PHIP signal into visible magnetization.

  14. New insight into the properties of proton conducting oxides from neutron total scattering

    SciTech Connect

    Proffen, Thomas E; Kim, Hyunjeong; Malavasi, Lorenzo; Flor, Giorgio

    2008-01-01

    In recent years there has been a growing interest in searching for new proton conducting materials that could be successfully used in medium temperature solid oxide fuel cells (SOFC). In particular, proton conducting oxides have been the subject of a massive research activity. Among the most promising oxide the acceptor doped cerates appears to be those most appealing in view of practical applications. A relevant aspect of these materials is the investigation of the local distortion of the structure arising from water incorporation. This kind of study is of great help in defining how the structure changes in order to accommodate the proton which is usually thought to enter the structure in form of hydroxyl group where the oxygen vacancy results from the acceptor doping on the Ce site. Atomistic simulation work confirmed that the preferential location of dopant ions is on the Ce site. To the best of our knowledge the only experimental work addressing the role of dopant and water incorporation on the local structure of V-doped cerates is a X-ray absorption spectroscopy (XAS) work carried out by Longo and coworkers at the Y K-edge. The main conclusion of that work was the observation that Y-doping induces a distortion of the parent BaCe0{sub 3} structure resulting in a significantly distorted Y local environment. However, local structure information derived from XAS study does not provide a direct structural information and depends strongly upon the model used to calcualte theoretical {chi}(k) which is not unique. Moreover, the XAS analysis usually provide significant information only up to the second shell. As a consequence, a more reliable and useful technique to investigate the local arrangement in these proton conducting oxides appears to be the Pair Distribution Function (PDF) analysis derived from total neutron scattering measurements. In the present work we investigated the pure BaCeO{sub 3} and the acceptor doped BaCe{sub 0.90}Y{sub 0.10}O{sub 2.85} compounds

  15. 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

  16. 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 perman