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Sample records for 90y ibritumomab tiuxetan

  1. Selecting patients for treatment with 90Y ibritumomab tiuxetan (Zevalin).

    PubMed

    Gregory, Stephanie A

    2003-12-01

    Yttrium 90 ibritumomab tiuxetan (Zevalin; Biogen Idec Inc, Cambridge, MA) was the first radioimmunotherapeutic agent approved by the US Food and Drug Administration. It is indicated for treating patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma, including patients with rituximab-refractory follicular non-Hodgkin's lymphoma. Proper patient selection is essential for optimizing the efficacy and safety of treatment with (90)Y ibritumomab tiuxetan. It may be advisable to use (90)Y ibritumomab tiuxetan relatively early in a patient's course of treatment because overall and complete response rates, and the estimated median duration of response, are higher among patients who have had fewer median prior antineoplastic regimens than among those who have had a greater median number of such regimens. Furthermore, the myeloablative effect of multiple courses of chemotherapy can preclude the later use of (90)Y ibritumomab tiuxetan. In contrast, other therapies, including chemotherapy and rituximab, can be used safely and successfully after (90)Y ibritumomab tiuxetan without concerns about increased hematologic toxicity from the previous radioimmunotherapy. The main adverse event associated with (90)Y ibritumomab tiuxetan therapy is hematologic toxicity and, as a result, only patients with adequate bone marrow reserves and less than 25% lymphoma marrow involvement should currently be considered for clinical therapy. PMID:14710399

  2. 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

  3. 90 Y-ibritumomab tiuxetan: a nearly forgotten opportunityr.

    PubMed

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

    2016-02-16

    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

  4. Use of 90Y-ibritumomab tiuxetan in non-Hodgkin's lymphoma.

    PubMed

    Marcus, Robert

    2005-02-01

    The increase in the incidence of non-Hodgkin's lymphoma (NHL) that has occurred over recent decades is expected to continue. Therapeutic options for patients with NHL have improved over the past 20 years, but almost all patients with low-grade lymphoma and approximately 50% of patients with high-grade lymphoma eventually die of their disease, regardless of the regimen used. Thus, there is a continuing need for novel therapeutic options. One such strategy is targeted radioimmunotherapy, which is an attractive approach because lymphoma cells are inherently sensitive to radiation. 90 Y-ibritumomab tiuxetan (Zevalin; Biogen Idec Inc, San Diego, CA, and Schering AG, Berlin, Germany) was the first radioimmunotherapy agent to be approved by the US Food and Drug Administration for the treatment of patients with relapsed, low-grade B-cell NHL. 90Y-ibritumomab tiuxetan comprises the murine IgG1 anti-CD20 antibody ibritumomab, covalently linked to the beta-emitter 90 Y by a chelator tiuxetan. A prospective trial comparing 90Y-ibritumomab tiuxetan with single-agent rituximab showed an overall response rate (ORR) to 90Y-ibritumomab tiuxetan of 80% (34% complete response [CR]/unconfirmed CR [CRu]) compared with 56% (20% CR/CRu) with rituximab (P = .002). Of patients achieving a CR/CRu, 32% were still in remission at 3 to 4 years of follow-up. Similar efficacy (83% ORR, 43% CR/CRu) has been reported with 90 Y-ibritumomab tiuxetan in patients with relapsed or refractory low-grade NHL with mild thrombocytopenia (platelet counts 100,000 to 149,000/mm3 ), and in patients with rituximab-refractory NHL (ORR 74% [CR 15%] compared with an ORR 32% to last rituximab treatment). Safety data compiled from patients entered into five studies have confirmed initial observations that the toxicities encountered with 90Y-ibritumomab tiuxetan therapy are mainly hematologic and transient. As part of a consolidated clinical approach to the ongoing development of 90Y-ibritumomab tiuxetan, studies are

  5. Efficacy and safety of 90Y ibritumomab tiuxetan (Zevalin) radioimmunotherapy for non-Hodgkin's lymphoma.

    PubMed

    Witzig, Thomas E

    2003-12-01

    Radioimmunotherapy, an emerging treatment option for certain patients with non-Hodgkin's lymphoma (NHL), enables the targeting of cytotoxic radiation to tumor cells with minimal irradiation of normal cells. Yttrium 90 ibritumomab tiuxetan (Zevalin; Biogen Idec Inc, Cambridge, MA) was approved in February 2002 for the treatment of patients with relapsed or refractory low-grade, follicular, or transformed B-cell NHL, including patients with rituximab-refractory NHL. Yttrium 90 ibritumomab tiuxetan is an effective treatment with a consistent overall response rate of 73% to 83%. It has a good safety profile and is generally well tolerated in the indicated population. The results of clinical trials show that (90)Y ibritumomab tiuxetan can be used effectively and safely in many patients with NHL, including those with mild thrombocytopenia and those with disease that is refractory to rituximab, without the adverse events associated with conventional chemotherapy and external beam radiation therapy. The use of (90)Y ibritumomab tiuxetan does not preclude subsequent therapy with other conventional treatment options. PMID:14710398

  6. Phase II study of (90)Y Ibritumomab tiuxetan (Zevalin) in patients with previously untreated marginal zone lymphoma.

    PubMed

    Lossos, Izidore S; Fabregas, Jesus C; Koru-Sengul, Tulay; Miao, Feng; Goodman, Deborah; Serafini, Aldo N; Hosein, Peter J; Stefanovic, Alexandra; Rosenblatt, Joseph D; Hoffman, James E

    2015-06-01

    The best upfront therapy for patients with non-gastric extranodal marginal zone lymphomas (MZLs) is not defined. We assessed the safety and efficacy of radioimmunotherapy with (90)yttrium ((90)Y) ibritumomab tiuxetan as upfront therapy in MZL (NCT00453102). A total of 16 patients were enrolled, 81% with advanced-stage disease and 44% with bulky disease. The overall response rate (ORR) at 12 weeks post-therapy was 87.5% (90% confidence interval [CI]: 65.6-97.7%), including a complete response in eight (50%), complete response unconfirmed in one (6%) and partial response in five (31%) patients. With a median follow-up of 65.6 months (range 4.0-96.5), the median progression-free survival (PFS) was 47.6 months (range 4.0-93.3) and median overall survival (OS) was not reached. The 5-year PFS was 40% (90% CI: 19.9-59.5%) and 5-year OS was 71.8% (90% CI: 46.8-86.5%). Overall, (90)Y ibritumomab tiuxetan was well tolerated and led to long-term responses and PFS rates. PMID:25315074

  7. Current status and future perspectives for yttrium-90 ((90)Y)-ibritumomab tiuxetan in stem cell transplantation for non-Hodgkin's lymphoma.

    PubMed

    Gisselbrecht, C; Bethge, W; Duarte, R F; Gianni, A M; Glass, B; Haioun, C; Martinelli, G; Nagler, A; Pettengell, R; Sureda, A; Tilly, H; Wilson, K

    2007-12-01

    Haematopoietic SCT is currently considered a therapeutic option mainly in relapsed or refractory non-Hodgkin's lymphoma (NHL) owing to high post-transplantation relapse rates and significant toxicity of conventional myeloablative conditioning for allogeneic SCT. Radiolabelled immunotherapy combines the benefits of monoclonal antibody targeting with therapeutic doses of radiation, and is a promising advance in the treatment of malignant lymphomas. It is now under investigation as a component of conditioning prior to SCT, with the aim of improving outcomes following SCT without increasing the toxicity of high-dose chemotherapy pre-transplant conditioning. An expert panel met at a European workshop in November 2006 to review the latest data on radiolabelled immunotherapy in the transplant setting, and its potential future directions, with a focus on (90)Y-ibritumomab tiuxetan. They reviewed data on the combination of standard/high/escalating dose (90)Y-ibritumomab tiuxetan with high-dose chemotherapy, and high/escalating dose (90)Y-ibritumomab tiuxetan as the sole myeloablative agent, prior to autologous SCT, and also (90)Y-ibritumomab tiuxetan as a component of reduced intensity conditioning prior to allogeneic SCT. The preliminary data are highly promising in terms of conditioning tolerability and patient outcomes following transplant; further phase II studies are now needed to consolidate these data and to investigate specific patient populations and NHL subtypes. PMID:17922042

  8. 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.

  9. 90Y-ibritumomab tiuxetan radiotherapy as first-line therapy for early stage low-grade B-cell lymphomas, including bulky disease.

    PubMed

    Samaniego, Felipe; Berkova, Zuzana; Romaguera, Jorge E; Fowler, Nathan; Fanale, Michelle A; Pro, Barbara; Shah, Jatin J; McLaughlin, Peter; Sehgal, Lalit; Selvaraj, Vijairam; Braun, Frank K; Mathur, Rohit; Feng, Lei; Neelapu, Sattva S; Kwak, Larry W

    2014-10-01

    (90) Y-ibritumomab-tiuxetan ((90) YIT) was used as a first-line therapy for patients with early-stage follicular lymphoma (FL) or marginal zone B-cell lymphoma (MZL). Thirty-one patients were treated, with an overall 3-month response rate of 100% (68% complete response, 29% unconfirmed complete response and 3% partial response). At a median follow-up of 56 months, ten patients (32%) had disease relapse or progression. The progression-free rates at 3 and 5 years were lower in males, patients with FL, stage II disease and non-bulky disease, although they did not reach statistical significance. Grade 3-4 neutropenia, thrombocytopenia and anaemia were 61%, 35%, and 3%, respectively. (90) YIT was well tolerated, including in those patients over 60 years old, and achieved high response rates in patients with early-stage low-grade B-cell lymphomas. Bulky disease did not adversely affect tumour response. PMID:25040450

  10. Long-term efficacy of (90)Y ibritumomab tiuxetan therapy in follicular non-Hodgkin lymphoma and health-related quality of life.

    PubMed

    Andrade-Campos, Marcio Miguel; Montes-Limón, Anel E; Soro-Alcubierre, Gloria; Grasa, José María; Lopez-Gómez, Luis; Baringo, Teresa; Giraldo, Pilar

    2014-12-01

    The aim of this study was to analyze the outcomes of 37 follicular lymphoma (FL) patients treated with (90)ytrium ibritumomab tiuxetan (90Y-IT), outside of clinical trial, according to protocol ISCRTN36210045, after ≥5 years follow-up to February 2014. Health-related quality of life (HRQoL) was evaluated with the SF-36, Spanish version, and compared with the general population of Spain. Patients had a mean age of 61.9 (range, 30-85) years and included 18 males. FLIPI, low: 25 (67.6 %), intermedium 9 (24.3 %), and low 3 (8.1 %). Previous therapy schedules >2: 48.6 % The median follow-up was 66 months, mean Time to Relapse (TTR) 71.3 months (58.8-83.8) median not reached. Thirty-four patients achieved complete response (91.8 %), and three no response. Mean overall survival: 82.3 months (71.6-92.9). Four patients presented with concomitant tumors (colon, breast, prostate, lung) after radioimmunotherapy, and three developed second primary neoplasms (esophagus, renal, and myelodysplastic syndrome in a relapsed patient who received fludarabine). Four of 10 deaths were related to lymphoma progression. Hematological toxicities were mild and easily managed. No patients required hospitalization. Negative scores were obtained in the physical and emotional roles items; however, the perception of general health and vitality were better than in the general population, with the best outcomes in non-relapsed patients. Radioimmunotherapy with 90Y-IT was safe and effective as long-term therapy in patients with FL. Early use of radioimmunotherapy could offer good, sustained responses with low toxicity over the long term and acceptable HRQoL. PMID:24985089

  11. Ongoing trials with yttrium 90-labeled ibritumomab tiuxetan in patients with non-Hodgkin's lymphoma.

    PubMed

    Micallef, Ivana N M

    2004-10-01

    Targeted radiation therapy or radioimmunotherapy has been an important recent advance in the treatment of patients with B-cell non-Hodgkin's lymphoma (NHL). Yttrium 90-labeled ibritumomab tiuxetan (Zevalin) comprises the murine monoclonal antibody ibritumomab, the linker chelator tiuxetan, and the radiolabeled isotope yttrium 90. Yttrium 90 ibritumomab tiuxetan has been shown to be efficacious in the treatment of B-cell NHL. Initial phase I/II trials established the therapeutic dose of ibritumomab tiuxetan for low-grade NHL to be 0.4 mCi/kg, or 0.3 mCi/kg for patients with mild thrombocytopenia. Currently, there are many ongoing trials of ibritumomab tiuxetan with different dose schedules and dose intensities in combination with chemotherapy and autologous or allogeneic stem cell transplantation in an attempt to improve response rate and duration and to study its effectiveness in other B-cell lymphomas including mantle cell lymphoma, and chronic lymphocytic leukemia. This article reviews the ongoing trials with 90Y ibritumomab tiuxetan. Radioimmunotherapy has great promise, and the safe incorporation of 90Y ibritumomab tiuxetan into treatment will hopefully result in improved survival for patients with NHL. PMID:15498147

  12. Imaging and dosing in radioimmunotherapy with yttrium 90 ibritumomab tiuxetan (Zevalin).

    PubMed

    Spies, Stewart M

    2004-01-01

    Yttrium 90 ibritumomab tiuxetan consists of the murine monoclonal antibody ibritumomab securely bound to the second-generation chelator tiuxetan, which attaches the high-energy pure beta emitter (90)Y, for therapy, or the gamma emitter indium 111, for imaging. The biodistribution of the therapeutic dose of (90)Y ibritumomab tiuxetan can be predicted by using an imaging dose of the antibody labeled with (111)In. Calculation of the therapeutic dose is simple and is based on patient weight and baseline platelet count: for patients with a platelet count of 150 x 10(9)/L or greater the dose of is 0.4 mCi/kg; for patients with mild thrombocytopenia (platelet count 100 x 10(9)/L to 149 x 10(9)/L) the dose is reduced to 0.3 mCi/kg; and the total dose should not exceed 32 mCi. Patients with platelet counts of less than 100 x 10(9)/L should not be treated with (90)Y ibritumomab tiuxetan. Imaging with (111)In ibritumomab tiuxetan is performed only to assess biodistribution of the radioimmunoconjugate. Uptake in sites of pathologic adenopathy, as well as other areas of lymphomatous involvement, is frequently seen on the images, but visualization of tumor uptake is not required to proceed with the therapeutic dose of (90)Y ibritumomab tiuxetan. PMID:14762739

  13. Phase I study of radioimmunotherapy with an anti-CD20 murine radioimmunoconjugate ((90)Y-ibritumomab tiuxetan) in relapsed or refractory indolent B-cell lymphoma.

    PubMed

    Watanabe, Takashi; Terui, Shoji; Itoh, Kuniaki; Terauchi, Takashi; Igarashi, Tadahiko; Usubuchi, Noriko; Nakata, Masanobu; Nawano, Shigeru; Sekiguchi, Naohiro; Kusumoto, Shigeru; Tanimoto, Kazuki; Kobayashi, Yukio; Endo, Keigo; Seriu, Taku; Hayashi, Masaki; Tobinai, Kensei

    2005-12-01

    We conducted a phase I study to evaluate the safety and efficacy of radioimmunotherapy with yttrium-90-ibritumomab tiuxetan (Y2B8) in Japanese patients with relapsed or refractory indolent B-cell lymphoma. Indium-111-labeled ibritumomab tiuxetan (In2B8; 3.5 or 5 mCi [129.5 or 185 MBq]) was administered on day 1, followed by serial gamma-camera imaging to investigate the distribution of In2B8 in the whole body of patients and to judge the feasibility of Y2B8 administration. Y2B8 with a dose of 0.3 mCi/kg (11.1 MBq/kg) or 0.4 mCi/kg (14.8 MBq/kg) was administered on day 8. Grade 4 neutropenia and grade 3 thrombocytopenia were observed in three of nine of the patients evaluated for safety. Critical toxicities (prolonged thrombocytopenia or severe non-hematological toxicities) were observed in two of six patients in the 0.4 mCi/kg (14.8 MBq/kg) dose group but were not seen in any of the three patients in the 0.3 mCi/kg (11.1 MBq/kg) dose group. The non-hematological toxicities of the nine patients were of grade 2 or less, except in two patients who had been heavily treated previously. They experienced critical toxicities such as infection, diarrhea, hyponatremia and prolonged thrombocytopenia, as well as other frequent grade 2 non-hematological toxicities. Although the pharmacokinetic profiles were similar to those in the US study, one of the two patients was clarified retrospectively as showing abnormal biodistribution of In2B8 in the bone marrow, as judged by an independent third party panel of radiologists. Five of the 10 participants achieved complete responses or unconfirmed complete responses and two partial responses. In conclusion, the recommended dose of Y2B8 for the subsequent phase II study for Japanese patients is 0.4 mCi/kg (14.8 MBq/kg). This dose of radioimmunotherapy was feasible when patients with altered biodistribution of In2B8 were excluded, and it was highly effective. (Cancer Sci 2005; 96: 903-910). PMID:16367911

  14. The use of Yttrium-90 Ibritumomab Tiuxetan (90Y-IT) as a consolidation therapy in high-risk patients with diffuse large B-cell lymphoma ineligible for autologous stem-cell transplantation

    PubMed Central

    Kisiel, Elżbieta; Sawczuk-Chabin, Joanna; Centkowski, Piotr; Knopińska-Posłuszny, Wanda; Khan, Omeir

    2015-01-01

    Aim of the study To evaluate the efficacy and safety of Yttrium-90 Ibritumomab Tiuxetan (90Y-IT) as a consolidation therapy in the management of DLBCL. Material and methods Patients with primary refractory or high-risk DLBCL (n = 18), ineligible for autologous stem-cell transplantation, were included in a retrospective study performed at three centers by the Polish Lymphoma Research Group (PLRG). All patients (mean age 61, range 35–82) either didn't achieve a complete response or didn't complete the scheduled therapy due to its complications. Response rates (CR, PR, SD, PD) according to Cheson criteria, overall survival (OS), progression-free survival (PFS) and adverse effects of radioimmunotherapy were analyzed. Results Consolidation radioimmunotherapy increased the CR rate from 38% (n = 7) to 82% (n = 15). One patient remained in PR, one patient remained in SD, while one patient remained in PD. During a median follow-up of five years, 11 patients (62%) were alive with no recurrence, 4 patients (22%) were alive with relapse while 3 patients (16%) died. There was no statistically significant difference in PFS between those in CR and those in PR before 90Y-IT. Conclusions Radioimmunotherapy is an effective consolidation therapy for high risk/refractory DLBCL patients and worthy of further investigation in prospective trials. PMID:26199570

  15. 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

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

    PubMed

    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 (90)Y-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

  17. Yttrium-90-ibritumomab tiuxetan radioimmunotherapy: a new treatment approach for B-cell non-Hodgkin's lymphoma.

    PubMed

    Witzig, Thomas E

    2004-02-01

    This article will review the clinical development of ibritumomab tiuxetan, a yttrium-90-conjugated monoclonal antibody to CD20, for patients with relapsed B-cell non-Hodgkin's lymphomas. Ibritumomab is the murine parent anti-CD20 antibody that was engineered to make the human chimeric antibody rituximab. Tiuxetan is an MX-DTPA chelator that is linked to ibritumomab to form ibritumomab tiuxetan. Since yttrium-90 ((90)Y) is a pure beta emitter and cannot be used for patient imaging, indium-111 ((111)In) is chelated to ibritumomab tiuxetan for tumor and normal organ imaging in clinical practice and for dosimetry in clinical trials. (90)Y-ibritumomab tiuxetan is the form used for therapy. This review discusses the clinical trials that have demonstrated the efficacy of ibritumomab tiuxetan and summarizes the safety data in patients with relapsed B-cell non-Hodgkin's lymphomas. Two phase I trials of (90)Y-ibritumomab tiuxetan were conducted to establish the toxicity profile and the maximum tolerated single dose that could be administered to outpatients without the use of stem cells or prophylactic growth factors. In the first trial, cold ibritumomab was used prior to ibritumomab tiuxetan; the second trial used the human chimeric antibody rituximab. The phase I trials determined that in patients with a platelet count of greater than or equal to 150 x 10(9)/l, a schedule of intravenous rituximab 250 mg/m(2) on days 1 and 8, and 0.4 mCi/ kg of intravenous (90)Y-ibritumomab tiuxetan on day 8 was safe and efficacious and did not require stem cells. A dose of 0.3 mCi/kg was recommended for patients with a baseline platelet count of 100,000- 149,000 x 10(6)/l. Adverse events were primarily hematologic, and nonhematologic adverse events were primarily due to rituximab. There was no normal organ toxicity. The overall response rate was 67% for all patients and 82% in patients with low-grade non-Hodgkin's lymphomas. A subsequent phase III trial randomized 143 eligible patients to

  18. 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

  19. Safety and efficacy of (90) yttrium-ibritumomab-tiuxetan for untreated follicular lymphoma patients. An Italian cooperative study.

    PubMed

    Ibatici, Adalberto; Pica, Gian Matteo; Nati, Sandro; Vitolo, Umberto; Botto, Barbara; Ciochetto, Chiara; Petrini, Mario; Galimberti, Sara; Ciabatti, Elena; Orciuolo, Enrico; Zinzani, Pier Luigi; Cascavilla, Nicola; Guolo, Fabio; Fraternali Orcioni, Giulio; Carella, Angelo M

    2014-03-01

    (90) Yttrium ((90) Y)-Ibritumomab-Tiuxetan combines the targeting advantage of a monoclonal antibody with the radiosensitivity of Follicular Lymphoma (FL). Previous studies showed that 90Y-IT is safe and effective in relapsed/refractory indolent FL, irrespective of prior treatment with rituximab. This multicentre trial aimed to evaluate the safety and the efficacy of "upfront" single-agent ((90) Y)-Ibritumomab-Tiuxetan in advanced-stage FL. The primary objective was the incidence of responses in terms of complete (CR) and partial remission (PR). Fifty patients with stage II "bulky", III or IV FL received a single treatment course with ((90) Y)-Ibritumomab-Tiuxetan as initial therapy. The median age was 60 years. Bone marrow involvement (<25%) was observed in 24 patients (48%) and 7 (14%) had an elevated lactate dehydrogenase level. The overall response (ORR) and CR rates were 94% and 86%, respectively with a median follow-up of 38·8 months. The median progression-free survival (PFS) was not reached, whereas the 3-year estimated PFS and overall survival (OS) rate was 63·4% and 90%, respectively. Grade 3/4 neutropenia and thrombocytopenia occurred in 30% and 26% of patients respectively; none experienced grade 3/4 non-haematological toxicity. No cases of secondary haematological malignancies were observed. ((90) Y)-Ibritumomab-Tiuxetan was demonstrated to be highly effective and safe as first-line treatment for advanced-stage FL. PMID:24344981

  20. Phase I trial of (90)Y-ibritumomab tiuxetan in patients with relapsed B-cell non-Hodgkin's lymphoma following high-dose chemotherapy and autologous stem cell transplantation.

    PubMed

    Vose, Julie M; Bierman, Philip J; Loberiza, Fausto R; Bociek, Robert G; Matso, Daniel; Armitage, James O

    2007-04-01

    Between January 2001 and September 2005, 19 patients with progressive B-cell non-Hodgkin's lymphoma were treated with a cohort-specific dose of yttrium-90 ibritumomab tiuxetan (0.10 - 0.20 mCi/kg) to determine appropriate dosing in patients who had previously received high-dose chemotherapy and autologous stem cell transplantation (ASCT). Patients were required to have adequate end organ function and bone marrow status. Patients had been treated with a median of three prior therapies (range, 1 - 9). The median time from ASCT to radioimmunotherapy was 28 months. Hematologic toxicities were dose-limiting and included grade 3 - 4 thrombocytopenia (53%), neutropenia (32%), and anemia (21%). The majority of grade 3 - 4 events occurred at the 0.2 mCi/kg dose level. Nine patients responded (complete response, complete response unconfirmed, or partial response) to the therapy. At a median follow-up of 37 months, the 1-year event-free and overall survival rates were 26% and 57%, respectively. A dose of 0.2 mCi/kg ibritumomab tiuxetan is safe and effective for patients with progressive disease after high-dose chemotherapy and ASCT. PMID:17454625

  1. [Radioimmunotherapy with yttrium-90 ibritumomab tiuxetan. Clinical considerations, radiopharmacy, radiation protection, perspectives].

    PubMed

    Schomäcker, K; Dietlein, M; Schnell, R; Pinkert, J; Eschner, W; Zimmermanns, B; Fischer, T; Engert, A; Schicha, H

    2005-01-01

    90Y-ibritumomab tiuxetan (Zevalin) is currently approved for radioimmunotherapy of patients with relapsed or refractory follicular non-Hodgkin's lymphoma pretreated with rituximab. Future directions are the combined use of 90Y-ibritumomab tiuxetan as part of the initial treatment and as first-line multi-agent therapy of relapsed disease. Current studies investigate patients with other than follicular indolent histologies, e. g. diffuse large cell lymphoma. Labelling of 90Y ibritumomab tiuxetan is a safe procedure, the radiochemical purity is not disturbed by a higher room temperature or by metallic impurity. Quality control is recommended by thin layer chromatography (TLC), strips >15 cm are favourable. TLC cannot distinguish between the correctly radiolabelled antibodies and radiocolloid impurity. If necessary, additional HPLC should be performed. Radiocolloid impurities are absorbed to the solid phase and do not reach the eluate. If the radiochemical purity test is insufficient (<95%), the additional cleaning using EconoPac 10 DG columns (Biorad, Hercules, CA, USA) is a reliable procedure to reduce the percentage of free radionuclide. However, this procedure is not part of the approval. PMID:16163413

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

    PubMed

    Rizzieri, David

    2016-09-01

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

  3. Antilymphoma treatments given subsequent to Yttrium 90 ibritumomab tiuxetan are feasible in patients with progressive non-Hodgkin's lymphoma: a review of the literature.

    PubMed

    Ansell, Stephen M; Schilder, Russell J; Pieslor, Peter C; Gordon, Leo I; Emmanouilides, Christos; Vo, Katie; Czuczman, Myron S; Witzig, Thomas E; Theuer, Charles; Molina, Arturo

    2004-12-01

    Yttrium 90-labeled ibritumomab tiuxetan is approved for the treatment of patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma (NHL). To date, the efficacy of repeated courses of radioimmunoconjugate treatment in patients whose disease has progressed has not been studied as a formal endpoint in a clinical trial setting. However, several clinical studies have been conducted in patients with progressive NHL who had previously received 90Y ibritumomab tiuxetan. A retrospective review of these studies has shown that clinical responses have been achieved with all types of subsequent treatment with no apparent impact on their efficacy. In addition, no significant differences in toxicities with subsequent therapies have been observed between patients who had previously received 90Y ibritumomab tiuxetan therapy and those who had not. These findings suggest that patients previously treated with 90Y ibritumomab tiuxetan can feasibly undergo other forms of treatment for progressive NHL, and that a clinical response to further treatment options is not precluded by administration of 90Y ibritumomab tiuxetan. PMID:15636698

  4. Yttrium 90-labeled ibritumomab tiuxetan radioimmunotherapy produces high response rates and durable remissions in patients with previously treated B-cell lymphoma.

    PubMed

    Gordon, Leo I; Witzig, Thomas; Molina, Arturo; Czuczman, Myron; Emmanouilides, Christos; Joyce, Robin; Vo, Katie; Theuer, Charles; Pohlman, Brad; Bartlett, Nancy; Wiseman, Greg; Darif, Mohamed; White, Christine

    2004-09-01

    We report updated time-to-event variables of a phase III randomized study comparing yttrium 90-labeled ibritumomab with rituximab standard therapy in 143 rituximab-naive patients with relapsed or refractory low-grade, follicular, or transformed CD20+ non-Hodgkin's lymphoma (NHL). Most patients (79%) had follicular lymphoma. Patients were randomized to receive a single intravenous (I.V.) dose of 90Y ibritumomab tiuxetan 0.4 mCi/kg (n = 73) or rituximab 375 mg/m2 I.V. weekly for 4 doses (n = 70). The radioimmunotherapy group was pretreated with 2 rituximab doses (250 mg/m2) to improve biodistribution and one dose of Indium 111-labeled ibritumomab tiuxetan for imaging. The overall response rate was 80% versus 56% (P = 0.002) and complete response (CR)/CR unconfirmed (CRu) rates were 34% for 90Y ibritumomab tiuxetan versus 20% for rituximab. With a median follow-up of 44 months, the data are mature as all ongoing patients in both groups exceeded the median Kaplan-Meier estimated time to progression (TTP), duration of response (DR), and time to next therapy. Although this study was not powered to detect differences in time-to-event variables, the results from this randomized trial demonstrate trends toward longer median TTP (15 vs. 10.2 months; P = 0.07), DR (16.7 vs. 11.2 months; P = 0.44) and time to next therapy (21.1 vs. 13.8 months; P = 0.27) in follicular NHL patients treated with 90Y ibritumomab tiuxetan compared with the rituximab control arm. In patients achieving a CR/CRu, the median TTP was 24.7 months for patients treated with 90Y ibritumomab tiuxetan compared with 13.2 months for rituximab-treated patients (P = 0.41), and ongoing responses of > 5 years have been observed. These results confirm that 90Y ibritumomab tiuxetan produces high response rates and durable remissions in patients with previously treated low-grade, follicular, and transformed NHL. PMID:15453924

  5. Ibritumomab tiuxetan radioimmunotherapy for patients with relapsed or refractory non-Hodgkin lymphoma and mild thrombocytopenia: a phase II multicenter trial.

    PubMed

    Wiseman, Gregory A; Gordon, Leo I; Multani, Pratik S; Witzig, Thomas E; Spies, Stewart; Bartlett, Nancy L; Schilder, Russell J; Murray, James L; Saleh, Mansoor; Allen, Roberta S; Grillo-López, Antonio J; White, Christine A

    2002-06-15

    Mildly thrombocytopenic patients with relapsed or refractory low-grade non-Hodgkin lymphoma (NHL) have an increased risk of chemotherapy-induced myelosuppression following treatment. The safety and efficacy of radioimmunotherapy with a reduced dose of (90)Y ibritumomab tiuxetan (0.3 mCi/kg [11 MBq/kg]; maximum 32 mCi [1.2 GBq]) was evaluated in 30 patients with mild thrombocytopenia (100-149 x 10(9) platelets/L) who had advanced, relapsed or refractory, low-grade, follicular, or transformed B-cell NHL. The ibritumomab tiuxetan regimen included an infusion of rituximab (250 mg/m(2)) and injection of (111)In ibritumomab tiuxetan (5 mCi [185 MBq]) for dosimetry evaluation, followed 1 week later with rituximab (250 mg/m(2)) and (90)Y ibritumomab tiuxetan (0.3 mCi/kg [11 MBq/kg]). Patients (median age, 61 years; 90% stage III/IV at study entry; 83% follicular lymphoma; and 67% with bone marrow involvement) had a median of 2 prior therapy regimens (range, 1-9). Estimated radiation-absorbed doses were well below the study-defined maximum allowable for all 30 patients. With the use of the International Workshop criteria for NHL response assessment, the overall response rate was 83% (37% complete response, 6.7% complete response unconfirmed, and 40% partial response). Kaplan-Meier estimated median time to progression (TTP) was 9.4 months (range, 1.7-24.6). In responders, Kaplan-Meier estimated median TTP was 12.6 months (range, 4.9-24.6), with 35% of data censored. Toxicity was primarily hematologic, transient, and reversible. The incidence of grade 4 neutropenia, thrombocytopenia, and anemia was 33%, 13%, and 3%, respectively. Reduced-dose ibritumomab tiuxetan is safe and well tolerated and has significant clinical activity in this patient population. PMID:12036859

  6. Radiation dosimetry results from a Phase II trial of ibritumomab tiuxetan (Zevalin) radioimmunotherapy for patients with non-Hodgkin's lymphoma and mild thrombocytopenia.

    PubMed

    Wiseman, Gregory A; Leigh, Bryan R; Erwin, William D; Sparks, Richard B; Podoloff, Donald A; Schilder, Russell J; Bartlett, Nancy L; Spies, Stewart M; Grillo-López, Antonio J; Witzig, Thomas E; White, Christine A

    2003-04-01

    This was a 30-patient Phase II trial of reduced-dose (90)Y ibritumomab tiuxetan (Zevalin) RIT for patients with low-grade, follicular, or transformed B-cell NHL and mild thrombocytopenia. Patients were given an imaging dose of (111)In-labeled ibritumomab tiuxetan for dosimetry measurements. One week later, patients were administered a therapeutic dose of 0.3 mCi/kg (11 MBq/kg) (90)Y ibritumomab tiuxetan. Both (111)In- and (90)Y-labeled ibritumomab tiuxetan doses were preceded by an infusion of 250 mg/m(2) rituximab (Rituxan, MabThera) an unlabeled chimeric anti-CD20 antibody, to clear peripheral blood B cells and improve biodistribution of the radiolabeled antibody. For all 30 patients, normal organ and red marrow radiation absorbed doses were well below protocol-defined limits of 2000 cGy and 300 cGy, respectively. Median radiation absorbed doses were 48 cGy to red marrow (range: 6.5-95 cGy), 393 cGy to liver (range: 92-1581 cGy), 522 cGy to spleen (range: 165-1711 cGy), 162 cGy to lungs (41-295 cGy), and 14 cGy to kidneys (0.03-65 cGy). Though most correlative analyses were negative, certain analyses demonstrated a statistically significant correlation between the severity or duration of thrombocytopenia and pharmacokinetic or dosimetric parameters. These correlations were not consistent across the total patient population, and therefore, could not be exploited to predict hematologic toxicity. PMID:12804042

  7. Unsuspected pneumonia detected by increased lung uptake on 111In-ibritumomab tiuxetan scan.

    PubMed

    Hwang, Misun; Joyce, Judith M; Klein, Herbert; Hou, Jing-Zhou

    2012-10-01

    99Y-ibritumomab tiuxetan (Zevalin) is a CD20-targeted radioimmunotherapy for the treatment of B-cell non-Hodgkin lymphoma approved by the FDA in 2002. The acquisition of an 111In ibritumomab tiuxetan scan (bioscan) to confirm normal biodistribution before treatment with 99Y-ibritumomab tiuxetan was initially required in the United States until November 2011. This is the first documented example of abnormal biodistribution due to unsuspected pneumonia detected by increased lung uptake on the bioscan. The pneumonia was treated and resolved before 99Y Zevalin, avoiding potential harm and indicating that a screening chest x-ray may be appropriate when a bioscan is not performed. PMID:22955077

  8. 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

  9. Retreatment with yttrium-90 ibritumomab tiuxetan in patients with B-cell non-Hodgkin's lymphoma.

    PubMed

    Shah, Jatin; Wang, Wenquan; Harrough, V Douglas; Saville, Wayne; Meredith, Ruby; Shen, Sui; Mueh, John; Lister, John; Jasthy, Sri; Maggass, Gregory; McKay, Charles; Krumdieck, Richard; Tharp, Morgan; Winter, Christine; Gregory, Stephanie; Buchholz, William; Awasthi, Sanjay; Jacobs, Samuel; Chung, Harold; Egner, James; Lobuglio, Albert F; Forero, Andres

    2007-09-01

    There is no data on safety and efficacy of a second course of ibritumomab tiuxetan. In this work, data on patients with B-cell NHL who were treated with two courses of ibritumomab tiuxetan were analyzed. Eighteen such patients were analyzed (age: 58 years, 48 - 91), with a median of four prior regimens (1 - 7), stem cell transplantation (n = 5), and radiation therapy (n = 6). After the first course, G3/4 neutropenia and thrombocytopenia was 35% and 41%; overall response rate (ORR) was 89%; time between courses was 16.6 months (6.0 - 42.7). After the second course, the incidence of G3/4 neutropenia and thrombocytopenia was 28% and 44%; and ORR 77%. There were no infectious or bleeding complications, secondary myelodysplastic syndromes, or leukemias. Retreatment with the ibritumomab tiuxetan regimen was well tolerated, with a safety profile similar to that of the first course. To conclude, patients who benefited from the first course of ibritumomab tiuxetan can benefit from retreatment. PMID:17786709

  10. Pilot trial of yttrium-90 ibritumomab tiuxetan consolidation following rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone chemotherapy in patients with limited-stage, bulky diffuse large B-cell lymphoma.

    PubMed

    Yang, Deok-Hwan; Kim, Won Seog; Kim, Seok Jin; Kim, Jin Seok; Kwak, Jae-Yong; Chung, Joo Seop; Oh, Sung Yong; Suh, Cheolwon; Lee, Je-Jung

    2012-05-01

    The clinical efficacy and safety of yttrium-90 ((90)Y)-ibritumomab tiuxetan consolidation treatment following rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) chemotherapy was investigated in patients with limited-stage and bulky diffuse large B-cell lymphoma (DLBCL). This prospective, multi-center, pilot trial included 21 patients who were newly diagnosed with stage I/II, bulky DLBCL and achieved a complete or partial response after six cycles of R-CHOP. The median size of bulky disease was 10.0 × 7.0 cm. After a median follow-up of 28.8 months, the overall response rate after (90)Y-ibritumomab tiuxetan consolidation treatment was 80.9%, including 4.8% partial response. However, six patients (28.6%) experienced a progression or relapse. The 3-year overall and progression-free survival rates were 85.0 ± 8.0% and 75.0 ± 9.7%, respectively. Grade 3-4 adverse events were mainly hematologic toxicities, such as thrombocytopenia (35%) and neutropenia (60%). One patient experienced grade 3 Pneumocystis carinii pneumonitis. Thus, (90)Y-ibritumomab tiuxetan consolidation following six cycles of R-CHOP resulted in an acceptable response with tolerable toxicity in patients with limited-stage and bulky DLBCL. PMID:22035417

  11. 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

  12. P53-Based Strategy for Protection of Bone Marrow from Y-90 Ibritumomab Tiuxetan

    PubMed Central

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

    2015-01-01

    Purpose The main drawbacks of radioimmunotherapy have been severe hematological toxicity and potential development of myelodysplastic syndrome and secondary leukemia. p53 activation is a major pathway by which normal tissues respond to DNA damaging agents such as chemotherapy and radiotherapy, resulting in injuries and pathological consequences. This pathway is separate from the tumor suppressor pathway of p53. We have previously reported that the use of low-dose arsenic (LDA) temporarily and reversibly suppresses p53 activation, thereby ameliorating normal tissue toxicity from 5-FU and X-ray. 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. Method and Materials Mice were subject to LDA pretreatment for three days, followed by Y-90 ibritumomab tiuxetan treatment. Both dose-course (10, 25, 50, 100 and 200 μCi) and time-course (6h, 24h, 72h, 1wk and 2wk) experiments were performed. The response of bone marrow cells to LDA was examined by examining the expression of NFκB, Glut1 and Glut3. H&E, γ-H2AX, and TUNEL staining was employed 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 damages 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 pretreatment did not have any detectable effect on either tumor growth or Y-90 ibritumomab tiuxetan (200 μCi)-induced tumor suppression. Conclusions

  13. 90Yttrium Ibritumomab Tiuxetan Therapy in Allogeneic Transplantation in B-cell Lymphoma with Extensive Marrow involvement and Chronic Lymphocytic Leukemia: Utility of Pre-transplantation Biodistribution

    PubMed Central

    Matesan, Manuela; Rajendran, Joseph; Press, Oliver W.; Maloney, David G.; Storb, Rainer F.; Cassaday, Ryan D.; Pagel, John M.; Oliveira, George; Gopal, Ajay K.

    2014-01-01

    Biodistribution data to-date using 111In- ibritumomab tiuxetan has been initially obtained in patients with <25% lymphomatous bone marrow involvement and adequate hematopoietic synthetic function. In this article we present the results of an analysis of the biodistribution data obtained from a cohort of patients with extensive bone marrow involvement, baseline cytopenias, and chronic lymphocytic leukemia (CLL). Thirty nine patients with diagnosis of B-cell lymphoma or CLL expressing the CD20 antigen, who had failed at least one prior regimen, and had evidence of persistent disease were included in this analysis, however only 38 of these completed the treatment. Semiquantitative analysis of the biodistribution was performed using regions of interest (ROI) over the liver, lungs, kidneys, spleen and sacrum. The observed interpatient variability including higher liver uptake in 4 patients is discussed. No severe solid organs toxicity was observed at the maximum administered activity of 1184 MBq (32 mCi) 90Yibritumomab tiuxetan. After accounting for differences in marrow involvement, patients with CLL exhibit comparable biodistributions to those with B-NHL. We found that the estimated sacral marrow uptake on 48 hour images in patients with bone marrow involvement may be an indicator of bone marrow involvement. There was no correlation between tumor visualization and response to treatment. These data suggest that the imaging step is not critical when the administered activity is below 1184 MBq (32 mCi). However our analysis confirms that the semiquantitative imaging data can be used to identify patients at risk for liver toxicity when higher doses of 90Y- ibritumomab tiuxetan are used. Patients with CLL can have excellent targeting of disease by 111Inibritumomab tiuxetan, indicating potential efficacy in this patient population. PMID:25076159

  14. A phase 1/2 trial of high-dose yttrium-90-ibritumomab tiuxetan in combination with high-dose etoposide and cyclophosphamide followed by autologous stem cell transplantation in patients with poor-risk or relapsed non-Hodgkin lymphoma

    PubMed Central

    Nademanee, Auayporn; Forman, Stephen; Molina, Arturo; Fung, Henry; Smith, David; Dagis, Andy; Kwok, Cheuk; Yamauchi, Dave; Anderson, Anne-Line; Falk, Peter; Krishnan, Amrita; Kirschbaum, Mark; Kogut, Neil; Nakamura, Ryotaro; O'Donnell, Margaret; Parker, Pablo; Popplewell, Leslie; Pullarkat, Vinod; Rodriguez, Roberto; Sahebi, Firoozeh; Smith, Eileen; Snyder, David; Stein, Anthony; Spielberger, Ricardo; Zain, Jasmine; White, Christine; Raubitschek, Andrew

    2005-01-01

    We conducted a phase 1/2 trial of high-dose 90Y-ibritumomab tiuxetan in combination with high-dose etoposide (VP-16) 40 to 60 mg/kg (day -4) and cyclophosphamide 100 mg/kg (day -2) followed by autologous stem cell transplantation (ASCT) in 31 patients with CD20+ non-Hodgkin lymphoma (NHL). Patients underwent dosimetry (day -21) with 5 mCi (185 MBq) 111In-ibritumomab tiuxetan following 250 mg/m2 rituximab, followed a week later by 90Y-ibritumomab tiuxetan to deliver a target dose of 1000 cGy to highest normal organ. Bone marrow biopsy was done on day -7 to estimate radiation dose and stem cells were reinfused when the radiation dose was estimated to be less than 5 cGy. The median 90Y-ibritumomab tiuxetan dose was 71.6 mCi (2649.2 MBq; range, 36.6-105 mCi; range, 1354.2-3885 MBq). Histology included follicular lymphoma (n = 12), diffuse large B-cell (n = 14), and mantle cell (n = 5). The median number of prior chemo-therapy treatments was 2. The treatment was well tolerated. The median times to reach an absolute neutrophil count greater than 500/μL and platelet count more than 20 000/μL were 10 days and 12 days, respectively. There were 2 deaths and 5 relapses. At a median follow-up of 22 months, the 2-year estimated overall survival and relapse-free survival rates are 92% and 78%, respectively. We conclude that high-dose 90Y-ibritumomab tiuxetan can be combined safely with high-dose etoposide and cyclophosphamide without an increase in transplant-related toxicity or delayed engraftment. (Blood. 2005;106:2896-2902) PMID:16002426

  15. RIT with Y90-Ibritumomab Tiuxetan in Follicular Non-Hodgkin Lymphoma: Evaluation of Recent Outcomes in a Single Institution

    PubMed Central

    Andrade Campos, Marcio Miguel; Montes Limón, Anel E.; Grasa, Jose María; Lievano, Paola; Baringo, Teresa; Giraldo, Pilar

    2012-01-01

    Background. Based on historical data we reviewed our hospital clinical database to analyse our updated information and therapy outcomes of follicular non-Hodgkin lymphoma (F-NHL) patients treated with 90Y-Ibritumomab tiuxetan. Patients and Methods. Between 2005 and 2011, 56 F-NHL patients were included in a clinical protocol conducted by a multidisciplinary team and treated in the same centre. All patients received 0.3 or 0.4 mCi/kg IV (88%) of 90Y-IT; response evaluation was performed 12 weeks after. Results. M/F 44.6%/55.4%, mean age 61.45 years (30–85); ECOG 0-1 96.9%. According to FLIPI score, distribution were good: 58.5%, intermediate: 29.2%, and poor: 12.3%. Previous therapies: >2: 40% (26). ORR was 94.6% (53/56). CR: 85.7%; CR according to previous disease: relapsed disease: 90% (27/30), refractory disease: 42.85% (3/7), consolidation with CR: 92.85% (13/14), and consolidation with PR: 100% (5/5). Global PR and NR were 8.9% (5) and 5.3% (3), respectively. Mean OS 63.86 months with a mean follow-up time of 57 months (2–73). Mean TTP: 52.65 months (95% CI: 43.83–61.48). Median OS and TTP were not achieved. No hospital submissions or deaths were registered. Conclusions. This study confirms the safety and high efficacy of 90Y-IT in F-NHL patients, RIT in early stage of disease could improve outcomes. PMID:23049552

  16. Autologous stem cell transplantation after conditioning with yttrium-90 ibritumomab tiuxetan plus BEAM in refractory non-Hodgkin diffuse large B-cell lymphoma: results of a prospective, multicenter, phase II clinical trial

    PubMed Central

    Briones, Javier; Novelli, Silvana; García-Marco, José A.; Tomás, José F.; Bernal, Teresa; Grande, Carlos; Canales, Miguel A.; Torres, Antonio; Moraleda, José M.; Panizo, Carlos; Jarque, Isidro; Palmero, Francisca; Hernández, Miguel; González-Barca, Eva; López, Dulce; Caballero, Dolores

    2014-01-01

    Lymphoma patients with persistent disease undergoing autologous transplantation have a very poor prognosis in the rituximab era. The addition of radioimmunotherapy to the conditioning regimen may improve the outcome for these patients. In a prospective, phase 2 study, we evaluated the safety and efficacy of the addition of 90Y-ibritumomab tiuxetan to the conditioning chemotherapy in patients with refractory diffuse large B-cell lymphoma. Thirty patients with induction failure (primary refractory; n=18) or refractory to salvage immunochemotherapy at relapse (n=12) were included in the study. The median age of the patients was 53 years (range, 25–67). All patients were given 90Y-ibritumomab tiuxetan at a fixed dose of 0.4 mCi/kg (maximum dose 32 mCi) 14 days prior to the preparative chemotherapy regimen. Histological examination showed that 22 patients had de novo diffuse large B-cell lymphoma and eight had transformed diffuse large B-cell lymphoma. All patients had persistent disease at the time of transplantation, with 25 patients considered to be chemorefractory. The median time to neutrophil recovery (>500 white blood cells/μL) was 11 days (range, 9–21), while the median time to platelet recovery (>20,000 platelets/μL) was 13 days (range, 11–35). The overall response rate at day +100 was 70% (95% CI, 53.6–86.4) with 60% (95% CI, 42.5–77.5) of patients obtaining a complete response. After a median follow-up of 31 months for alive patients (range, 16–54), the estimated 3-year overall and progression-free survival rates are 63% (95% CI, 48–82) and 61% (95% CI, 45–80), respectively. We conclude that autologous transplantation with conditioning including 90Y-ibritumomab tiuxetan is safe and results in a very high response rate with promising survival in this group of patients with refractory diffuse large B-cell lymphoma with a very poor prognosis. Study registered at European Union Drug Regulating Authorities Clinical Trials (EudraCT) N. 2007

  17. 90-yttrium-ibritumomab tiuxetan consolidation of fludarabine, mitoxantrone, rituximab in intermediate/high-risk follicular lymphoma: updated long-term results after a median follow-up of 7 years.

    PubMed

    Casadei, Beatrice; Pellegrini, Cinzia; Pulsoni, Alessandro; Annechini, Giorgia; De Renzo, Amalia; Stefoni, Vittorio; Broccoli, Alessandro; Gandolfi, Letizia; Quirini, Federica; Tonialini, Lorenzo; Morigi, Alice; Argnani, Lisa; Zinzani, Pier Luigi

    2016-06-01

    Radioimmunotherapy (RIT) after an induction phase with conventional chemoimmunotherapy became an attractive strategy of consolidation for patients with advanced follicular lymphoma: in particular, in many studies RIT was represented by yttrium-90-ibritumomab tiuxetan ((90) Y-IT). Independently by the different front-line treatment, updates on the long-term follow-up of these studies are needed because the disease course of follicular lymphoma is characterised by multiple relapses and progressively shorter durations of response. We report updated long-term efficacy and toxicity results of a multicenter phase II study on sequential treatment with four cycles of fludarabine, mitoxantrone, and rituximab followed by (90) Y-IT as front-line therapy for untreated patients with intermediate/high-risk follicular lymphoma. With a median follow-up of 84 months, only 19/49 (38.8%) complete response patients relapsed, yielding an estimated long-term disease-free survival of 62.6%. The 7-year overall survival was 72.7%. Four (7.3%) second acute myeloid leukemia occurred, with a median time following RIT of 42 months. A relevant patients' responsiveness to subsequent therapies occurred: approximately 65% of relapsed patients obtained a good clinical response after the second-line treatment. These data represented the first evidence of a real role even in the long period of 90Y-IT after a fludarabine-containing regimen plus rituximab in the treatment of high-risk follicular lymphoma. PMID:26990782

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

    PubMed Central

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

    2015-01-01

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

  19. Bortezomib may be safely combined with Y-90-ibritumomab tiuxetan in patients with relapsed/refractory follicular non-Hodgkin lymphoma: a phase I trial of combined induction therapy and bortezomib consolidation.

    PubMed

    Roy, Rupali; Evens, Andrew M; Patton, David; Gallot, Lillia; Larson, Annette; Rademaker, Alfred; Cilley, Jeffrey; Spies, Stewart; Variakojis, Daina; Gordon, Leo I; Winter, Jane N

    2013-03-01

    Preclinical studies suggest that bortezomib, through inhibition of nuclear factor-κB (NF-κB) activation, may enhance the effects of radioimmunotherapy. This phase I trial was designed to determine the maximum tolerated dose (MTD) of weekly bortezomib induction combined with Y-90-ibritumomab tiuxetan followed at the time of count recovery by weekly bortezomib consolidation in patients with relapsed/refractory follicular or transformed non-Hodgkin lymphoma. Grade 3 or 4 toxicities were observed in eight of nine treated patients, and all but one of these toxicities were hematologic. One patient had grade 3 cardiotoxicity. A dose limiting toxicity (DLT) of grade 4 thrombocytopenia was observed in two of three patients treated with bortezomib at 1.6 mg/m(2), resulting in a MTD of 1.3 mg/m(2). The overall response rate was 89% (two complete response [CR], six partial response [PR], one stable disease [SD]), with a median progression-free survival of 6.5 months (range: 3-22.5+ months). A phase II trial at the MTD is under way to better define the toxicity and effectiveness of this regimen. PMID:22906230

  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. PMID:23573825

  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. Ibritumomab Injection

    MedlinePlus

    ... have received ibritumomab injection.do not have any vaccinations without talking to your doctor.you should know ... cells) and myelodysplastic syndrome (condition in which blood cells do not ... online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

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

    ClinicalTrials.gov

    2016-06-15

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

  5. 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

  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. 90Y-labeled monoclonal antibodies for cancer therapy.

    PubMed

    Washburn, L C; Hwa Sun, T T; Crook, J E; Byrd, B L; Carlton, J E; Hung, Y W; Steplewski, Z S

    1986-01-01

    Monoclonal antibody 17-1A, which has specificity for colorectal carcinoma, was labeled with 90Y (10-20% radiolabeling yield). Tissue distribution studies in tumor-bearing nude mice were carried out. 90Y-labeled 17-1A showed good uptake in the SW 948 colon carcinoma cell line. However, 90Y-labeled A5C3, a monoclonal antihepatitis virus antibody studied as a control, showed similar uptake in this tumor. Neither antibody was taken up well by a WM-9 melanoma. It is believed that the loss of specificity observed is due to the low specific activity of the 90Y-labeled monoclonal antibody preparations used. This hypothesis is supported by radioimmunoassay data. PMID:3793501

  9. 90Y labeled phosphorodiamidate morpholino oligomer for pretargeting radiotherapy.

    PubMed

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

    2011-12-21

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

  10. A 90Y labeled phosphorodiamidate morpholino oligomer for pretargeting radiotherapy

    PubMed Central

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

    2011-01-01

    While 188Re has been used successfully in mice for tumor radiotherapy by MORF/cMORF pretargeting, previous radiolabeling of the 18 mer amine-derivatized cMORF with 90Y, a longer physical half life nuclide, was not very successful. After developing a method involving a pre-purification heating step during conjugation that increases labeling efficiency and label stability, the biodistribution of 90Y-DOTA-Bn-SCN-cMORF was measured in normal mice and in MORF-CC49 pretargeted mice that bear LS174T tumors. Absorbed radiation doses were then estimated and compared to those estimated for 188Re. The pharmacokinetics of the 90Y-DOTA-cMORF in normal mice and in the pretargeted nude mice was similar to that observed previously with 99mTc- and 188Re-MAG3-cMORFs. While the 90Y-DOTA-cMORF cleared rapidly from normal tissues, tumor clearance was very slow and tumor radioactivity accumulation was constant for at least 7 days such that the tumor/blood (T/B) ratio increased linearly from 6 to 25 over this period. Therefore by extrapolation, normal tissue toxicities following administration of therapeutic doses of 90Y may be comparable to that observed for 188Re in which the T/B increased from 5 to 20. In conclusion, radiolabeling of DOTA-cMORF with 90Y was improved by introducing a prepurification heating step during conjugation. The 90Y-DOTA-cMORF provided a similar T/B ratio and biodistribution to that of 188Re-MAG3-cMORF and retained well in the tumor pretargeted with MORF-CC49. Because of the longer physical half life, the T/NT absorbed radiation dose ratios were improved in most organs and especially in blood. PMID:21985267

  11. 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

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

    PubMed Central

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

    2016-01-01

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

  13. 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

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

    SciTech Connect

    Dezarn, William A.; Kennedy, Andrew S.

    2007-06-15

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

  15. 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.

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

    PubMed Central

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

    2015-01-01

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

  17. 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.

  18. 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

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

    ClinicalTrials.gov

    2016-07-08

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

  20. 90Sr content in 90Y-labeled SIR-spheres and Zevalin.

    PubMed

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

    2014-11-01

    Three different 90Y internally administered radionuclide therapies are currently used in both standard-of-care and clinical trial procedures atMD Anderson Cancer Center. TheraSphere and SIR-Spheres therapies utilize 90Y-labeled microspheres, while Zevalin is an 90Y-labeled radioimmunotherapeutic agent. Several publications have indicated radionuclidic impurities resulting from 90Y production methods. The 90Y in SIR-Spheres and Zevalin are produced from a 90Sr/90Y generator, which leaves measurable quantities of 90Sr in the final product. TheraSphere 90Y is produced in a nuclear reactor which results in a large number of impurities, most notably 88Y and 91Y. Product information sheets reference these impurities with specific limits given. These limits represent a tiny fraction of the total product activity, and in the case of TheraSphere and SIR-Spheres gamma-emitting impurities, this has been verified in the literature. An analysis of 90Sr impurities in SIR-Spheres and Zevalin is presented in this paper. Impurity quantities were found to be within the vendors’ documented limits. PMID:25272027

  1. Peptide receptor radionuclide therapy with 90Y-DOTATATE/90Y-DOTATOC in patients with progressive metastatic neuroendocrine tumours: assessment of response, survival and toxicity

    PubMed Central

    Vinjamuri, S; Gilbert, T M; Banks, M; McKane, G; Maltby, P; Poston, G; Weissman, H; Palmer, D H; Vora, J; Pritchard, D M; Cuthbertson, D J

    2013-01-01

    Background: Peptide receptor radionuclide therapy (PRRT) is an established treatment for patients with metastatic neuroendocrine tumours (NETs), although which factors are associated with an improved overall survival (OS) remains unclear. The primary aim of this study is to determine to what extent a radiological response to 90Y-DOTATOC/90Y-DOTATATE PRRT is associated with an improved OS. The association of biochemical and clinical response to OS were assessed as secondary outcome measures. Methods: A retrospective analysis was conducted on 57 patients: radiological response was classified using RECIST criteria, biochemical response was classified using WHO criteria and clinical response was assessed subjectively. Responses were recorded as positive response (PR), stable disease (SD) or progressive disease (PD), and survival analysed. Results: Radiological response was achieved in 71.5% (24.5% PR, 47% SD) and was associated with a greater OS (51 and 56 months, respectively), compared with PD (18 months). A biochemical or clinical response post PRRT were not associated with a statistically significant improvement in OS. However, when combined with radiological response a survival benefit was observed according to the number of outcomes (radiological, biochemical, clinical), in which a response was observed. Mild haematological toxicity was common, renal toxicity was rare. Conclusion: In patients with progressive metastatic NETs receiving 90Y-DOTATOC/90Y-DOTATATE PRRT, a radiological response with either a PR or a SD post therapy confers a significant OS benefit. PMID:23492685

  2. Evaluation of carrier added and no carrier added 90Y-EDTMP as bone seeking therapeutic radiopharmaceutical.

    PubMed

    Khalid, Muhammad; Bokhari, Tanveer Hussain; Ahmad, Mushtaq; Bhatti, Haq Nawaz; Iqbal, Munawar; Ghaffar, Abdul; Qadir, Muhammad Imran

    2014-07-01

    The optimum conditions to label ethylenediaminetetramethylene phosphonate (EDTMP) compound with (90)y as a potential candidate for bone metastases therapy were investigated. Yttrium-90 is a pure β-emitter and can be obtained by (89)y (n,γ) (90)y nuclear reaction in a reactor or from an in-house generator system ((90)sr(90)y). The preparation of (90)Y-EDTMPis described using (90)y, which was obtained from neutron irradiation of y2o3 as well as from a laboratory scale organic resin-based (90)sr--(90)y generator. Because of the radiolabeling yield of 90Y-EDTMP on ligand/metal molar ratio, incubation time and ph was evaluated. Under optimum parameters, the radiolabeling yields of (90)Y-EDTMP were <95% for no-carrier-added as well as carrier-added (90)y. The biodistribution of no-carrier-added and carrier-added (90)Y-EDTMP complexes in rats was identical. The results indicate that (90)y (carrier-added)-edtmp is also an effective bone pain palliation agent because of its rapid blood clearance, greater uptake in bones and little absorption in soft tissues. PMID:25015445

  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. 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

  5. Evaluation of quantitative planar 90Y bremsstrahlung whole-body imaging

    NASA Astrophysics Data System (ADS)

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

    2009-10-01

    With high-dose administration of 90Y labeled antibodies, it is possible to image 90Y without an admixture of 111In. We have earlier shown that it is possible to perform quantitative 90Y bremsstrahlung SPECT for dosimetry purposes with reasonable accuracy. However, whole-body (WB) activity quantification with the conjugate view method is not as time consuming as SPECT and has been the method of choice for dosimetry. We have investigated the possibility of using a conjugate view method where scatter-, backscatter- and septal-penetration compensations are performed by inverse filtering and attenuation correction is performed with a WB x-ray image, for total-body and organ activity quantification of 90Y. The method was evaluated using both Monte Carlo simulated scintillation camera images using realistic source distributions, and by an experimental phantom study. The method was evaluated in terms of image quality and accuracy of the activity quantification. The experimental phantom study was performed using the RSD torso phantom with 90Y activity uniformly distributed in the liver insert. A GE Discovery VH/Hawkeye system was used to acquire the image. The simulation study was performed for a realistic activity distribution in the NCAT anthropomorphic phantom where 90Y bremsstrahlung images were generated using the SIMIND MC program. Two different phantom configurations and two activity distributions were simulated. To mimic the RSD phantom experiment one simulation study was also made with 90Y activity located only in the liver. The SIMIND program was configured to resemble a GE Discovery VH/Hawkeye system. An x-ray projector program was used to generate whole-body x-ray images from the NCAT phantom for attenuation correction in the conjugate view method. Organ activities were calculated from ROIs that exactly covered the organs. Corrections for background activity, overlapping activity and source extension in the depth direction were applied on the ROI data. The total

  6. 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. PMID:18006608

  7. 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

  8. Development and evaluation of an improved quantitative 90Y bremsstrahlung SPECT method

    PubMed Central

    Rong, Xing; Du, Yong; Ljungberg, Michael; Rault, Erwann; Vandenberghe, Stefaan; Frey, Eric C.

    2012-01-01

    Purpose: Yttrium-90 (90Y) is one of the most commonly used radionuclides in targeted radionuclide therapy (TRT). Since it decays with essentially no gamma photon emissions, surrogate radionuclides (e.g., 111In) or imaging agents (e.g., 99mTc MAA) are typically used for treatment planning. It would, however, be useful to image 90Y directly in order to confirm that the distributions measured with these other radionuclides or agents are the same as for the 90Y labeled agents. As a result, there has been a great deal of interest in quantitative imaging of 90Y bremsstrahlung photons using single photon emission computed tomography (SPECT) imaging. The continuous and broad energy distribution of bremsstrahlung photons, however, imposes substantial challenges on accurate quantification of the activity distribution. The aim of this work was to develop and evaluate an improved quantitative 90Y bremsstrahlung SPECT reconstruction method appropriate for these imaging applications. Methods: Accurate modeling of image degrading factors such as object attenuation and scatter and the collimator-detector response is essential to obtain quantitatively accurate images. All of the image degrading factors are energy dependent. Thus, the authors separated the modeling of the bremsstrahlung photons into multiple categories and energy ranges. To improve the accuracy, the authors used a bremsstrahlung energy spectrum previously estimated from experimental measurements and incorporated a model of the distance between 90Y decay location and bremsstrahlung emission location into the SIMIND code used to generate the response functions and kernels used in the model. This improved Monte Carlo bremsstrahlung simulation was validated by comparison to experimentally measured projection data of a 90Y line source. The authors validated the accuracy of the forward projection model for photons in the various categories and energy ranges using the validated Monte Carlo (MC) simulation method. The

  9. [sup 90]Y-labeled antibody uptake by human tumor xenografts and the effect of systemic administration of EDTA

    SciTech Connect

    Rowlinson-Busza, G.; Snook, D.; Epenetos, A.A. )

    1994-03-30

    A human tumor xenograft model was used to compare the tumor and normal tissue uptake of a tumor-associated monoclonal antibody radiolabeled with [sup 125]I or [sup 90]Y. Nude mice bearing SC xenografts of the human colon adenocarcinoma, HT29, were injected with a mixture of [sup 125]I- and [sup 90]Y-DTPA-labeled AUA1 monoclonal antibody, which recognizes an antigen expressed on the surface of the tumor cells. In addition, the effect of systemic ethylenediaminetetraacetic acid (EDTA) administration on [sup 90]Y-labeled antibody clearance, tumor uptake of antibody and bone accumulation of [sup 90]Y was studied in a nude mouse model of intraperitoneal cancer. Both the absolute amount (%id[center dot]g[sup -1]) and the tumor:normal tissue ratios were superior for the [sup 90]Y-labeled antibody, compared with the iodinated antibody, with the notable exception of bone. These results suggest that [sup 90]Y is a preferable isotope to iodine for radioimmunotherapy of solid masses, but that myelotoxicity due to bone uptake of released [sup 90]Y will limit the radiation dose which can be given when DTPA is used to chelate the [sup 90]Y. The [sup 90]Y-labeled antibody showed similar serum stability in vitro in the presence or absence of EDTA after incubation for up to 48 h. In vivo, urine excretion of [sup 90]Y was significantly enhanced in mice receiving daily injections of 20 mg EDTA for 3 days, commencing 2 h after intraperitoneal antibody administration, compared with control mice. There was no significant difference in the tumor uptake of [sup 90]Y-labeled antibody in EDTA-treated and control mice at any time-point up to 9 days postinjection. However, the bone levels of [sup 90]Y were significantly reduced in EDTA-treated mice at all times from 1 to 9 days. Based on these results, it should be possible to increase the amount of [sup 90]Y-labeled antibody administered, by chelating the released [sup 90]Y with systemic EDTA to facilitate its excretion. 50 refs., 5 figs.

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

    PubMed

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

    2016-03-01

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

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

    NASA Astrophysics Data System (ADS)

    Kossert, Karsten; Nähle, Ole J.

    2015-09-01

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

  12. A Comparison of Techniques for 90Y PET/CT Image-Based Dosimetry Following Radioembolization with Resin Microspheres

    PubMed Central

    Pasciak, Alexander S.; Bourgeois, Austin C.; Bradley, Yong C.

    2014-01-01

    90Y PET/CT following radioembolization has recently been established as a viable diagnostic tool, capable of producing images that are both quantitative and have superior image quality than alternative 90Y imaging modalities. Because radioembolization is assumed to be a permanent implant, it is possible to convert quantitative 90Y PET image sets into data representative of spatial committed absorbed-dose. Multiple authors have performed this transformation using dose-point kernel (DPK) convolution to account for the transport of the high-energy 90Y β-particles. This article explores a technique called the Local Deposition Method (LDM), an alternative to DPK convolution for 90Y image-based dosimetry. The LDM assumes that the kinetic energy from each 90Y β-particle is deposited locally, within the voxel where the decay occurred. Using the combined analysis of phantoms scanned using 90Y PET/CT and ideal mathematical phantoms, an accuracy comparison of DPK convolution and the LDM has been performed. Based on the presented analysis, DPK convolution provides no detectible accuracy benefit over the LDM for 90Y PET-based dosimetry. For PET systems with 90Y resolution poorer than 3.25 mm at full-width and half-max using a small voxel size, the LDM may produce a dosimetric solution that is more accurate than DPK convolution under ideal conditions; however, image noise can obscure some of the perceived benefit. As voxel size increases and resolution decreases, differences between the LDM and DPK convolution are reduced. The LDM method of post-radioembolization dosimetry has the advantage of not requiring additional post-processing. The provided conversion factors can be used to determine committed absorbed-dose using conventional PET image analysis tools. The LDM is a recommended option for routine post-radioembolization 90Y dosimetry based on PET/CT imaging. PMID:24904832

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

    PubMed

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

    2016-07-01

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

  14. Multimodality imaging following 90Y radioembolization: a comprehensive review and pictorial essay.

    PubMed

    Atassi, Bassel; Bangash, Affaan K; Bahrani, Ammar; Pizzi, Giuseppi; Lewandowski, Robert J; Ryu, Robert K; Sato, Kent T; Gates, Vanessa L; Mulcahy, Mary F; Kulik, Laura; Miller, Frank; Yaghmai, Vahid; Murthy, Ravi; Larson, Andrew; Omary, Reed A; Salem, Riad

    2008-01-01

    Radioembolization with yttrium 90 (90Y) microspheres represents an emerging transarterial therapy for the treatment of liver malignancies that continues to generate interest in the medical community. The classic indication of treatment response is a reduction in tumor size; however, parenchymal changes (eg, necrosis, lack of enhancement, specific findings at positron emission tomography and functional magnetic resonance imaging) and other benign findings (pleural effusions, perivascular edema, contralateral hypertrophy, ring enhancement, perihepatic fluid, fibrosis) may occur following treatment, requiring proper image interpretation. With classic imaging findings and surrogates (time to progression, duration of response, disease-free interval), response rates range from 20% to 80% in patients treated for hepatocellular carcinoma or metastatic disease to the liver. Complications of 90Y radioembolization include cholecystitis, abscess, and bilomas and should be recognized early in the imaging follow-up of these patients. Radiologists who are involved in the posttreatment assessment of patients undergoing 90Y radioembolization should be familiar with the imaging findings and potential imaging pitfalls associated with this therapy. PMID:18203932

  15. 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.

  16. Treatment of Advanced Pancreatic Carcinoma with 90Y-Clivatuzumab Tetraxetan: A Phase I Single-Dose Escalation Trial

    PubMed Central

    Gulec, Seza A.; Cohen, Steven J.; Pennington, Kenneth L.; Zuckier, Lionel S.; Hauke, Ralph J.; Horne, Heather; Wegener, William A.; Teoh, Nick; Gold, David V.; Sharkey, Robert M.; Goldenberg, David M.

    2014-01-01

    Purpose Humanized antibody hPAM4 specifically binds a mucin glycoprotein expressed in pancreatic adenocarcinomas. This phase I study evaluated a single dose of 90Y-clivatuzumab tetraxetan (90Y-labeled hPAM4) in patients with advanced pancreatic cancer. Experimental Design Twenty-one patients (4 stage III; 17 stage IV) received 111In-hPAM4 for imaging and serum sampling before 90Y-hPAM4. Study procedures evaluated adverse events, safety laboratories, computed tomography (CT) scans, biomarkers, pharmacokinetics, radiation dosimetry, and immunogenicity (HAHA). Results 111In-hPAM4 showed normal biodistribution with radiation dose estimates to red marrow and solid organs acceptable for radioimmunotherapy and with tumor targeting in 12 patients. One patient withdrew before 90Y-hPAM4; otherwise, 20 patients received 90Y doses of 15 (n = 7), 20 (n = 9), and 25 mCi/m2 (n = 4). Treatment was well tolerated; the only significant drug-related toxicities were (NCI CTC v.3) grade 3 to 4 neutropenia and thrombocytopenia increasing with 90Y dose. There were no bleeding events or serious infections, and most cytopenias recovered to grade 1 within 12 weeks. Three patients at 25 mCi/m2 encountered dose-limiting toxicity with grade 4 cytopenias more than 7 days, establishing 20 mCi/m2 as the maximal tolerated 90Y dose. Two patients developed HAHA of uncertain clinical significance. Most patients progressed rapidly and with CA19-9 levels increasing within 1 month of therapy, but 7 remained progression-free by CT for 1.5 to 5.6 months, including 3 achieving transient partial responses (32%–52% tumor diameter shrinkage). Conclusion 90Y-Clivatuzumab tetraxetan was well tolerated with manageable hematologic toxicity at the maximal tolerated 90Y dose, and is a potential new therapeutic for advanced pancreatic cancer. PMID:21527562

  17. 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.

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

    PubMed

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

    2013-01-01

    Craniopharyngioma is a histologically benign and frequently cystic intracranial tumor. It may present aggressive behavior due to compression from nearby structures. Its therapeutic management is complicated because although surgery is the usual treatment of choice, it is not exempt of high morbidity and mortality and frequent tumor recurrence. In craniopharyngiomas with a significant cystic component,internal irradiation with radioactive isotopes is a therapeutic alternative to conventional treatments. We present the cases of four patients with cystic craniopharyngiomas who were treated with intracystic administration of 90Y-colloid, and their evolution after the treatment. PMID:23291161

  19. 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

  20. Cerenkov luminescence imaging of αv β6 integrin expressing tumors using (90) Y-labeled peptides.

    PubMed

    Satpati, Drishty; Hausner, Sven H; Bauer, Nadine; Sutcliffe, Julie L

    2014-07-01

    Cerenkov luminescence imaging (CLI) is an emerging preclinical molecular imaging modality that tracks the radiation emitted in the visible spectrum by fast moving charged decay products of radionuclides. The aim of this study was in vitro and in vivo evaluation of the two radiotracers, (90) Y-DOTA-PEG28 -A20FMDV2 ((90) Y-1) and (90) Y-DOTA-Ahx-A20FMDV2 ((90) Y-2) (>99% radiochemical purity, 3.7 GBq/µmol specific activity) for noninvasive assessment of tumors expressing the integrin αv β6 and their future use in tumor targeted radiotherapy. Cell binding and internalization in αv β6 -positive cells was (90) Y-1: 10.1 ± 0.8%, 50.3 ± 2.1%; (90) Y-2: 22.4 ± 1.7%, 44.7 ± 1.5% with <5% binding to αv β6 -negative control cells. Biodistribution studies showed maximum αv β6 -positive tumor uptake of the radiotracers at 1-h post injection (p.i.) ((90) Y-1: 0.64 ± 0.15% ID/g; (90) Y-2: 0.34 ± 0.11% ID/g) with high renal uptake (>25% ID/g at 24 h). Because of the lower tumor uptake and high radioactivity accumulation in kidneys (that could not be reduced by pre-administration of either lysine or furosemide), the luminescence signal from the αv β6 -positive tumor was not clearly detectable in CLI images. The studies suggest that CLI is useful for indicating major organ uptake for both radiotracers; however, it reaches its limitation when there is low signal-to-noise ratio. PMID:25042833

  1. Production of large quantities of 90Y by ion-exchange chromatography using an organic resin and a chelating agent.

    PubMed

    Castillo, Abmel Xiques; Pérez-Malo, Marylaine; Isaac-Olivé, Keila; Mukhallalati, Heyam; González, Edgar Casanova; Berdeguez, Mirta Torres; Díaz, Néstor Cornejo

    2010-11-01

    The performance of a system composed of an organic cation exchanger (Dowex 50Wx8) and a chelating agent (EDTA) previously described for the successful production of (90)Y via a (90)Sr/(90)Y generator is assessed under dynamic conditions. In an attempt to overcome the established limitation of ion-exchange resins for the separation of subcurie quantities of activity, (90)Y is repeatedly isolated from an 11.8-GBq (320 mCi) (90)Sr cow using a three-column tandem arrangement. The high recovery and radionuclidic purity obtained for (90)Y and the parameters of the separation (time, eluant concentration, pH and flow rate range) strongly suggest that Ci quantities of (90)Y can be handled satisfactorily by the ion-exchange method. No replacement or treatment of the cow, low waste generation and (90)Sr losses less than 0.1% after each run were observed during the present study which, in combination with the low cost of this resin, may result in an attractive alternate method for the production of large quantities of (90)Y. PMID:21055624

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

    PubMed

    Mitsuhashi, T; Sakanoue, M

    1977-10-01

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

  3. Prediction of tumor response to experimental radioimmunotherapy with {sup 90}Y in nude mice

    SciTech Connect

    Dillehay, L.E.; Mayer, R.; Zhang, Y.G.

    1995-09-30

    The purpose of this investigation was to identify those factors that predict variability in tumor response to {sup 90}Y-radioimmunotherapy based on measurement of incorporated activity and physical dimensions of individual tumors and to apply the concept of effective dose to radioimmunotherapy. Human colon carcinoma xenografts growing in nude mice were treated with anti-CEA antibodies labeled with {sup 90}Y directly or through a bispecific antibody/labeled hapten system. Tumor response was measured as the delay in growth to eight times the treatment volume. Noninvasive activity (based on bremsstrahlung radiation) and dimension measurements were made in these animals at several times after label injection. The following parameters were compared for their ability to predict individual tumor response: (a) injected activity, (b) injected activity times a factor based on average uptake as a function of volume, (c) in vivo activity per volume measured in each animal at a single time, (d) the integral over time of in vivo activity per volume in each animal, and (e) the minimum dose for each animal in a uniformly active ellipsoid whose total activity and dimensions varied over time the same as the tumor. After correcting for differences in injected activity, two parameters account for much of the variability in tumor response. One of these is the general trend of larger tumors to take up less activity per volume. Additional variability can be accounted for by the in vivo activity per volume measurements. The minimum dose as introduced here is likely to be useful in estimating the biologically effective dose delivered by each treatment. 27 refs., 5 figs., 1 tab.

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

    DOE PAGESBeta

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

    2015-03-18

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

  5. 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

  6. 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.

  7. Production of glass microspheres comprising 90Y and (177)Lu for treating of hepatic tumors with SPECT imaging capabilities.

    PubMed

    Poorbaygi, Hosein; Reza Aghamiri, Seyed Mahmoud; Sheibani, Shahab; Kamali-Asl, Alireza; Mohagheghpoor, Elham

    2011-10-01

    Our objective was to determine if glass microspheres impregnated with two radionuclides, (90)Y as source of therapeutic beta emissions and (177)Lu as source of diagnostic gamma emissions can be useful for SPECT imaging during or after application of the (90)Y microspheres for treating of hepatic tumors. The glass-based microspheres labeled with (89)Y and lutetium (YAS (Lu)) or (89)Y and ytterbium (YAS (Yb)) were prepared by the sol-gel process where sol droplets directly were formed to gel microspheres. Results of the neutron activation indicate that such a combination of glass, microspheres allow bio-distribution studies by SPECT imaging with high resolution. PMID:21723135

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

    SciTech Connect

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

    2014-05-15

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

  9. Post-mortem considerations of Yttrium-90 90Y microsphere therapy procedures.

    PubMed

    Nelson, Kevin; Vause, Paul E; Koropova, Polina

    2008-11-01

    Yttrium-90 (Y) microspheres, either in the form of resin beads or glass, are currently used to treat unresectable hepatocellular cancer. It has been discovered that long-lived contaminants, principally Eu and Eu, can be found in the waste generated by this procedure. Recently, at our medical facility, an elevated count rate was discovered on a deceased patient scheduled to have an autopsy and who had undergone Y microsphere therapy nearly 5 months previously. Regulatory issues arose when the family of the patient requested that the body of the deceased be cremated. In this particular instance the exposure rate from the body was below regulatory concern; however, the potential contamination and exposure from these long-lived contaminants cannot be ignored for individuals working in the autopsy room, funeral home embalming area, and crematorium. Information provided to potential patients in pamphlet form from the manufacturer failed to identify the existence of long-lived contaminants and possible difficulties associated with cremation. To ensure potential Y microsphere patients and family members are aware of the possible existence of long-lived contaminants, a patient consent and notification form has been developed. The proper disposal of residual material associated with these procedures, i.e., long-lived radioactive contaminants in explanted organs, pose additional difficulties. Further education of medical staff and funeral home directors with crematoriums is necessary. Close cooperation with the regulatory authority was instrumental in resolving this situation. PMID:18849708

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

    PubMed

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

    2016-10-01

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

  11. 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.

  12. 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

  13. 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

  14. Hepatectomy After Yttrium-90 (Y90) Radioembolization-Induced Liver Fibrosis.

    PubMed

    Maker, Ajay V; August, Carey; Maker, Vijay K; Weisenberg, Elliot

    2016-04-01

    An obese 55-year-old woman with nonalcoholic fatty liver disease presented 7 years after resection of a T3N1 ileal carcinoid tumor with an elevated chromogranin A, multifocal metastatic disease to the liver, and carcinoid syndrome. She underwent right hepatic artery yttrium-90 (Y90) radioembolization, followed a month later by selective Y90 treatment to segment IV. She then presented to our clinic 10 months later, remaining symptomatic with flushing, diarrhea, anxiety, myalgia, pain, and persistent night sweats despite Sandostatin administration. At least 11 tumors were identified in the right lobe of the liver and three in segment IV on liver-specific imaging. These lesions were stable over a year with no new lesions. At exploration, there was marked hypertrophy of the left lateral segment due to the yttrium-90 treatment of segments IV-VIII, corresponding with preoperative volumetrics predicting a functional liver remnant (FLR) of 40% after extended right hepatectomy. The right lobe and segment IV were fibrotic, hard, and visibly damaged. The gland had a thick, fibrotic capsule, and the parenchyma was dense, inflexible, and difficult to dissect, consistent with the previously reported morbidity of these operations. Extended right hepatectomy was performed. Final pathology demonstrated 15 foci of metastatic well-differentiated neuroendocrine carcinoma that were negative for necrosis, as was expected given her continued symptoms despite radioembolization. Numerous amorphous spheres, frequently in clusters, were present in segments IV-VIII in vessels and approximating tumors consistent with prior Y90 radioembolization. The patient had an uneventful post-operative recovery and remains symptom free on follow-up. Treatment options for metastatic tumors to the liver have increased in recent years and currently include radioembolization in selected patients. Surgical cytoreduction and complete metastasectomy continue to offer improvement in symptoms, quality of life, and

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

    SciTech Connect

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

    2013-10-01

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

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

    PubMed

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

    2014-01-01

    Anthropomorphic tissue-equivalent hand phantoms were achieved to measure the extremity dose involved in Zevalin (90)Y-labelling and patient delivering procedure for radioimmunotherapy treatment of non-Hodgkin lymphoma. The extremity doses to hands and wrists of operators were measured by using thermoluminescent detectors mounted on the developed phantoms. Measurements of chest- and lens-equivalent doses performed on a Rando phantom are also reported. PMID:23960242

  17. Inhibitory effects of 90Sr/90Y β-irradiation on alkali burn-induced corneal neovascularization in rats

    PubMed Central

    LIN, YUANQIANG; MA, QINGJIE; LIN, SHAN; ZHOU, HONGYAN; WEN, QIANG; GAO, SHI; CHENG, GUANGHUI

    2016-01-01

    The aim of the present study was to investigate the inhibitory effects of 90Sr-90Y β-irradiation in a rat model of alkali burn-induced corneal neovascularization (CNV). Alkali burn-induced CNV was induced in the right eyes of 30 female Wistar rats, which were randomly divided into the following three groups (n=10/group): i) The alkali burn control group, which received a balanced salt solution treatment; ii) group 1, which received treatment with angiogenesis inhibitors; and iii) group 2, which received 90Sr-90Y β-irradiation treatment. A further 10 female Wistar rats comprised a blank control group and received only balanced salt solution. Digital photographs of the corneas were acquired and the area of NV was calculated. In addition, the expression levels of matrix metalloproteinase (MMP)-9, vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)-1 and VEGFR-2 in alkali-burned rat corneas were determined using western blot analysis. The results suggested that the number of new vessels and the area of CNV were significantly decreased in groups 1 and 2, as compared with the alkali burn group at each time point (P<0.05). In addition, the number of inflammatory cells and the degree of edema were decreased in groups 1 and 2, as compared with the alkali burn group, with group 2 exhibiting the most marked reduction. Western blot analysis demonstrated that the expression levels of MMP-9, VEGF, VEGFR-1 and VEGFR-2 were significantly decreased in groups 1 and 2, as compared with the alkali burn control group, with group 2 exhibiting the most significant reduction (P<0.05). The results of the present study suggested that 90Sr-90Y β-irradiation and angiogenesis inhibitor treatments were able to inhibit alkali burn-induced CNV, although 90Sr-90Y β-irradiation may be more effective. PMID:26893623

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

    SciTech Connect

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

    2004-12-01

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

  19. 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.

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

    PubMed Central

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

    2014-01-01

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

  2. Treatment of lung tumor colonies with 90Y targeted to blood vessels: comparison with the alpha-particle emitter 213Bi.

    PubMed

    Kennel, S J; Stabin, M; Yoriyaz, H; Brechbiel, M; Mirzadeh, S

    1999-01-01

    An in vivo lung tumor model system for radioimmunotherapy of lung metastases was used to test the relative effectiveness of the vascular- targeted beta-particle emitter 90Y, and alpha-particle emitter, 213Bi. Yttrium-90 was shown to be stably bound by CHXa" DTPA-MAb 201B conjugates and delivered efficiently to lung tumor blood vessels. Dosimetry calculations indicated that the lung received 16.2 Gy/MBq from treatment with 90Y MAb 201B, which was a sevenfold greater absorbed dose than any other organ examined. Therapy was optimal for 90Y with 3 MBq injected. Bismuth-213 MAb 201B also delivered a similar absorbed dose (15Gy/MBq) to the lung. Yttrium-90 was found to be slightly more effective against larger tumors than 213Bi, consistent with the larger range of 2 MeV beta particles from 90Y than the 8 MeV alpha particles from 213Bi. Treatment of EMT-6 tumors growing in immunodeficient SCID mice with 90Y or 213Bi MAb 201 resulted in significant destruction of tumor colonies; however, 90Y MAb 201B was toxic for the SCID mice, inflicting acute lung damage. In another tumor model, IC-12 rat tracheal carcinoma growing in SCID mouse lungs, 90Y therapy was more effective than 213Bi at destroying lung tumors. However, 90Y MAb 201B toxicity for the lung limited any therapeutic effect. We conclude that, although vascular-targeted 90Y MAb can be an effective therapeutic agent, particularly for larger tumors, in this model system, acute damage to the lung may limit its application. PMID:10096515

  3. 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.

  4. 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.

  5. Attenuation of bremsstrahlung from 90Sr-90Y, 147Pm and 204Tl in thick target compounds

    NASA Astrophysics Data System (ADS)

    Manjunatha, H. C.

    2014-11-01

    The external bremsstrahlung (EB) produced by beta particles such as from 90Sr-90Y, 147Pm and 204Tl in PbCl2, PbF2, Pb(NO3)2 and CdO were measured using NaI(Tl) crystal. The beta stopper technique is employed to measure the integral intensities above 100 keV energy in different absorber thicknesses. Attenuation of the external bremsstrahlung, excited by 90Sr-90Y, 147Pm and 204Tl beta-emitters in the same compounds has also been studied. The measured attenuation parameter is not constant with absorber thickness and it increases with increasing Zmod of the absorber. Whereas, the mass attenuation coefficient of gamma rays of equivalent energy is independent of the absorber thickness. This confirms that the attenuation of EB in an absorber does not conform to a single exponential law, unlike the absorption of monoenergetic gamma rays. Rather it may be a combination of a large number of exponential terms.

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

    PubMed

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

    2014-09-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-09-01

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

  8. 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. PMID:25638490

  9. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-06-01

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

  10. Gateways to clinical trials.

    PubMed

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

    2003-10-01

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

  11. Radiometals as payloads for radioimmunotherapy for lymphoma.

    PubMed

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

    2004-10-01

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

  12. Radiobiological Optimization of Combination Radiopharmaceutical Therapy Applied to Myeloablative Treatment of Non-Hodgkin’s Lymphoma

    PubMed Central

    Hobbs, Robert F; Wahl, Richard L; Frey, Eric C; Kasamon, Yvette; Song, Hong; Huang, Peng; Jones, Richard J; Sgouros, George

    2014-01-01

    Combination treatment is a hallmark of cancer therapy. Although the rationale for combination radiopharmaceutical therapy was described in the mid ‘90s, such treatment strategies have only been implemented clinically recently, and without a rigorous methodology for treatment optimization. Radiobiological and quantitative imaging-based dosimetry tools are now available that enable rational implementation of combined targeted radiopharmaceutical therapy. Optimal implementation should simultaneously account for radiobiological normal organ tolerance while optimizing the ratio of two different radiopharmaceuticals required to maximize tumor control. We have developed such a methodology and applied it to hypothetical myeloablative treatment of non-hodgkin’s lymphoma (NHL) patients using 131I-tositumomab and 90Y-ibritumomab tiuxetan. Methods The range of potential administered activities (AA) is limited by the normal organ maximum tolerated biologic effective doses (MTBEDs) arising from the combined radiopharmaceuticals. Dose limiting normal organs are expected to be the lungs for 131I-tositumomab and the liver for 90Y-ibritumomab tiuxetan in myeloablative NHL treatment regimens. By plotting the limiting normal organ constraints as a function of the AAs and calculating tumor biological effective dose (BED) along the normal organ MTBED limits, the optimal combination of activities is obtained. The model was tested using previously acquired patient normal organ and tumor kinetic data and MTBED values taken from the literature. Results The average AA values based solely on normal organ constraints was (19.0 ± 8.2) GBq with a range of 3.9 – 36.9 GBq for 131I-tositumomab, and (2.77 ± 1.64) GBq with a range of 0.42 – 7.54 GBq for 90Y-ibritumomab tiuxetan. Tumor BED optimization results were calculated and plotted as a function of AA for 5 different cases, established using patient normal organ kinetics for the two radiopharmaceuticals. Results included AA ranges

  13. Large-scale purification of 90Sr from nuclear waste materials for production of 90Y, a therapeutic medical radioisotope.

    PubMed

    Wester, Dennis W; Steele, Richard T; Rinehart, Donald E; DesChane, Jaquetta R; Carson, Katharine J; Rapko, Brian M; Tenforde, Thomas S

    2003-07-01

    A major limitation on the supply of the short-lived medical isotope 90Y (t1/2 = 64 h) is the available quantity of highly purified 90Sr generator material. A radiochemical production campaign was therefore undertaken to purify 1,500 Ci of 90Sr that had been isolated from fission waste materials. A series of alkaline precipitation steps removed all detectable traces of 137Cs, alpha emitters, and uranium and transuranic elements. Technical obstacles such as the buildup of gas pressure generated upon mixing large quantities of acid with solid 90Sr carbonate were overcome through safety features incorporated into the custom-built equipment used for 90Sr purification. Methods are described for analyzing the chemical and radiochemical purity of the final product and for accurately determining by gravimetry the quantities of 90Sr immobilized on stainless steel filters for future use. PMID:12878120

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

    PubMed

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

    2015-11-01

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

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

    PubMed

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

    2009-12-01

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

  16. Separation of carrier-free {sup 90}Y from high level waste by extraction chromatographic technique using 2-ethylhexyl-2-ethylhexyl phosphonic acid (KSM-17)

    SciTech Connect

    Achuthan, P.V.; Dhami, P.S.; Kannan, R.; Gopalakrishnan, V.; Ramanujam, A.

    2000-01-01

    An extraction chromatographic technique has been developed for the separation of carrier-free {sup 90}Y from the {sup 90}Sr present in the high level waste (HLW) of the Purex process. When a Purex HLW solution in 2--3 M HNO{sub 3} is passed through a CMPO-Chromosorb-102 (CAC) column, all the trivalent, tetravalent, and hexavalent ions are sorbed. The effluent from this experiment, after adjusting the pH to 2 with NaOH, was passed through a 2-ethylhexyl-2-ethylhexyl phosphonic acid (KSM-17)-Chromosorb-102 (KSMC) extraction chromatographic column where only {sup 90}Y was sorbed. All the other ions ({sup 90}Sr, {sup 137}Cs, {sup 125}Sb, {sup 106}Ru, {sup 106}Rh, etc.) were washed off with dilute HNO{sub 3} (pH 2), and carrier-free {sup 90}Y was eluted with 0.5 M HNO{sub 3}. This technique can yield {sup 90}Y in mCi levels in pure form for medical applications. The {sup 90}Sr can be used repeatedly after allowing for {sup 90}Y buildup.

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

    PubMed

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

    2015-09-01

    Local treatment of unresectable tumors is challenging, particularly with radioactivity. Current practice relies on external beam irradiation or on a variety of medical devices for brachytherapy. Both approaches proved useful in controlling tumor growth, but are characterized by poor compliance of the patient, significant side-effects, high costs, and technological complexity, which hamper widespread use. The authors recently described a novel form of radionuclide therapy based on the oxidized form of avidin that, chemically reacting with tissue proteins, can secure radioactive biotin within the injected tissue, either when precomplexed or when taken from the blood stream after intravenous administration. AvidinOX-pretargeted (177)Lu-biotinDOTA ((177)Lu-ST2210) is currently under clinical investigation for the treatment of liver oligometastases from colorectal cancer (clinicaltrials.gov/NCT02053324). In the present work, the authors show that injected AvidinOX can link tissues of various natures such as prostate, kidney, breast, or brain and can react by contact with scraped tissues such as skin or urinary bladder. AvidinOX injected into human OSC19 tongue cancer masses orthotopically transplanted in nude mice takes up intravenously administered (90)Y-ST2210, which exerts significant antitumor activity, while preserving the integrity and functionality of the tongue. Present data confirm that AvidinOX-based radionuclide therapy is an innovative and promising approach for the local treatment of inoperable tumors. PMID:26167947

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

    PubMed Central

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

    2015-01-01

    Abstract Local treatment of unresectable tumors is challenging, particularly with radioactivity. Current practice relies on external beam irradiation or on a variety of medical devices for brachytherapy. Both approaches proved useful in controlling tumor growth, but are characterized by poor compliance of the patient, significant side-effects, high costs, and technological complexity, which hamper widespread use. The authors recently described a novel form of radionuclide therapy based on the oxidized form of avidin that, chemically reacting with tissue proteins, can secure radioactive biotin within the injected tissue, either when precomplexed or when taken from the blood stream after intravenous administration. AvidinOX-pretargeted 177Lu-biotinDOTA (177Lu-ST2210) is currently under clinical investigation for the treatment of liver oligometastases from colorectal cancer (clinicaltrials.gov/NCT02053324). In the present work, the authors show that injected AvidinOX can link tissues of various natures such as prostate, kidney, breast, or brain and can react by contact with scraped tissues such as skin or urinary bladder. AvidinOX injected into human OSC19 tongue cancer masses orthotopically transplanted in nude mice takes up intravenously administered 90Y-ST2210, which exerts significant antitumor activity, while preserving the integrity and functionality of the tongue. Present data confirm that AvidinOX-based radionuclide therapy is an innovative and promising approach for the local treatment of inoperable tumors. PMID:26167947

  19. Radioimmunotherapy of Solid Tumors: Searching for the Right Target

    PubMed Central

    Song, Hong; Sgouros, George

    2015-01-01

    Radioimmunotherapy of solid tumors remains a challenge despite the tremendous success of 90Y ibritumomab tiuxetan (Zevalin) and 131I Tositumomab (Bexxar) in treating non-Hodgkin’s lymphoma. For a variety of reasons, clinical trials of radiolabeled antibodies against solid tumors have not led to responses equivalent to those seen against lymphoma. In contrast, promising responses have been observed with unlabeled antibodies that target solid tumor receptors associated with cellular signaling pathways. These observations suggest that anti-tumor efficacy of the carrier antibody might be critical to achieving clinical responses. Here, we review and compare tumor antigens targeted by radiolabeled antibodies and unlabeled antibodies used in immunotherapy. The review shows that the trend for radiolabeled antibodies under pre-clinical development is to also target antigens associated with signaling pathways that are essential for the growth and survival of the tumor. PMID:21034423

  20. 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

  1. 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

  2. 90Y-daclizumab, an anti-CD25 monoclonal antibody, provided responses in 50% of patients with relapsed Hodgkin’s lymphoma

    PubMed Central

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

    2015-01-01

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

  3. Monte Carlo characterization of biocompatible beta-emitting 90Y glass seed incorporated with the radionuclide 153Sm as a SPECT marker for brachytherapy applications.

    PubMed

    Hadadi, Asghar; Sadeghi, Mahdi; Sardari, Dariush; Khanchi, Alireza; Shirazi, Alireza

    2013-01-01

    A glass seed consisting of the β--emitting radionuclide 90Y incorporated with radionuclide 153Sm as SPECT marker is proposed for potential application in brachytherapy in order to reduce the undesirable dose to healthy adjacent organs. The aim of this work is to determine the dosimetric characteristics, as suggested in the AAPM TG-60/TG-149 reports, for this seed using Monte Carlo simulation. Monte Carlo codes MCNP5, EGSnrc, and FLUKA were used to calculate the absorbed dose distribution around the seed. Dosimetric parameters, such as reference absorbed dose rate, radial dose function, and one-dimensional (1D) and two-dimensional (2D) anisotropy functions, were obtained. The computational results from these three codes are in agreement within 5.4% difference on average. The absorbed dose rate at the reference point was estimated to be 5.01 cGy h-1 μCi-1 and self absorption of YAS glass seed amounted to 30.51%. The results showed that, with thermal neutron bombardment of 5 hours in a typical flux, sufficient activity for applications in brachytherapy may be achieved. With a 5 mCi initial activity, the total dose of a YAS glass seed was estimated to be 1.38 Gy at 1.0 cm from the seed center. Comparing with gamma emitting seeds, the 90Y seed could reduce undesirable doses to adjacent organs, because of the rapid dose falloff of beta ray. Because of the high R90 value of 5.5 mm, fewer number of 90Y seeds will be required for an interstitial brachytherapy treatment using permanent implant, in comparison with other beta-emitting seeds. The results would be helpful in the development of the radioactive implants using 90Y glass seeds for the brachytherapy treatment. PMID:24036862

  4. Chemotherapy tolerance after radioimmunotherapy with 90Y-CC49 monoclonal antibody in patients with advanced non-small cell lung cancer: clinical effects and hematologic toxicity.

    PubMed

    Robert, Francisco; Busby, Elizabeth M; LoBuglio, Albert F

    2003-06-01

    The purpose of this retrospective analysis was to evaluate the hematologic toxicity and clinical outcome of salvage chemotherapy following (90)Y-CC49 radioimmunotherapy (RIT) in patients with non-small cell lung cancer (NSCLC). Sixteen patients from a total of 37 who were enrolled in a phase I trial of (90)Y-CC49 monoclonal therapy were treated with post-RIT salvage chemotherapy at our institution. Five patients had received chest radiation therapy prior to RIT, and seven patients had prior chemotherapy. The majority of these patients were treated with doses of (90)Y of >/= 14 mCi/m(2) (8-20 mCi/m(2)), and four of them received concurrent 96-hour taxol infusion. The maximum tolerated dose of this study was exceeded at 17 mCi/m(2), and grade 4 thrombocytopenia/neutropenia were the dose-limiting toxicities. Twelve patients received one chemotherapy regimen as salvage therapy, and four patients had more than one regimen. Four patients (25%) experienced reversible grade 4 neutropenia, but no grade 4 thrombocytopenia was observed. Five patients had stable disease. The median survival from start of salvage therapy was 5.5 months. Our data suggest that therapy with RIT did not significantly affect survival of these patients. Taking into consideration the potential clinical relevance of integration of RIT with other treatment modalities, it is important to expand this clinical experience in order to support combined modality strategies. PMID:12954119

  5. 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.

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

    PubMed

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

    2006-06-01

    SS receptors are overexpressed in many tumors, mainly of neuroendocrine origin, thus enabling the treatment with SS analogs. The clinical experience of receptor radionuclide therapy with the new analog [90Y-DOTA0-Tyr3 ]-octreotide [90Y-DOTATOC] has been developed over the last decade and is gaining a pivotal role in the therapeutic workout of these tumors. It is well known that some procedures performed in diagnostic and therapeutic management of endocrine tumors, such as agobiopsy and hepatic chemoembolization, can be associated with the occurrence of symptoms related to the release of vasoactive amines and/or hormonal peptides from tumor cell lysis. This is the first report of a severe carcinoid crisis developed after receptor radionuclide therapy with 90Y-DOTATOC administered in a patient affected by liver metastases from bronchial neuroendocrine tumor (atypical carcinoid). Despite protection with H1 receptor antagonists, octreotide and corticosteroids, few days after the therapy the patient complained of persistent flushing of the face and upper trunk, severe labial and periocular oedema, diarrhoea and loss of appetite. These symptoms increased and required new hospitalisation. The patient received iv infusion of octreotide associated with H1 and H2 receptor antagonists and corticosteroid therapy, which induced symptom remission within few days. The case here reported confirms that radionuclide therapy is highly effective in determining early rupture of metastatic tissue and also suggests that pre-medication should be implemented before the radiopeptide administration associated with a close monitoring of the patient in the following days. PMID:16840837

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

    PubMed

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

    2016-08-01

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

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

    PubMed

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

    2005-08-01

    Several short-lived, high-energy beta emitters are being proposed as the radionuclide components for molecular- targeted potential cancer therapeutic agents. The laboratory mice used to determine the efficacy of these new agents have organs that are relatively small compared to the ranges of these high-energy particles. The dosimetry model developed by Hui et al. was extended to provide realistic beta-dose estimates for organs in mice that received therapeutic radiopharmaceuticals containing (90)Y, (188)Re, (166)Ho, (149)Pm, (64)Cu, and (177)Lu. Major organs in this model included the liver, spleen, kidneys, lungs, heart, stomach, small and large bowel, thyroid, pancreas, bone, marrow, carcass, and a 0.025-g tumor. The study as reported in this paper verifies their results for (90)Y and extends them by using their organ geometry factors combined with newly calculated organ self-absorbed fractions from PEREGRINE and MCNP. PEREGRINE and MCNP agree to within 8% for the worst-case organ with average differences (averaged over all organs) decreasing from 5% for (90)Y to 1% for (177)Lu. When used with typical biodistribution data, the three different models predict doses that are in agreement to within 5% for the worst-case organ. The beta-absorbed fractions and cross-organ-deposited energy provided in this paper can be used by researchers to predict mouse-organ doses and should contribute to an improved understanding of the relationship between dose and radiation toxicity in mouse models where use of these isotopes is favorable. PMID:16114992

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

    PubMed

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

    2016-08-15

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

  10. 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

  11. 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.

  12. (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. PMID:22267274

  13. Kidney Dosimetry in 177Lu and 90Y Peptide Receptor Radionuclide Therapy: Influence of Image Timing, Time-Activity Integration Method, and Risk Factors

    PubMed Central

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

    2013-01-01

    Kidney dosimetry in 177Lu and 90Y PRRT requires 3 to 6 whole-body/SPECT scans to extrapolate the peptide kinetics, and it is considered time and resource consuming. We investigated the most adequate timing for imaging and time-activity interpolating curve, as well as the performance of a simplified dosimetry, by means of just 1-2 scans. Finally the influence of risk factors and of the peptide (DOTATOC versus DOTATATE) is considered. 28 patients treated at first cycle with 177Lu DOTATATE and 30 with 177Lu DOTATOC underwent SPECT scans at 2 and 6 hours, 1, 2, and 3 days after the radiopharmaceutical injection. Dose was calculated with our simplified method, as well as the ones most used in the clinic, that is, trapezoids, monoexponential, and biexponential functions. The same was done skipping the 6 h and the 3 d points. We found that data should be collected until 100 h for 177Lu therapy and 70 h for 90Y therapy, otherwise the dose calculation is strongly influenced by the curve interpolating the data and should be carefully chosen. Risk factors (hypertension, diabetes) cause a rather statistically significant 20% increase in dose (t-test, P < 0.10), with DOTATATE affecting an increase of 25% compared to DOTATOC (t-test, P < 0.05). PMID:23865075

  14. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-12-01

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

  15. A novel method for the preparation of large-area 90Sr/90Y sources for the calibration of hand contamination monitors.

    PubMed

    Kumar, Manoj; Gandhi, Shyamala S; Chakravarty, Rubel; Nuwad, J; Udhayakumar, J; Dash, Ashutosh

    2013-09-01

    This paper describes a method for the preparation of large-area (90)Sr/(90)Y polymer film sources for the calibration of hand contamination monitors. The process consists of solvent extraction of predictable quantity of (90)Sr into an organic solvent containing di-tert-butyl-cyclohexano-18-crown-6 (DCH18C6), formation of a polymeric solution of poly(methyl methacrylate) (PMMA), pouring the (90)Sr-embedded polymer solution over a surface of a defined area followed by evaporation to create a thin film and peeling-off of the radioactive PMMA film. Quality control tests of the radioactive films were carried out to ensure nonleachability, uniform distribution of activity and stability. Sources having 5kBq±428Bq were prepared using this method and routinely used for calibration of contamination monitors. PMID:23714116

  16. Efficacy of low-dose 90Sr-90Y therapy combined with topical application of 0.5% timolol maleate solution for the treatment of superficial infantile hemangiomas

    PubMed Central

    ZHU, HONG-JIAN; LIU, QINGHONG; DENG, XIAO-LI; GUAN, YAN-XING

    2015-01-01

    The aim of the present study was to investigate the clinical efficacy and safety of low-dose 90Sr-90Y therapy combined with the topical application of 0.5% timolol maleate solution for the treatment of superficial infantile hemangiomas (IHs). A total of 72 infants with hemangiomas were allocated at random into the observation group (17 cases aged ≤3 months, 20 cases aged >3 months) or the control group (15 cases aged ≤3 months, 20 cases aged >3 months). The observation group was treated with low-dose 90Sr-90Y combined with timolol, while the control group received an identical dose of 90Sr-90Y with physiological saline. Data were collected for statistical analysis, and treatment efficacy was compared between the two groups. In the observation group, 100% (37/37) of subjects exhibited an ‘excellent’ response to the treatment, while 94.1% (16/17) of patients aged ≤3 months and 85.0% (17/20) aged >3 months were classed as being cured. In the control group, the treatment was classed as ‘effective’ in 100% (35/35) of the subjects, while the excellent response rate was 86.7% (13/15) among the infants aged ≤3 months and 75.0% (15/20) among the infants aged >3 months. The ‘cure’ rates in the control group were 66.7% (10/15) and 60.0% (12/20) for the ≤3-month- and >3-month-old subjects, respectively. The excellent response and cure rates were notably higher in the observation group than those in the control group. Comparison between the two groups revealed a χ2 value of 13.90 (P<0.01) for excellent responses in subjects aged ≤3 months, while for patients aged >3 months the χ2 value was 28.57 (P<0.01). Analysis of the cure responses gave similar results [≤3 months, χ2=23.22 (P<0.01); >3 months, χ2=15.67 (P<0.01)]. At 3–4 months after the first course of treatment, the cure rate was 33.3% (11/33) in the observation group, which was significantly higher than the rate of 18.32% (4/22) in the control group (χ2=5.92, P<0.05). No serious adverse

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  19. 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

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

    PubMed Central

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

    2015-01-01

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

  1. Radioimmunotherapy for Waldenstrom's macroglobulinemia.

    PubMed

    Emmanouilides, Christos

    2003-04-01

    Radioimmunotherapy targeting CD20 is a promising novel treatment for lymphoma. Prior trials have established the safe dose of Zevalin ((90)Y-ibritumomab tiuxetan; IDEC Pharmaceuticals) for patients with no more than 25% bone marrow (BM) involvement. Zevalin is expected to be an effective treatment for WM; however, the safe dose has not been defined. A phase I clinical trial has been designed to define the maximum-tolerated dose (MTD) of Zevalin in patients with WM and BM involvement up to 50%. Eligible patients need to have adequate hematologic indices (absolute neutrophil count [ANC] > 1,500/microL, platelets > 100,000/microL). The starting dose of (90)Y-Zevalin is 0.08 mCi/kg. Dose escalation by 0.04 mCi/kg in cohorts of three to six patients will be performed. Patients will be re-treated at 12 weeks if there is no complete response, no progression, and no dose-limiting toxicity. If the degree of BM involvement remains in the 20% to 50% range, re-treatment will involve a similar dose of Zevalin; if it is <20%, patients will receive Zevalin to the maximum allowed cumulative dose of 0.4 mCi/kg (or 0.3 mCi/kg for mild thrombocytopenia). Despite the phase I design, the re-treatment provision is expected to result in significant clinical benefit. PMID:12720148

  2. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-01-01

    [90Y-DOTA-Tyr3]octreotate, Abatacept, ABT-888, ACE-011, Adefovir dipivoxil, Alosetron hydrochloride, Aminolevulinic acid methyl ester, Amlodipine, Apaziquone, Aripiprazole, AS-101, Atomoxetine hydrochloride, Atrasentan, Azacitidine; Bevacizumab, Biphasic insulin aspart, Bortezomib, Bosentan, Brivanib alaninate; CERE-120, Cetuximab, Ciclesonide, Cinacalcet hydrochloride, Combretastatin A-1 phosphate, Conatumumab, CT-322; Dabigatran etexilate, Darunavir, Deforolimus, Desloratadine, Doripenem, Doxorubicin eluting beads, Duloxetine hydrochloride, Dutasteride; Escitalopram oxalate, Eszopiclone, Etravirine, Exenatide, Ezetimibe, Ezetimibe/simvastatin; Fluticasone furoate, Fondaparinux sodium; Gabapentin enacarbil, Ghrelin (human), Golimumab; IC-51, IDM-2, JX-594; Lidocaine/prilocaine, Liraglutide, Lopinavir, Lopinavir/ritonavir, Lumiracoxib; Men ACWY, MxdnG1; Naproxcinod; OBP-301, Omalizumab; Paclitaxel nanoparticles, Pasireotide, Pazopanib hydrochloride, Pegaptanib octasodium, Peginterferon alfa-2a, Pegvisomant, Pemetrexed disodium, Pimecrolimus, Prasterone, Pregabalin; Raclopride, Ranelic acid distrontium salt, Ranibizumab, RB-006, Recombinant human relaxin H2, REG1, Regadenoson, Reximmune-C, Rilonacept; Saxagliptin, SCH-697243, Solifenacin succinate, Sorafenib; Tadalafil, Tapentadol hydrochloride, Tenofovir disoproxil fumarate, Tenofovir disoproxil fumarate/emtricitabine, Tipifarnib, Tolvaptan; Vardenafil hydrochloride hydrate, Vicriviroc, Volociximab, Vorinostat; WB-1001; Yttrium 90 (90Y) ibritumomab tiuxetan. PMID:19798455

  3. Anti-CD22 90Y-epratuzumab tetraxetan combined with anti-CD20 veltuzumab: a phase I study in patients with relapsed/refractory, aggressive non-Hodgkin lymphoma.

    PubMed

    Witzig, Thomas E; Tomblyn, Michael B; Misleh, Jamal G; Kio, Ebenezer A; Sharkey, Robert M; Wegener, William A; Goldenberg, David M

    2014-11-01

    A lingering criticism of radioimmunotherapy in non-Hodgkin lymphoma is the use of cold anti-CD20 antibody along with the radiolabeled anti-CD20 antibody. We instead combined radioimmunotherapy with immunotherapy targeting different B-cell antigens. We evaluated the anti-CD22 (90)Y-epratuzumab tetraxetan with the anti-CD20 veltuzumab in patients with aggressive lymphoma in whom at least one prior standard treatment had failed, but who had not undergone stem cell transplantation. Eighteen patients (median age 73 years, median of 3 prior treatments) received 200 mg/m(2) veltuzumab once-weekly for 4 weeks, with (90)Y-epratuzumab tetraxetan at planned doses in weeks 3 and 4, and (111)In-epratuzumab tetraxetan in week 2 for imaging and dosimetry. Veltuzumab effectively lowered levels of B cells in the blood prior to the radioimmunotherapy doses. No significant immunogenicity or change in pharmacokinetics of either agent occurred in combination. (111)In imaging showed tumor targeting with acceptable radiation dosimetry to normal organs. For (90)Y-epratuzumab tetraxetan, transient myelosuppression was dose-limiting with 6 mCi/m(2) (222 MBq/m(2)) × 2 being the maximal tolerated dose. Of 17 assessable patients, nine (53%) had objective responses according to the 2007 revised treatment response criteria, including three (18%) complete responses (2 relapsing after 11 and 13 months, 1 continuing to be clinically disease-free at 19 months), and six (35%) partial responses (1 relapsing after 14 months, 5 at 3 - 7 months). Responses occurred in patients with different lymphoma histologies, treated at different (90)Y dose levels, and with a predicted risk of poor outcome, most importantly including five of the six patients treated with the maximal tolerated dose (2 of whom achieved durable complete responses). In conclusion, the combination of (90)Y-epratuzumab tetraxetan and veltuzumab was well-tolerated with encouraging therapeutic activity in this difficult-to-treat population

  4. 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. PMID:22172388

  5. 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

  6. Multicenter evaluation of the safety and efficacy of radioembolization in patients with unresectable colorectal liver metastases selected as candidates for 90Y resin microspheres

    PubMed Central

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

    2015-01-01

    Background Metastatic colorectal cancer liver metastases Outcomes after RadioEmbolization (MORE) was an investigator-initiated case-control study to assess the experience of 11 US centers who treated liver-dominant metastases from colorectal cancer (mCRC) using radioembolization [selective internal radiation therapy (SIRT)] with yttrium-90-(90Y)-labeled resin microspheres. Methods Data from 606 consecutive patients who received radioembolization between July 2002 and December 2011 were collected by an independent research organization. Adverse events (AEs) and survival were compared across lines of treatment using Fisher’s exact test and Kaplan-Meier estimates, respectively. Results Patients received a median of 2 (range, 0-6) lines of prior chemotherapy; 35.1% had limited extrahepatic metastases. Median tumor-to-liver ratio and -activity administered at first procedure were 15% and 1.17 GBq, respectively. Hospital stay was <24 hours in 97.8% cases. Common grade ≥3 AEs over 184 days follow-up were: abdominal pain (6.1%), fatigue (5.5%), hyperbilirubinemia (5.4%), ascites (3.6%) and gastrointestinal ulceration (1.7%). There was no statistical difference in AEs across treatment lines (P>0.05). Median survivals [95% confidence interval (CI)] following radioembolization as a 2nd-line, 3rd-line, or 4th-plus line were 13.0 (range, 10.5-14.6), 9.0 (range, 7.8-11.0), and 8.1 (range, 6.4-9.3) months, respectively; and significantly prolonged in patients with ECOG 0 vs. ≥1 (P=0.009). Statistically significant independent variables for survival at radioembolization were: disease stage [extrahepatic metastases, extent of liver involvement (tumor-to-treated-liver ratio)], liver function (uncontrolled ascites, albumin, alkaline phosphatase, aspartate transaminase), leukocytes, and prior chemotherapy. Conclusions Radioembolization appears to have a favorable risk/benefit profile, even among mCRC patients who had received ≥3 prior lines of chemotherapy. PMID:25830033

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

    NASA Astrophysics Data System (ADS)

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

    2012-07-01

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

  8. Anti-CD22 90Y-epratuzumab tetraxetan combined with anti-CD20 veltuzumab: a phase I study in patients with relapsed/refractory, aggressive non-Hodgkin lymphoma

    PubMed Central

    Witzig, Thomas E.; Tomblyn, Michael B.; Misleh, Jamal G.; Kio, Ebenezer A.; Sharkey, Robert M.; Wegener, William A.; Goldenberg, David M.

    2014-01-01

    A lingering criticism of radioimmunotherapy in non-Hodgkin lymphoma is the use of cold anti-CD20 antibody along with the radiolabeled anti-CD20 antibody. We instead combined radioimmunotherapy with immunotherapy targeting different B-cell antigens. We evaluated the anti-CD22 90Y-epratuzumab tetraxetan with the anti-CD20 veltuzumab in patients with aggressive lymphoma in whom at least one prior standard treatment had failed, but who had not undergone stem cell transplantation. Eighteen patients (median age 73 years, median of 3 prior treatments) received 200 mg/m2 veltuzumab once-weekly for 4 weeks, with 90Y-epratuzumab tetraxetan at planned doses in weeks 3 and 4, and 111In-epratuzumab tetraxetan in week 2 for imaging and dosimetry. Veltuzumab effectively lowered levels of B cells in the blood prior to the radioimmunotherapy doses. No significant immunogenicity or change in pharmacokinetics of either agent occurred in combination. 111In imaging showed tumor targeting with acceptable radiation dosimetry to normal organs. For 90Y-epratuzumab tetraxetan, transient myelosuppression was dose-limiting with 6 mCi/m2 (222 MBq/m2) × 2 being the maximal tolerated dose. Of 17 assessable patients, nine (53%) had objective responses according to the 2007 revised treatment response criteria, including three (18%) complete responses (2 relapsing after 11 and 13 months, 1 continuing to be clinically disease-free at 19 months), and six (35%) partial responses (1 relapsing after 14 months, 5 at 3 – 7 months). Responses occurred in patients with different lymphoma histologies, treated at different 90Y dose levels, and with a predicted risk of poor outcome, most importantly including five of the six patients treated with the maximal tolerated dose (2 of whom achieved durable complete responses). In conclusion, the combination of 90Y-epratuzumab tetraxetan and veltuzumab was well-tolerated with encouraging therapeutic activity in this difficult-to-treat population. PMID:25150258

  9. 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.

  10. Mechanism and energetics for complexation of {sup 90}Y with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), a model for cancer radioimmunotherapy

    SciTech Connect

    Jang, Y.H.; Blanco, M.; Dasgupta, S.; Keire, D.A.; Shively, J.E.; Goddard, W.A. III

    1999-07-07

    A promising cancer therapy involves the use of the macrocyclic polyaminoacetate DOTA (1,4,6,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) attached to a tumor-targeting antibody complexed with the {beta} emitter {sup 90}Y{sup 3+}. However, incorporation of the {sup 90}Y into the DOTA conjugate is too slow. To identify the origins of this problem, ab initio quantum chemistry methods (B3LYP/:ACVP* and HF/LACVP*) were used to predict structures and energetics. The authors find that the initial complex YH{sub 2}(DOTA){sup +} is 4-coodinate (the four equivalent carboxylate oxygens), which transforms to YH(DOTA) (5-coordinate with one ring N and four carboxylate oxygens), and finally to Y(DOTA){sup {minus}}, which is 8-coordinate (four oxygens and four nitrogens). The rate-determining step is the conversion of YH(DOTA) to Y(DOTA){sup {minus}}, which was calculated to have an activation free energy (aqueous phase) of 8.4 kcal/mol, in agreement with experimental results (8.1--9.3 kcal/mol) for various metals to DOTA [Kumar, K.; Tweedle, M.F. Inorg. Chem. 1993, 32, 4193--4199; Wu, S.L.; Horrocks, W.D., Jr., Inorg. Chem. 1995, 34, 3724--2732]. On the basis of this mechanism the authors propose a modified chelate, DO3AlPr, which has calculated at a much faster rate of incorporation.

  11. Radioimmunotherapy in relapsed follicular lymphoma previously treated by autologous bone marrow transplant: a report of eight new cases and literature review.

    PubMed

    Peyrade, Frederic; Triby, Caroline; Slama, Bohane; Fontana, Xavier; Gressin, Remy; Broglia, Jean-Marc; Lepeu, Gerard; Carrier, Patricia; Peyrottes, Isabelle; Darcourt, Jacques; Bondiau, Pierre-Yves; Thyss, Antoine

    2008-09-01

    Multicenter, retrospective study of standard-dose RIT in eight heavily pre-treated patients with CD20-positive follicular lymphoma who had relapsed after previous autologous bone marrow transplantation (ABMT). Patients underwent nine courses of (90)Y-ibritumomab tiuxetan (0.3 or 0.4 mCi/kg body weight). Responses included five CR, two PR, one SD and one PD. Median DFS was 12 months with median follow-up of 17 months and 1-year OS was 83% (7/8 patients). Grade 4 thrombocytopenia occurred in 7/9 treatments, with no episodes of bleeding, and only two patients received a platelet transfusion. One patient, who had 20% bone marrow involvement at the time of relapse diagnosis, presented with Grade 4 thrombocytopenia and Grade 4 neutropenia and died of septic shock 6 months after RIT. One other case of Grade 4 neutropenia, without a serious infectious syndrome, was observed. Standard-dose RIT seems feasible and potentially effective after ABMT in correctly selected patients with follicular lymphoma. PMID:18661403

  12. Radioimmunotherapy of relapsed indolent non-Hodgkin lymphoma with 131I-rituximab in routine clinical practice: 10-year single-institution experience of 142 consecutive patients.

    PubMed

    Leahy, Michael F; Turner, J Harvey

    2011-01-01

    Radioimmunotherapy of indolent non-Hodgkin lymphoma (NHL) has achieved objective response rates in clinical trials comparable with standard rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy, but is relatively underused in routine practice. In this article, we report our clinical experience in 142 consecutive patients who received iodine-131 rituximab radioimmunotherapy for low-grade, predominantly follicular, relapsed NHL. Objective response rates of 67%, with complete response (CR) in 50% and median overall survival of 32 months, matched the response rates in a phase 2 clinical trial of (131)I-rituximab radioimmunotherapy and compares favorably with those reported for (131)I-tositumomab or (90)Y-ibritumomab tiuxetan. Progression-free survival was 18 months overall and 32 months in CR or CR-unconfirmed patients. Our patients comprised 107 (75%) follicular lymphoma, 21 (15%) small lymphocytic lymphoma, 6 (4%) mucosa-associated lymphoid tissue/marginal zone lymphoma, and 8 (6%) mantle-cell lymphoma, with median follow-up of 32 months and 8-year overall survival of 48%. Toxicity was limited to hematologic grade 4 neutropenia, occurring in 10% and thrombocytopenia in 6%. There were no episodes of bleeding or infection requiring hospital admission. Radioimmunotherapy with (131)I-rituximab in routine clinical outpatient practice provides cost-effective, safe treatment of relapsed/refractory indolent NHL, with half of patients achieving durable, complete remission with potential for repeat radioimmunotherapy on relapse. PMID:20864582

  13. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-05-01

    (-)-Gossypol; Abacavir sulfate/lamivudine, ACAM-1000, ACE-011, Agomelatine, AGS-004, Alemtuzumab, Alvocidib hydrochloride, AMG-317, Amlodipine, Aripiprazole, Atazanavir sulfate, Azacitidine; Becatecarin, Belinostat, Bevacizumab, BMS-387032, BMS-690514, Bortezomib; Casopitant mesylate, Cetuximab, Choline fenofibrate, CK-1827452, Clofarabine, Conivaptan hydrochloride; Dabigatran etexilate, DADMe-Immucillin-H, Darbepoetin alfa, Darunavir, Dasatinib, DC-WT1, Decitabine, Deferasirox, Degarelix acetate, Denenicokin, Denosumab, Dienogest, Duloxetine hydrochloride; Ecogramostim, Eculizumab, Edoxaban tosilate, Elacytarabine, Elesclomol, Eltrombopag olamine, Enfuvirtide, Enzastaurin hydrochloride, Eribulin mesilate, Erlotinib hydrochloride, Escitalopram oxalate, Eszopiclone, Etravirine; Flibanserin, Fludarabine, Fondaparinux sodium, Fosamprenavir calcium; Gefitinib, Genistein; I-131-L19-SIP, Idrabiotaparinux sodium, Imatinib mesylate, IMGN-901, Ipilimumab; Laromustine, Lenalidomide, Liposomal cisplatin, Liraglutide, Lisdexamfetamine mesilate, Lopinavir, Lopinavir/ritonavir; Maraviroc, MDV-3100, Mecasermin rinfabate, MP-470, Mycophenolic acid sodium salt; Naproxcinod, NB-002, Nesiritide, Nilotinib hydrochloride monohydrate, NK-012; Palonosetron hydrochloride, Panobinostat, Pegfilgrastim, Peginterferon alfa-2a, Pitavastatin calcium, PL-3994, Plerixafor hydrochloride, Plitidepsin, PM-10450; Raltegravir potassium, Recombinant human soluble thrombomodulin, ReoT3D, RHAMM R3 peptide, Rivaroxaban, Romiplostim, Rosuvastatin calcium, Rozrolimupab; Sabarubicin hydrochloride, Salinosporamide A, Sirolimus-eluting stent, Smallpox (Vaccinia) Vaccine, Live, Sorafenib; Tenofovir disoproxil fumarate, Tenofovir disoproxil fumarate/emtricitabine, Teriparatide, Tipifarnib, Tipranavir, Trabectedin, Trifluridine/TPI; Vardenafil hydrochloride hydrate, Vinflunine, Volociximab, Vorinostat; Ximelagatran; Yttrium 90 (90Y) ibritumomab tiuxetan; Ziprasidone hydrochloride, Zoledronic acid monohydrate

  14. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-11-01

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

  15. Radioimmunotherapy of lymphoma: Bexxar and Zevalin.

    PubMed

    Goldsmith, Stanley J

    2010-03-01

    Radioimmunotherapy is a form of targeted radionuclide therapy that uses a monoclonal antibody to deliver localized radiation. It is most appropriate for treatment of multiple tumor sites that cannot be readily excised surgically or irradiated using external beam radiation or brachytherapy. At present, 2 products, Bexxar ((131)I-tositumomab and unlabeled tositumomab, GlaxoSmithKline, Triangle Park, NC) and Zevalin ((90)Y-ibritumomab tiuxetan and unlabeled rituximab, Spectrum Pharmaceuticals, Irvine, CA and Cell Therapeutics, Seattle, WA) are approved for treatment of non-Hodgkin's lymphoma in certain clinical situations in the United States and Canada. Zevalin is available also in Europe, and there are plans to make both agents more widely available. The therapeutic dose to be used depends upon a number of patient-specific variables. Both regimen achieve a complete response or partial response in approximately 3 of 4 patients, with a duration of remission lasting many years in some cases. This article reviews the basis for dose selection, the nuclear medicine procedures involved, the results obtained to date, and issues related to patient and staff safety. PMID:20113680

  16. Gateways to clinical trials.

    PubMed

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

    2006-01-01

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

  17. 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. PMID:21451322

  18. 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

  19. 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.

  20. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-11-01

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

  1. Gateways to clinical trials.

    PubMed

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

    2004-06-01

    ; Valganciclovir hydrochloride, val-mCyd, vardenafil hydrochloride hydrate, vinflunine, voriconazole; Ximelagatran, XTL-002; Yttrium 90 (90Y) ibritumomab tiuxetan. PMID:15319815

  2. 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

  3. Gateways to clinical trials.

    PubMed

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

    2006-09-01

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

  4. 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. PMID:15349141

  5. 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. PMID:19455266

  6. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-04-01

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

  7. Gateways to clinical trials.

    PubMed

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

    2004-10-01

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

  8. Gateways to clinical trials.

    PubMed

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

    2007-10-01

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

  9. 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

  10. 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.

  11. Gateways to clinical trials.

    PubMed

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

    2006-10-01

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

  12. Radioimmunotherapy of non-Hodgkin's lymphoma: clinical development of the Zevalin regimen.

    PubMed

    Theuer, Charles P; Leigh, Bryan R; Multani, Pratik S; Allen, Roberta S; Liang, Bertrand C

    2004-01-01

    Zevalin (ibritumomab tiuxetan; IDEC Pharmaceuticals Corporation, San Diego, CA, USA) was approved by the United States Food and Drug Administration on February 19, 2002, following 9 years of clinical development. Six clinical studies supported the Zevalin Biologics License Application. The Zevalin regimen is indicated for the treatment of patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma (NHL), and for those with follicular NHL refractory to Rituxan (rituximab, MabThera; IDEC Pharmaceuticals Corporation, San Diego, CA and Genentech, South San Francisco, CA). In the year following FDA approval, approximately 1300 patients were treated in clinical trials or with the commercially available product. PMID:15504711

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

    PubMed Central

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

    2014-01-01

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

  14. 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.

  15. 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)

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

    PubMed

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

    2015-10-01

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

  17. Determination of Radiation Absorbed Dose to Primary Liver Tumors and Normal Liver Tissue Using Post-Radioembolization 90Y PET

    PubMed Central

    Srinivas, Shyam M.; Natarajan, Navin; Kuroiwa, Joshua; Gallagher, Sean; Nasr, Elie; Shah, Shetal N.; DiFilippo, Frank P.; Obuchowski, Nancy; Bazerbashi, Bana; Yu, Naichang; McLennan, Gordon

    2014-01-01

    Background: Radioembolization with Yttrium-90 (90 Y) microspheres is becoming a more widely used transcatheter treatment for unresectable hepatocellular carcinoma (HCC). Using post-treatment 90 Y positron emission tomography/computerized tomography (PET/CT) scans, the distribution of microspheres within the liver can be determined and quantitatively assessed. We studied the radiation dose of 90 Y delivered to liver and treated tumors. Methods: This retrospective study of 56 patients with HCC, including analysis of 98 liver tumors, measured and correlated the dose of radiation delivered to liver tumors and normal liver tissue using glass microspheres (TheraSpheres®) to the frequency of complications with modified response evaluation criteria in solid tumors (mRECIST). 90 Y PET/CT and triphasic liver CT scans were used to contour treated tumor and normal liver regions and determine their respective activity concentrations. An absorbed dose factor was used to convert the measured activity concentration (Bq/mL) to an absorbed dose (Gy). Results: The 98 studied tumors received a mean dose of 169 Gy (mode 90–120 Gy; range 0–570 Gy). Tumor response by mRECIST criteria was performed for 48 tumors that had follow-up scans. There were 21 responders (mean dose 215 Gy) and 27 non-responders (mean dose 167 Gy). The association between mean tumor absorbed dose and response suggests a trend but did not reach statistical significance (p = 0.099). Normal liver tissue received a mean dose of 67 Gy (mode 60–70 Gy; range 10–120 Gy). There was a statistically significant association between absorbed dose to normal liver and the presence of two or more severe complications (p = 0.036). Conclusion: Our cohort of patients showed a possible dose–response trend for the tumors. Collateral dose to normal liver is non-trivial and can have clinical implications. These methods help us understand whether patient adverse events, treatment success, or treatment failure can be attributed to the dose that the tumor or normal liver received. PMID:25353006

  18. Radioimmunotherapy and autologous stem cell transplantation for the treatment of B-cell lymphomas.

    PubMed

    Cilley, Jeffrey; Winter, Jane N

    2006-01-01

    Relapse continues to be the primary cause of treatment failure in patients with non-Hodgkin's lymphomas (NHL) undergoing high-dose therapy and autologous stem cell transplantation. The anti-CD20 radioimmunoconjugates, Y-90 ibritumomab tiuxetan (Zevalin; Biogen Idec, Inc., Cambridge, MA, USA) and I-131 tositumomab (Bexxar; Corixa, Seattle, WA; and Glaxo Smith Kline; Philadelphia, PA, USA) have been associated with high response rates, durable remissions and limited toxicity apart from myelosuppression, making them ideal candidates for use in autotransplantation. Tested first as single agents in relapsed patients with indolent and transformed NHL, and then at much higher doses with stem cell support, these agents have now been combined with high-dose chemotherapy prior to autologous stem cell transplant. Radioimmunoconjugates have been used to replace total body irradiation (TBI) in some studies and to augment standard chemotherapy regimens in others. Thus far the results are promising, with combinations of radioimmunoconjugates and chemotherapy producing long-lasting responses in high-risk patients with no more toxicity than that caused by standard conditioning regimens. These results are notable in light of the fact that the dose of radiation delivered to the tumor is 10-fold higher than the dose achievable with TBI. Whether this increase in radiation dose to the targeted lymphoma translates into more durable remissions and an improvement in overall survival requires further investigation. PMID:16434379

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

    PubMed

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

    2004-12-01

    The United States Food and Drug Administration (FDA) has approved unconjugated monoclonal antibodies (MAbs) for immunotherapy (IT) of B-cell lymphoma, breast cancer and acute myeloid leukemia. More recently, approval has been given for conjugated ZevalinTM ((90)yttrium ibritumomab tiuxetan, IDEC-Y2B8, Biogen Idec, Cambridge, MA) and BexxarTM ((131)I-tositumomab, Corixa, Corp., Seattle, WA and GlaxoSmithKline, Philadelphia, PA) anti-CD20 MAbs for use in radioimmunotherapy (RIT) of non-Hodgkin's lymphoma (NHL), thus redefining the standard care of cancer patients. Because of, and despite a lack of basis for concern about allergic reactions due to human antibody responses to these foreign proteins, assays were developed to determine HAGA (human anti-globulin antibody) levels that developed in patient sera following treatment with MAbs. Strategies were also devised to ''humanize'' MAbs and to temporarily block patient immune function with drugs in order to decrease the seroconversion rates, with considerable success. On the other hand, a survival advantage has been observed in some patients who developed a HAGA following treatment. This correlates with development of an anti-idiotype antibody cascade directed toward the MAbs used to treat these patients. What follows is a selective review of HAGA and its effect on cancer treatment over the past 2 decades. PMID:15640788

  20. Radioimmunoconjugates for the treatment of cancer.

    PubMed

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

    2014-10-01

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

  1. 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. PMID:23026974

  2. Electron-Ion Mixed Conduction of BaCe0.90Y0.10O3-δ Thin Film Generated by Ru Substitution

    NASA Astrophysics Data System (ADS)

    Ochi, Masanori; Tsuchiya, Takashi; Yamaguchi, Shohei; Suetsugu, Takaaki; Suzuki, Naoya; Kobayashi, Masaki; Minohara, Makoto; Horiba, Koji; Kumigashira, Hiroshi; Higuchi, Tohru

    2016-03-01

    The structural and electrical properties of a c-axis-oriented BaCe0.85Ru0.05Y0.10O3-δ (BCRY) thin film on an Al2O3(0001) substrate depending on film thickness have been studied. The lattice constant of the c-axis decreases with increasing film thickness. The electrical conductivity is higher in the thin film with a small lattice constant. The activation energy (EA) of the dry BCRY thin film with a high conductivity is 0.26 eV, which corresponds to half of that of the bulk ceramic. The BCRY thin film exhibits electron-ion mixed conduction with a small EA of 0.18 eV below 400 °C in H2O atmosphere. The Ce3+ state created by oxygen vacancies, which locates at the top of the valence band, plays an important role in the electron-ion mixed conduction or proton conduction of the BCRY thin film.

  3. 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.

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

    PubMed Central

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

    2016-01-01

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

  5. 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.

  6. A phase II trial of RCHOP followed by radioimmunotherapy for early stage (stages I/II) diffuse large B-cell non-Hodgkin lymphoma: ECOG3402.

    PubMed

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

    2015-09-01

    Patients with early stage diffuse large B-cell lymphoma (DLBCL) receive RCHOP (rituximab cyclophosphamide, doxorubicin, vincristine, prednisone) alone or with involved field radiotherapy (IFRT). Anti-CD20 radioimmunotherapy (RIT) delivers radiation to microscopic sites outside of known disease. This phase II study aimed to achieve a functional complete response (CR) rate of ≥75% to RCHOP and (90) Yttrium-ibritumomab tiuxetan RIT. Patients with stages I/II DLBCL received 4-6 cycles of RCHOP followed by RIT [14·8 MBq/kg (0·4 mCi/kg)]; patients with positron emission tomographypositive sites of disease after RCHOP/RIT received 30 Gy IFRT. Of the 62 patients enrolled; 53 were eligible. 42% (22/53) had stage I/IE; 58% (31/53) stage II/IIE. After RCHOP, 79% (42/53) were in CR/unconfirmed CR. Forty-eight patients proceeded to RIT. One partial responder after RIT received IFRT and achieved a CR. The best response after RCHOP + RIT in all 53 patients was a functional CR rate of 89% (47/53; 95% confidence interval: 77-96%). With a median follow-up of 5·9 years, 7 (13%) patients have progressed and 4 (8%) have died (2 with DLBCL). At 5 years, 78% of patients remain in remission and 94% are alive. Chemoimmunotherapy and RIT is an active regimen for early stage DLBCL patients. Eighty-nine percent of patients achieved functional CR without the requirement of IFRT. This regimen is worthy of further study for early stage DLBCL in a phase III trial. PMID:25974212

  7. Collection of hematopoietic stem cells after previous radioimmunotherapy is feasible and does not impair engraftment after autologous stem cell transplantation in follicular lymphoma.

    PubMed

    Derenzini, Enrico; Stefoni, Vittorio; Maglie, Roberto; Casadei, Beatrice; Pellegrini, Cinzia; Broccoli, Alessandro; Stefani, Giulia; Fanti, Stefano; Motta, Maria Rosa; Narducci, Riccardo; Argnani, Lisa; Zinzani, Pier Luigi

    2013-12-01

    Major concerns about radioimmunotherapy (RIT) administration early in the course of follicular lymphoma (FL) are long-term toxicity and the theoretical impairment of hematopoietic stem cell (HSC) harvest, but few data are available about mobilization rates after RIT. This study evaluates the impact of prior therapy with RIT (yttrium-90 ibritumomab tiuxetan) and different chemotherapy regimens in all FL patients (N = 103) attempting HSC mobilization at our institution over the last 7 years. Sixty-nine patients received R-CHOP (rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone) or CHOP-like regimens, 21 patients received R-FM (rituximab-fludarabine-mitoxantrone), and 13 patients received RIT before HSC mobilization. Median CD34+ cell yield at first mobilization was 7.2 × 10(6)/kg in the R-CHOP group versus 4.3 in the R-FM group versus 1.7 in the RIT group (P = .02 R-CHOP versus R-FM; P < .0001 R-CHOP versus RIT; P < .02 R-FM versus RIT). Although 8 of 13 patients initially failed to collect enough HSC after RIT, a second and/or salvage harvest was successfully performed in 7 patients, with 10 of 13 patients (77%) finally undergoing autologous stem cell transplantation (ASCT). No differences in engraftment kinetics were observed between the three groups (R-CHOP versus R-FM versus RIT). Although mobilization was significantly impaired in patients previously treated with RIT, a salvage HSC harvest and ASCT after RIT were safe and feasible in most patients. PMID:24055654

  8. Long-term outcomes of patients with persistent indolent B cell malignancies undergoing nonmyeloablative allogeneic transplantation.

    PubMed

    Cassaday, Ryan D; Storer, Barry E; Sorror, Mohamed L; Sandmaier, Brenda M; Guthrie, Katherine A; Maloney, David G; Rajendran, Joseph G; Pagel, John M; Flowers, Mary E; Green, Damian J; Rezvani, Andrew R; Storb, Rainer F; Press, Oliver W; Gopal, Ajay K

    2015-02-01

    Relapse is least common in patients with indolent B cell (iB) malignancies (ie, iB non-Hodgkin lymphoma [NHL]) who undergo nonmyeloablative allogeneic transplantation (NMAT) in complete remission (CR). However, for the many patients unable to achieve this state, outcomes are poorly described and methods to improve results are unknown. We sought to describe the long-term follow-up and predictive factors for these poor-risk patients unable to achieve CR before NMAT. We identified and evaluated patients with iB-NHL including chronic lymphocytic leukemia treated with fludarabine/total body irradiation-based NMAT that had evidence of persistent disease before NMAT. From December 1998 to April 2009, 89 patients were identified, most commonly with small/chronic lymphocytic lymphoma (n = 62) and follicular lymphoma (n = 24). Pretransplant anti-CD20 radioimmunotherapy (RIT) using standard yttrium-90-ibritumomab tiuxetan was administered to 18 patients (20%) who more frequently had chemoresistant disease (81% versus 39%, P = .003), disease bulk > 5 cm (61% versus 15%, P < .001), thrombocytopenia < 25k/μL (33% versus 7%, P = .002), and Hematopoietic Cell Transplant Comorbidity Index scores ≥ 3 (72% versus 37%, P = .006). After adjusting for these imbalances, RIT-treated patients had improved rates of progression-free survival (PFS) (hazard ratio [HR] = .4; 95% confidence interval [CI], .2 to .9, P = .02) and overall survival (OS) (HR = .3; 95% CI, .1 to .8, P = .008) compared with the non-RIT group. The 3-year adjusted estimates of PFS and OS for the RIT and non-RIT groups were 71% and 87% versus 44% and 59%, respectively. The use of RIT was the only factor independently associated with improved PFS and OS. Rates of nonrelapse mortality and graft-versus-host disease (GVHD) were similar between the 2 groups, although over 70% of patients developed clinically significant acute or chronic GVHD. In conclusion, despite relatively high rates of GVHD, patients with persistent i

  9. Long-Term Outcomes of Patients with Persistent Indolent B-cell Malignancies Undergoing Nonmyeloablative Allogeneic Transplantation

    PubMed Central

    Cassaday, Ryan D.; Storer, Barry E.; Sorror, Mohamed L.; Sandmaier, Brenda M.; Guthrie, Katherine A.; Maloney, David G.; Rajendran, Joseph G.; Pagel, John M.; Flowers, Mary E.; Green, Damian J.; Rezvani, Andrew R.; Storb, Rainer F.; Press, Oliver W.; Gopal, Ajay K.

    2015-01-01

    Relapse is least common in patients with indolent B-cell malignancies (iB-NHL) who undergo nonmyeloablative allogeneic transplantation (NMAT) in complete remission (CR). However, for the many patients unable to achieve this state, outcomes are poorly described and methods to improve results are unknown. We sought to describe the long-term follow-up and predictive factors for these poor-risk patients unable to achieve CR prior to NMAT. We identified and evaluated patients with iB-NHL including chronic lymphocytic leukemia (CLL) treated with fludarabine/total body irradiation-based NMAT that had evidence of persistent disease prior to NMAT. From December 1998 to April 2009, 89 patients were identified, most commonly with small lymphocytic lymphoma/CLL (N = 62) and follicular lymphoma (N = 24). Pretransplant anti-CD20 radioimmunotherapy (RIT) using standard yttrium-90-ibritumomab tiuxetan was administered to 18 (20%), who more frequently had chemoresistant disease (81% vs 39%, P = 0.003), disease bulk >5 cm (61% vs 15%, P <0.001), thrombocytopenia <25k/µL (33% vs 7%, P = 0.002), and Hematopoietic Cell Transplant Comorbidity Index scores of ≥3 (72% vs 37%, P = 0.006). After adjusting for these imbalances, RIT-treated patients had improved PFS (HR = 0.4, 95% CI: 0.2–0.9, P = 0.02) and OS (HR = 0.3, 95% CI: 0.1–0.8, P = 0.008) compared to the non-RIT group. The 3-year adjusted estimates of PFS and OS for the RIT and non-RIT groups were 71% and 87%, vs 44% and 59% (respectively). The use of RIT was the only factor independently associated with improved PFS and OS. Rates of non-relapse mortality and graft-versus-host disease (GVHD) were similar between the two groups, though over 70% of patients developed clinically-significant acute or chronic GVHD. In conclusion, despite relatively high rates of GVHD, patients with persistent iB-NHL can derive durable benefit from NMAT. PMID:25445025

  10. Comparison of Residence Time Estimation Methods for Radioimmunotherapy Dosimetry and Treatment Planning—Monte Carlo Simulation Studies

    PubMed Central

    He, Bin; Wahl, Richard L.; Du, Yong; Sgouros, George; Jacene, Heather; Flinn, Ian; Frey, Eric C.

    2008-01-01

    Estimating the residence times in tumor and normal organs is an essential part of treatment planning for radioimmunotherapy (RIT). This estimation is usually done using a conjugate view whole body scan time series and planar processing. This method has logistical and cost advantages compared to 3-D imaging methods such as Single photon emission computed tomography (SPECT), but, because it does not provide information about the 3-D distribution of activity, it is difficult to fully compensate for effects such as attenuation and background and overlapping activity. Incomplete compensation for these effects reduces the accuracy of the residence time estimates. In this work we compare residence times estimates obtained using planar methods to those from methods based on quantitative SPECT (QSPECT) reconstructions. We have previously developed QSPECT methods that provide compensation for attenuation, scatter, collimator-detector response, and partial volume effects. In this study we compared the use of residence time estimation methods using QSPECT to planar methods. The evaluation was done using the realistic NCAT phantom with organ time activities that model 111In ibritumomab tiuxetan. Projection data were obtained using Monte Carlo simulations (MCS) that realistically model the image formation process including penetration and scatter in the collimator-detector system. These projection data were used to evaluate the accuracy of residence time estimation using a time series of QSPECT studies, a single QSPECT study combined with planar scans and the planar scans alone. The errors in the residence time estimates were <3.8%, <15%, and 2%–107% for the QSPECT, hybrid planar/QSPECT, and planar methods, respectively. The quantitative accuracy was worst for pure planar processing and best for pure QSPECT processing. Hybrid planar/QSPECT methods, where a single QSPECT study was combined with a series of planar scans, provided a large and statistically significant improvement

  11. Radioimmunotherapy and Autologous Stem-Cell Transplantation in the Treatment of B-Cell Non-Hodgkin Lymphoma.

    PubMed

    Shimoni, Avichai; Zwas, Shifra Tzila

    2016-03-01

    High-dose chemotherapy and autologous stem-cell transplantation (ASCT) is the standard therapy for patients with chemosensitive-relapsed or chemosensitive-refractory aggressive lymphoma. The use of rituximab, an anti-CD20 monoclonal antibody, has dramatically changed the outcome of patients with aggressive lymphoma, increasing both response and survival rates. However, despite this progress a significant proportion of patients are still refractory or relapse after frontline rituximab-containing therapy. Moreover, it is increasingly more difficult to rescue these patients with current salvage chemotherapy and ASCT approaches. Novel approaches are needed for these high-risk patients, especially in the rituximab era. Radioimmunotherapy (RIT) is a form of targeted therapy using the parent monoclonal antibody to deliver radiation emitted by a conjugated radioisotope, to the vicinity of antigen-positive tissues. Two radioimmunoconjugates--yttrium-90 ibritumomab tiuxetan (Zevalin) and iodine-131 tositumomab (Bexxar) have been in clinical use. There are multiple studies demonstrating the safety and efficacy of both agents in both indolent and aggressive lymphoma. Radiolabeled antibodies are ideal candidates to combine with high-dose chemotherapy and ASCT. RIT targets radiation to disease sites while limiting exposure of uninvolved critical organs, thus it can safely replace total-body irradiation during conditioning for ASCT. The major toxicity and limiting factor in RIT is myelotoxicity that is easily reversed by stem-cell rescue. RIT can be combined at standard doses with high-dose chemotherapy or can be given in escalated doses either alone or with high-dose chemotherapy before ASCT. Several phase II studies have shown the safety and potential efficacy of both agents using these approaches. A small randomized study comparing standard-dose Zevalin with combination of carmustine, etoposide, cytarabine, and melphalan (BEAM) high-dose chemotherapy and BEAM alone suggested a

  12. 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. PMID:17043628

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

    PubMed Central

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

    2009-01-01

    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

  14. 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

  15. Gateways to clinical trials.

    PubMed

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

    2005-06-01

    , fluvastatin sodium, fondaparinux sodium; Gaboxadol, gamma-hydroxybutyrate sodium, gefitinib, gelclair, gemcitabine, gemfibrozil, glibenclamide, glyminox; Haloperidol, heparin sodium, HPV 16/HPV 18 vaccine, human insulin, human insulin; Icatibant, imatinib mesylate, indium 111 (111In) ibritumomab tiuxetan, infliximab, INKP-100, iodine (I131) tositumomab, IoGen, ipratropium bromide, ixabepilone; L-870810, lamivudine, lapatinib, laquinimod, latanoprost, levonorgestrel, licochalcone a, liposomal doxorubicin, lopinavir, lopinavir/ritonavir, lorazepam, lovastatin; Maraviroc, maribavir, matuzumab, MDL-100907, melphalan, methotrexate, methylprednisolone, mitomycin, mitoxantrone hydrochloride, MK-0431, MN-001, MRKAd5 HIV-1 gag/pol/nef, MRKAd5gag, MVA.HIVA, MVA-BN Nef, MVA-Muc1-IL-2, mycophenolate mofetil; Nelfinavir mesilate, nesiritide, NSC-330507; Olanzapine, olmesartan medoxomil, omalizumab, oral insulin, osanetant; PA-457, paclitaxel, paroxetine, paroxetine hydrochloride, PCK-3145, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, perillyl alcohol, pexelizumab, pimecrolimus, pitavastatin calcium, porfiromycin, prasterone, prasugrel, pravastatin sodium, prednisone, pregabalin, prinomastat, PRO-2000, propofol, prostate cancer vaccine; Rasagiline mesilate, rhBMP-2/ACS, rhBMP-2/BCP, rhC1, ribavirin, rilpivirine, ritonavir, rituximab, Ro-26-9228, rosuvastatin calcium, rosuvastatin sodium, rubitecan; Selodenoson, simvastatin, sirolimus, sitaxsentan sodium, sorafenib, SS(dsFv)-PE38, St. John's Wort extract, stavudine; Tacrolimus, tadalafil, tafenoquine succinate, talaglumetad, tanomastat, taxus, tegaserod maleate, telithromycin, tempol, tenofovir, tenofovir disoproxil fumarate, testosterone enanthate, TH-9507, thalidomide, tigecycline, timolol maleate, tiotropium bromide, tipifarnib, torcetrapib, trabectedin, travoprost, travoprost/timolol, treprostinil sodium; Valdecoxib, vardenafil hydrochloride hydrate, varenicline, VEGF-2 gene therapy, venlafaxine hydrochloride

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

    PubMed

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

    2009-02-01

    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

  17. The Impact of 3D Volume-of-Interest Definition on Accuracy and Precision of Activity Estimation in Quantitative SPECT and Planar Processing Methods

    PubMed Central

    He, Bin; Frey, Eric C.

    2010-01-01

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

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

    PubMed

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

    2007-08-01

    Anti-CD20 monoclonal antibodies (mAbs), unlabeled rituximab (Rituxan, Biogen Idec Inc., Cambridge, MA; and Genentech Inc., South San Francisco, CA) or radiolabeled 90Y-ibritumomab (Zevalin, Biogen Idec Inc., Cambridge, MA) and 131I-tositumomab (Bexxar; Glaxo Smith Kline, Research Triangle Park, NC), have proven to be effective therapy for non-Hodgkin's lymphoma (NHL), but also induce immediate and persistent decreases in normal peripheral blood lymphocytes (PBLs). Lym-1, a mAb that selectively targets malignant lymphocytes, also has induced therapeutic responses and prolonged survival in patients with NHL when labeled with iodine-131 (131I). We have retrospectively examined its effect on PBLs in 41 NHL patients that had received 131I-Lym-1 therapy. Absolute lymphocyte counts (ALCs) were evaluated before and after the first and last 131I-Lym-1 infusion. Modest decreases in PBLs were observed in most of the patients. Using strict criteria to define recovery, time to recovery was determined for 19 patients, with the remainder censored because of insufficient follow-up (median follow up for censored patients: 22 days). Using Kaplan-Meier estimates, it would be predicted that 31% of patients would recover by 28 days and that median time to recovery would be 44 days after the last 131I-Lym-1 infusion. No predictors were found for time to recovery, considering such factors as the administered Lym-1 or 131I dose, spleen volume, or radiation doses to the body, marrow, or spleen. The data suggest that the effect of 131I-Lym-1 on ALC is the result of a nonspecific radiation effect, rather than a specific Lym-1 mAb effect. The shorter time required for ALC recovery after 131I-Lym-1 when compared to that reported for anti-CD20 mAbs, whether radiolabeled or otherwise, is probably related to differing mechanisms for lymphocytotoxicity and lesser Lym-1 antigenic density on normal B-lymphocytes. PMID:17803447

  19. Theranostic Imaging of Yttrium-90.

    PubMed

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

    2015-01-01

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

  20. Theranostic Imaging of Yttrium-90

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-06-01

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

  2. Post-radioembolization yttrium-90 PET/CT - part 1: diagnostic reporting

    PubMed Central

    2013-01-01

    Background Yttrium-90 (90Y) positron emission tomography with integrated computed tomography (PET/CT) represents a technological leap from 90Y bremsstrahlung single-photon emission computed tomography with integrated computed tomography (SPECT/CT) by coincidence imaging of low abundance internal pair production. Encouraged by favorable early experiences, we implemented post-radioembolization 90Y PET/CT as an adjunct to 90Y bremsstrahlung SPECT/CT in diagnostic reporting. Methods This is a retrospective review of all paired 90Y PET/CT and 90Y bremsstrahlung SPECT/CT scans over a 1-year period. We compared image resolution, ability to confirm technical success, detection of non-target activity, and providing conclusive information about 90Y activity within targeted tumor vascular thrombosis. 90Y resin microspheres were used. 90Y PET/CT was performed on a conventional time-of-flight lutetium-yttrium-oxyorthosilicate scanner with minor modifications to acquisition and reconstruction parameters. Specific findings on 90Y PET/CT were corroborated by 90Y bremsstrahlung SPECT/CT, 99mTc macroaggregated albumin SPECT/CT, follow-up diagnostic imaging or review of clinical records. Results Diagnostic reporting recommendations were developed from our collective experience across 44 paired scans. Emphasis on the continuity of care improved overall diagnostic accuracy and reporting confidence of the operator. With proper technique, the presence of background noise did not pose a problem for diagnostic reporting. A counter-intuitive but effective technique of detecting non-target activity is proposed, based on the pattern of activity and its relation to underlying anatomy, instead of its visual intensity. In a sub-analysis of 23 patients with a median follow-up of 5.4 months, 90Y PET/CT consistently outperformed 90Y bremsstrahlung SPECT/CT in all aspects of qualitative analysis, including assessment for non-target activity and tumor vascular thrombosis. Parts of viscera closely

  3. 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.

  4. 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

  5. Yttrium-90 Radioembolization for Colorectal Cancer Liver Metastases: A Single Institution Experience

    PubMed Central

    Nace, Gary W.; Steel, Jennifer L.; Amesur, Nikhil; Zajko, Albert; Nastasi, Bryon E.; Joyce, Judith; Sheetz, Michael; Gamblin, T. Clark

    2011-01-01

    Purpose. We sought to evaluate our experience using yttrium-90 (90Y) resin microsphere hepatic radioembolization as salvage therapy for liver-dominant metastatic colorectal cancer (mCRC). Methods. A retrospective review of consecutive patients with unresectable mCRC who were treated with 90Y after failing first and second line systemic chemotherapy. Demographics, treatment dose, biochemical and radiographic response, toxicities, and survival were examined. Results. Fifty-one patients underwent 90Y treatments of which 69% were male. All patients had previously undergone extensive chemotherapy, 31% had undergone previous liver-directed therapy and 24% had a prior liver resection. Using RECIST criteria, either stable disease or a partial response was seen in 77% of patients. Overall median survival from the time of first 90Y treatment was 10.2 months (95% CI = 7.5–13.0). The absence of extrahepatic disease at the time of treatment with 90Y was associated with an improved survival, median survival of 17.0 months (95% CI = 6.4–27.6), compared to those with extrahepatic disease at the time of treatment with 90Y, 6.7 months (95% CI = 2.7–10.6 Conclusion: 90Y therapy is a safe locoregional therapy that provides an important therapeutic option to patients who have failed first and second line chemotherapy and have adequate liver function and performance status. PMID:22312513

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

    PubMed Central

    2013-01-01

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

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

    SciTech Connect

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

    2014-04-01

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

  8. Transfer standard for beta decay radionuclides in radiotherapy.

    PubMed

    Thieme, Klaus; Beinlich, Uwe; Fritz, Eberhard

    2004-01-01

    The measurement of the activity of therapeutic radiopharmaceuticals prior to the administration to patients is normally achieved via the use of radionuclide calibrators. An accurate measurement of the activity of pure beta-emitters is complex. Calibration problems can be solved by combining a primary calibration with a 90Y reference solution and a 90Sr/90Y transfer standard with a solid source, simulating geometric effects caused by high energetic beta radiation. The recent development of a 90Sr/90Y transfer standard for this purpose is reported. PMID:14987695

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. A new method for determining the efficiency of large-area beta sources constructed from anodized aluminum foils.

    PubMed

    Stanga, D; Maringer, F J; Ionescu, E

    2011-01-01

    A new method has been developed for determining the efficiency of large-area beta sources in anodized aluminum foils using transmission measurements. The method was applied to the efficiency measurement of a (90)Sr-(90)Y large-area reference source. Measurement results show that the method can provide efficiency values for (90)Sr-(90)Y reference sources with standard uncertainties smaller than 2.9%, which are far below the limit of 10% required by ISO 8769. PMID:20817476

  16. Particle delivery to the benthos of coastal Lake Michigan

    NASA Astrophysics Data System (ADS)

    Waples, James T.

    2015-12-01

    A 2-D non-steady state model was applied to measured profiles of 234Th/238U and 90Y/90Sr disequilibria in a shallow (22 m) water column of coastal Lake Michigan. Downward fluxes of 234Th and 90Y were primarily driven by onshore horizontal advection. Concordance between 234Th and 90Y-derived mass flux estimates from the water column could only be realistically achieved under a nuclide scavenging scenario dominated by direct sorption on bottom or near-bottom sediment and vertical convection in the water column—not sinking particles. An estimated vertical 234Th/90Y flux ratio of ˜0.31 in the water column agreed with measured 234Th/90Y activity ratios on collected ejecta from bottom dwelling dreissenid mussels (0.26 ± 0.05) and not with water column particles (3.3 ± 1.3). A similar 238U/90Sr parent nuclide activity ratio of 0.30 ± 0.02 suggests that both 234Th and 90Y are scavenged in toto below the maximum sampling depth (17 m) and near the sediment/water interface. Determining the mechanism by which particles are transported to the bottom is important for understanding not only how benthos are supplied with water column material, but also how particle fluxes should be measured and calculated.

  17. Synergy of Taxol and radioimmunotherapy with yttrium-90-labeled chimeric L6 antibody: Efficacy and toxicity in breast cancer xenografts

    PubMed Central

    DeNardo, Sally J.; Kukis, David L.; Kroger, Linda A.; O’Donnell, Robert T.; Lamborn, Kathleen R.; Miers, Laird A.; DeNardo, David G.; Meares, Claude F.; DeNardo, Gerald L.

    1997-01-01

    Synergistic multimodality therapy is needed for breast cancer. Breast cancer frequently has p53 mutations that result in cells less likely to undergo apoptosis when exposed to DNA damaging therapies. Taxol (paclitaxel) is more effective in the presence of mutant p53. 90Y-labeled DOTA-peptide-ChL6 (90Y-ChL6, where ChL6 is chimeric L6 antibody and DOTA is 1,4,7,10-tetraazacyclododecane-N,N′,N",N‴-tetraacetic acid) is a novel radioimmunoconjugate for targeting radiation to cancer. It has a stable metal chelator and a peptide linker that can be catabolized by hepatic lysozymes. This study was designed to assess potential synergism between Taxol and 90Y-ChL6 in a highly anaplastic breast cancer model, HBT 3477. There was no tumor response in mice receiving ChL6 or Taxol alone. In mice receiving 90Y-ChL6 alone, 79% (15 of 19) of tumors responded although none were cured. If Taxol was administered 24–72 hours before 90Y-ChL6, again, 79% (23 of 29) of tumors responded but 21% were cured. When Taxol was administered 6 or 24 hours after 90Y-ChL6, 100% (46 of 46) of tumors responded and 48% were cured. Taxol given with 90Y-ChL6 did not substantially increase toxicity. Enhancement of the therapeutic effect when Taxol was added to 90Y-ChL6 therapy for HBT 3477 xenografts was striking. The synergistic therapeutic effect of Taxol with 90Y-ChL6 may relate to the p53 mutant status and BCL2 expression in HBT 3477 cells, observations that increase the likelihood that the results of this study are relevant to therapy for breast cancer in patients. In conclusion, Taxol seemed to be synergistic with 90Y-ChL6 in this human breast cancer model. Up to 50% of these anaplastic breast cancer xenografts were cured by combined modality therapy. PMID:9108094

  18. 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.

  19. 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.

  20. 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.

  1. [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.

  2. 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.

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

    SciTech Connect

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

    2005-01-15

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-02-01

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

  5. Yttrium-90 hepatic radioembolization: clinical review and current techniques in interventional radiology and personalized dosimetry.

    PubMed

    Tong, Aaron K T; Kao, Yung Hsiang; Too, Chow Wei; Chin, Kenneth F W; Ng, David C E; Chow, Pierce K H

    2016-06-01

    In recent years, yttrium-90 ((90)Y) microsphere radioembolization has been establishing itself as a safe and efficacious treatment for both primary and metastatic liver cancers. This extends to both first-line therapies as well as in the salvage setting. In addition, radioembolization appears efficacious for patients with portal vein thrombosis, which is currently a contraindication for surgery, transplantation and transarterial chemoembolization. This article reviews the efficacy and expanding use of (90)Y microsphere radioembolization with an added emphasis on recent advances in personalized dosimetry and interventional radiology techniques. Directions for future research into combination therapies with radioembolization and expansion into sites other than the liver are also explored. PMID:26943239

  6. Post-radioembolization yttrium-90 PET/CT - part 2: dose-response and tumor predictive dosimetry for resin microspheres

    PubMed Central

    2013-01-01

    Background Coincidence imaging of low-abundance yttrium-90 (90Y) internal pair production by positron emission tomography with integrated computed tomography (PET/CT) achieves high-resolution imaging of post-radioembolization microsphere biodistribution. Part 2 analyzes tumor and non-target tissue dose-response by 90Y PET quantification and evaluates the accuracy of tumor 99mTc macroaggregated albumin (MAA) single-photon emission computed tomography with integrated CT (SPECT/CT) predictive dosimetry. Methods Retrospective dose quantification of 90Y resin microspheres was performed on the same 23-patient data set in part 1. Phantom studies were performed to assure quantitative accuracy of our time-of-flight lutetium-yttrium-oxyorthosilicate system. Dose-responses were analyzed using 90Y dose-volume histograms (DVHs) by PET voxel dosimetry or mean absorbed doses by Medical Internal Radiation Dose macrodosimetry, correlated to follow-up imaging or clinical findings. Intended tumor mean doses by predictive dosimetry were compared to doses by 90Y PET. Results Phantom studies demonstrated near-perfect detector linearity and high tumor quantitative accuracy. For hepatocellular carcinomas, complete responses were generally achieved at D70 > 100 Gy (D70, minimum dose to 70% tumor volume), whereas incomplete responses were generally at D70 < 100 Gy; smaller tumors (<80 cm3) achieved D70 > 100 Gy more easily than larger tumors. There was complete response in a cholangiocarcinoma at D70 90 Gy and partial response in an adrenal gastrointestinal stromal tumor metastasis at D70 53 Gy. In two patients, a mean dose of 18 Gy to the stomach was asymptomatic, 49 Gy caused gastritis, 65 Gy caused ulceration, and 53 Gy caused duodenitis. In one patient, a bilateral kidney mean dose of 9 Gy (V20 8%) did not cause clinically relevant nephrotoxicity. Under near-ideal dosimetric conditions, there was excellent correlation between intended tumor mean doses by predictive dosimetry and those

  7. Preparation of (90)YCl(3) radiopharmaceutical precursor for nuclear medicine using technology of centrifugal extractors.

    PubMed

    Srank, J; Melichar, F; Filyanin, A T; Tomes, M; Beran, M

    2010-12-01

    Separation of (90)Y from a parent solution of (90)Sr-(90)Y in 0.5 M nitric acid by two-stage liquid-liquid extraction has been investigated using centrifugal extractors. The extraction agent used was 0.25 M di-(2-ethylhexyl)phosphoric acid (D2EHPA) in n-dodecane. Back-extraction used 5 M HCl. Evaporation of HCl was performed in a rotary vacuum evaporator. Experience gained during the design, construction and running of more than 100 hot separations is presented. A short description of analytical methods used and results of the determination of chemical, radionuclidic and radiochemical purities and sterility are given. PMID:20692176

  8. Side Effects of Yttrium-90 Radioembolization

    PubMed Central

    Riaz, Ahsun; Awais, Rafia; Salem, Riad

    2014-01-01

    Limited therapeutic options are available for hepatic malignancies. Image guided targeted therapies have established their role in management of primary and secondary hepatic malignancies. Radioembolization with yttrium-90 (90Y) microspheres is safe and efficacious for treatment of hepatic malignancies. The tumoricidal effect of radioembolization is predominantly due to radioactivity and not ischemia. This article will present a comprehensive review of the side effects that have been associated with radioembolization using 90Y microspheres. Some of the described side effects are associated with all transarterial procedures. Side effects specific to radioembolization will also be discussed in detail. Methods to decrease the incidence of these potential side effects will also be discussed. PMID:25120955

  9. Radioembolization in the Treatment of Neuroendocrine Tumor Metastases to the Liver

    PubMed Central

    Vyleta, Martin; Coldwell, Douglas

    2011-01-01

    Surgical excision remains the preferred treatment for resectable hepatic metastases of neuroendocrine tumors. In cases of more disseminated hepatic disease, transarterial radioembolization with Yttrium-90- (90Y-) labeled microspheres has been demonstrated as a viable option for symptom and locoregional tumor control. On an outpatient basis, radioembolization can be utilized from early line to salvage phases, in various combinations with systemic therapies. Review of available data shows encouraging safety and efficacy profiles for the intraarterial application of 90Y for the treatment of mNETs of the liver. Symptom control and decrease in somatostatin analog use can be achieved, as well as prolonged survival. PMID:22235376

  10. Dose distribution to spinal structures from intrathecally administered yttrium-90

    NASA Astrophysics Data System (ADS)

    Mardirossian, George; Hall, Michael; Montebello, Joseph; Stevens, Patrick

    2006-01-01

    Previous treatment of cerebrospinal fluid (CSF) malignancies by intrathecal administration of 131I-radiolabelled monoclonal antibodies has led to the assumption that more healthy tissue will be spared when a pure beta-emitter such as 90Y replaces 131I. The purpose of this study is to compare and quantitatively evaluate the dose distribution from 90Y to the CSF space and its surrounding spinal structures to 131I. A 3D digital phantom of a section of the T-spine was constructed from the visible human project series of images which included the spinal cord, central canal, subarachnoid space, pia mater, arachnoid, dura mater, vertebral bone marrow and intervertebral disc. Monte Carlo N-particle (MCNP4C) was used to model the 90Y and 131I radiation distribution. Images of the CSF compartment were convolved with the radiation distribution to determine the dose within the subarachnoid space and surrounding tissues. 90Y appears to be a suitable radionuclide in the treatment of central nervous system (CNS) malignancies when attached to mAb's and the dose distribution would be confined largely within the vertebral foramen. This choice may offer favourable dose improvement to the subarachnoid and surface of spinal cord over 131I in such an application.

  11. 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…

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

    NASA Astrophysics Data System (ADS)

    Lubberink, Mark; Lundqvist, Hans; Tolmachev, Vladimir

    2002-02-01

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

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

    PubMed

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

    2015-12-01

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

  14. The role of 18F-FDG positron emission tomography in the follow-up of liver tumors treated with 90Yttrium radioembolization

    PubMed Central

    Bagni, Oreste; Filippi, Luca; Schillaci, Orazio

    2015-01-01

    In the last years, radioembolization (RE) has emerged as a novel technique for the treatment of malignant hepatic lesions using 90Y embedded in spheres, which are infused directly into the hepatic arterial circulation. 90Y-spheres, once implanted in liver, can release a significant radiation burden to neoplastic cells with a relative low dose to normal parenchyma. 90Y RE results as a combination of embolization and radiation therapy, thus the standard radiologic follow up modalities may be not sufficiently accurate to assess tumor response to treatment. 18Fluoro-deoxyglucose Positron Emission Tomography (18F-FDG PET) detects glucose uptake and metabolic activity in tumor cells. 18F-FDG PET has become a well established diagnostic tool in many oncological scenarios. Furthermore, PET response criteria (PERCIST) have been recently introduced to categorize the metabolic response to therapy of cancer patients. Several semiquantitative parameters, such as SUVmax and its changes, the Functional Tumor Volume and the Total Lesion Glycolysis can be useful to accurately assess tumor changes after therapy. The purpose of this article is to present the literature on the role of 18F-FDG PET in the evaluation of patients with primary and secondary liver tumors treated with 90Y RE. PMID:26069856

  15. 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.

  16. Use Of Yttrium-90 Microspheres In Patients With Advanced Hepatocellular Carcinoma & Portal Vein Thrombosis

    PubMed Central

    Tsai, Andrea L.; Burke, Charles T.; Kennedy, Andrew S.; Moore, Dominic T.; Mauro, Matthew A.; Dixon, Robert D.; Stavas, Joseph M.; Bernard, Stephen A.; Khandani, Amir H.; O'Neil, Bert H.

    2010-01-01

    Purpose Patients with portal vein thrombosis (PVT) and hepatocellular carcinoma (HCC) have limited treatment options due to increased disease burden and diminished hepatic perfusion. 90Y-microspheres may be better tolerated than chemoembolization in these patients. Here we review the safety and efficacy of 90Y-microsphere use for HCC with major PVT. Materials and Methods A retrospective review of HCC with main (n=10) or first (n=12) branch PVT treated with 90Y-microspheres (n=22) was conducted. CLIP scores ranged from 2 to 5 with 18% scoring 4 or greater. Response was determined 8-12 weeks following treatment using magnetic resonance or computed tomography and RECIST criteria. Overall survival was estimated by the Kaplan-Meier method. Results 32 treatments (26 glass, 6 resin) were administered to 22 patients. Common grade 1–2 toxicities included abdominal pain (38%), nausea (28%), fatigue (22%). Four post-therapy hospitalizations occurred, all <48hrs in duration. 1 death occurred 10 days following therapy Response data: 2 partial responses, progressive disease 42%, stable disease 50% of treatments. Median overall survival (OS) was 7 months from time of initial 90Y-microsphere treatment. Child-Pugh A patients had a median OS of 7.7 months; B and C = 2.7 months (p = 0.01). Median OS for CLIP scores 2–3 was 7 months versus 1.3 months for scores 4–5 (p = 0.04). Conclusions 90Y-microspheres are tolerated in patients with HCC and major PVT. Compared with chemoembolization, rates of severe adverse events appear low. Radiographic response rates are low. Median OS of 7 months is promising and warrants further study versus systemic therapy. PMID:20691606

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

    NASA Astrophysics Data System (ADS)

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

    2007-09-01

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

  18. Initial clinical experience evaluating Yttrium-90-chimeric T84.66 anticarcinoembryonic antigen antibody and autologous hematopoietic stem cell support in patients with carcinoembryonic antigen-producing metastatic breast cancer.

    PubMed

    Wong, J Y; Somlo, G; Odom-Maryon, T; Williams, L E; Liu, A; Yamauchi, D; Wu, A M; Yazaki, P; Wilczynski, S; Shively, J E; Forman, S; Doroshow, J H; Raubitschek, A A

    1999-10-01

    cT84.66 is a human/murine IgG1 with high affinity and specificity for carcinoembryonic antigen (CEA). An earlier Phase I trial defined the maximum tolerated dose for 90Y-diethylenetriaminepentaacetic acid (DTPA)-cT84.66 at 22 mCi/m2. Dose-limiting toxicities were reversible leukopenia and thrombocytopenia. The purpose of this Phase I trial was to evaluate the feasibility and toxicities of administering higher activities of 90Y-DTPA-cT84.66 with stem cell support in patients with CEA-producing breast cancer. Patients with CEA-producing breast cancer refractory to standard therapies underwent peripheral stem cell collection followed by infusion of 111indium-DTPA-cT84.66. Those patients demonstrating tumor targeting received a single therapy dose of 90Y-DTPA-cT84.66, followed by Ca-DTPA infusion for 72 h posttherapy. Stem cells were reinfused following a divided schedule. To date, seven patients have been accrued to this trial. Each patient received an imaging dose of (111)In-cT84.66. Six patients demonstrated tumor imaging and received a single cycle of 90Y-cT84.66 at 15 mCi/m2 (three patients) and 22.5 mCi/m2 (three patients). One patient did not demonstrate tumor imaging and was not treated. At these administered activities, 90Y-cT84.66 was well tolerated. No dose-limiting toxicities have been observed. All patients demonstrated hematopoietic recovery after stem cell infusion. One patient demonstrated stable disease for 4 months; one patient had stable disease and reduction of bone pain for 3 months; and a third patient experienced >50% reduction of an ovarian metastasis, resolution of malignant pleural effusion, stable pleural metastases, and stable bone scan for 14 months. Preliminary results from this ongoing Phase I trial are promising and demonstrate the feasibility and potential for antitumor effects of stem cell supported 90Y-cT84.66 therapy in patients with CEA-producing breast cancers. PMID:10541368

  19. A quick liquid scintillation counting technique for analysis of ⁹⁰Sr in environmental samples.

    PubMed

    Wang, Jeng-Jong

    2013-11-01

    In this study, to improve the problem of waiting for the growth of (90)Y for Cerenkov counting and save the time of (90)Sr analysis, an organic cocktail sample was counted by a liquid scintillation counting system immediately after the purification of (90)Sr without waiting for the growth of (90)Y. The chemical separation and the measurement procedures for (90)Sr radioactivity analysis can be completed in 24h. In order to verify the performance of the improved method, the activity of (90)Sr in six environmental reference samples was determined after radiochemical purification with a crown-ether resin column, and subsequent measurement by both the Cerenkov and the organic cocktail liquid scintillation counting methods. The results revealed that the organic cocktail liquid scintillation counting was quicker and had higher efficiency and lower minimum detectable activity (MDA) than the Cerenkov counting. PMID:23582495

  20. 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

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

    PubMed Central

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

    2005-01-01

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

  2. 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

  3. Current status of transarterial radioembolization.

    PubMed

    Mahnken, Andreas H

    2016-05-28

    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: (90)Y-resin and (90)Y-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

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

    PubMed

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

    2016-01-21

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

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

    SciTech Connect

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

    2011-11-01

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

  6. Estimation of the radiation dose from radiotherapy for skin haemangiomas in childhood: the ICTA software for epidemiology

    NASA Astrophysics Data System (ADS)

    Shamsaldin, A.; Lundell, M.; Diallo, I.; Ligot, L.; Chavaudra, J.; de Vathaire, F.

    2000-12-01

    Radium applicators and pure beta emitters have been widely used in the past to treat skin haemangioma in early childhood. A well defined relationship between the low doses received from these applicators and radiation-induced cancers requires accurate dosimetry. A human-based CT scan phantom has been used to simulate every patient and treatment condition and then to calculate the source-target distance when radium and pure beta applicators were used. The effective transmission factor ϕ(r) for the gamma spectrum emitted by the radium sources applied on the skin surface was modelled using Monte Carlo simulations. The well-known quantization approach was used to calculate gamma doses delivered from radium applicators to various anatomical points. For 32P, 90Sr/90Y applicators and 90Y needles we have used the apparent exponential attenuation equation. The dose calculation algorithm was integrated into the ICTA software (standing for a model that constructs an Individualized phantom based on CT slices and Auxological data), which has been developed for epidemiological studies of cohorts of patients who received radium and beta-treatments for skin haemangioma. The ϕ(r) values obtained for radium skin applicators are in good agreement with the available values in the first 10 cm but higher at greater distances. Gamma doses can be calculated with this algorithm at 165 anatomical points throughout the body of patients treated with radium applicators. Lung heterogeneity and air crossed by the gamma rays are considered. Comparison of absorbed doses in water from a 10 mg equivalent radium source simulated by ICTA with those measured at the Radiumhemmet, Karolinska Hospital (RAH) showed good agreement, but ICTA estimation of organ doses did not always correspond those estimated at the RAH. Beta doses from 32P, 90Sr/90Y applicators and 90Y needles are calculated up to the maximum beta range (11 mm).

  7. A Pretherapy Biodistribution and Dosimetry Study of Indium-111-Radiolabeled Trastuzumab in Patients with Human Epidermal Growth Factor Receptor 2-Overexpressing Breast Cancer

    PubMed Central

    Raubitschek, Andrew; Yamauchi, Dave; Williams, Lawrence E.; Wu, Anna M.; Yazaki, Paul; Shively, John E.; Colcher, David; Somlo, George

    2010-01-01

    Abstract Purpose The purposes of this study were to evaluate the organ biodistribution, pharmacokinetics, immunogenicity, and tumor uptake of 111Indium (111In)-MxDTPA-trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancers and to determine whether 90Y-MxDTPA-trastuzumab should be evaluated in subsequent clinical therapy trials. Experimental Design Patients with HER2-overexpressing breast cancers who were to undergo planned trastuzumab therapy first received unlabeled trastuzumab (4–8 mg/kg IV), followed 4 hours later by 5 mCi 111In-MxDTPA-trastuzumab (10 mg antibody). Serial blood samples, 24-hour urine collections, and nuclear scans were performed at defined time points for 7 days. Results Eight (8) patients received 111In-MxDTPA-trastuzumab, which was well tolerated with no adverse side-effects. Three (3) of 7 patients with known lesions demonstrated positive imaging on nuclear scans. No antiantibody responses were observed for 2 months postinfusion. Organ doses (cGy/mCi) assuming radiolabeling with 90Y were 19.9 for heart wall, 17.6 for liver, 4.6 for red marrow, and 2.8 for the whole body. Tumor doses ranged from 24 to 172 cGy/mCi. Conclusions In summary, results from this study indicate that 90Y-MxDTPA-trastuzumab is an appropriate agent to evaluate in therapy trials. No evidence of an immune response to 111In-MxDTPA-trastuzumab was detected, predicting for the ability to administer multiple cycles. With the exception of cardiac uptake, pharmacokinetics and organ biodistribution were comparable to other 90Y-labeled monoclonal antibodies previously evaluated in the clinic. Cardiac uptake was comparable to hepatic uptake and therefore predicted to not be prohibitively high as to result in dose-limiting cardiotoxicity. PMID:20707718

  8. 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

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

    SciTech Connect

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

    1995-05-01

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

  10. Brachytherapy treatment simulation of strontium-90 and ruthenium-106 plaques on small size posterior uveal melanoma using MCNPX code

    NASA Astrophysics Data System (ADS)

    Barbosa, N. A.; da Rosa, L. A. R.; Facure, A.; Braz, D.

    2014-02-01

    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 aim of this work consisted in using the Monte Carlo code MCNPX to calculate the 3D dose distribution on a mathematical model of the human eye, considering 90Sr/90Y and 160Ru/160Rh beta-ray eye applicators, in order to treat a posterior uveal melanoma with a thickness 3.8 mm from the choroid surface. Mathematical models were developed for the two ophthalmic applicators, CGD produced by BEBIG Company and SIA.6 produced by the Amersham Company, with activities 1 mCi and 4.23 mCi respectively. They have a concave form. These applicators' mathematical models were attached to the eye model and the dose distributions were calculated using the MCNPX *F8 tally. The average doses rates were determined in all regions of the eye model. The *F8 tally results showed that the deposited energy due to the applicator with the radionuclide 106Ru/106Rh is higher in all eye regions, including tumor. However the average dose rate in the tumor region is higher for the applicator with 90Sr/90Y, due to its high activity. Due to the dosimetric characteristics of these applicators, the PDD value for 3 mm water is 73% for the 106Ru/106Rh applicator and 60% for 90Sr/90Y applicator. For a better choice of the applicator type and radionuclide it is important to know the thickness of the tumor and its location.

  11. 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.

  12. Pulsed high intensity focused ultrasound increases penetration and therapeutic efficacy of monoclonal antibodies in murine xenograft tumors

    PubMed Central

    Wang, Shutao; Shin, In Soo; Hancock, Hilary; Jang, Beom-su; Kim, Hyung-sub; Lee, Sang Myung; Zderic, Vesna; Frenkel, Victor; Pastan, Ira; Paik, Chang H.; Dreher, Matthew R.

    2014-01-01

    The success of radioimmunotherapy for solid tumors remains elusive due to poor biodistribution and insufficient tumor accumulation, in part, due to the unique tumor microenvironment resulting in heterogeneous tumor antibody distribution. Pulsed high intensity focused ultrasound (pulsed-HIFU) has previously been shown to increase the accumulation of 111In labeled B3 antibody (recognizes Lewisy antigen). The objective of this study was to investigate the tumor penetration and therapeutic efficacy of pulsed-HIFU exposures combined with 90Y labeled B3 mAb in an A431 solid tumor model. The ability of pulsed-HIFU (1 MHz, spatial averaged temporal peak intensity = 2685 Wcm−2; pulse repetition frequency = 1 Hz; duty cycle = 5%) to improve the tumor penetration and therapeutic efficacy of 90Y labeled B3 mAb (90Y-B3) was evaluated in Ley-positive A431 tumors. Antibody penetration from the tumor surface and blood vessel surface was evaluated with fluorescently labeled B3, epi-fluorescent microscopy, and custom image analysis. Tumor size was monitored to determine treatment efficacy, indicated by survival, following various treatments with pulsed-HIFU and/or 90Y-B3. The pulsed-HIFU exposures did not affect the vascular parameters including microvascular density, vascular size, and vascular architecture; although 1.6-fold more antibody was delivered to the solid tumors when combined with pulsed-HIFU. The distribution and penetration of the antibodies were significantly improved (p-value < 0.05) when combined with pulsed-HIFU, only in the tumor periphery. Pretreatment with pulsed-HIFU significantly improved (p-value < 0.05) survival over control treatments. PMID:22732476

  13. Patient biodistribution of intraperitoneally administered yttrium-90-labeled antibody.

    PubMed

    Hnatowich, D J; Chinol, M; Siebecker, D A; Gionet, M; Griffin, T; Doherty, P W; Hunter, R; Kase, K R

    1988-08-01

    Although 90Y is one of the best radionuclides for radioimmunotherapeutic applications, the lack of gamma rays in its decay complicates the estimation of radiation dose since its biodistribution cannot be accurately determined by external imaging. A limited clinical trial has been conducted with tracer doses (1 mCi) of 90Y in five patients who then received second-look surgery such that tissue samples were obtained for accurate radioactivity quantitation by in vitro counting. The anti-ovarian antibody OC-125 as the F(ab')2 fragment was coupled with diethylenetriaminepentaacetic acid, radiolabeled with 90Y and administered intraperitoneally to patients with suspected or documented ovarian cancer. Size exclusion and ion exchange high performance liquid chromatography analysis of patient ascitic fluid and serum samples showed no evidence of radiolabel instability although a high molecular weight species (presumably immune complex) was observed in three patients. Total urinary excretion of radioactivity prior to surgery averaged 7% of the administered radioactivity while at surgery the mean organ accumulation was 8% of the administered radioactivity in serum, 10% in liver, 7% in bone marrow, and 19% in bone with large patient to patient variation. The mean tumor/normal tissue radioactivity ratio varied between 3 and 25. On the assumption that the above radioactivity levels were achieved immediately following administration, that the radioactivity remained in situ until decayed and that the dimensions of tumor were sufficient to completely attenuate the emissions of 90Y, the dose to tumor for a 1-mCi administration would be approximately 50 rad with normal tissues receiving approximately 8 rad. PMID:3404257

  14. 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. PMID:22917942

  15. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2008-01-01

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

  17. Can imaging patterns of neuroendocrine hepatic metastases predict response yttruim-90 radioembolotherapy?

    PubMed Central

    Neperud, Julia; Mahvash, Armeen; Garg, Naveen; Murthy, Ravi; Szklaruk, Janio

    2013-01-01

    AIM: To evaluate the response to treatment in patients with neuroendocrine tumor liver metastases following yttrium-90 (90Y) radioembolotherapy, as a function of image patterns at presentation for 90Y radioembolotherapy. METHODS: The study cohort consisted of patients with hepatic metastatic neuroendocrine tumors treated with 90Y at our institution during a two-year time period. Hepatic metastases were evaluated on a pre-therapy study assessing relative arterial enhancement compared to liver, lesion size, necrosis of the lesion, and associated tumor burden in the liver. We used six response criteria: Response Evaluation Criteria in Solid Tumors (RECIST) size, World Health Organization (WHO) size, European Association for the Study of the Liver (EASL) necrosis guidelines, Choi size, Choi necrosis and combination of Choi size and necrosis. RESULTS: About 65 lesions in 17 patients met study criteria and formed the cohort. Statistically significant response was found for lesions < 5 cm vs those ≥ 5 cm with RECIST (P = 0.04), WHO (P = 0.002) and combined Choi criteria (P = 0.02). Hyperenhancing lesions demonstrated greater response only with the Choi size criteria (P = 0.04). Lesions with ≤ 50% necrosis on the pre-scan had statistically significant greater response with the Choi necrosis criteria (P = 0.01). There was no statistical significance for response comparing lesions < 2 cm vs ≥ 2 cm or in comparing the degrees of tumor burden. CONCLUSION: Based on our findings in this study, it is suggested that initial imaging findings, as listed above, are not a good predictor of response to 90Y radioembolization. PMID:23807902

  18. 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.

  19. 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.

  20. 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.

  1. Long-term follow-up study of gastroduodenal lesions after radioembolization of hepatic tumors

    PubMed Central

    Rodríguez-Lago, Iago; Carretero, Cristina; Herráiz, Maite; Subtil, José C; Betés, Maite; Rodríguez-Fraile, Macarena; Sola, Jesús J; Bilbao, José I; Muñoz-Navas, Miguel; Sangro, Bruno

    2013-01-01

    AIM: To evaluate the long-term natural history of the gastroduodenal lesions secondary to extrahepatic embolization with Ytrium 90 (90Y) spheres. METHODS: From September 2003 to January 2012, 379 procedures of liver radioembolization (RE) using resin microspheres loaded with 90Y were performed in our center. We have retrospectively compiled the data from 379 RE procedures performed in our center. We report a comprehensive clinical, analytical, endoscopic and histologic long-term follow-up of a series of patients who developed gastroduodenal lesions after the treatment. RESULTS: Six patients (1.5%) developed gastrointestinal symptoms and had gastrointestinal lesions as shown by upper endoscopy in the next 12 wk after RE. The mean time between RE and the appearance of symptoms was 5 wk. Only one patient required endoscopic and surgical treatment. The incidence of gastrointestinal ulcerations was 3.75% (3/80) when only planar images were used for the pre-treatment evaluation. It was reduced to 1% (3/299) when single-photon emission computed tomography (SPECT) images were also performed. The symptoms that lasted for a longer time were nausea and vomiting, until 25 mo after the treatment. CONCLUSION: All patients were free from severe symptoms at the end of follow-up. The routine use of SPECT has decreased the incidence of gastrointestinal lesions due to unintended deployment of 90Y particles. PMID:23704826

  2. 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

  3. 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.

  4. Predictors of Long-Term Outcome from Intraperitoneal Radioimmunotherapy for Ovarian Cancer

    PubMed Central

    You, Zhiying; Alvarez, Ronald; Partridge, Edward; Grizzle, William; LoBuglio, Albert

    2012-01-01

    Abstract Data was analyzed from 92 patients > 5 years after intraperitoneal (IP) radionuclide therapy (RIT) with 90Y- or 177Lu-CC49 to determine prognostic factors. Patients had CC49 antibody-reactive ovarian cancer confined to the abdominal cavity after primary debulking and chemotherapy. The first 27 patients received IP 177Lu-CC49 alone; the remainder received Interferon (IFN), to increase the expression of the tumor-associated glycoprotein-72 (TAG-72) antigen, +/− IP paclitaxel (25–100 mg/m2) 2 days before RIT. Factors assessed by univariate (and some multivariate) analysis included age, race, body size, interval between initial diagnosis and RIT, interval between 2nd look surgery and RIT, 90Y versus 177Lu, MBq dose, paclitaxel dose, grade of tumor, extent of initial surgery, size of disease deposits prior to RIT, intensity of TAG reactivity, the addition of unlabeled antibody, and the development of human anti-mouse antibody and/or serum sickness after murine antibody. A statistically significant improvement in progression-free survival (p≤0.05) was noted for less bulky disease and younger age. Administration of paclitaxel plus IFN, an immune response, and use of 90Y showed a favorable nonsignificant trend. Dose escalation of radionuclide did not change risk of progression; thus, this therapy may have therapeutic efficacy at modest dose levels. PMID:22239432

  5. Transarterial RAdioembolization versus ChemoEmbolization for the treatment of hepatocellular carcinoma (TRACE): study protocol for a randomized controlled trial

    PubMed Central

    2012-01-01

    Background Hepatocellular carcinoma is a primary malignant tumor of the liver that accounts for an important health problem worldwide. Only 10 to 15% of hepatocellular carcinoma patients are suitable candidates for treatment with curative intent, such as hepatic resection and liver transplantation. A majority of patients have locally advanced, liver restricted disease (Barcelona Clinic Liver Cancer (BCLC) staging system intermediate stage). Transarterial loco regional treatment modalities offer palliative treatment options for these patients; transarterial chemoembolization (TACE) is the current standard treatment. During TACE, a catheter is advanced into the branches of the hepatic artery supplying the tumor, and a combination of embolic material and chemotherapeutics is delivered through the catheter directly into the tumor. Yttrium-90 radioembolization (90Y-RE) involves the transarterial administration of minimally embolic microspheres loaded with Yttrium-90, a β-emitting isotope, delivering selective internal radiation to the tumor. 90Y-RE is increasingly used in clinical practice for treatment of intermediate stage hepatocellular carcinoma, but its efficacy has never been prospectively compared to that of the standard treatment (TACE). In this study, we describe the protocol of a multicenter randomized controlled trial aimed at comparing the effectiveness of TACE and 90Y-RE for treatment of patients with unresectable (BCLC intermediate stage) hepatocellular carcinoma. Methods/design In this pragmatic randomized controlled trial, 140 patients with unresectable (BCLC intermediate stage) hepatocellular carcinoma, with Eastern Cooperative Oncology Group performance status 0 to 1 and Child-Pugh A to B will be randomly assigned to either 90Y-RE or TACE with drug eluting beads. Patients assigned to 90Y-RE will first receive a diagnostic angiography, followed by the actual transarterial treatment, which can be divided into two sessions in case of bilobar disease

  6. In vitro and in vivo evaluation of novel ligands for radioimmunotherapy.

    PubMed

    Chong, Hyun-Soon; Milenic, Diane E; Garmestani, Kayhan; Brady, Erik D; Arora, Hans; Pfiester, Candice; Brechbiel, Martin W

    2006-05-01

    Novel ligands cis-2,6-bis[N,N-bis(carboxymethyl)aminomethyl]-1-piperidineacetic acid (PIP-DTPA), cis-[(1R,11S)-6,9,15-Tris-carboxymethyl-3,6,9,15-tetraazabicyclo[9.3.1]pentadec-3-yl]-acetic acid (PIP-DOTA), cis-{2,7-bis-[bis-carboxymethyl-amino)-methyl]-azepan-1-yl}-acetic acid (AZEP-DTPA), [2-(4,7-bis-carboxymethyl-[1,4,7]triazacyclononan-1-yl-ethyl]-2-carbonylmethyl-amino]-tetraacetic acid (NETA) and [{4-carboxymethyl-7-[2-(carboxymethylamino)-ethyl]-perhydro-1,4,7-triazonin-1-yl}-acetic acid (NPTA) are investigated as potential chelators of 177Lu, 90Y, 212Pb and 213Bi for radioimmunotherapy (RIT). The new ligands are radiolabeled with 177Lu, 86/88/90Y, 203Pb and 205/6Bi, and in vitro stability and in vivo stability of the radiolabeled complexes are assessed in human serum and athymic mice, respectively. In vitro studies indicate that all radiolabeled complexes with the exception of 90Y-AZEP-DTPA are stable in serum for 5-11 days. All new ligands examined herein are found to tightly hold 177Lu in vivo. Piperidine-backboned DTPA (PIP-DTPA) complexes radiolabeled with all radioisotopes examined display excellent in vivo stability, that is, excretion without dissociation. The azepane-backboned DTPA derivative, AZEP-DTPA, appears ineffective in binding all but 177Lu in vivo. NETA and NPTA radiolabeled with 86Y or 177Lu exhibit rapid blood clearance and low organ uptakes. Significant accretion in the kidney, femur and/or liver is observed with 203Pb-labeled AZEP-DTPA, PIP-DOTA and NPTA. Both 203Pb-PIP-DOTA and 205/6Bi-PIP-DOTA result in moderate to high renal accumulation of radioactivity. NETA exhibits improved renal accumulation with respect to PIP-DOTA for 205/6Bi but also shows significant liver uptake. Of all ligands studied, only PIP-DTPA appears to effectively bind 203Pb and 205/6Bi in vivo. PIP-DTPA, PIP-DOTA, NETA and NPTA all show strong evidence of rapid blood clearance and low organ uptake for 177Lu and 90Y. Serum stability and in vivo biodistribution

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

    PubMed Central

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

    2010-01-01

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

  8. 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

  9. 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.

  10. Phase II trial of yttrium-90-DOTA-biotin pretargeted by NR-LU-10 antibody/streptavidin in patients with metastatic colon cancer.

    PubMed

    Knox, S J; Goris, M L; Tempero, M; Weiden, P L; Gentner, L; Breitz, H; Adams, G P; Axworthy, D; Gaffigan, S; Bryan, K; Fisher, D R; Colcher, D; Horak, I D; Weiner, L M

    2000-02-01

    A Phase II study of yttrium-90-tetra-azacyclododecanetetra-acetic acid-biotin (90Y-DOTA-biotin) pretargeted by NR-LU-10 antibody/streptavidin (SA) was performed. The primary objectives of the study were to evaluate the efficacy and safety of this therapy in patients with metastatic colon cancer. Twenty-five patients were treated with a single dose of 110 mCi/m2 (mean administered dose, 106.5 +/- 10.3 mCi/m2) of 90Y-DOTA-biotin. There were three components of the therapy. Patients first received NR-LU-10/SA on day 1. A clearing agent (biotin-galactose-human serum albumin) was administered approximately 48 h after the NR-LU-10/SA to remove residual circulating unbound NR-LU-10/SA. Lastly, 24 h after administration of clearing agent, patients received biotin-DOTA-labeled with 110 mCi/m2 90Y. All three components of the therapy were administered i.v. Both hematological and nonhematological toxicities were observed. Diarrhea was the most frequent grade 4 nonhematological toxicity (16%; with 16% grade 3 diarrhea). Hematological toxicity was less severe with 8% grade 3 and 8% grade 4 neutropenia and 8% grade 3 and 16% grade 4 thrombocytopenia. The overall response rate was 8%. Two partial responders had freedom from progression of 16 weeks. Four patients (16%) had stable disease with freedom from progression of 10-20 weeks. Despite the relatively disappointing results of this study in terms of therapeutic efficacy and toxicity, proof of principle was obtained for the pretargeting approach. In addition, valuable new information was obtained about normal tissue tolerance to low-dose-rate irradiation that will help to provide useful guidelines for future study designs. PMID:10690517

  11. 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

  12. 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.

  13. Therapeutic outcome of patients suffering from malignant melanomas of the conjunctiva.

    PubMed Central

    Lommatzsch, P. K.; Lommatzsch, R. E.; Kirsch, I.; Fuhrmann, P.

    1990-01-01

    Eighty-one cases of conjunctival melanoma treated between 1960 and 1988 were studied to determine factors that might affect outcome in patients with such lesions. The therapeutic procedures performed were local excision (16), local excision followed by brachytherapy with Sr-90/Y-90 (32), local excision followed by cryotherapy with liquid nitrogen (16), brachytherapy with Sr-90/Y-90 (12), local excision followed by external beam irradiation (3), and local excision followed by brachytherapy and cryotherapy (2). The median follow-up period was 5.5 years (longest 26, shortest 1 year). Sixty two patients (76.5%) showed a complete regression of the melanoma, 19 (23.5%) developed recurrences, and 15 (18.5%) died from metastases. The melanomas had developed with almost equal frequency from a pre-existing naevus (25.9%), from primary acquired melanosis (25.9%), and 'de novo' (30.9%). Small tumours had a higher chance of regressing (80.6%) than larger ones (68.6%). The cumulative survival rate was 76% after five years and 60% after 10 years from any causes of death and 87.6% after five years and 76.3% after 10 years from deaths caused by metastases. Most deaths from metastases occurred within 5 years. At 88.5%, the cumulative survival rate of patients with small tumours (less than one quadrant of the bulbar conjunctiva and less than 2 mm thickness) was significantly higher than that of patients with larger tumours (more than one quadrant of the bulbar conjunctiva and/or more than 2 mm thickness) with 65% after eight years. Local excision followed by beta ray irradiation (Sr-90/Y-90) or cryotherapy can be recommended as the treatment of choice. Nevertheless the behaviour of conjunctival melanomas remains unpredictable in individual cases. Images PMID:2285686

  14. Radionuclide liver cancer therapies: from concept to current clinical status.

    PubMed

    Vente, Maarten A D; Hobbelink, Monique G G; van Het Schip, Alfred D; Zonnenberg, Bernard A; Nijsen, Johannes F W

    2007-07-01

    Primary and secondary liver cancer have longtime been characterized by an overall poor prognosis since the majority of patients are not candidates for surgical resection with curative intent, systemic chemotherapy alone has rarely resulted in long-term survival, and the role of conventional external beam radiation therapy has traditionally been limited due to the relative sensitivity of the liver parenchyma to radiation. Therefore, a host of new treatment options have been developed and clinically introduced, including radioembolization techniques, which are the main topic of this paper. In these locoregional treatments liver malignancies are passively targeted because, unlike the normal liver, the blood supply of intrahepatic tumors is almost uniquely derived from the hepatic artery. These internal radiation techniques consist of injecting either yttrium-90 ((90)Y) microspheres, or iodine-131 ((131)I) or rhenium-188 ((188)Re) labeled lipiodol into the hepatic artery. Radioactive lipiodol is used exclusively for treatment of primary liver cancer, whereas (90)Y microsphere therapy is applied for treatment of both primary and metastatic liver cancers. Favorable clinical results have been achieved, particularly when (90)Y microspheres were used in conjunction with systemic chemotherapy. The main advantages of radiolabeled lipiodol treatment are that it is relatively inexpensive (especially (188)Re-HDD-lipiodol) and that the administration procedure is somewhat less complex than that of the microspheres. Holmium-166 ((166)Ho) loaded poly(L-lactic acid) microspheres have also been developed and are about to be clinically introduced. Since (166)Ho is a combined beta-gamma emitter and highly paramagnetic as well, it allows for both (quantitative) scintigraphic and magnetic resonance imaging. PMID:17630919

  15. 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.

  16. 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

  17. Tumor vascular disruption using various radiation types

    PubMed Central

    2014-01-01

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

  18. 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. PMID:17768331

  19. 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.

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

    PubMed

    Knox, Susan J; Levy, Ronald

    2015-02-01

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

  1. Hepatic imaging response to radioembolization with yttrium-90-labeled resin microspheres for tumor progression during systemic chemotherapy in patients with colorectal liver metastases

    PubMed Central

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

    2015-01-01

    Background To assess response and the impact of imaging artifacts following radioembolization with yttrium-90-labeled resin microspheres (90Y-RE) based on the findings from a central independent review of patients with liver-dominant metastatic colorectal cancer (mCRC). Methods Patients with mCRC who received 90Y-RE (SIR-Spheres®; Sirtex Medical, Sydney, Australia) at nine US institutions between July 2002 and December 2011 were included in the analysis. Tumor response was assessed at baseline and 3 months using either the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 or 1.1. For each lesion, known artifacts affecting the interpretation of response (peri-tumoral edema and necrosis) were documented. Survivals (Kaplan-Meier analyses) were compared in responders [partial response (PR)] and non-responders [stable (SD) or progressive disease (PD)]. Results Overall, 195 patients (mean age 62 years) received 90Y-RE after a median of 2 (range, 1-6) lines of prior chemotherapy. Using RECIST 1.0 and RECIST 1.1, 7.6% and 6.9% of patients were partial responders, 47.3% and 48.1% had SD, and 55.0% and 55.0% PD, respectively. RECIST 1.0 and RECIST 1.1 showed excellent agreement {Kappa =0.915 [95% confidence interval (CI): 0.856-0.975]}. Peri-tumoral edema was documented in 32.8%, necrosis in 48.1% and both in 57.3% of cases (using RECIST 1.0). Although baseline characteristics were similar in responders and non-responders (P>0.05), responders survived significantly longer in an analysis according to RECIST 1.0: PR median (95% CI) 25.2 (range, 9.2-49.4) months vs. SD 15.8 (range, 9.3-21.1) months vs. PD 7.1 (range, 6.0-9.5) months (P<0.0001). Conclusions RECIST 1.0 and RECIST 1.1 imaging responses provide equivalent interpretations in the assessment of hepatic tumors following 90Y-RE. Radiologic lesion responses at 3 months must be interpreted with caution due to the significant proportion of patients with peri-tumoral edema and necrosis, which may lead to an

  2. Safety of knee radiosynovectomy with yttrium - 90

    NASA Astrophysics Data System (ADS)

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

    2011-09-01

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

  3. Evaluation of uncertainties in 90Sr-body-burdens obtained by whole-body count: application of Bayes' rule to derive detection limits by analysis of a posteriori data

    SciTech Connect

    Kozheurov, V. P.; Zalyapin, V. I.; Shagina, N. B.; Tokareva, E. E.; Degteva, M. O.; Tolstykh, E. I.; Anspaugh, L. R.; Napier, Bruce A.

    2002-10-01

    A whole body counter (WBC) designed to measure bremsstrahlung from 90Y, the short-lived daughter of 90Sr, has been used since 1974 to measure 90Sr-body burdens in residents along the Techa River, which was contaminated by releases from the Mayak Production Association. Bayes' rule has been applied to the a posteriori WBC data in order to derive the uncertainties associated with the data: The lower limit of reliable detection is 2.0kBq and the uncertainty of routine measurements is 1.6kBq.

  4. Evaluation of uncertainties in 90Sr-body-burdens obtained by whole-body count: application of Bayes' rule to derive detection limits by analysis of a posteriori data.

    PubMed

    Kozheurov, V P; Zalyapin, V I; Shagina, N B; Tokarevaa, E E; Degteva, M O; Tolstykh, E I; Anspaugh, L R; Napier, B A

    2002-10-01

    A whole body counter (WBC) designed to measure bremsstrahlung from 90Y, the short-lived daughter of 90Sr, has been used since 1974 to measure 90Sr-body burdens in residents along the Techa River, which was contaminated by releases from the Mayak Production Association. Bayes' rule has been applied to the a posteriori WBC data in order to derive the uncertainties associated with the data: The lower limit of reliable detection is 2.0 kBq and the uncertainty of routine measurements is 1.6 kBq. PMID:12361332

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

    PubMed

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

    1998-07-01

    To evaluate radiometal-labeled humanized BrE-3 (huBrE-3) monoclonal antibody as a radioimmunolocalization and therapeutic agent in breast cancer patients, tumor localization, pharmacokinetics, radiation dosimetry, and immunogenicity of (111)In-labeled combined 1-p-isothiocyanatobenzyl 3-methyl- and 1-p-isothiocyanatobenzyl 4-methyldiethylenetriamine pentaacetic acid (MX-DTPA) huBrE-3 were studied. Seven women with BrE-3 antigen-positive, metastatic breast carcinoma underwent (111)In huBrE-3 infusion (5 mCi; 50 mg), followed by serial gamma camera imaging and plasma sampling. Region of interest analysis of images was used to make radiation absorbed dose estimates for (111)In huBrE-3. Data were extrapolated to 90Y huBrE-3. Human anti-human antibody (HAHA) response was measured in serum samples obtained up to 3 months after infusion. Patients tolerated infusions well. Seventy-six percent of 105 known sites of disease were identified on planar and single-photon emission computed tomography scans. For six of seven patients, a biexponential model fit the plasma time-activity curve best with an average T1/2alpha=10.6+/-8.5 (SD) h and average T1/2beta=114.2+/-39.2 h. Radiation absorbed dose estimates for (111)In huBrE-3 for whole body averaged 0.53+/-.08 rads/mCi. Dose estimates for 90Y huBrE-3 for marrow averaged 8.4+/-11.9 rads/mCi, and for tumors, 70+/-31.5 rads/mCi. Liver radioactivity uptake averaged 19.7+/-8.8% injected dose at 24 h after infusion, translating into an average radiation absorbed dose 21.1+/-12 rads/90Y mCi administered. Only one of seven patients demonstrated a low level of HAHA response. Although the plasma half-lives are longer and marrow dose higher for radiolabeled huBrE-3 compared with the murine construct, the excellent tumor localization, good tumor dosimetry, and low immunogenicity support the use of 90Y-huBrE-3 antibody for radioimmunotherapy of breast cancer. PMID:9676842

  6. Tank waste isotope contributions

    SciTech Connect

    VANKEUREN, J.C.

    1999-08-26

    This document presents the results of a calculation to determine the relative contribution of selected isotopes to the inhalation and ingestion doses for a postulated release of Hanford tank waste. The fraction of the dose due to {sup 90}Sr, {sup 90}Y, {sup 137}Cs and the alpha emitters for single shell solids and liquids, double shell solids and liquids, aging waste solids and liquids and all solids and liquids. An effective dose conversion factor was also calculated for the alpha emitters for each composite of the tank waste.

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

    PubMed

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

    2012-05-01

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

  8. Personalized predictive lung dosimetry by technetium-99m macroaggregated albumin SPECT/CT for yttrium-90 radioembolization

    PubMed Central

    2014-01-01

    Background For yttrium-90 (90Y) radioembolization, the common practice of assuming a standard 1,000-g lung mass for predictive dosimetry is fundamentally incongruent with the modern philosophy of personalized medicine. We recently developed a technique of personalized predictive lung dosimetry using technetium-99m (99mTc) macroaggregated albumin (MAA) single photon emission computed tomography with integrated CT (SPECT/CT) of the lung as part of our routine dosimetric protocol for 90Y radioembolization. Its rationales are the technical superiority of SPECT/CT over planar scintigraphy, ease and convenience of lung auto-segmentation CT densitovolumetry, and dosimetric advantage of patient-specific lung parenchyma masses. Methods This is a retrospective study of our pulmonary clinical outcomes and comparison of lung dosimetric accuracy and precision by 99mTc MAA SPECT/CT versus conventional planar methodology. 90Y resin microspheres (SIR-Spheres) were used for radioembolization. Diagnostic CT densitovolumetry was used as a reference for lung parenchyma mass. Pulmonary outcomes were based on follow-up diagnostic CT chest or X-ray. Results Thirty patients were analyzed. The mean lung parenchyma mass of our Southeast Asian cohort was 822 ± 103 g standard deviation (95% confidence interval 785 to 859 g). Patient-specific lung parenchyma mass estimation by CT densitovolumetry on 99mTc MAA SPECT/CT is accurate (bias −21.7 g) and moderately precise (95% limits of agreement −194.6 to +151.2 g). Lung mean radiation absorbed doses calculated by 99mTc MAA SPECT/CT and planar methodology are both accurate (bias <0.5 Gy), but 99mTc MAA SPECT/CT offers better precision over planar methodology (95% limits of agreement −1.76 to +2.40 Gy versus −3.48 to +3.31 Gy, respectively). None developed radiomicrosphere pneumonitis when treated up to a lung mean radiation absorbed dose of 18 Gy at a median follow-up of 4.4 months. Conclusions Personalized predictive lung

  9. 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.

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

    SciTech Connect

    Ootsuyama, A.; Tanooka, H.

    1989-03-15

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

  11. Technology evaluation: epratuzumab, Immunomedics/Amgen.

    PubMed

    Juweid, Malik

    2003-04-01

    Immunomedics and Amgen are developing the unconjugated form of the anti-CD22 humanized monoclonal antibody, epratuzumab, for the potential treatment of lymphoma, non-Hodgkin's lymphoma (NHL) and certain autoimmune conditions. Immunogenics is also developing the radioisotope-linked (90Y) form of epratuzumab. The monoclonal antibody is currently undergoing phase III clinical trials for the potential treatment of aggressive lymphoma. By January 2003, epratuzumab had received Orphan Drug status in the US for its potential in the treatment of NHL. PMID:12772511

  12. Assessment of acquisition protocols for routine imaging of Y-90 using PET/CT

    PubMed Central

    2013-01-01

    Background Despite the early theoretical prediction of the 0+-0+ transition of 90Zr, 90Y-PET underwent only recently a growing interest for the development of imaging radioembolization of liver tumors. The aim of this work was to determine the minimum detectable activity (MDA) of 90Y by PET imaging and the impact of time-of-flight (TOF) reconstruction on detectability and quantitative accuracy according to the lesion size. Methods The study was conducted using a Siemens Biograph® mCT with a 22 cm large axial field of view. An IEC torso-shaped phantom containing five coplanar spheres was uniformly filled to achieve sphere-to-background ratios of 40:1. The phantom was imaged nine times in 14 days over 30 min. Sinograms were reconstructed with and without TOF information. A contrast-to-noise ratio (CNR) index was calculated using the Rose criterion, taking partial volume effects into account. The impact of reconstruction parameters on quantification accuracy, detectability, and spatial localization of the signal was investigated. Finally, six patients with hepatocellular carcinoma and four patients included in different 90Y-based radioimmunotherapy protocols were enrolled for the evaluation of the imaging parameters in a clinical situation. Results The highest CNR was achieved with one iteration for both TOF and non-TOF reconstructions. The MDA, however, was found to be lower with TOF than with non-TOF reconstruction. There was no gain by adding TOF information in terms of CNR for concentrations higher than 2 to 3 MBq mL−1, except for infra-centimetric lesions. Recovered activity was highly underestimated when a single iteration or non-TOF reconstruction was used (10% to 150% less depending on the lesion size). The MDA was estimated at 1 MBq mL−1 for a TOF reconstruction and infra-centimetric lesions. Images from patients treated with microspheres were clinically relevant, unlike those of patients who received systemic injections of 90Y. Conclusions Only

  13. Quantitative and Qualitative Assessment of Yttrium-90 PET/CT Imaging

    PubMed Central

    Büsing, Karen-Anett; Schönberg, Stefan O.; Bailey, Dale L.; Willowson, Kathy; Glatting, Gerhard

    2014-01-01

    Yttrium-90 is known to have a low positron emission decay of 32 ppm that may allow for personalized dosimetry of liver cancer therapy with 90Y labeled microspheres. The aim of this work was to image and quantify 90Y so that accurate predictions of the absorbed dose can be made. The measurements were performed within the QUEST study (University of Sydney, and Sirtex Medical, Australia). A NEMA IEC body phantom containing 6 fillable spheres (10–37 mm ∅) was used to measure the 90Y distribution with a Biograph mCT PET/CT (Siemens, Erlangen, Germany) with time-of-flight (TOF) acquisition. A sphere to background ratio of 8∶1, with a total 90Y activity of 3 GBq was used. Measurements were performed for one week (0, 3, 5 and 7 d). he acquisition protocol consisted of 30 min-2 bed positions and 120 min-single bed position. mages were reconstructed with 3D ordered subset expectation maximization (OSEM) and point spread function (PSF) for iteration numbers of 1–12 with 21 (TOF) and 24 (non-TOF) subsets and CT based attenuation and scatter correction. Convergence of algorithms and activity recovery was assessed based on regions-of-interest (ROI) analysis of the background (100 voxels), spheres (4 voxels) and the central low density insert (25 voxels). For the largest sphere, the recovery coefficient (RC) values for the 30 min –2-bed position, 30 min-single bed and 120 min-single bed were 1.12±0.20, 1.14±0.13, 0.97±0.07 respectively. For the smaller diameter spheres, the PSF algorithm with TOF and single bed acquisition provided a comparatively better activity recovery. Quantification of Y-90 using Biograph mCT PET/CT is possible with a reasonable accuracy, the limitations being the size of the lesion and the activity concentration present. At this stage, based on our study, it seems advantageous to use different protocols depending on the size of the lesion. PMID:25369020

  14. 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.

  15. Peptide Receptor Radionuclide Therapy (PRRT) of Medullary and Nonmedullary Thyroid Cancer Using Radiolabeled Somatostatin Analogues.

    PubMed

    Salavati, Ali; Puranik, Ameya; Kulkarni, Harshad R; Budiawan, Hendra; Baum, Richard P

    2016-05-01

    As therapeutic options in advanced medullary and non-iodine avid differentiated (nonmedullary) thyroid cancers are limited and associated with significant toxicity, targeting of somatostatin receptors (SSTRs) for internal radiation therapy provides a promising option. Theranostics (therapy and diagnosis) using radiolabeled somatostatin analogues has proved to be a milestone in the management of SSTR-expressing tumors. Peptide receptor radionuclide therapy using (177)Lu-labeled or (90)Y-labeled somatostatin analogues may have a significant role in the management of medullary and nonmedullary thyroid cancers in those patients where PET/CT with (68)Ga-labeled somatostatin analogues demonstrates significant SSTR expression. PMID:27067502

  16. 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

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

    PubMed

    Kulkarni, Harshad R; Baum, Richard P

    2014-01-01

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

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

    PubMed

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

    2016-03-01

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

  19. 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.

  20. 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.

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

    DOE PAGESBeta

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

    2015-07-22

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

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

    DOE PAGESBeta

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

    2016-03-24

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

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

    PubMed

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

    2015-11-17

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

  4. 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. PMID:21044994

  5. 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.

  6. 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.

  7. 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

  8. Luminescence properties after X-ray irradiation for dosimetry

    NASA Astrophysics Data System (ADS)

    Hong, Duk-Geun; Kim, Myung-Jin

    2016-05-01

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

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

    SciTech Connect

    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 ({sup 14}C) (0.156 MeV), good linearity and homogeneity. The noise level is below 50/(cm{sup 2}.sec). Successful imaging with this system has been performed with beta-emitters {sup 14}C, sulfur-35 ({sup 35}S), iodine-131 ({sup 131}I), yttrium-90 (90Y), and positron emitters gallium-68 ({sup 68}Ga), and fluorine-18 ({sup 18}F). Dynamic studies of axonal transport of {sup 35}S-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. 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.

  11. High efficiency production and purification of 86Y based on electrochemical separation.

    PubMed

    Lukić, Dragoljub; Tamburella, Claire; Buchegger, Franz; Beyer, Gerd-Jürgen; Comor, Jozef J; Seimbille, Yann

    2009-04-01

    As an intermediate half-life positron emitter (86)Y is an attractive radioisotope for positron emission tomography (PET) studies, particularly for patient specific dosimetry planning of (90)Y-based radiotherapy procedures. It can be conveniently produced by a small-sized cyclotron via the (86)Sr(p,n)(86)Y nuclear reaction. The optimization of the electrochemical separation of (86)Y from the target material and its purification was done by modeling the whole production cycle using (90)Y. The radionuclide was isolated using four electrodes in two electrolytic steps. In the first step two Pt plate anodes and a Pt Winkler cathode were used and the electro-deposition yield was determined in constant current mode of operation. In addition, the influence of pH on the efficiency of this first step was investigated. The second electrolysis, with Winkler electrode as anode and a Pt wire as cathode, was also performed in constant current mode of operation. The kinetics of recovery of the deposited activity on the Pt wire was investigated in acidic solutions. The optimized electrochemical method was then applied for (86)Y separation and purification. This modified procedure was proved to be faster and simpler than the previously proposed electrochemical techniques and is more convenient for automation of the routine production of (86)Y. PMID:19181533

  12. 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. PMID:26257288

  13. 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.

  14. 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.

  15. Analysing saturable antibody binding based on serum data and pharmacokinetic modelling

    NASA Astrophysics Data System (ADS)

    Kletting, Peter; Kiryakos, Hady; Reske, Sven N.; Glatting, Gerhard

    2011-01-01

    In radioimmunotherapy, organ dose calculations are frequently based on pretherapeutic biodistribution measurements, assuming equivalence between pretherapeutic and therapeutic biodistribution. However, when saturation of antibody binding sites is important, this assumption might not be justified. Residual antibody and different amounts of administered antibody may lead to a considerably altered therapeutic biodistribution. In this study we developed a method based on serum activity measurements to investigate this effect in radioimmunotherapy with 90Y-labelled anti-CD66 antibody. Pretherapeutic and therapeutic serum activity data of ten patients with acute leukaemia were fitted to a set of four parsimonious pharmacokinetic models. All models included the key mechanisms of antibody binding, immunoreactivity and degradation; however, they differed with respect to linear or nonlinear binding and global or individual fitting of the model parameters. The empirically most supported model was chosen according to the corrected Akaike information criterion. The nonlinear models were most supported by the data (sum of probabilities ≈100%). Using the presented method, we identified relevant saturable binding for radioimmunotherapy with 90Y-labelled anti-CD66 antibody solely based on serum data. This general method may also be applicable to investigate other systems where saturation of binding sites might be important.

  16. Peptide receptor radionuclide therapy (PRRT) for GEP-NETs.

    PubMed

    Bergsma, Hendrik; van Vliet, Esther I; Teunissen, Jaap J M; Kam, Boen L R; de Herder, Wouter W; Peeters, Robin P; Krenning, Eric P; Kwekkeboom, Dik J

    2012-12-01

    Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues plays an increasing role in the treatment of patients with inoperable or metastasised gatroenteropancreatic neuroendocrine tumours (GEP-NETs). (90)Y-DOTATOC and (177)Lu-DOTATATE are the most used radiopeptides for PRRT with comparable tumour response rates (about 15-35%). The side effects of this therapy are few and mild. However, amino acids should be used for kidney protection, especially during infusion of (90)Y-DOTATOC. Options to improve PRRT may include combinations of radioactive labelled somatostatin analogues and the use of radiosensitising drugs combined with PRRT. Other therapeutic applications of PRRT may include intra-arterial administration, neo-adjuvant treatment and additional PRRT cycles in patients with progressive disease, who have benefited from initial therapy. Considering the mild side-effects, PRRT may well become the first-line therapy in patients with metastasised or inoperable GEP-NETs if more widespread use of PRRT can be accomplished. PMID:23582925

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

    PubMed

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

    2013-01-01

    Kidney dosimetry in (177)Lu and (90)Y PRRT requires 3 to 6 whole-body/SPECT scans to extrapolate the peptide kinetics, and it is considered time and resource consuming. We investigated the most adequate timing for imaging and time-activity interpolating curve, as well as the performance of a simplified dosimetry, by means of just 1-2 scans. Finally the influence of risk factors and of the peptide (DOTATOC versus DOTATATE) is considered. 28 patients treated at first cycle with (177)Lu DOTATATE and 30 with (177)Lu DOTATOC underwent SPECT scans at 2 and 6 hours, 1, 2, and 3 days after the radiopharmaceutical injection. Dose was calculated with our simplified method, as well as the ones most used in the clinic, that is, trapezoids, monoexponential, and biexponential functions. The same was done skipping the 6 h and the 3 d points. We found that data should be collected until 100 h for (177)Lu therapy and 70 h for (90)Y therapy, otherwise the dose calculation is strongly influenced by the curve interpolating the data and should be carefully chosen. Risk factors (hypertension, diabetes) cause a rather statistically significant 20% increase in dose (t-test, P < 0.10), with DOTATATE affecting an increase of 25% compared to DOTATOC (t-test, P < 0.05). PMID:23865075

  18. 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. PMID:17548464

  19. 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

  20. 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

  1. 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

  2. Differences among Monte Carlo codes in the calculations of voxel S values for radionuclide targeted therapy and analysis of their impact on absorbed dose evaluations

    SciTech Connect

    Pacilio, M.; Lanconelli, N.; Lo Meo, S.; Betti, M.; Montani, L.; Torres Aroche, L. A.; Coca Perez, M. A.

    2009-05-15

    Several updated Monte Carlo (MC) codes are available to perform calculations of voxel S values for radionuclide targeted therapy. The aim of this work is to analyze the differences in the calculations obtained by different MC codes and their impact on absorbed dose evaluations performed by voxel dosimetry. Voxel S values for monoenergetic sources (electrons and photons) and different radionuclides ({sup 90}Y, {sup 131}I, and {sup 188}Re) were calculated. Simulations were performed in soft tissue. Three general-purpose MC codes were employed for simulating radiation transport: MCNP4C, EGSnrc, and GEANT4. The data published by the MIRD Committee in Pamphlet No. 17, obtained with the EGS4 MC code, were also included in the comparisons. The impact of the differences (in terms of voxel S values) among the MC codes was also studied by convolution calculations of the absorbed dose in a volume of interest. For uniform activity distribution of a given radionuclide, dose calculations were performed on spherical and elliptical volumes, varying the mass from 1 to 500 g. For simulations with monochromatic sources, differences for self-irradiation voxel S values were mostly confined within 10% for both photons and electrons, but with electron energy less than 500 keV, the voxel S values referred to the first neighbor voxels showed large differences (up to 130%, with respect to EGSnrc) among the updated MC codes. For radionuclide simulations, noticeable differences arose in voxel S values, especially in the bremsstrahlung tails, or when a high contribution from electrons with energy of less than 500 keV is involved. In particular, for {sup 90}Y the updated codes showed a remarkable divergence in the bremsstrahlung region (up to about 90% in terms of voxel S values) with respect to the EGS4 code. Further, variations were observed up to about 30%, for small source-target voxel distances, when low-energy electrons cover an important part of the emission spectrum of the radionuclide

  3. A measurement system for alpha and beta surface emission rate using MWPC

    NASA Astrophysics Data System (ADS)

    Lin, Ye; Fang, Fang; Ren, Jia-Fu; He, Lin-Feng; Tang, Fang-Dong; Xu, Yi-He; Ding, Wei-Cheng

    2015-05-01

    We have developed a large area multi-wire proportional counter (MWPC) as a standard for the measurement of alpha and beta surface emission rate at the Shanghai Institute of Measurement and Testing Technology (SIMT). To shorten the preparation time for chamber gas refilling, a self-designed gas control unit was adopted. Various characteristics of the system have been studied. The uncertainties were analysed. Three certified alpha plane sources (Am-241) and six certified beta plane sources (Tl-204 and Sr-90/Y-90) were measured by this system. The results show excellent agreement with the surface emission rate reported by the National Institute of Measuring, China (NIM) that En values of all measured sources are within ±1. Supported by National Natural Science Foundation of China (41204133)

  4. 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. PMID:10081145

  5. Yttrium-90 Radioembolization of Hepatic Metastases from Colorectal Cancer

    PubMed Central

    Raval, Mihir; Bande, Dinesh; Pillai, Anil K.; Blaszkowsky, Lawrence S.; Ganguli, Suvranu; Beg, Muhammad S.; Kalva, Sanjeeva P.

    2014-01-01

    Liver metastases from colorectal cancer (CRC) result in substantial morbidity and mortality. The primary treatment is systemic chemotherapy, and in selected patients, surgical resection; however, for patients who are not surgical candidates and/or fail systemic chemotherapy, liver-directed therapies are increasingly being utilized. Yttrium-90 (Y-90) microsphere therapy, also known as selective internal radiation therapy (SIRT) or radioembolization, has proven to be effective in terms of extending time to progression of disease and also providing survival benefit. This review focuses on the use of Y-90 microsphere therapy in the treatment of liver metastases from CRC, including a comprehensive review of published clinical trials and prospective studies conducted thus far. We review the methodology, outcomes, and side effects of Y-90 microsphere therapy for metastatic CRC. PMID:25120951

  6. 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.

  7. Recent progress in the application of extraction chromatography to radionuclide separations for nuclear medicine.

    SciTech Connect

    Dietz, M. L.; Chemistry

    2004-01-01

    Numerous methods have been described for the separation and purification of radionuclides for application in diagnostic and therapeutic nuclear medicine, among them ion exchange, solvent extraction, and various forms of chromatography. Although extraction chromatography has previously been shown to provide a means of performing a number of separations of potential use in radionuclide generator systems, the application of the technique to generator development has thus far been limited. Recent work directed at improved methods for the determination of radionuclides in biological and environmental samples has led to the development of a series of novel extraction chromatographic resins exhibiting enhanced metal ion retention from strongly acidic media and excellent selectivity, among them materials suitable for the isolation of {sup 212}Bi, {sup 90}Y, and {sup 213}Bi. These resins, along with extraction chromatographic materials employing functionalized supports to improve their physical stability or metal ion retention properties, are shown to offer promise in the development of improved radionuclide generators.

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

    PubMed

    Searle, Ben

    2010-08-01

    The 57th Annual Meeting of the Society of Nuclear Medicine, held in Salt Lake City, UT, USA, included topics covering new developments in imaging agents and radiopharmaceutical therapies in the field of nuclear medicine. This conference report highlights selected presentations related to imaging of the brain, the prediction of heart disease, and the detection and treatment of various cancers. Investigational drugs discussed include TF-2 plus [68Ga]IMP-288 and TF-2 plus [111In]IMP-288 (both Immunomedics Inc), [11C]PBR-170 (Royal Prince Alfred Hospital/Australian Nuclear Science & Technology Organization), [11C]LY-2795050 (Eli Lilly & Co), yttrium (90Y) clivatuzumab tetraxetan (Garden State Cancer Center/Immunomedics Inc), [18F]LMI-1195 (Lantheus Medical Imaging Inc), fluciclovine (18F) (GE Healthcare/Nihon Medi-Physics Co Ltd), [99mTc]MIP-1340 and [99mTc]MIP-1407 (both Molecular Insight Pharmaceuticals Inc). PMID:20721816

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  10. DEVELOPMENT OF AN IMPROVED DOSE-RECONSTRUCTION SYSTEM FOR THE TECHA RIVER POPULATION AFFECTED BY THE OPERATION OF THE MAYAK PRODUCTION ASSOCIATION

    SciTech Connect

    Degteva, M O.; Vorobiova, M I.; Tolstykh, E I.; Shagina, N B.; Shishkina, Elena A.; Anspaugh, L R.; Napier, Bruce A.; Bougrov, N G.; Shved, Valentina A.; Tokareva, E. E.

    2006-07-01

    The Techa River Dosimetry System (TRDS) has been developed to provide estimates of doses received by approximately 30,000 members of the Extended Techa River Cohort (ETRC). Members of the ETRC were exposed beginning in 1949 to significant levels of external and internal (mainly from 90Sr) dose, but at low-to-moderate dose rates. Members of this cohort are being studied in an effort to test the hypothesis that exposure at low-to-moderate dose rates has the same effectiveness as exposure at high dose rates. The current version of the TRDS is known as TRDS-2000 and is the subject of this paper. The dose from 90Sr (and 89Sr) are supported strongly by {approx}30,000 measurements made with a tooth-beta counter, measurements of bones collected at autopsy, and {approx}30,000 measurements made with a special whole body counter that detects the bremsstrahlung from 90Y.

  11. Purification of radionuclides for nuclear medicine: The multicolumn selectivity inversion generator concept

    NASA Astrophysics Data System (ADS)

    Horwitz, E. P.; Bond, A. H.

    2003-01-01

    A new radionuclide generator system has been developed and demonstrated for the production of 212Bi from 224Ra/212Pb and for 90Y from 90Sr. The new concept, called a Multicolumn Selectivity Inversion Generator, involves the selective retention of the desired daughter radionuclide from a solution of the parent or parents by a primary separation column followed by stripping the daughter radionuclide from the primary column, and immediately without feed adjustment, passing the daughter through a secondary separation (guard) column that retains the parents while the daughter elutes unrestrained. The new generator system minimises the effects of radiation damage to the support material permiting the reliable production of nuclides of high chemical and radionuclidic purity.

  12. 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.

  13. 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.

  14. 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. PMID:26020026

  15. Superselective radioembolization of hepatocellular carcinoma: 5-year results of a prospective study.

    PubMed

    Rösler, H; Triller, J; Baer, H U; Geiger, L; Beer, H F; Becker, C; Blumgart, L H

    1994-10-01

    Twenty patients with unresectable hepatocellular carcinoma (HCC) were followed up to 5 years after transarterial radiotherapy with 90Y-resin particles. Diagnostic radioembolizations of 99mTc-macroaggregates facilitated scintigraphic assessment of activity distribution, dose evaluation and final procedural verification. The overall survival rates were 56, 38 and 14% (after 1, 2 and 3 years, resp.). Patients with unifocal HCC and a single feeding artery (n = 7) even presented 83, 67 and 40% (2 alive after 2.75 and 4 years). With multiple arteries (n = 7), the longest survival was 26 months. Patients with multifocal HCC survived up to 33 months after selective radioembolization. Quality of life was improved in all. Survival was positively correlated with absorbed dose but residual/recurrent tumour occurred even after > or = 300 Gy. Post-treatment symptoms were minimal (35 applications), pulmonary shunt rates were correctly predicted and pulmonary complications avoided. PMID:7997379

  16. Radiopharmaceuticals developed at the University of Missouri research reactor

    SciTech Connect

    Ketring, A.R.; Ehrhardt, G.J.; Day, D.E.

    1997-12-01

    The University of Missouri Research Reactor (MURR) has put a great deal of effort in the last two decades into development of radiotherapeutic beta emitters as nuclear medicine radiotherapeutics for malignancies. This paper describes the development of two of these drugs, {sup 153}Sm ethylenediaminetetra-methylene phosphonic acid (EDTMP) (Quadramet{trademark}) and {sup 90}Y glass microspheres (TheraSphere{trademark}). Samarium-153 EDTMP is a palliative used to treat the pain of metastatic bone cancer without the side effects of narcotic pain killers. Yttrium-90 glass microspheres are delivered via hepatic artery catheter to embolize the capillaries of liver tumors and deliver a large radiation dose for symptom palliation and life prolonging purposes.

  17. 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.

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

    SciTech Connect

    Ootsuyama, A.; Tanooka, H. )

    1991-01-01

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

  19. The perturbation correction factor of ionisation chambers in beta-radiation fields.

    PubMed

    Böhm, J

    1980-01-01

    In determining the absorbed dose in a solid medium by means of gas-filled ionisation chambers, the perturbation of the radiation field by the chamber needs to be taken into account. So far, an appropriate correction factor has neither been calculated nor measured for beta-radiation. This work describes its experimental determination for an extrapolation chamber and beta-radiation fields of 147Pm, 204Tl, and 90Sr + 90Y. The results show that the correction factor may be assumed to be the product of a shield factor and a scatter factor the magnitudes of which depend on the chamber geometry and the radiation field. The change of the perturbation correction factor with phantom depth is important for the measurement of depth dose curves. This is demonstrated by an example. PMID:7360793

  20. A novel method for measuring K-shell photoelectric parameters of high-Z elements

    NASA Astrophysics Data System (ADS)

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

    2006-06-01

    The K-shell jump ratio, jump factor and the ratio of total to K-shell photoelectric cross section at K edge have been determined for Hf, Ta, Au and Pb by adopting a novel method. In this method, continuous external bremsstrahlung (EB) photons are produced in a thin nickel elemental converter by beta particles from a 90Sr-90Y weak beta source. The spectrum of EB photons transmitted through the elemental targets of Hf, Ta, Au and Pb is recorded with an HPGe detector coupled to an 8K multichannel analyser. The transmitted spectrum shows a sharp decrease in intensity at the K-shell binding energy of the target atom. The region of sharp decrease is fitted to a sigmoidal function and the K-shell jump ratio, jump factor and the ratio of total to the K-shell photoelectric cross section at K edge are determined. The measured values are compared with the theoretical values.

  1. 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.

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

    PubMed

    Uhrhan, K; Drzezga, A; Sudbrock, F

    2014-11-01

    In this work, the radiation exposure in nuclear medicine is evaluated by measuring dose rates in the proximity of patients and those in close contact to sources like capsules and syringes. A huge number of different survey meters (SMs) are offered commercially. This topic has recently gained interest since dosemeters and active personal dosemeters (APD) for the new dose quantities (ambient and directional dose equivalent) have become available. One main concern is the practical use of SMs and APD in daily clinical routines. Therefore, the radiation field of four common radiopharmaceuticals containing (18)F, (90)Y, (99m)Tc and (131)I in radioactive sources or after application to the patient was determined. Measurements were carried out with different SMs and for several distances. Dose rates decline significantly with the distance to the patient, and with some restrictions, APD can be used as SMs. PMID:25071244

  3. 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.

  4. Multicenter Phase II Study of Sequential Radioembolization-Sorafenib Therapy for Inoperable Hepatocellular Carcinoma

    PubMed Central

    Chow, Pierce K. H.; Poon, Donald Y. H.; Khin, Maung-Win; Singh, Harjit; Han, Ho-Seong; Goh, Anthony S. W.; Choo, Su-Pin; Lai, Hee-Kit; Lo, Richard H. G.; Tay, Kiang-Hiong; Lim, Teong-Guan; Gandhi, Mihir; Tan, Say-Beng; Soo, Khee-Chee

    2014-01-01

    Background The safety and tolerability of sequential radioembolization-sorafenib therapy is unknown. An open-label, single arm, investigator-initiated Phase II study (NCT0071279) was conducted at four Asia-Pacific centers to evaluate the safety and efficacy of sequential radioembolization-sorafenib in patients with hepatocellular carcinoma (HCC) not amenable to curative therapies. Methods Sorafenib (400 mg twice-daily) was initiated 14 days post-radioembolization with yttrium-90 (90Y) resin microspheres given as a single procedure. The primary endpoints were safety and tolerability and best overall response rate (ORR) using RECIST v1.0.Secondary endpoints included: disease control rate (complete [CR] plus partial responses [PR] and stable disease [SD]) and overall survival (OS). Results Twenty-nine patients with Barcelona Clinic Liver Cancer (BCLC) stage B (38%) or C (62%) HCC received a median of 3.0 GBq (interquartile range, 1.0) 90Y-microspheres followed by sorafenib (median dose/day, 600.0 mg; median duration, 4.1 months). Twenty eight patients experienced ≥1 toxicity; 15 (52%) grade ≥3. Best ORR was 25%, including 2 (7%) CR and 5 (18%) PR, and 15 (54%) SD. Disease control was 100% and 65% in BCLC stage B and C, respectively. Two patients (7%) had sufficient response to enable radical therapy. Median survivals for BCLC stage B and C were 20.3 and 8.6 months, respectively. Conclusions This study shows the potential efficacy and manageable toxicity of sequential radioembolization-sorafenib. Trial Registration ClinicalTrials.gov NCT00712790. PMID:24614178

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

    PubMed Central

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

    2014-01-01

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

  6. Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma

    PubMed Central

    Salem, Riad; Lewandowski, Robert J; Kulik, Laura; Wang, Edward; Riaz, Ahsun; Ryu, Robert K; Sato, Kent T; Gupta, Ramona; Nikolaidis, Paul; Miller, Frank H; Yaghmai, Vahid; Ibrahim, Saad M; Senthilnathan, Seanthan; Baker, Talia; Gates, Vanessa L; Atassi, Bassel; Newman, Steven; Memon, Khairuddin; Chen, Richard; Vogelzang, Robert L; Nemcek, Albert A; Resnick, Scott A; Chrisman, Howard B; Carr, James; Omary, Reed A; Abecassis, Michael; Benson, Al B; Mulcahy, Mary F

    2010-01-01

    Background and Aims Chemoembolization is a standard treatment for hepatocellular carcinoma (HCC). Radioembolization with 90Y microspheres is a new, transarterial approach to radiation therapy. We performed a comparative effectiveness analysis of these therapies in patients with HCC. Methods We collected data from 463 patients who were treated with transarterial locoregional therapies (chemoembolization or radioembolization) over a 9-year period. We excluded patients who were not appropriate for comparison and analyzed data from 245 (122 who received chemoembolization and 123 who received radioembolization). Patients were followed for signs of toxicity; all underwent imaging analysis at baseline and follow-up timepoints. Overall survival was the primary outcome measure. Secondary outcomes included safety, response rate, and time-to-progression. Uni- and multi-variate analyses were performed. Results Abdominal pain and increased transaminase activity were more frequent following chemoembolization (P<.05). There was a trend that patients treated with radioembolization had a higher response rate than with chemoembolization (49% vs. 36%, P=0.104). Although time-to-progression was longer following radioembolization than chemoembolization (13.3 months vs 8.4 months, P=0.046), median survival times were not statistically different (17.4 months vs 20.5 months, P=0.232). Among patients with intermediate-stage disease, survival was similar between groups that received chemoembolization (17.5 months) and radioembolization (17.2 months, P=0.42). Conclusion Patients with HCC treated by chemoembolization or radioembolization with 90Y microspheres had similar survival times. Radioembolization resulted in longer time-to-progression and less toxicity than chemoembolization. Post-hoc analyses of sample size indicated that a randomized study with >1000 patients would be required to establish equivalence of survival times between patients given the different therapies. PMID:21044630

  7. Yttrium-90 radioembolization stops progression of targeted breast cancer liver metastases after failed chemotherapy

    PubMed Central

    Gordon, Andrew C.; Gradishar, William J.; Kaklamani, Virginia G.; Thuluvath, Avesh J.; Ryu, Robert K.; Sato, Kent T.; Gates, Vanessa L.; Salem, Riad; Lewandowski, Robert J.

    2016-01-01

    PURPOSE The purpose of this open-label, retrospective report was to determine the safety and effectiveness of locoregional therapy with yttrium-90 (90Y) radioembolization for patients with progressing breast cancer liver metastases (BCLM) despite polychemotherapy. MATERIALS & METHODS Seventy-five patients with progressing BCLM and stable extrahepatic disease were treated with radioembolization at our institution. Retrospective review of a prospectively collected database was performed to evaluate clinical and biochemical toxicities, tumor response, overall survival (OS), and time to progression (TTP). Radiologic response assessments included Response Evaluation Criteria in Solid Tumors in primary index lesions and metabolic activity on positron emission tomography. Univariate and multivariate analyses were performed. RESULTS 30-day mortality was 4% (n=3). Grade 3+ clinical toxicity and hyperbilirubinemia occurred in 7.6% (n=5) and 5.9% (n=4), respectively. The rate of partial response was 35.3% (n=24), 63.2% (n=43) had stable disease, and progressive disease occurred in 1.5% (n=1). PET imaging was available in 25 patients and 21 (84%) had a complete or partial response or stable disease. The median OS was 6.6mo (95% CI, 5.0 to 9.2mo). The hazard ratio (HR) for OS was .39 (95% CI, .23 to .66) for tumor burden <25% compared to greater tumor burden in multivariate analysis. Elevated bilirubin reduced OS. The HR for hepatic progression was .22 (95% CI, .05 to .98) for solitary compared to multifocal disease. CONCLUSIONS Locoregional therapy with 90Y radioembolization is safe and stops or delays the progression of targeted chemorefractory breast cancer liver metastases. Adverse prognosticators are identified. PMID:25156827

  8. In vivo localization of ⁹⁰Y and ¹⁷⁷Lu radioimmunoconjugates using Cerenkov luminescence imaging in a disseminated murine leukemia model.

    PubMed

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

    2014-10-15

    Cerenkov radiation generated by positron-emitting radionuclides can be exploited for a molecular imaging technique known as Cerenkov luminescence imaging (CLI). Data have been limited, however, on the use of medium- to high-energy β-emitting radionuclides of interest for cancer imaging and treatment. We assessed the use of CLI as an adjunct to determine localization of radioimmunoconjugates to hematolymphoid tissues. Radiolabeled (177)Lu- or (90)Y-anti-CD45 antibody (Ab; DOTA-30F11) was administered by tail vein injection to athymic mice bearing disseminated murine myeloid leukemia, with CLI images acquired at times afterward. Gamma counting of individual organs showed preferential uptake in CD45(+) tissues with significant retention of radiolabeled Ab in sites of leukemia (spleen and bone marrow). This result was confirmed in CLI images with 1.35 × 10(5) ± 2.2 × 10(4) p/s/cm(2)/sr and 3.45 × 10(3) ± 7.0 × 10(2) p/s/cm(2)/sr for (90)Y-DOTA-30F11 and (177)Lu-DOTA-30F11, respectively, compared with undetectable signal for both radionuclides using the nonbinding control Ab. Results showed that CLI allows for in vivo visualization of localized β-emissions. Pixel intensity variability resulted from differences in absorbed doses of the associated energies of the β-emitting radionuclide. Overall, our findings offer a preclinical proof of concept for the use of CLI techniques in tandem with currently available clinical diagnostic tools. PMID:25261237

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

    PubMed

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

    2014-11-01

    A new resin selective for Sr has been developed and characterised for the direct binding of (90)Sr from environmental waters with minimal pre-treatment. The new selective resin comprises of a mixture of two extractants, 4,4'(5')-bis-t-butylcyclohexano-18-crown-6 and di(2-ethyl-hexyl)phosphoric acid, sorbed onto Amberchrom CG-71. Sr uptake is shown to be high (the distribution weight coefficient Dw >100 mL g(-1)) across a range of environmentally realistic conditions (pH 2-8 and up to 11,500 mg L(-1) NaCl, 500 mg L(-1) Ca, 400 mg L(-1) K and 1300 mg L(-1) Mg). The Sr capacity of the resin is shown to be 7.7±0.4 mg g(-1), meaning that the resin has a sufficient capacity to quantitatively remove Sr from most environmental water samples. The reasonably fast uptake kinetics of the resin (95±4% of strontium bound within 30 min) results in a resin that is applicable to both batch- and column-type separation procedures. A range of potentially co-extracted radio-elements have been identified and an elution scheme has been developed to separate interferences, including (90)Y, from (90)Sr. The clean elution of (90)Sr permits immediate measurement by radiometric means, with no need for complicated spectral processing or waiting for secular equilibrium between (90)Sr and (90)Y. The characterised resin is applicable for use in rapid determination procedures, enabling the swift analysis of water samples required by monitoring schemes at contaminated nuclear sites and in the aftermath of nuclear accidents. PMID:25127642

  10. 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.

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

    SciTech Connect

    Watson, David J.; Strom, Daniel J.

    2011-02-25

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

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

    PubMed

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

    2005-01-01

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

  13. Yttrium-90 radioembolization for advanced inoperable hepatocellular carcinoma

    PubMed Central

    Lee, Victor Ho-Fun; Leung, Dennis KC; Luk, Mai-Yee; Tong, Chi-Chung; Law, Martin WM; Ng, Sherry CY; Wong, Ka-Kin; Poon, Ronnie TP; Kwong, Dora LW; Leung, To-Wai

    2015-01-01

    Background Advanced inoperable hepatocellular carcinoma (HCC) conferring a grave prognosis may benefit from yttrium-90 (90Y) radioembolization. Methods Thirty patients with advanced inoperable HCC including those with any lesion >8 cm in maximal diameter or multiple bi-lobar lesions (totally more than five lesions), or portal vein thrombosis treated with radioembolization were reviewed. Treatment efficacy and safety were evaluated. Univariate and multivariate analyses were performed for identifying potential prognostic factors. Results After a median follow-up of 18.3 months, the response rate was 30.0%, and the disease control rate was 50.0%. Median overall progression-free survival (PFS) and overall survival (OS) were 3.3 months and 13.2 months, respectively. Longer median PFS was noted in those who had transarterial chemoembolization before radioembolization (7.3 months vs 3.1 months; P=0.021) and duration of alfafeto protein (AFP) response ≥6 months (11.8 months vs 3.0 months; P<0.001). Longer median OS was also revealed in those without portal vein thrombosis (17.1 months vs 4.4 months; P=0.015) and those whose duration of AFP response was ≥6 months (21.2 months vs 8.6 months; P=0.001). Seventeen patients (56.7%) developed treatment-related complications including five (16.7%) grade 3 events. Multivariate analysis revealed that treatment responders (P=0.001) and duration of AFP response ≥6 months (P=0.006) were prognostic of PFS, whereas the absence of portal vein invasion (P=0.025), treatment responders (P=0.010), and duration of AFP response ≥6 months (P=0.001) were prognostic of OS. Conclusion 90Y radioembolization is an alternative treatment with a promising outcome for poor-risk advanced inoperable HCC. PMID:26640386

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

    PubMed

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

    2014-02-15

    The vast majority of patients with plasma cell neoplasms die of progressive disease despite high response rates to novel agents. Malignant plasma cells are very radiosensitive, but the potential role of radioimmunotherapy (RIT) in the management of plasmacytomas and multiple myeloma has undergone only limited evaluation. Furthermore, CD38 has not been explored as a RIT target despite its uniform high expression on malignant plasma cells. In this report, both conventional RIT (directly radiolabeled antibody) and streptavidin-biotin pretargeted RIT (PRIT) directed against the CD38 antigen were assessed as approaches to deliver radiation doses sufficient for multiple myeloma cell eradication. PRIT demonstrated biodistributions that were markedly superior to conventional RIT. Tumor-to-blood ratios as high as 638:1 were seen 24 hours after PRIT, whereas ratios never exceeded 1:1 with conventional RIT. (90)Yttrium absorbed dose estimates demonstrated excellent target-to-normal organ ratios (6:1 for the kidney, lung, liver; 10:1 for the whole body). Objective remissions were observed within 7 days in 100% of the mice treated with doses ranging from 800 to 1,200 μCi of anti-CD38 pretargeted (90)Y-DOTA-biotin, including 100% complete remissions (no detectable tumor in treated mice compared with tumors that were 2,982% ± 2,834% of initial tumor volume in control animals) by day 23. Furthermore, 100% of animals bearing NCI-H929 multiple myeloma tumor xenografts treated with 800 μCi of anti-CD38 pretargeted (90)Y-DOTA-biotin achieved long-term myeloma-free survival (>70 days) compared with none (0%) of the control animals. PMID:24371230

  15. 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.

  16. Radioembolization with yttrium-90 resin microspheres for neuroendocrine tumor liver metastases

    PubMed Central

    Peker, Ahmet; Çiçek, Okan; Soydal, Çiğdem; Küçük, Nuriye Özlem; Bilgiç, Sadık

    2015-01-01

    PURPOSE We aimed to evaluate the effectiveness and safety of radioembolization with yttrium-90 (90Y) microspheres in cases with unresectable neuroendocrine tumor liver metastases (NETLMs). METHODS Thirty patients (mean age, 55 years) underwent resin-based 90Y radioembolization for unresectable NETLM at a single institution between April 2008 and June 2013. Post-treatment tumor response was assessed by cross-sectional imaging using the Response Evaluation Criteria in Solid Tumors (RECIST). Prognostic variables that affected survival were determined. RESULTS The mean follow-up was 23.0±19.4 months and the median overall survival was 39 months (95% CI, 12.6–65.4 months), with one- and two-year survival rates of 71% and 45%, respectively. Imaging follow-up using RECIST at three-month intervals demonstrated partial response in 43%, complete remission in 3%, stable disease in 37%, and progressive disease in 17% of patients. Extent of tumor involvement was found to have a statistically significant influence on overall survival (P = 0.03). The existence of extrahepatic disease at the time of radioembolization, radiographic response, age, and primary neuroendocrine tumor site were not significant prognostic factors. CONCLUSION The current study demonstrates the effectiveness and safety of radioembolization for the treatment of unresectable NETLMs. We identified that the extent of tumor involvement has a significant effect on overall survival. The use of imaging methods reflecting metabolic activity or cellularity such as scintigraphy or diffusion-weighted MRI would be more appropriate, for the response evaluation of liver metastases after radioembolization. PMID:25430526

  17. 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.

  18. 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.

  19. Radioimmunotherapy of infectious diseases

    PubMed Central

    Dadachova, Ekaterina; Casadevall, Arturo

    2009-01-01

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

  20. A miniature MOSFET radiation dosimeter probe.

    PubMed

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

    1994-11-01

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

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

    PubMed

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

    2013-01-01

    Peptide receptor radionuclide therapy (PRRT), with (90)Y-DOTATOC and (177)Lu-DOTATATE as most clinically used radiopeptides, is widely used in the management of metastatic neuroendocrine tumors. With respect to radiation dosimetry, the kidneys are the critical organ for (90)Y-DOTATOC. Renal irradiation is significant because of reabsorption of the radiopeptide from the proximal tubuli and the resulting retention in the interstitium, mainly in the inner cortical zone. The high energy and consequently wide range in tissue of the yttrium-90 beta particle result in high absorbed doses to the kidney cortex and medulla. Accurate renal dosimetry can help minimizing radiation nephropathy. We report a case of a 69-year-old candidate for PRRT with an acceptable kidney function at the time of screening. When performing (111)In-octreotide pretreatment dosimetry 3 weeks later, we observed a drastic deterioration in kidney function, caused by undisclosed non-steroidal anti-inflammatory drug intake. The calculated kidney biological effective dose (BED) was 153 Gy after four projected cycles. PRRT was canceled as our full-course BED limit is 37 Gy and the patient was switched to morphine analgesics. Renal function normalized after 3 months and repeated dosimetry yielded an acceptable kidney BED of 28 Gy after four projected cycles (7 Gy/cycle). This case emphasizes that acute kidney insufficiency can yield toxic kidney doses in a single therapy cycle, with an inherent risk of persistent renal insufficiency. All clinical factors which might influence kidney function should be verified at screening and before PRRT administration. PMID:22961123

  2. 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.

  3. 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

  4. 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

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

    SciTech Connect

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

    2010-06-01

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

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

    PubMed Central

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

    2011-01-01

    The shape of composite peak 5 in the glow curve of LiF:Mg,Ti (TLD-100) following 90Sr/90Y 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 90Sr/90Y 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. PMID:21149323

  7. 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. PMID:21149323

  8. 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

  9. 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

  10. Yttrium-90-labeled microsphere tracking during liver selective internal radiotherapy by bremsstrahlung pinhole SPECT: feasibility study and evaluation in an abdominal phantom

    PubMed Central

    2011-01-01

    contrast. This fills the gap between the performance of90Y-PET and bremsstrahlung pinhole SPECT which is a more affordable technique and could even be used during the catheterization procedure in order to optimize the90Y activity to inject. PMID:22214246

  11. 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

  12. [166Dy]Dy/166Ho hydroxide macroaggregates: an in vivo generator system for radiation synovectomy.

    PubMed

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

    2004-12-01

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

  13. 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

  14. 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.

  15. 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

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

    PubMed

    Watson, David J; Strom, Daniel J

    2011-04-01

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

  17. Radiochemical Sensor for Continuous and Remote Liquid Effluents Monitoring

    SciTech Connect

    Tarancon, A.; Garcia, J.F.; Rauret, G.; Padro, A.

    2008-07-01

    On-line radioactivity monitoring in liquid effluents is an increasing need according to the international regulations at present. Classical activity determination procedures include the sequence of sampling, chemical treatment, measurement and data treatment. These steps are man-power consuming, generate a great amount of waste and introduce an important delay between the potential pollution event and its detection and quantification. To overcome these limitations, we have developed a radiochemical sensor for liquid effluents capable of sending information about the specific activity and volume of a contamination episode to a remote position, on line and continuously. The capabilities of the sensor developed here allow detecting and quantifying contamination pulses of alpha, beta and gamma emitters of different volumes and activity levels included in a continuous stream. Sensor receptor includes two detection systems, one addressed to determine alpha, beta and gamma events and the other to detect sample gamma emissions. Detailed sensor structure will be shown at the conference because patent is in process at this moment. Detection efficiencies (%) obtained in the alpha-beta-gamma system for the range of contamination volumes considered (2- 300 ml) are: 1.6 - 3.2%, for Pu-240; 22.2 - 58.4%, for Sr-90/Y-90 and 8.8 -17.7%, for Cs-134. In the gamma system, values for Cs-134 detection range from 0.6% to 1.3%. Prediction errors obtained show that sensor is capable to detect Sr-90/Y-90 contamination pulses of at least 2 ml and 3 Bq/ml with a relative error lower of 10% in activity and 60% in volume. When contamination pulse increases up to 7 ml, relative errors decrease to 5% for both magnitudes. For Pu-240 and Cs-134, when contamination pulses are of at least 7 ml and 300 Bq/ml, the relative errors obtained in determinations performed in the alpha-beta-gamma system are lower than 10% in activity and 20 % in volume. The same errors are obtained in the gamma system for Cs

  18. 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

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

    PubMed

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

    2016-06-21

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

  20. 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.

  1. A novel method for large-area sources preparation for the calibration of beta- and alpha-contamination monitors.

    PubMed

    Tsoupko-Sitniko, V; Picolo, J L; Carrier, M; Peulon, S; Moutard, G

    2002-01-01

    A method is proposed for the preparation of large-area reference sources for the calibration of beta- and alpha-contamination monitors. It is based on the incorporation, by the ion-exchange mechanism, of the radionuclide in a thin film of a conducting polymer ion-exchanger preliminarily grown on a metal support. Conducting pyrrole-based polymer functionalized by carboxylic cation-exchange groups is used to prepare 60Co and 90Sr-90Y beta-particle sources. Electrochemical polymerization of the corresponding monomer on different conducting supports is studied and a special electrochemical equipment developed permitting the preparation of large-area polymer films of controlled and reproducible thickness. The ion-exchanger obtained is characterized in terms of chemical affinity for cations Co2+ and Sr2+. Incorporation of the radionuclides in the large-area ion-exchanger films thus obtained is studied and optimized with respect to the uniform distribution of the radionuclide. The performance of the procedure is demonstrated using the example of circular sources 44 mm in diameter prepared on stainless steel supports. The sources obtained are characterized in terms of activity, beta-particle flux, uniformity and source efficiency. PMID:11839017

  2. 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.

  3. 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.

  4. 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.

  5. Monte Carlo studies for medical imaging detector optimization

    NASA Astrophysics Data System (ADS)

    Fois, G. R.; Cisbani, E.; Garibaldi, F.

    2016-02-01

    This work reports on the Monte Carlo optimization studies of detection systems for Molecular Breast Imaging with radionuclides and Bremsstrahlung Imaging in nuclear medicine. Molecular Breast Imaging requires competing performances of the detectors: high efficiency and high spatial resolutions; in this direction, it has been proposed an innovative device which combines images from two different, and somehow complementary, detectors at the opposite sides of the breast. The dual detector design allows for spot compression and improves significantly the performance of the overall system if all components are well tuned, layout and processing carefully optimized; in this direction the Monte Carlo simulation represents a valuable tools. In recent years, Bremsstrahlung Imaging potentiality in internal radiotherapy (with beta-radiopharmaceuticals) has been clearly emerged; Bremsstrahlung Imaging is currently performed with existing detector generally used for single photon radioisotopes. We are evaluating the possibility to adapt an existing compact gamma camera and optimize by Monte Carlo its performance for Bremsstrahlung imaging with photons emitted by the beta- from 90 Y.

  6. Yttrium-90 Microspheres: A Review of Its Emerging Clinical Indications

    PubMed Central

    Khajornjiraphan, Natthida; Thu, Nyein Aye; Chow, Pierce Kah Hoe

    2015-01-01

    Background Many patients with liver malignancies are not candidates for resection, and systemic therapies are often not effective. Radioembolization (RE) is an alternative treatment for this group of patients. The safety and efficacy of RE with yttrium 90 (Y90) in patients with hepatocellular carcinoma (HCC) or metastatic colon cancer to the liver have been proven in several studies. However, fewer studies have focussed on the safety and efficacy of RE with Y90 in other extrahepatic primary and secondary liver cancers. The effect on outcomes of concomitant use of Y90 with a systemic therapy is still currently under investigation. Summary A review of the published data on the use of RE as stand-alone, concomitant or sequential with other treatment modalities in HCC and other primary and secondary liver cancer is reported here. Key message RE for the treatment of HCC and other extrahepatic, primary and secondary liver cancer has reasonable efficacy and acceptable toxicities. Definitive studies to establish the role of RE in the treatment of such malignancies are warranted. PMID:26020025

  7. Current Challenges in Personal Dosimetry at the U.S. DOE Hanford Site

    SciTech Connect

    Rathbone, Bruce A. ); McDonald, Joseph C. ); Traub, Richard J. )

    2002-10-01

    Abstract - This paper presents an overview of the dosimetry system, dose equivalent calculation methodology, and QA/QC practices used at the U.S. Department of Energy Hanford site. It describes some of the problems encountered in accurately measuring dose equivalent quantities under a broad range of field conditions that do not necessarily correlate with laboratory calibration conditions and the approach taken to solve these problems. Personnel at Hanford are monitored with a combination of Harshaw model 8825 and 8816 thermoluminescent dosimeters and CR-39? track etch dosimeters. Extremities are monitored using the ICN MeasuRing loaded with a Harshaw XD740 chipstrate TLD. All dosimeters employ LiF:Mg,Ti elements that are read onsite with Harshaw model 8800 and 6600 TLD readers. CR-39? dosimeters are electrochemically etched in non-commercial etch chambers and counted with an automated track counting system developed by Pacific Northwest National Laboratory. Problems with over response of the 8825 with respect to Hp(0.07), under response of the 8825 with respect to Hp(3), and over response of the 8825 with respect to Hp(10) in Hanford's 90Sr/90Y beta radiation fields are discussed. Approaches to measurement of the operational quantities for field conditions and algorithm solutions to the above problems are described. Methods used to calibrate the ring dosimeter for Hanford field conditions together with limitations of the ring dosimeter in measuring Hp(0.07) for extremities, particularly when covered with protective clothing, are also discussed.

  8. Current challenges in personal dosimetry at the US DOE Hanford site.

    PubMed

    Rathbone, B A; McDonald, J C; Traub, R J

    2002-01-01

    An overview is presented of the dosimetry system, dose equivalent calculation methodology, and QA/QC practices used at the US Department of Energy Hanford site. It describes some of the problems encountered in accurately measuring dose equivalent quantities under a broad range of field conditions that do not necessarily correlate with laboratory calibration conditions and the approach taken to solve these problems. Personnel at Hanford are monitored with a combination of Harshaw model 8825 and 8816 thermoluminescence dosemeters and CR-39 etched track dosemeters. Extremities are monitored using the ICN MeasuRing loaded with a Harshaw XD740 chipstrate TLD. All dosemeters employ LiF:Mg,Ti elements that are read on-site with Harshaw model 8800 and 6600 TLD readers. CR-39 dosemeters are electrochemically etched in non-commercial etch chambers and counted with an automated track counting system developed by Pacific Northwest National Laboratory. Problems with over response of the 8825 with respect to Hp(0.07), under-response of the 8825 with respect to Hp(3), and over response of the 8825 with respect to Hp(10) in Hanford's 90Sr/90Y beta radiation fields are discussed. Approaches to measurement of the operational quantities for field conditions and algorithm solutions to the above problems are described. Methods used to calibrate the ring dosemeter for Hanford field conditions together with limitations of the ring dosemeter in measuring Hp(0.07) for extremities, particularly when covered with protective clothing, are also discussed. PMID:12382727

  9. 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

  10. Physics of pure and non-pure positron emitters for PET: a review and a discussion.

    PubMed

    Conti, Maurizio; Eriksson, Lars

    2016-12-01

    With the increased interest in new PET tracers, gene-targeted therapy, immunoPET, and theranostics, other radioisotopes will be increasingly used in clinical PET scanners, in addition to (18)F. Some of the most interesting radioisotopes with prospective use in the new fields are not pure short-range β(+) emitters but can be associated with gamma emissions in coincidence with the annihilation radiation (prompt gamma), gamma-gamma cascades, intense Bremsstrahlung radiation, high-energy positrons that may escape out of the patient skin, and high-energy gamma rays that result in some e (+)/e (-) pair production. The high level of sophistication in data correction and excellent quantitative accuracy that has been reached for (18)F in recent years can be questioned by these effects. In this work, we review the physics and the scientific literature and evaluate the effect of these additional phenomena on the PET data for each of a series of radioisotopes: (11)C, (13)N, (15)O, (18)F, (64)Cu, (68)Ga, (76)Br, (82)Rb, (86)Y, (89)Zr, (90)Y, and (124)I. In particular, we discuss the present complications arising from the prompt gammas, and we review the scientific literature on prompt gamma correction. For some of the radioisotopes considered in this work, prompt gamma correction is definitely needed to assure acceptable image quality, and several approaches have been proposed in recent years. Bremsstrahlung photons and (176)Lu background were also evaluated. PMID:27271304

  11. Use of Yttrium-90 Microspheres in the Treatment of Unresectable Hepatic Metastases From Breast Cancer

    SciTech Connect

    Coldwell, Douglas M. Kennedy, Andrew S.; Nutting, Charles W.

    2007-11-01

    Purpose: Therapy for patients with unresectable liver metastases from breast cancer that were refractory to multiple treatment regimens was performed using radioactive microspheres. High doses of radiation were delivered to tumors from these permanently implanted yttrium-90 ({sup 90}Y) microspheres, delivered through the hepatic arterial vessels. Methods and Materials: Women from three institutions were selected for treatment, after screening that demonstrated vascular access to all tumors and after imaging confirmed that microspheres would be implanted only in the liver tumors. All patients were followed with laboratory and imaging studies at regular intervals until death. Toxicities, both acute and late were recorded, and actuarial survival determined. Results: A total of 44 women were treated from April 2002 to April 2005. Median follow-up of these women was 14 months (1-42 months). No treatment-related procedure deaths or radiation related veno-occlusive liver failures were found. Computed tomographic imaging partial response was 47% and positron emission tomographic response 95%. Conclusion: In this group of heavily pretreated patients, radioactive microspheres produced an encouraging median survival, with acceptable toxicity and a significant objective response rate, suggesting that further investigation of this approach is warranted.

  12. 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.

  13. Pixel-based parametric source depth map for Cerenkov luminescence imaging

    NASA Astrophysics Data System (ADS)

    Altabella, L.; Boschi, F.; Spinelli, A. E.

    2016-01-01

    Optical tomography represents a challenging problem in optical imaging because of the intrinsically ill-posed inverse problem due to photon diffusion. Cerenkov luminescence tomography (CLT) for optical photons produced in tissues by several radionuclides (i.e.: 32P, 18F, 90Y), has been investigated using both 3D multispectral approach and multiviews methods. Difficult in convergence of 3D algorithms can discourage to use this technique to have information of depth and intensity of source. For these reasons, we developed a faster 2D corrected approach based on multispectral acquisitions, to obtain source depth and its intensity using a pixel-based fitting of source intensity. Monte Carlo simulations and experimental data were used to develop and validate the method to obtain the parametric map of source depth. With this approach we obtain parametric source depth maps with a precision between 3% and 7% for MC simulation and 5-6% for experimental data. Using this method we are able to obtain reliable information about the source depth of Cerenkov luminescence with a simple and flexible procedure.

  14. Monoclonal antibodies reactive with human breast or ovarian carcinoma: In vivo applications

    SciTech Connect

    Thor, A.D.; Edgerton, S.M. )

    1989-10-01

    Monoclonal antibodies (MoAbs) are unique and useful bioprobes that allow in vivo targeting of membrane-associated or circulating antigens. Most of the clinical trials to date have used low dosages of radiolabeled MoAb given in a single dose. Newer studies have included antibody fragments, repeated injections, intraperitoneal (IP) administration, and other labels such as 90Y. Clinical MoAb trials are often arduous, expensive, and time-consuming to perform. Before human use, animal studies and extensive MoAb characterization are required. The production of pharmaceutical grade, radiolabeled MoAb is technically difficult and costly. Clinical trials require administrative and patient consent as well as extensive written protocols. These studies necessitate interdepartmental and intradepartmental cooperation and coordination. Furthermore, the use of in vivo radiolabeled probes impacts many levels of health care providers from janitorial, nursing, and technical staff to laboratories and physicians. Simple blood tests or disposal of body excretions may concern nursing or technical staff with the possibility of radiation exposure. The responsibility for study design, personnel involvement, and prospective use in patients without a definitive cancer diagnosis ultimately rests with the physician. While many issues have been addressed, additional clinical trials, consideration of safety issues, and standardization between institutions will be necessary before the use of radiolabeled MoAb for diagnosis, management, or therapy of human tumors becomes routine. Continued cooperation and funding should ensure its achievement. 136 references.

  15. 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.

  16. Visualizing the origins of selfish de novo mutations in individual seminiferous tubules of human testes.

    PubMed

    Maher, Geoffrey J; McGowan, Simon J; Giannoulatou, Eleni; Verrill, Clare; Goriely, Anne; Wilkie, Andrew O M

    2016-03-01

    De novo point mutations arise predominantly in the male germline and increase in frequency with age, but it has not previously been possible to locate specific, identifiable mutations directly within the seminiferous tubules of human testes. Using microdissection of tubules exhibiting altered expression of the spermatogonial markers MAGEA4, FGFR3, and phospho-AKT, whole genome amplification, and DNA sequencing, we establish an in situ strategy for discovery and analysis of pathogenic de novo mutations. In 14 testes from men aged 39-90 y, we identified 11 distinct gain-of-function mutations in five genes (fibroblast growth factor receptors FGFR2 and FGFR3, tyrosine phosphatase PTPN11, and RAS oncogene homologs HRAS and KRAS) from 16 of 22 tubules analyzed; all mutations have known associations with severe diseases, ranging from congenital or perinatal lethal disorders to somatically acquired cancers. These results support proposed selfish selection of spermatogonial mutations affecting growth factor receptor-RAS signaling, highlight its prevalence in older men, and enable direct visualization of the microscopic anatomy of elongated mutant clones. PMID:26858415

  17. 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.

  18. 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.

  19. 142-Sm - a suitable positron emitter for uptake monitoring in 153-Sm EDTMP therapy

    SciTech Connect

    Beyer, G.J.; Donath, A.; Morel, C.

    1996-05-01

    The positron emitting isotopes {sup 86}Y and 83Sr are favoured candidates for monitoring the individual nuclide uptake in bone metastases with PET when {sup 90}Y or {sup 89}Sr are used in the therapy. It therefore seemed to be logical to propose the short-lived positron emitter {sup 142}Sm to perform the in vivo dosimetry in case cf {sup 153}Sm EDTMP therapy. {sup 142}Sm (72 min, 50 % positron branching) forms the 40 sec {sup 142}Pm with 95% positron decay rate. Three aspects will be discussed in the paper: the production of several GBq of the {sup 142}Sm in the required high quality, systematic studies of the biokinetic behaviour of radio-lanthanides with EDTMP as ligand and first dynamic PET studies using rabbits as animal model. Spallation reaction of 1 GeV protons interacting with a 100/g/cm{sup 2} Ta target in combination with an on line isotope separation process was used for the production of the radionuclides. The on line isotope separator facility ISOLDE at CERN provides excellent possibilities to produce {sup 142}Sm in multi GBq quantities, isotopically clean and carrier free. All other radio-lanthanides used in the study were produced at the ISOLDE facility as well. Using a number of long-lived radio-lanthanides we studied systematically the biokinetics of the lanthanides at different EDTMP concentrations and established clear relationships between biokinetics, EDTMP concentration and the ionic radius of the radioisotope used.

  20. Electrical and structural properties of BaCe0.85Ru0.05Y0.10O3‑δ thin film prepared by RF magnetron sputtering

    NASA Astrophysics Data System (ADS)

    Ochi, Masanori; Tsuchiya, Takashi; Yamaguchi, Shohei; Suetsugu, Takaaki; Suzuki, Naoya; Kobayashi, Masaki; Minohara, Makoto; Horiba, Koji; Kumigashira, Hiroshi; Higuchi, Tohru

    2016-06-01

    The a- and c-axes-oriented BaCe0.85Ru0.05Y0.10O3‑δ (BCRY) thin films have been deposited on Nb-SrTiO3(100) substrates by radio frequency (RF) magnetron sputtering. Such BCRY thin films have mixed valence states of Ce4+ and Ce3+. The activation energies (E A) for the conductivity of films thicker than 200 nm are 0.23–0.26 eV, which corresponds to half E A of bulk ceramics, below 400 °C. The BCRY thin films exhibit ion conduction at the bulk region and electron–ion mixed conduction at the surface region. Proton conduction is also observed in the surface state in addition to the mixed conduction. The Fermi levels (E F) locate at the middle position in the band gap region, although E F of the BaCe0.90Y0.10O3‑δ thin films locates on the valence band side. These results indicate that the Ru5+ ions and protons act as donor ions in BCRY thin films.

  1. 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

  2. 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.

  3. Safety and Efficacy of Combined Yttrium 90 Resin Radioembolization with Aflibercept and FOLFIRI in a Patient with Metastatic Colorectal Cancer

    PubMed Central

    De Souza, Andre; Saif, Muhammad Wasif

    2015-01-01

    Background. When associated with isolated four or fewer liver foci, metastatic colorectal cancer is amenable to surgical resection. Alternative therapeutic methods for isolated liver metastases include radioembolization with yttrium 90 (Y90) and transarterial chemoembolization (TACE). We present here a case of a patient with two sites of liver metastatic disease from colorectal cancer who underwent Y90 radioembolization combined with aflibercept and FOLFIRI. Case Report. A 56-year-old female with history of bilateral breast cancer and metastatic colon cancer with prior hemicolectomy and 4 previous chemotherapy regimens developed liver metastasis. She was started on aflibercept and FOLFIRI and concurrently underwent two treatments of radioembolization with Y90, initially targeting the largest right lobe tumor, and then a subsequent treatment targeting the smaller left lobe tumor with retreatment of the right lobe tumor. Her liver metastases exhibited partial response on imaging utilizing the modified RECIST criteria. Interestingly, the patient CEA levels decreased after the procedure. Discussion. This is the first reported case of a patient managed with radioembolization with Y90 combined with aflibercept, an anti-VEGF treatment, and FOLFIRI. An ongoing randomized clinical trial aims to define the role of combined targeted therapy and chemotherapy with radioembolization with Y90. PMID:25866690

  4. Improved Čerenkov counting techniques based on a free parameter model.

    PubMed

    Kossert, K; Grau Carles, A; Nähle, O J

    2014-04-01

    In the past few years, two Čerenkov methods were developed to make activity measurements of high-energy beta emitters in liquid scintillation counters with two or three photomultiplier tubes (PMTs) possible. Both methods are based on a free parameter model and make use of the Frank and Tamm theory for the emission of Čerenkov light. In this article, additional effects are discussed and further improvements are presented. The dependence of the refractive index of water on the wavelength can now be taken into account, which has also an influence on the upper limit of the wavelength region for the production of Čerenkov light. In addition, the dependence of the PMT response on the wavelength is taken into account. Finally, it is possible to take a potential asymmetry of efficiencies in a system with three PMTs into account. To this end, three free parameters are assigned to each individual PMT and then determined by means of a downhill simplex optimization algorithm. The computed counting efficiencies for a triple-to-double coincidence ratio (TDCR) system were compared with experimental data for (32)P, (89)Sr, and (90)Y. PMID:24457420

  5. Optically stimulated luminescence: Searching for new dosimetric materials

    NASA Astrophysics Data System (ADS)

    Yoshimura, E. M.; Yukihara, E. G.

    2006-09-01

    Optically stimulated luminescence (OSL) is increasingly being used as a dosimetric technique in various fields such as medical, environmental and space dosimetry, and sediment and archaeological dating. Nevertheless few compounds are suitable as OSL materials. In this work, a survey was made of various insulators, searching for candidates for new OSL dosimeters. Natural and synthetic crystals and glasses from numerous sources are included. Luminescence was stimulated with blue LEDs (470 nm) and with IR laser (830 nm) provided by an automatic reader. Irradiation was performed with a 90Sr/ 90Y beta source, and the emitted light was measured with a photomultiplier tube, protected with suitable optical filters. Thermoluminescence (TL) of the samples was also measured, with the same equipment, to evaluate the thermal and optical stability of the defects related to OSL and TL. Among the various investigated materials, Al 2O 3:Cr, Mg, Fe, MgAl 2O 4 spinels, Mg 2SiO 4:Tb, and natural fluorite show potential as OSL dosimeters. Some materials, as barium aluminoborate glasses, although showing intense OSL signals, present a high fading at room temperature. In that situation the OSL signal is related to low temperature TL peaks that also fade at room temperature. None of the investigated materials was specially prepared to be used as an OSL dosimeter, which means that work can be done, mainly in the impurity nature and content, in order to improve OSL signals and to overcome some of the shortcomings that were noticed.

  6. Age dependencies of 90Sr incorporation in dental tissues: comparative analysis and interpretation of different kinds of measurements obtained for residents on the Techa River.

    PubMed

    Tolstykh, Evgenia I; Shishkina, Elena A; Degteva, Marina 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, the radiochemical determination of 90Sr in whole teeth, and the measurement of dose in teeth by use of electron paramagnetic resonance. Presented in this paper are results of 2,514 tooth-beta counter measurements, 334 radiochemical measurements, and 218 electron paramagnetic resonance 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 tooth-beta counter data are the most reliable in terms of reconstruction of 90Sr intake; this is due in part to the fact that the tooth-beta counter measures four teeth (all at position 1) with essentially the same time periods of mineralization and because there are a large number of tooth-beta counter measurements. The main utility of electron paramagnetic resonance 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. PMID:13678281

  7. Development of an improved dose reconstruction system for the Techa River population affected by the operation of the Mayak Production Association.

    PubMed

    Degteva, M O; Vorobiova, M I; Tolstykh, E I; Shagina, N B; Shishkina, E A; Anspaugh, L R; Napier, B A; Bougrov, N G; Shved, V A; Tokareva, E E

    2006-07-01

    The Techa River Dosimetry System (TRDS) has been developed to provide estimates of dose received by approximately 30,000 members of the Extended Techa River Cohort (ETRC). Members of the ETRC were exposed beginning in 1949 to significant levels of external and internal (mainly from (90)Sr) dose but at low to moderate dose rates. Members of this cohort are being studied in an effort to test the hypothesis that exposure at low to moderate dose rates has the same ability to produce stochastic health effects as exposure at high dose rates. The current version of the TRDS is known as TRDS-2000 and is the subject of this paper. The estimated doses from (90)Sr are supported strongly by approximately 30,000 measurements made with a tooth beta-particle counter, measurements of bones collected at autopsy, and approximately 38,000 measurements made with a special whole-body counter that detects the bremsstrahlung from (90)Y. The median doses to the red bone marrow and the bone surface are 0.21 and 0.37 Gy, respectively. The maximum doses to the red bone marrow and bone surface are 2.0 and 5.2 Gy, respectively. Distributions of dose to other organs are provided and are lower than the values given above. Directions for future work are discussed. PMID:16808612

  8. Bases for secondary standards for residual radionuclides in soil and some recommendations for cost-effective operational implementation.

    PubMed

    Anspaugh, L R; Daniels, J I

    1996-05-01

    The future use of land contaminated with radionuclides depends upon scientifically defensible bases for setting limits for radionuclides in soil. The purpose of this work is to develop such bases for establishing "posting criteria" to protect nonradiological workers at the Nevada Test Site and to provide a rationale for cost-effective measurements to readily determine the boundary conditions. The analysis begins with a mandated limit on total effective dose equivalent (1 mSv y(-1)) via all pathways. The possible pathways of exposure are external gamma exposure, inhalation of resuspended material, and incidental soil ingestion. These pathways are evaluated for each radionuclide of interest on the Nevada Test Site, and the results are used to define for each radionuclide the deposition-density limits for each pathway of exposure. The minimum deposition-density limits are noted to occur via the external gamma-exposure pathway for most radionuclides; exceptions are incidental soil ingestion for 90Sr/90Y and inhalation for 238Pu, 239,240Pu, and 241Am. The limiting values of deposition density or average concentration in soil are then determined appropriately by combining all pathways. Procedures are developed for dealing with mixtures of many radionuclides and to apply the principles developed so that even a simple measurement of external gamma-exposure rate may be used to define the boundary conditions in the field, provided that the relative abundance of the radionuclide mixture is known and that the defining level of exposure rate is sufficiently above background. PMID:8690586

  9. GaP betavoltaic cells as a power source

    NASA Technical Reports Server (NTRS)

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

    1991-01-01

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

  10. ¹¹¹In-DTPA⁰-octreotide (Octreoscan), ¹³¹I-MIBG and other agents for radionuclide therapy of NETs.

    PubMed

    Bomanji, Jamshed B; Papathanasiou, Nikolaos D

    2012-02-01

    This paper is a critical review of the literature on NET radionuclide therapy with (111)In-DTPA(0)-octreotide (Octreoscan) and (131)I-MIBG, focusing on efficacy and toxicity. Some potential future applications and new candidate therapeutic agents are also mentioned. Octreoscan has been a pioneering agent for somatostatin receptor radionuclide therapy. It has achieved symptomatic responses and disease stabilization, but it is now outperformed by the corresponding β-emitter agents (177)Lu-DOTATATE and (90)Y-DOTATOC. (131)I-MIBG is the radionuclide therapy of choice for inoperable or metastatic phaeochromocytomas/paragangliomas, which avidly concentrate this tracer via the noradrenaline transporter. Symptomatic, biochemical and tumour morphological response rates of 50-89%, 45-74% and 27-47%, respectively, have been reported. (131)I-MIBG is a second-line radiopharmaceutical for treatment of enterochromaffin carcinoids, mainly offering the benefit of amelioration of hormone-induced symptoms. High specific activity, non-carrier-added (131)I-MIBG and meta-astato((211)At)-benzylguanidine (MABG) are tracers with potential for enhanced therapeutic efficacy, yet their integration into clinical practice awaits further exploration. Amongst other promising agents, radiolabelled exendin analogues show potential for imaging and possibly therapy of insulinomas, while preclinical studies are currently evaluating DOTA peptides targeting the CCK-2/gastrin receptors that are overexpressed by medullary thyroid carcinoma cells. PMID:22388626

  11. Cross-fire doses from beta-emitting radionuclides in targeted radiotherapy. A theoretical study based on experimentally measured tumor characteristics.

    PubMed

    Enger, S A; Hartman, T; Carlsson, J; Lundqvist, H

    2008-04-01

    A mathematical model based upon histological findings of cell cluster distributions in primary breast cancers and lymph node metastases was developed. The model is unique because it accounts for tumor cell cluster formations within both primary tumors and metastases. The importance of inter-cell cluster cross-fire radiation dose for beta-emitting radionuclides of different energies was studied. The cell clusters were simulated as spheres with 15, 25 and 50 microm radii having a homogeneous radioactivity distribution. The self-dose as well as the dose distribution around the spheres was calculated for seven radionuclides, (90)Y, (188)Re, (32)P, (186)Re, (159)Gd, (131)I and (177)Lu using the GEANT4 Monte Carlo code. Generally, the self-dose was decreasing with increasing energy of the emitted beta particles. An exception was (188)Re which, compared to (32)P, had higher beta energy as well as higher self-dose. This was due to the higher emission of conversion and Auger electrons in the (188)Re-decay. When the cell clusters had a mean distance that was shorter than the maximum range of beta-particles, then the inter-cluster cross-fire radiation contributed significantly to the absorbed dose. Thus, high-energy beta-particles may, in spite of a low self-dose to single clusters, still be favorable to use due to the contribution of inter-cluster cross-fire radiation. PMID:18364546

  12. Results of fibre and toner flotation depending on oleic acid dosage.

    PubMed

    Trumic, Maja S; Trumic, Milan Z; Vujic, Bogdana; Andric, Ljubisa; Bogdanovic, Grozdanka

    2016-09-01

    The literature was reviewed with respect to deinking flotation methods with toner samples, specifically emphasizing the speciation of copy machine and laser printing, which produce an increasing quantity of paper that is difficult to recycle. Speciation here refers to the physical-chemical characteristics of the toner, which change because of the polymerization (fusion) and oxidation process, due to exposure to heat, light and oxygen (air) during the printing process. To simulate the deinking flotation, after the ideal disintegration process, samples of toner were prepared in order to provide free toner particles. Synthetic toner has iron content and the same physical-chemical features as free disintegrated printed toner particles.We report the toner (I) and fibre (Y) recovery and the brightness (B) of laboratory filter pads formed of deinked product as deinking efficiencies. The application of oleic acid as the collector in the flotation stage gives a better flotation recovery in alkaline than in acidic conditions. The highest brightness (BF = 93.66%) and flotation recoveries (I = 90, Y = 92.82%) were achieved during testing at an oleic acid concentration of 3.38·10(-6) mol l(-1), which is the lowest dose used. This makes the use of oleic acid economical and environmentally friendly. PMID:27354017

  13. 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.

  14. The neoplastic transformation potential of mammography X rays and atomic bomb spectrum radiation.

    PubMed

    Heyes, G J; Mill, A J

    2004-08-01

    Considerable controversy currently exists regarding the biological effectiveness of 29 kVp X rays which are used for mammography screening. This issue must be resolved to enable proper evaluation of radiation risks from breast screening. Here a definitive assessment of the biological effectiveness of 29 kVp X rays compared to the quality of radiation to which the atomic bomb survivors were exposed is presented for the first time. The standard radiation sources used were (a) an atomic bomb simulation spectrum and (b) 2.2 MeV electrons from a strontium-90/yttrium-90 (90Sr/90Y) radioactive source. The biological end point used was neoplastic transformation in vitro in CGL1 (HeLa x human fibroblast hybrid) cells. No significant difference was observed for the biological effectiveness of the two high-energy sources for neoplastic transformation. A limiting relative biological effectiveness (RBE(M)) of 4.42 +/- 2.02 was observed for neoplastic transformation by 29 kVp X rays compared to these two sources. This compares with values of 4.67 +/- 3.93 calculated from previously published data and 3.58 +/- 1.77 when the reference radiation was 200 and 220 kVp X rays. This suggests that the risks associated with mammography screening may be approximately five times higher than previously assumed and that the risk-benefit relationship of mammography exposures may need to be re-examined. PMID:15387138

  15. Radioembolization in the treatment of unresectable liver tumors: experience across a range of primary cancers.

    PubMed

    Coldwell, Douglas; Sangro, Bruno; Salem, Riad; Wasan, Harpreet; Kennedy, Andrew

    2012-04-01

    Radioembolization is a proven treatment to slow disease progression and improve survival in patients with colorectal cancer liver metastases and hepatocellular carcinoma. Accumulating evidence supports its use in metastases from neuroendocrine tumors and breast cancer. Cancers with radiobiologic profiles similar to those of colorectal and breast cancer, including melanoma, lung cancer, and nodular cholangiocarcinoma, are being studied as candidates for radioembolization. This treatment modality has also been shown to downsize hepatic tumors for potentially curative ablation in patients with breast, pancreatic, and colorectal cancer. Radioembolization using either yttrium-90 ((90)Y)-labeled resin or glass microspheres represents a promising therapy for liver-only or liver-predominant tumors in patients with 1 or more variables, including adequate or sufficient functional liver reserve, good performance status, and absence of other significant comorbidities. Therapeutic efficacy and safety can be best achieved by use of careful dosimetric techniques and treatment planning. Radioembolization could be considered after progression of liver metastases during treatment hiatus, at an early therapeutic line in tumors that respond poorly to chemotherapy, or in treatment-refractory disease. PMID:21127414

  16. Direct dose confirmation of quantitative autoradiography with micro-TLD measurements for radioimmunotherapy

    SciTech Connect

    Griffith, M.H.; Yorke, E.D.; Wessels, B.W.; DeNardo, G.L.; Neacy, W.P.

    1988-11-01

    Autoradiography has shown marked heterogeneous distribution of radioactivity in all ten radiolabeled monoclonal antibody/tumor combinations evaluated by our laboratories for radioimmunotherapy (RIT) in mice. Quantitative autoradiography was performed on two of these combinations (131I-B72.3/colorectal carcinoma and 131I-LYM-1/Raji B-cell lymphoma) to obtain a correlation of film density with radiolabeled antibody distribution. Through the use of sectioned mini-thermoluminescent dosimeter(s) (TLD) or micro-TLD, isodose curves were generated from the film gradient density lines. A computer program was written to compare theoretical absorbed dose calculations to measured micro-TLD values. First-order agreement was reached for both antibody/tumor systems: (a) B72.3/colorectal system--810 cGy measured/824 cGy calculated per 200 microCi injected and (b) LYM-1/lymphoma system--1,740 cGy measured/1,580 cGy calculated per 656 microCi injected (1 cGy = 1 rad). Additionally, the measured absorbed dose heterogeneity over a 500-micron length of up to 400% which suggests that the use of quantitative autoradiography is necessary in order to correctly determine the underlying radiobiological effects of RIT. Theoretical computer modeling based on similar autoradiographic activity distributions has also provided a convenient means of assessing absorbed dose variation patterns from other radiolabels such as 90Y.

  17. Cubical S values for use with SPECT, PET, and autoradiographic imaging data in performing small-scale dosimetry

    SciTech Connect

    Costes, S.V.; Bouchet, L.G.; Bolch, W.E.

    1996-06-01

    A traditional assumption made in nuclear medicine dosimetry methodologies such as the MIRD schema is that the activity in the source organ is uniformly distributed. Localization techniques such as quantitative SPEC and PET imaging allow one to dispense with this assumption and look at realistic nonuniform activity distributions in selected organs or organ regions. Therapy applications further emphasize the need for direct treatment of nonuniformities. Many researchers have relied upon elaborate computational techniques such as dose kernels to assess dose distributions in these regions. In this work, a simplified approach is proposed which allows direct use of the MIRD schema in conjunction with imaging data to rapidly assess organ dose distributions with minimal computational effort. The EGS4 radiation transportcode has been used with a cubical array of tissue voxel elements for a centrally located source cube of {sup 32}P, {sup 131}I, {sup 89}Sr, {sup 90}Y, and {sup 99m}Tc. Three sets of voxel dimensions are considered: 6 mm for SPECT images, 3 mm for PET images, and 50 {mu}m for autoradiography. Radionuclide S values are subsequently tabulated as a single function of the source-to-target voxel separation distance. Isodose contours are shown for (1) a mouse renal cell carcinoma with {sup 131}I-labeled antibody, (2) a human colon adenocarcinoma with {sup 131}I-labeled antibody, and (3) various tumors directly injected With {sup 32}P.

  18. Application and dosimetric requirements for 68Ga-labeled somatostatin analogues in targeted radionuclide therapy for gastroenteropancreatic neuroendocrine tumors

    PubMed Central

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

    2015-01-01

    Neuroendocrine tumors (NETs) are associated with variable prognosis, with grade 1 and 2 NETs having a more favorable outcome than G3 ones (also called carcinoma). GEP-NET patients need highly individualized interdisciplinary evaluations and treatment. New treatment options have become available (i.e., sunitinib, mTOR inhibitors) with significant improvements in progression-free survival. Peptide receptor radionuclide therapy (PRRT) using 90Y or 177Lu-labeled somatostatin analogs has also shown promise in the treatment of advanced progressive NETs but randomized clinical trials comparing with other modalities are still lacking. SST-targeting represents the essence of theranostics. 68Ga-DOTA-SSTa can be used as companion imaging agents to assist in such a radionuclide therapy selection. 68Ga-DOTA-SSTa PET/CT might also provide critical information for prognosis, tumor response assessement to PRRT, and internal dosimetry. It is also expected that the development of novel receptor-targeting radiopharmaceuticals will contribute to the development of molecular-based personalized medicine approaches. PMID:26384594

  19. Treatment of hepatocellular carcinoma (HCC) by intra-arterial infusion of radio-emitter compounds: trans-arterial radio-embolisation of HCC.

    PubMed

    Andreana, Lorenzo; Isgrò, Graziella; Marelli, Laura; Davies, Neil; Yu, Dominic; Navalkissoor, Shaunak; Burroughs, Andrew K

    2012-10-01

    Traditional radiotherapy is only effective in treating hepatocellular cancer (HCC) in doses above 50 Gy, but this is above the recommended liver radiation exposure of about 35 Gy, which is an important limitation making this treatment unsuitable for routine clinical practice. Trans-arterial radio-embolisation (TARE), consists of delivery of compounds linked to radio-emitter particles which end up in hepatic end-arterioles or show affinity for the neoplasm itself, allowing localised delivery of doses beyond 120 Gy. These are well tolerated in patients treated with this type of internal radiation therapy. TARE for HCC is used for palliative treatment of advanced disease which cannot be treated in other ways, or for tumour down-staging before liver transplantation, or as adjuvant therapy for surgically resected HCC. Tumour response after TARE is between 25% and 60% if assessed by using RECIST criteria, and 80% by EASL criteria. In this review we outline the advantages and limitations of radio-emitter therapy including 131-I, 90-Y and 188-Re. We include several observational, and all comparative studies using these compounds. In particular we compare TARE to trans-arterial chemo-embolisation and other intra-arterial techniques. PMID:22169503

  20. 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.

  1. The role of SPECT/CT in radioembolization of liver tumours.

    PubMed

    Ahmadzadehfar, Hojjat; Duan, Heying; Haug, Alexander R; Walrand, Stephan; Hoffmann, Martha

    2014-05-01

    Radioembolization (RE) with (90)Y microspheres is a promising catheter-based therapeutic option for patients with unresectable primary and metastatic liver tumours. Its rationale arises from the dual blood supply of liver tissue through the hepatic artery and the portal vein. Metastatic hepatic tumours measuring >3 mm derive 80 - 100 % of their blood supply from the arterial rather than the portal hepatic circulation. Typically, an angiographic evaluation combined with (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) scan precedes therapy to map the tumour feeding vessels as well as to avoid the inadvertent deposition of microspheres in organs other than the liver. Prior to administration of (99m)Tc-MAA, prophylactic coil embolization of the gastroduodenal artery is recommended to avoid extrahepatic deposition of the microspheres. SPECT/CT allows direct correlation of anatomic and functional information in patients with unresectable liver disease. SPECT/CT is recommended to assess intrahepatic distribution as well as extrahepatic gastrointestinal uptake in these patients. Pretherapeutic SPECT/CT is an important component of treatment planning including catheter positioning and dose finding. A post-therapy bremsstrahlung (BS) scan should follow RE to verify the distribution of the administered tracer. BS SPECT/CT imaging enables better localization and definition of intrahepatic and possible extrahepatic sphere distribution and to a certain degree allows posttreatment dosimetry. In this paper we address the usefulness and significance of SPECT/CT in therapy planning and therapy monitoring of RE. PMID:24442600

  2. Therapeutic Strategies in HCC: Radiation Modalities

    PubMed Central

    Gallicchio, R.; Nardelli, A.; Mainenti, P.; Nappi, A.; Capacchione, D.; Simeon, V.; Sirignano, C.; Abbruzzi, F.; Barbato, F.; Landriscina, M.

    2016-01-01

    Patients with hepatocellular carcinoma (HCC) comply with an advanced disease and are not eligible for radical therapy. In this distressed scenario new treatment options hold great promise; among them transarterial chemoembolization (TACE) and transarterial metabolic radiotherapy (TAMR) have shown efficacy in terms of both tumor shrinking and survival. External radiation therapy (RTx) by using novel three-dimensional conformal radiotherapy has also been used for HCC patients with encouraging results while its role had been limited in the past for the low tolerance of surrounding healthy liver. The rationale of TAMR derives from the idea of delivering exceptional radiation dose locally to the tumor, with cell killing intent, while preserving normal liver from undue exposition and minimizing systemic irradiation. Since the therapeutic efficacy of TACE is being continuously disputed, the TAMR with 131I Lipiodol or 90Y microspheres has gained consideration providing adequate therapeutic responses regardless of few toxicities. The implementation of novel radioisotopes and technological innovations in the field of RTx constitutes an intriguing field of research with important translational aspects. Moreover, the combination of different therapeutic approaches including chemotherapy offers captivating perspectives. We present the role of the radiation-based therapies in hepatocellular carcinoma patients who are not entitled for radical treatment. PMID:27563661

  3. Radiolabeled Somatostatin Analogue Therapy Of Gastroenteropancreatic Cancer.

    PubMed

    Bodei, Lisa; Kwekkeboom, Dik J; Kidd, Mark; Modlin, Irvin M; Krenning, Eric P

    2016-05-01

    Peptide receptor radionuclide therapy (PRRT) has been utilized for more than two decades and has been accepted as an effective therapeutic modality in the treatment of inoperable or metastatic gastroenteropancreatic neuroendocrine neoplasms (NENs) or neuroendocrine tumors (NETs). The two most commonly used radiopeptides for PRRT, (90)Y-octreotide and (177)Lu-octreotate, produce disease-control rates of 68%-94%, with progression-free survival rates that compare favorably with chemotherapy, somatostatin analogues, and newer targeted therapies. In addition, biochemical and symptomatic responses are commonly observed. In general, PRRT is well tolerated with only low to moderate toxicity in most individuals. In line with the need to place PRRT in the therapeutic sequence of gastroenteropancreatic NENs, a recently sponsored phase III randomized trial in small intestine NENs treated with (177)Lu-octreotate vs high-dose octreotide long-acting release demonstrated that (177)Lu-octreotate significantly improved progression-free survival. Other strategies that are presently being developed include combinations with targeted therapies or chemotherapy, intra-arterial PRRT, and salvage treatments. Sophisticated molecular tools need to be incorporated into the management strategy to more effectively define therapeutic efficacy and for an early identification of adverse events. The strategy of randomized controlled trials is a key issue to standardize the treatment and establish the position of PRRT in the therapeutic algorithm of NENs. PMID:27067503

  4. Myeloid neoplasms after chemotherapy and PRRT: myth and reality.

    PubMed

    Bodei, Lisa; Modlin, Irvin M; Luster, Markus; Forrer, Flavio; Cremonesi, Marta; Hicks, Rodney J; Ezziddin, Samer; Kidd, Mark; Chiti, Arturo

    2016-08-01

    Peptide receptor radionuclide therapy (PRRT) with (90)Y-octreotide or (177)Lu-octreotate is an effective treatment for inoperable or metastatic neuroendocrine tumors (NETs), particularly well-differentiated gastroenteropancreatic or bronchopulmonary NETs. PRRT is generally extremely well tolerated, with modest toxicity to target organs, kidney and bone marrow. Nevertheless, a priori concerns regarding long-term effects lead clinicians such as Brieau and coworkers, in this ERC issue, to ascribe to the combination of alkylating agents and PRRT the apparently high occurrence (n=4) of myeloproliferative events (therapy-related myeloid neoplasms (t-MNs)) in a small cohort of 20 progressive, advanced digestive NETs treated with PRRT after chemotherapy. Anecdotal reports of myelotoxic events should be placed in the correct perspective of larger series, where the reported incidence of these events is ~2%, with the aim of promoting a balanced awareness of the issue and unbiased and reasonable overall conclusions. For a comprehensive definition of the issue, we provide an evaluation of the occurrence of t-MN in patients treated with various myelotoxic treatments. PMID:27353035

  5. Relationships between tumor size and curablity for uniformly targeted therapy with beta-emitting radionuclides

    SciTech Connect

    O`Donoghue, J.A.; Bardies, M.; Wheldon, T.E. |

    1995-10-01

    Targeted radionuclide therapy is a new form of radiotherapy that differs in some important respects from external beam irradiation. One of the most important differences is due to the finite range of ionizing beta particles emitted as a result of radionuclide disintegration. The effects of particle range have important implications for the curability of tumors. We used a mathematical model to examine tumor curability and its relationship to tumor size for 22 beta-emitting radionuclides that may have therapeutic potential. The model assumed a uniform distribution of radionuclide throughout. For targeted radionuclide therapy, the relationship between tumor curability and tumor size is different from that for conventional external beam radiotherapy. With targeted radionuclides, there is an optimal tumor size for cure. Tumors smaller than the optimal size are less vulnerable to irradiation from radionuclides because a substantial proportion of the disintegration energy escapes and is deposited outside the tumor volume. We found an optimal tumor size for radiocurability by each of the 22 radionuclides considered. Optimal cure diameters range from less than 1 mm for short-range emitters such as {sup 199}Au and {sup 33}P to several centimeters for long-range emitters such as {sup 90}Y and {sup 188}Re. The energy emitted per disintegration may be used to predict optimal cure size for uniform distributions of radionuclide. 17 refs., 8 figs., 3 tabs.

  6. New antibody conjugates in cancer therapy.

    PubMed

    Govindan, Serengulam V; Goldenberg, David M

    2010-01-01

    Targeting of radiation, drugs, and protein toxins to cancers selectively with monoclonal antibodies (MAbs) has been a topic of considerable interest and an area of continued development. Radioimmunotherapy (RAIT) of lymphoma using directly labeled MAbs is of current interest after approval of two radiolabeled anti-CD20 MAbs, as illustrated with the near 100% overall response rate obtained in a recent clinical trial using an investigational radiolabeled anti-CD22 MAb, 90Y-epratuzumab. The advantage of pretargeted RAIT over directly labeled MAbs is continuing to be validated in preclinical models of lymphoma and solid tumors. Importantly, the advantages of combining RAIT with radiation sensitizers, with immunotherapy, or a drug conjugate targeting a different antigen are being studied clinically and preclinically. The area of drug-conjugated antibodies is progressing with encouraging data published for the trastuzumab-DM1 conjugate in a phase I clinical trial in HER2-positive breast cancer. The Dock-and-Lock platform technology has contributed to the design and the evaluation of complex antibody-cytokine and antibody-toxin conjugates. This review describes the advances made in these areas, with illustrations taken from advances made in the authors' institutions. PMID:20953556

  7. Utilization of wavelength-shifting fibers coupled to ZnS(Ag) and plastic scintillator for simultaneous detection of alpha/beta particles

    NASA Astrophysics Data System (ADS)

    Ifergan, Y.; Dadon, S.; Israelashvili, I.; Osovizky, A.; Gonen, E.; Yehuda-Zada, Y.; Smadja, D.; Knafo, Y.; Ginzburg, D.; Kadmon, Y.; Cohen, Y.; Mazor, T.

    2015-06-01

    Low level radioactive surface contamination measurements require lightweight, large area and high efficiency detector. In most existing scintillation detectors there is a tradeoff between effective area and scintillation light collection. By using wavelength shifting (WLS) fibers the scintillation light may be collected efficiently also in a large area detector. In this study, WLS fibers were coupled to a beta sensitive plastic scintillator layer and to a alpha sensitive silver-activated zinc sulfide ZnS(Ag) layer for detecting both alpha and beta particles. The WLS fibers collect the scintillation light from the whole detector and transfer it to a single PMT. This first prototype unique configuration enables monitoring radioactive contaminated surfaces by both sides of the detector and provides high gamma rejection. In this paper, the detector structure, as well as the detector's measured linear response, will be described. The measured detection efficiency of 238Pu alpha particles (5.5 MeV) is ~63%. The measured detection efficiency for beta particles is ~89% for 90Sr-90Y (average energy of 195.8 keV, 934.8 keV), ~50% for 36Cl (average energy of 251.3 keV), and 35% for 137Cs (average energy of 156.8 keV).

  8. Waste/Rock Interactions Technology Program. Status report on LWR spent-fuel leach tests

    SciTech Connect

    Katayama, Y.B.; Bradley, D.J.; Harvey, C.O.

    1980-11-01

    Spent fuels with burnups of 9000, 28,000 and 54,500 MWd/MTU have been leach tested at 25/sup 0/C. Three leach-test procedures (Paige, IAEA and static) were used. IAEA and static tests were conducted in five different solutions: deionized water, sodium bicarbonate, sodium chloride, calcium chloride and Waste Isolation Pilot Plant B brine solutions. Elemental leach data are reported based on the release of /sup 90/Sr/sup +90/Y, /sup 106/Ru, /sup 137/Cs, /sup 144/Ce, /sup 154/Eu, /sup 239 +240/Pu, /sup 125/Sb, /sup 244/Cm, /sup 129/I, /sup 99/Tc, and total uranium. This is the first report on /sup 129/I and /sup 99/Tc from spent fuel. Termination of the Paige test showed that the plateout (radionuclide adsorption) on the test apparatus had negligible effect on the leach rate of cesium and plutonium, but a major (up to a factor of 50 times) effect on the curium leach rate. Three-hundred additional days of leach testing by the IAEA procedure, from 467 to 769 d, showed a continuation of the leaching trends observed during the first 467 d. Results from the first two static leach test series, 2 and 8 d, gave the /sup 129/I and /sup 99/Tc release numbers.

  9. 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.

  10. The Role of 18F-FDG-PET and PET/CT in Patients with Colorectal Liver Metastases Undergoing Selective Internal Radiation Therapy with Yttrium-90: A First Evidence-Based Review

    PubMed Central

    Annunziata, Salvatore; Treglia, Giorgio; Galiandro, Federica

    2014-01-01

    Purpose. To provide a first evidence-based review of the literature on the role of fluorine-18-fluorodeoxyglucose positron emission tomography and positron emission tomography/computed tomography (FDG-PET and PET/CT) in patients with colorectal liver metastases (CRLM) undergoing selective internal radiation therapy (SIRT) with yttrium-90 (90Y) microspheres. Methods. A comprehensive computer literature search was conducted to find relevant published articles on whole-body FDG-PET or PET/CT in patients with CRLM undergoing SIRT. Results. We identified 19 studies including 833 patients with CRLM undergoing SIRT. The role of FDG-PET or PET/CT was analysed in treatment planning, treatment response evaluation, and as prognostic tool. Conclusion. FDG-PET and PET/CT provide additional information in treatment evaluation of CRLM patients treated with SIRT and may have a role in treatment planning and patient selection. FDG-PET/CT is emerging as good prognostic tool in these patients. PMID:24672385

  11. 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.

  12. Response of ionization chamber based pocket dosimeter to beta radiation.

    PubMed

    Kumar, Munish; Gupta, Anil; Pradhan, S M; Bakshi, A K; Chougaonkar, M P; Babu, D A R

    2013-12-01

    Quantitative estimate of the response of ionization chamber based pocket dosimeters (DRDs) to various beta sources was performed. It has been established that the ionization chamber based pocket dosimeters do not respond to beta particles having energy (Emax)<1 MeV and same was verified using (147)Pm, (85)Kr and (204)Tl beta sources. However, for beta particles having energy >1 MeV, the DRDs exhibit measureable response and the values are ~8%, ~14% and ~27% per mSv for natural uranium, (90)Sr/(90)Y and (106)Ru/(106)Rh beta sources respectively. As the energy of the beta particles increases, the response also increases. The response of DRDs to beta particles having energy>1 MeV arises due to the fact that the thickness of the chamber walls is less than the maximum range of beta particles. This may also be one of the reasons for disparity between doses measured with passive/legal dosimeters (TLDs) and DRDs in those situations in which radiation workers are exposed to mixed field of gamma photons and beta particles especially at uranium processing plants, nuclear (power and research) reactors, waste management facilities and fuel reprocessing plants etc. The paper provides the reason (technical) for disparity between the doses recorded by TLDs and DRDs in mixed field of photons and beta particles. PMID:23978508

  13. 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

  14. 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.

  15. [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. PMID:9864832

  16. 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

  17. Determination of the K absorption edge energy of Ho in element and its compounds using the bremsstrahlung technique

    NASA Astrophysics Data System (ADS)

    Niranjana, K. M.; Badiger, N. M.

    2013-05-01

    The K shell binding energies of Ho in element and in compounds Ho2O3 and HoF3 have been measured for the first time by adopting a novel method. The method involves a weak beta source, an external bremsstrahlung (EB) converter, element and compound targets and a high-resolution HPGe detector coupled to a 16K multichannel analyser. A spectrum of continuous EB photons, produced by the interaction of beta particles from a 90Sr-90Y radioactive source with an iron foil, is allowed to pass through the element and compound targets of Ho. The spectrum of transmitted EB photons is measured with a high-resolution HPGe detector spectrometer. The transmitted spectrum shows a sudden drop in intensity at K shell binding energy of the target. Such a sudden drop, which is essentially due to the onset of the K shell photoelectric effect, has been used to determine the K shell binding energy of Ho in element. The K shell binding energies of Ho in Ho2O3 and HoF3 compounds have also been determined using the same technique. From these data, the chemical shift in the K shell binding energy has been measured. It is found to be positive for Ho2O3 and negative for HoF3, indicating the dependence of the chemical shift on the crystal structure.

  18. Robustness of plastic scintillation microspheres in the continuous measurement of different river waters.

    PubMed

    Tarancón, A; Novella, O; Batlle, M; Pujadas, M; Cros, J; García, J F

    2016-08-01

    Plastic scintillation microspheres (PSm) represent one of the most promising options for monitoring alpha and beta radioactivity in river water. For that reason, a study of the stability of PSm packed into a cell against the continuous flow of river water with different degrees of turbidity was performed over a period of 100h. The results showed that the volume of the cell became stable after 15h of pumping and continued to be stable throughout the 100h of the experiment. During this period of time, the detection efficiency of the PSm, in terms of efficiency*volume, presented mean values of 0.75(3)% for (3)H and 272(11)% for (90)Sr/(90)Y. No dependence on flow time or river water type was observed. The background was also constant for 100h and for the different water types, although (222)Rn should be removed from the water beforehand to prevent its accumulation in the PSm. Since PSm did not present any degradation throughout the whole experiment, PSm can undoubtedly be used for monitoring radioactivity with low reagent consumption, low waste generation and low maintenance costs. PMID:27235888

  19. Correction factors for the ISO rod phantom, a cylinder phantom, and the ICRU sphere for reference beta radiation fields of the BSS 2

    NASA Astrophysics Data System (ADS)

    Behrens, R.

    2015-03-01

    The International Organization for Standardization (ISO) requires in its standard ISO 6980 that beta reference radiation fields for radiation protection be calibrated in terms of absorbed dose to tissue at a depth of 0.07 mm in a slab phantom (30 cm x 30 cm x 15 cm). However, many beta dosemeters are ring dosemeters and are, therefore, irradiated on a rod phantom (1.9 cm in diameter and 30 cm long), or they are eye dosemeters possibly irradiated on a cylinder phantom (20 cm in diameter and 20 cm high), or area dosemeters irradiated free in air with the conventional quantity value (true value) being defined in a sphere (30 cm in diameter, made of ICRU tissue (International Commission on Radiation Units and Measurements)). Therefore, the correction factors for the conventional quantity value in the rod, the cylinder, and the sphere instead of the slab (all made of ICRU tissue) were calculated for the radiation fields of 147Pm, 85Kr, 90Sr/90Y, and, 106Ru/106Rh sources of the beta secondary standard BSS 2 developed at PTB. All correction factors were calculated for 0° up to 75° (in steps of 15°) radiation incidence. The results are ready for implementation in ISO 6980-3 and have recently been (partly) implemented in the software of the BSS 2.

  20. Genome-Wide Analysis of Group A Streptococci Reveals a Mutation That Modulates Global Phenotype and Disease Specificity

    PubMed Central

    2006-01-01

    Many human pathogens produce phenotypic variants as a means to circumvent the host immune system and enhance survival and, as a potential consequence, exhibit increased virulence. For example, it has been known for almost 90 y that clinical isolates of the human bacterial pathogen group A streptococci (GAS) have extensive phenotypic heterogeneity linked to variation in virulence. However, the complete underlying molecular mechanism(s) have not been defined. Expression microarray analysis of nine clinical isolates identified two fundamentally different transcriptomes, designated pharyngeal transcriptome profile (PTP) and invasive transcriptome profile (ITP). PTP and ITP GAS differed in approximately 10% of the transcriptome, including at least 23 proven or putative virulence factor genes. ITP organisms were recovered from skin lesions of mice infected subcutaneously with PTP GAS and were significantly more able to survive phagocytosis and killing by human polymorphonuclear leukocytes. Complete genome resequencing of a mouse-derived ITP GAS revealed that the organism differed from its precursor by only a 7-bp frameshift mutation in the gene (covS) encoding the sensor kinase component of a two-component signal transduction system implicated in virulence. Genetic complementation, and sequence analysis of covR/S in 42 GAS isolates confirmed the central role of covR/S in transcriptome, exoproteome, and virulence modulation. Genome-wide analysis provides a heretofore unattained understanding of phenotypic variation and disease specificity in microbial pathogens, resulting in new avenues for vaccine and therapeutics research. PMID:16446783

  1. 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.

  2. [Neuroendocrine tumors: Peptide receptors radionuclide therapy (PRRT)].

    PubMed

    Papamichail, Dimitris G; Exadaktylou, Paraskevi E; Chatzipavlidou, Vasiliki D

    2016-01-01

    Neuroendocrine tumors (neuroendocrine tumors-NET) are a heterogeneous group of neoplasms with a common embryological origin and diverse biological behavior, derived from cells of the neuroendocrine system, the system APUD (amine precursor uptake and decarboxylation). They are characterized by overexpression of all five somatostatin receptors (SSTR1-SSTR5), particularly type 2 (SST2). Surgical resection of the tumor is the treatment option, with a possibility of complete remission in patients with limited disease. Somatostatin analogs (octreotide and lanreotide) are the treatment of choice in patients with residual disease, particularly when it comes to NET non-pancreatic origin. Systemic chemotherapy is administered primarily to patients with poorly differentiated carcinomas. PRRT treatment is recommended in case of non-responsiveness of the disease. The ideal candidates for PRRT are patients with unresectable disease of high and intermediate differentiation. Somatostatine analogs radiolabelled with Indium-111 ((111)In), Yttrium-90 ((90)Y), Lutetium-177 ((177)Lu) and Bismuth-213 ((213)Bi), are selectively concentrated in the tumor cells, causing maximum tissue damage to tumors and with fewer effects on healthy tissue and the immune system. In the current review, it was demonstrated that patients with unresectable grade 1 or 2 disease showed increased PFS (progression free survival) and OS (overall survival), while quality of life was improved after PRRT treatment as compared to somatostatin analogs, chemotherapy and other targeted therapies. PMID:27035909

  3. Effect of quench on alpha/beta pulse shape discrimination of liquid scintillation cocktails.

    PubMed

    DeVol, Timothy A; Theisen, Christopher D; DiPrete, David P

    2007-05-01

    The objectives of this paper are (1) to illustrate that knowledge of the external quench parameter is insufficient to properly setup a pulse shape discriminating liquid scintillation counter (LSC) for quantitative measurement, (2) to illustrate dependence on pulse shape discrimination on the radionuclide (more than just radiation and energy), and (3) to compare the pulse shape discrimination (PSD) of two commercial instruments. The effects various quenching agents, liquid scintillation cocktails, radionuclides, and LSCs have on alpha/beta pulse shape discriminating liquid scintillation counting were quantified. Alpha emitting radionuclides (239)Pu and (241)Am and beta emitter (90)Sr/(90)Y were investigated to quantify the nuclide dependence on alpha/beta pulse shape discrimination. Also, chemical and color quenching agents, nitromethane, nitric acid, and yellow dye impact on alpha/beta pulse shape discrimination using PerkinElmer Optiphase "HiSafe" 2 and 3, and Ultima Gold AB liquid scintillation cocktails were determined. The prepared samples were counted on the PerkinElmer Wallac WinSpectral 1414 alpha/beta pulse shape discriminating LSC. It was found that for the same level of quench, as measured by the external quench parameter, different quench agents influenced the pulse shape discrimination and the pulse shape discrimination parameters differently. The radionuclide also affects alpha/beta pulse shape discrimination. By comparison with the PerkinElmer Tri-carb 3150 TR/AB, the Wallac 1414 exhibited better pulse shape discrimination capability under the same experimental conditions. PMID:17440321

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

    PubMed

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

    2004-12-01

    The objective of this work was to establish a new procedure for 228Ra determination of natural waters via preconcentration of radium on MnO2 and separation of its daughter, 228Ac, using Diphonix ion exchange resin. Following removal of potential interferences via passage through an initial Diphonix Resin column, the first daughter of 228Ra, 228Ac, is isolated by chromatographic separation via a second Diphonix column. A holding time of > 30 h for 228Ac ingrowth in between the two column separations ensures secular equilibrium. Barium-133 is used as a yield tracer. Actinium-228 is eluted from the second Diphonix Resin with 5 ml 1M 1-Hydroxyethane-1,1-diphosphonic acid (HEDPA) and quantified by addition of scintillation cocktail and LSC counting. Radium (and 133Ba) from the load and rinse solutions from the 2nd Diphonix column may be prepared for alpha spectrometry (for determination of 223Ra, 224Ra, and 226Ra) by BaSO4 microprecipitation and filtration. Decontamination tests indicate that U, Th, and Ra series nuclides do not interfere with these measurements, although high contents of 90Sr (90Y) require additional treatment for accurate measurement of 228Ra. Addition of stable Sr as a "hold back" carrier during the initial MnO2 preconcentration step was shown to remove most 90Sr interference. PMID:15388106

  5. 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

  6. Late nonstochastic changes in pig skin after. beta. irradiation

    SciTech Connect

    Peel, D.M.; Hopewell, J.W.; Wells, J.; Charles, M.W.

    1985-03-01

    Late radiation-induced changes in pig skin have been assessed following irradiation with ..beta..-rays from a 22.5- or 15-mm-diameter /sup 90/Sr//sup 90/Y source and a 19- or 9-mm-diameter /sup 170/Tm source. Late damage, in terms of dermal atrophy, was assessed 2 years after irradiation from measurements of dermal thickness of 40-50% of the control value, occurred at a dose of approx. 40 Gy from the 22.5-mm source and approx. 75 Gy from the 15-mm source. In the case of /sup 170/Tm the 19- and 9-mm sources produced similar degrees of atrophy at equal doses. Maximum atrophy occurred at approx. 70 Gy, when the dermis was approx. 70% of the thickness of normal skin. Significant late tissue atrophy was seen at doses, from both types of radiation, which only produced minimal erythema in the early reaction. Such late reactions need to be taken into account when revised radiological protection criteria are proposed for skin.

  7. 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. PMID:22642386

  8. 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.

  9. 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.

  10. 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.

  11. Skin dose calculations for uranium fuel particles below 500 microns in diameter.

    PubMed

    Pöllänen, R; Toivonen, H

    1995-03-01

    Two different methods for skin dose calculations, VARSKIN Mod 2 and PSS are compared for a spherical uranium fuel particle (diameter 1-500 microns) deposited on the skin. Nuclide-specific beta dose rate at different skin depths for a particle of unit activity is determined as a function of particle size. Both methods show that the effects of self-shielding must be included in the dose calculations for low and medium energy beta emitters. Skin dose rate is drastically overestimated when point source approximation is used. For high energy beta emitters (e.g., 90Y, 106Rh, and 144Pr) the volume source can be approximated as a point source. The difference in doses is then below 20% for particles up to 100 microns in diameter. The models give equal results deep in the skin (in terms of range of the beta particles). The reason is that the correction due to the diminished backscattering in air-tissue interface is insignificant at large distances. For three-dimensional sources the backscattering correction should be introduced in the VARSKIN Mod 2. PMID:7860313

  12. Targeted radionuclide therapies for pancreatic cancer.

    PubMed

    Shah, M; Da Silva, R; Gravekamp, C; Libutti, S K; Abraham, T; Dadachova, E

    2015-08-01

    Pancreatic malignancies, the fourth leading cause of cancer deaths, have an aggressive behavior with poor prognosis, resulting in a 5-year survival rate of only 4%. It is typically a silent malignancy until patients develop metastatic disease. Targeted radionuclide therapies of cancer such as radiolabeled peptides, which bind to the receptors overexpressed by cancer cells and radiolabeled antibodies to tumor-specific antigens provide a viable alternative to chemotherapy and external beam radiation of metastatic cancers. Multiple clinical trials of targeted radionuclide therapy of pancreatic cancer have been performed in the last decade and demonstrated safety and potential efficacy of radionuclide therapy for treatment of this formidable disease. Although a lot of progress has been made in treatment of pancreatic neuroendocrine tumors with radiolabeled (90)Y and (177)Lu somatostatin peptide analogs, pancreatic adenocarcinomas remain a major challenge. Novel approaches such as peptides and antibodies radiolabeled with alpha emitters, pre-targeting, bispecific antibodies and biological therapy based on the radioactive tumorlytic bacteria might offer a potential breakthrough in treatment of pancreatic adenocarcinomas. PMID:26227823

  13. 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. PMID:22388631

  14. Targeted radionuclide therapies for pancreatic cancer

    PubMed Central

    Shah, M.; Da Silva, R.; Gravekamp, C.; Libutti, S. K.; Abraham, T.; Dadachova, E.

    2016-01-01

    Pancreatic malignancies, the 4th leading cause of cancer deaths, have an aggressive behavior with poor prognosis, resulting in a five-year survival rate of only 4%. It is typically a silent malignancy until patients develop metastatic disease. Targeted radionuclide therapies of cancer such as radiolabeled peptides which bind to the receptors overexpressed by cancer cells and radiolabeled antibodies to tumor-specific antigens provide a viable alternative to chemotherapy and external beam radiation of metastatic cancers. Multiple clinical trials of targeted radionuclide therapy of pancreatic cancer have been performed in the last decade and demonstrated safety and potential efficacy of radionuclide therapy for treatment of this formidable disease. While a lot progress has been made in treatment of pancreatic neuroendocrine tumors with radiolabeled with 90Y and 177Lu somatostatin peptide analogues, pancreatic adenocarcinomas remain a major challenge. Novel approaches such as peptides and antibodies radiolabeled with alpha emitters, pre-targeting, bispecific antibodies and biological therapy based on the radioactive tumorlytic bacteria might offer a potential breakthrough in treatment of pancreatic adenocarcinomas. PMID:26227823

  15. Bone Marrow Recovery and Subsequent Chemotherapy Following Radiolabeled Anti-Prostate-Specific Membrane Antigen Monoclonal Antibody J591 in Men with Metastatic Castration-Resistant Prostate Cancer

    PubMed Central

    Tagawa, Scott T.; Akhtar, Naveed H.; Nikolopoulou, Anastasia; Kaur, Gurveen; Robinson, Brian; Kahn, Renee; Vallabhajosula, Shankar; Goldsmith, Stanley J.; Nanus, David M.; Bander, Neil H.

    2013-01-01

    Radioimmunotherapy (RIT) has demonstrated efficacy with acceptable toxicity leading to approval in non-Hodgkin’s lymphoma, but has been slower to develop for the treatment of advanced solid tumors. Prostate cancer (PC) represents a good candidate for RIT based upon high exposure to circulating antibodies at common disease sites with a specific, highly expressed cell-surface antigen of prostate-specific membrane antigen. Four phase I and II trials utilizing 177Lu- or 90Y-J591 have been reported. Long-term toxicity and chemotherapy administration was analyzed. As expected, the only serious toxicity observed was myelosuppression. Grade 4 thrombocytopenia occurred in 33.3% without significant hemorrhage and grade 4 neutropenia occurred in 17.3% with 0.07% febrile neutropenia. Nearly all subjects (97.3%) recovered to grade 0 or 1 platelets and all had complete neutrophil recovery. The majority (81.3%) received chemotherapy at any time, with 61.3% receiving chemotherapy following RIT. Ten subjects underwent bone marrow biopsies at some point in their disease course following RIT for low counts; all had diffuse PC infiltration without evidence of myelodysplasia or leukemia. As expected, myelosuppression occurs following therapeutic doses of RIT for men with metastatic castration-resistant PC. However, toxicity is predictable and self-limited, with the majority of patients who do not refuse able to receive cytotoxic chemotherapy following RIT. PMID:23986881

  16. Therapeutic Strategies in HCC: Radiation Modalities.

    PubMed

    Gallicchio, R; Nardelli, A; Mainenti, P; Nappi, A; Capacchione, D; Simeon, V; Sirignano, C; Abbruzzi, F; Barbato, F; Landriscina, M; Storto, G

    2016-01-01

    Patients with hepatocellular carcinoma (HCC) comply with an advanced disease and are not eligible for radical therapy. In this distressed scenario new treatment options hold great promise; among them transarterial chemoembolization (TACE) and transarterial metabolic radiotherapy (TAMR) have shown efficacy in terms of both tumor shrinking and survival. External radiation therapy (RTx) by using novel three-dimensional conformal radiotherapy has also been used for HCC patients with encouraging results while its role had been limited in the past for the low tolerance of surrounding healthy liver. The rationale of TAMR derives from the idea of delivering exceptional radiation dose locally to the tumor, with cell killing intent, while preserving normal liver from undue exposition and minimizing systemic irradiation. Since the therapeutic efficacy of TACE is being continuously disputed, the TAMR with (131)I Lipiodol or (90)Y microspheres has gained consideration providing adequate therapeutic responses regardless of few toxicities. The implementation of novel radioisotopes and technological innovations in the field of RTx constitutes an intriguing field of research with important translational aspects. Moreover, the combination of different therapeutic approaches including chemotherapy offers captivating perspectives. We present the role of the radiation-based therapies in hepatocellular carcinoma patients who are not entitled for radical treatment. PMID:27563661

  17. 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. PMID:25594357

  18. 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

  19. 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

  20. 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

  1. Production and Clinical Applications of Radiopharmaceuticals and Medical Radioisotopes in Iran.

    PubMed

    Jalilian, Amir Reza; Beiki, Davood; Hassanzadeh-Rad, Arman; Eftekhari, Arash; Geramifar, Parham; Eftekhari, Mohammad

    2016-07-01

    -meta-iodobenzylguanidine for treatment of neuroblastoma, pheochromocytoma, and other neuroendocrine tumors has been steadily increasing in major academic university hospitals. Also (153)Sm-EDTMP, (177)Lu-EDTMP, (90)Y-citrate, (90)Y-hydroxyapatite colloid, (188/186)Re-sulfur colloid, and (188/186)Re-HEDP have been locally developed and now routinely available for bone pain palliation and radiosynovectomy. Cu-64 has been available to the nuclear medicine community for some time. With recent reports in diagnostic and therapeutic applications of this agent especially in the field of oncology, we anticipate an expansion in production and availability. The initiation of the production line for gallium-68 generator is one of the latest exciting developments. We are proud that Iran would be joining the club of few nations with production lines for this type of generator. There are also quite a number of SPECT and PET tracers at research and preclinical stage of development preliminarily introduced for possible future clinical applications. Availability of fluorine-18 tracers and gallium-68 generators would no doubt allow rapid dissemination of PET/CT practices in various parts of our large country even far from a cyclotron facility. Also, local production and availability of therapeutic radiopharmaceuticals are going to open exciting horizons in the field of nuclear medicine therapy. Given the available manpower, local infrastructure of SPECT imaging, and rapidly growing population, the production of Tc-99m generators and cold kit would continue to flourish in Iran. PMID:27237443

  2. 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.

  3. 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 embolizat