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Journal articles on the topic 'Bismuth 213'

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Published: 4 June 2021

Last updated: 1 February 2022

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1

Lucignani, Giovanni. "Alpha-particle radioimmunotherapy with astatine-211 and bismuth-213." European Journal of Nuclear Medicine and Molecular Imaging 35, no. 9 (2008): 1729–33. http://dx.doi.org/10.1007/s00259-008-0856-4.

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2

Dzhuzha, D., and S. Myasoyedov. "Radionuclide therapy with alpha-emitters." Radiation Diagnostics, Radiation Therapy, no. 4 (2019): 37–47. http://dx.doi.org/10.37336/2707-0700-2019-4-4.

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In this review the main streams of using alpha-emitters radium-223, actinium-225, bismuth-213, astatine-211 in complex treatment of malignant tumors are reviewed. The features of radiobiological actions of alpha-emission make its more effective in hundred times than beta-emission. The efficacy of this kind of radionuclide therapy does not dependent from chemoresistance and radioresistance to beta-emitters. The results of experimental and initial clinical investigation, which indicate on promising further investigations in this direction, were revealed. Key words: radionuclide therapy of malignant tumors, alpha-emitters, radium-223, actinium-225, bismuth-213, astatine-211.

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3

Rizvi, Syed M. Abbas, Emma YanJun Song, Chand Raja, et al. "Preparation and testing of bevacizumab radioimmunoconjugates with Bismuth-213 and Bismuth-205 / Bismuth-206." Cancer Biology & Therapy 7, no. 10 (2008): 1547–54. http://dx.doi.org/10.4161/cbt.7.10.6538.

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4

Ahenkorah, Stephen, Irwin Cassells, Christophe M. Deroose, et al. "Bismuth-213 for Targeted Radionuclide Therapy: From Atom to Bedside." Pharmaceutics 13, no. 5 (2021): 599. http://dx.doi.org/10.3390/pharmaceutics13050599.

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In contrast to external high energy photon or proton therapy, targeted radionuclide therapy (TRNT) is a systemic cancer treatment allowing targeted irradiation of a primary tumor and all its metastases, resulting in less collateral damage to normal tissues. The α-emitting radionuclide bismuth-213 (213Bi) has interesting properties and can be considered as a magic bullet for TRNT. The benefits and drawbacks of targeted alpha therapy with 213Bi are discussed in this review, covering the entire chain from radionuclide production to bedside. First, the radionuclide properties and production of 225Ac and its daughter 213Bi are discussed, followed by the fundamental chemical properties of bismuth. Next, an overview of available acyclic and macrocyclic bifunctional chelators for bismuth and general considerations for designing a 213Bi-radiopharmaceutical are provided. Finally, we provide an overview of preclinical and clinical studies involving 213Bi-radiopharmaceuticals, as well as the future perspectives of this promising cancer treatment option.

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5

Eychenne, Romain, Michel Chérel, Férid Haddad, François Guérard, and Jean-François Gestin. "Overview of the Most Promising Radionuclides for Targeted Alpha Therapy: The “Hopeful Eight”." Pharmaceutics 13, no. 6 (2021): 906. http://dx.doi.org/10.3390/pharmaceutics13060906.

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Among all existing radionuclides, only a few are of interest for therapeutic applications and more specifically for targeted alpha therapy (TAT). From this selection, actinium-225, astatine-211, bismuth-212, bismuth-213, lead-212, radium-223, terbium-149 and thorium-227 are considered as the most suitable. Despite common general features, they all have their own physical characteristics that make them singular and so promising for TAT. These radionuclides were largely studied over the last two decades, leading to a better knowledge of their production process and chemical behavior, allowing for an increasing number of biological evaluations. The aim of this review is to summarize the main properties of these eight chosen radionuclides. An overview from their availability to the resulting clinical studies, by way of chemical design and preclinical studies is discussed.

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6

Morgenstern, Alfred, Christos Apostolidis, and Frank Bruchertseifer. "Supply and Clinical Application of Actinium-225 and Bismuth-213." Seminars in Nuclear Medicine 50, no. 2 (2020): 119–23. http://dx.doi.org/10.1053/j.semnuclmed.2020.02.003.

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7

Jurcic, Joseph G. "Clinical Studies with Bismuth-213 and Actinium-225 for Hematologic Malignancies." Current Radiopharmaceuticals 11, no. 3 (2018): 192–99. http://dx.doi.org/10.2174/1874471011666180525102814.

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8

Balieu, Sébastien, Abdel Malek Bouraiou, Bertrand Carboni, and Bernard Boitrel. "Synthesis of a boronic ester-appended bismuth(III) porphyrin as a potential alpha-particle bi-emitter." Journal of Porphyrins and Phthalocyanines 12, no. 01 (2008): 11–18. http://dx.doi.org/10.1142/s1088424608000030.

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As 213 Bi , a spontaneous alpha-emitting radioisotope, and 10 B , a neutron-activated source of alpha particles, have been found to be potential tools in the treatment of cancer patients, a novel bismuth porphyrin, bearing both boron atoms and a strap with a hanging carboxylic group, was synthesized.

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9

Kowalik, Mateusz, Joanna Masternak, and Barbara Barszcz. "Recent Research Trends on Bismuth Compounds in Cancer Chemoand Radiotherapy." Current Medicinal Chemistry 26, no. 4 (2019): 729–59. http://dx.doi.org/10.2174/0929867324666171003113540.

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Background:Application of coordination chemistry in nanotechnology is a rapidly developing research field in medicine. Bismuth complexes have been widely used in biomedicine with satisfactory therapeutic effects, mostly in Helicobacter pylori eradication, but also as potential antimicrobial and anti-leishmanial agents. Additionally, in recent years, application of bismuth-based compounds as potent anticancer drugs has been studied extensively.Methods:Search for data connected with recent trends on bismuth compounds in cancer chemo- and radiotherapy was carried out using web-based literature searching tools such as ScienceDirect, Springer, Royal Society of Chemistry, American Chemical Society and Wiley. Pertinent literature is covered up to 2016.Results:In this review, based on 213 papers, we highlighted a number of current problems connected with: (i) characterization of bismuth complexes with selected thiosemicarbazone, hydrazone, and dithiocarbamate classes of ligands as potential chemotherapeutics. Literature results derived from 50 papers show that almost all bismuth compounds inhibit growth and proliferation of breast, colon, ovarian, lung, and other tumours; (ii) pioneering research on application of bismuth-based nanoparticles and nanodots for radiosensitization. Results show great promise for improvement in therapeutic efficacy of ionizing radiation in advanced radiotherapy (described in 36 papers); and (iii) research challenges in using bismuth radionuclides in targeted radioimmunotherapy, connected with choice of adequate radionuclide, targeting vector, proper bifunctional ligand and problems with 213Bi recoil daughters toxicity (derived from 92 papers).Conclusion:This review presents recent research trends on bismuth compounds in cancer chemo- and radiotherapy, suggesting directions for future research.

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10

Bruchertseifer, Frank, Alban Kellerbauer, Rikard Malmbeck, and Alfred Morgenstern. "Targeted alpha therapy with bismuth-213 and actinium-225: Meeting future demand." Journal of Labelled Compounds and Radiopharmaceuticals 62, no. 11 (2019): 794–802. http://dx.doi.org/10.1002/jlcr.3792.

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11

Lange, Jaclyn L., Patrick R. W. J. Davey, Michelle T. Ma, et al. "An octadentate bis(semicarbazone) macrocycle: a potential chelator for lead and bismuth radiopharmaceuticals." Dalton Transactions 49, no. 42 (2020): 14962–74. http://dx.doi.org/10.1039/d0dt02673e.

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12

Jurcic, Joseph G. "Targeted Alpha-Particle Immunotherapy with Bismuth-213 and Actinium-225 for Acute Myeloid Leukemia." Journal of Postgraduate Medicine, Education and Research 47, no. 1 (2013): 14–17. http://dx.doi.org/10.5005/jp-journals-10028-1051.

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ABSTRACT Lintuzumab, a humanized anti-CD33 antibody, targets myeloid leukemia cells and has modest activity against acute myeloid leukemia (AML). To increase the antibody's potency yet avoid nonspecific cytotoxicity seen with β-emitting isotopes, lintuzumab was conjugated to the α-emitters bismuth-213 (213Bi) and actinium-225 (225Ac). The 46-minute half-life of 213Bi limits its widespread use. Therefore, 225Ac was also conjugated to various antibodies using DOTA-SCN. We conducted a phase I trial of 213Bi-lintuzumab and subsequently administered cytarabine with 213Bi-lintuzumab in a phase I/II study. The toxicity and biological activity of 225Ac-linutuzumab in patients with relapsed/refractory AML in a phase I dose-escalation trial was determined. An initial phase I trial demonstrated the feasibility, safety and antileukemic activity of 213Bi-lintuzumab. 213Bi-lintuzumab produced responses in 24% of AML patients receiving doses ≥ 37 MBq/kg after partial cytoreduction with cytarabine. 225Ac-labeled immunoconjugates killed in vitro at doses at least 1,000 times lower than 213Bi analogs. Eighteen patients with relapsed/refractory AML received 18.5 to 148 kBq/kg of 225Ac-lintuzumab in a phase I study. Dose-limiting toxicities were myelosuppression lasting >35 days in one patient and death due to sepsis in two patients. The maximum tolerated dose (MTD) was 111 KBg/kg. Bone marrow blast reductions were seen across all dose levels. Targeted α- particle immunotherapy with 213Bi- and 225Ac-lintuzumab is safe, has significant antileukemic effects, and can produce remissions after partial cytoreduction. How to cite this article Jurcic JG. Targeted Alpha-Particle Immunotherapy with Bismuth-213 and Actinium-225 for Acute Myeloid Leukemia. J Postgrad Med Edu Res 2013;47(1): 14-17.

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13

Dekempeneer, Yana, Vicky Caveliers, Matthias D’huyvetter, et al. "Combining Bismuth-213 with Nanobodies: Finding the Perfect Match for Targeted Alpha Therapy." Journal of Medical Imaging and Radiation Sciences 50, no. 4 (2019): S74. http://dx.doi.org/10.1016/j.jmir.2019.11.029.

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14

Dekempeneer, Yana, Vicky Caveliers, Matthias D’huyvetter, et al. "Combining Bismuth-213 with Nanobodies: Finding the Perfect Match for Targeted Alpha Therapy." Journal of Medical Imaging and Radiation Sciences 50, no. 1 (2019): S7—S8. http://dx.doi.org/10.1016/j.jmir.2019.03.024.

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15

Bray, Lane A., Joel M. Tingey, Jaquetta R. DesChane, et al. "Development of a Unique Bismuth (Bi-213) Automated Generator for Use in Cancer Therapy." Industrial & Engineering Chemistry Research 39, no. 9 (2000): 3189–94. http://dx.doi.org/10.1021/ie990068r.

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16

Sandmaier, Brenda M., Wolfgang A. Bethge, D. Scott Wilbur, et al. "Bismuth 213–labeled anti-CD45 radioimmunoconjugate to condition dogs for nonmyeloablative allogeneic marrow grafts." Blood 100, no. 1 (2002): 318–26. http://dx.doi.org/10.1182/blood-2001-12-0322.

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Abstract To lower treatment-related mortality and toxicity of conventional marrow transplantation, a nonmyeloablative regimen using 200 cGy total-body irradiation (TBI) and mycophenolate mofetil (MMF) combined with cyclosporine (CSP) for postgrafting immunosuppression was developed. To circumvent possible toxic effects of external-beam γ irradiation, strategies for targeted radiation therapy were investigated. We tested whether the short-lived (half-life, 46 minutes) α-emitter bismuth 213 (213Bi) conjugated to an anti-CD45 monoclonal antibody (mAb) could replace 200 cGy TBI and selectively target hematopoietic tissues in a canine model of nonmyeloablative DLA-identical marrow transplantation. Biodistribution studies using iodine 123–labeled anti-CD45 mAb showed uptake in blood, marrow, lymph nodes, spleen, and liver. In a dose-escalation study, 7 dogs treated with the 213Bi–anti-CD45 conjugate (213Bi dose, 0.1-5.9 mCi/kg [3.7-218 MBq/kg]) without marrow grafts had no toxic effects other than a mild, reversible suppression of blood counts. On the basis of these studies, 3 dogs were treated with 0.5 mg/kg 213Bi-labeled anti-CD45 mAb (213Bi doses, 3.6, 4.6, and 8.8 mCi/kg [133, 170, and 326 MBq/kg]) given in 6 injections 3 and 2 days before grafting of marrow from DLA-identical littermates. The dogs also received MMF (10 mg/kg subcutaneously twice daily the day of transplantation until day 27 afterward) and CSP (15 mg/kg orally twice daily the day before transplantation until 35 days afterward). The therapy was well tolerated except for transient elevations in levels of transaminases in 3 dogs, followed by, in one dog, ascites. All dogs had prompt engraftment and achieved stable mixed hematopoietic chimerism, with donor contributions ranging from 30% to 70% after more than 27 weeks of follow-up. These results will form the basis for additional studies in animals and later the design of clinical trials using213Bi as a nonmyeloablative conditioning regimen with minimal toxicity.

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17

Apostolidis, C., M. Betti, R. Carlos-Márquez, et al. "Production of carrier free actinium-225/bismuth-213 from thorium-229 for alpha-immunotherapy." Journal of Labelled Compounds and Radiopharmaceuticals 44, S1 (2001): S806—S808. http://dx.doi.org/10.1002/jlcr.25804401283.

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18

Bryan, Ruth A., Zewei Jiang, Thomas Jandl, et al. "Treatment of experimental pancreatic cancer with 213-Bismuth-labeled chimeric antibody to single-strand DNA." Expert Review of Anticancer Therapy 14, no. 10 (2014): 1243–49. http://dx.doi.org/10.1586/14737140.2014.952285.

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19

Rizvi, Syed M. Abbas, Chang Fa Qu, Yan Jun Song, Chand Raja, and Barry J. Allen. "In vivo studies of pharmacokinetics and efficacy of bismuth-213 labeled antimelanoma monoclonal antibody 9.2.27." Cancer Biology & Therapy 4, no. 7 (2005): 763–68. http://dx.doi.org/10.4161/cbt.4.7.1868.

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20

Kennel, S. J., M. Stabin, J. C. Roeske, et al. "Radiotoxicity of Bismuth-213 Bound to Membranes of Monolayer and Spheroid Cultures of Tumor Cells." Radiation Research 151, no. 3 (1999): 244. http://dx.doi.org/10.2307/3579935.

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21

Rosenblat, Todd L., Michael R. McDevitt, Deborah A. Mulford та ін. "Sequential Cytarabine and α-Particle Immunotherapy with Bismuth-213–Lintuzumab (HuM195) for Acute Myeloid Leukemia". Clinical Cancer Research 16, № 21 (2010): 5303–11. http://dx.doi.org/10.1158/1078-0432.ccr-10-0382.

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22

Song, Emma Y., Chang F. Qu, Syed M. A. Rizvi, et al. "Bismuth-213 radioimmunotherapy with C595 anti–MUC1 monoclonal antibody in an ovarian cancer ascites model." Cancer Biology & Therapy 7, no. 1 (2008): 76–80. http://dx.doi.org/10.4161/cbt.7.1.5132.

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23

Cherel, M., and F. Davodeau. "301 BISMUTH-213 RADIOIMMUNOTHERAPY WITH AN ANTI-MCD138 MONOCLONAL ANTIBODY IN A MULTIPLE MYELOMA MOUSE MODEL." Radiotherapy and Oncology 102 (March 2012): S160—S161. http://dx.doi.org/10.1016/s0167-8140(12)70263-3.

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24

Gouard, S., A. Pallardy, J. Gaschet, et al. "Comparative analysis of multiple myeloma treatment by CD138 antigen targeting with bismuth-213 and Melphalan chemotherapy." Nuclear Medicine and Biology 41 (May 2014): e30-e35. http://dx.doi.org/10.1016/j.nucmedbio.2014.02.008.

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25

Mulford, Deborah A., Neeta Pandit-Taskar, Michael R. McDevitt, et al. "Sequential Therapy with Cytarabine and Bismuth-213 (213Bi)-Labeled-HuM195 (Anti-CD33) for Acute Myeloid Leukemia (AML)." Blood 104, no. 11 (2004): 1790. http://dx.doi.org/10.1182/blood.v104.11.1790.1790.

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Abstract HuM195, a humanized anti-CD33 monoclonal antibody, targets myeloid leukemia cells and has activity against minimal residual disease. To enhance the potency of native HuM195 and avoid nonspecific cytotoxicity seen with β-emitting radioimmunoconjugates, the α-emitting radiometal 213Bi was conjugated to HuM195. The feasibility, safety, and antileukemic activity of therapy with 213Bi-HuM195 were shown in a phase I trial (Jurcic et al. Blood 2002). Because of the short-range (50–80 μm) and high linear energy transfer (8400 keV) of α particles, radioimmunotherapy with 213Bi is ideally suited for the treatment of residual disease. To determine the effects of 213Bi-HuM195 after partial cytoreduction with chemotherapy, we treated 25 patients (median age, 67 years; range, 49–80) with cytarabine 200 mg/m2/day for 5 days followed by 213Bi-HuM195 in a phase I/II trial. Fourteen patients had relapsed or primary refractory AML; 5 patients had previously untreated de novo AML, and 6 patients had untreated secondary AML. Sixteen patients had intermediate-risk cytogenetics, and 9 had poor-risk cytogenetics. During the phase I portion of the study, cohorts of 3–6 patients were treated with 0.5, 0.75, 1, and 1.25 mCi/kg. At the 1.25 mCi/kg dose level, 2 of the 4 patients had dose-limiting myelosuppression (grade 4 leukopenia lasting ≥ 35 days) and 1 patient died of progressive pneumonia. Therefore, the maximum tolerated dose was determined to be 1 mCi/kg. No responses were seen at the first two dose levels. Seven of the 19 patients (37%) who received 1 mCi/kg (n=15) or 1.25 mCi/kg (n=4) responded. There were 2 CRs lasting 9 and 12 months; 3 CRp (CR with incomplete platelet recovery) lasting 1, 2, and 6 months and 2 PRs lasting 3 and 8 months. The median time from initiation of chemotherapy to recovery of leukocyte counts was 34 days (range, 21–59 days). Delayed count recovery was attributed to persistent leukemia in 6 patients. Neutropenic fever occurred in all patients, and 19 patients had documented infections. At the phase II dose level, two of the 15 patients died of progressive infections, and one had grade 4 hyperbilirubinemia. The most common extramedullary toxicities were transient, low-grade elevations in liver function tests (n=19) and serum creatinine (n=11). Thirteen patients had infusion-related reactions following the first injection of 213Bi-HuM195, typically characterized by reversible grade 1 or 2 fever and/or chills. One patient had orthostatic hypotension and syncope after the first antibody infusion associated with concomitant bacteremia. Sequential administration of cytarabine and 213Bi-HuM195 is tolerable and can produce complete remissions in patients with AML.

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26

Morgenstern, Alfred, Frank Bruchertseifer, and Christos Apostolidis. "Bismuth-213 and Actinium-225 – Generator Performance and Evolving Therapeutic Applications of Two Generator-Derived Alpha-Emitting Radioisotopes." Current Radiopharmaceuticals 5, no. 3 (2012): 221–27. http://dx.doi.org/10.2174/1874471011205030221.

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27

RUDDY, F., A. DULLOO, J. SEIDEL, and B. PETROVI. "Separation of the alpha-emitting radioisotopes actinium-225 and bismuth-213 from thorium-229 using alpha recoil methods." Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms 213 (January 2004): 351–56. http://dx.doi.org/10.1016/s0168-583x(03)01580-5.

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28

Adams, G. P., C. C. Shaller, L. L. Chappell та ін. "Delivery of the α-emitting radioisotope bismuth-213 to solid tumors via single-chain Fv and diabody molecules". Nuclear Medicine and Biology 27, № 4 (2000): 339–46. http://dx.doi.org/10.1016/s0969-8051(00)00103-7.

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29

Rosenblat, Todd, Michael R. McDevitt, Deborah A. Mulford, et al. "Sequential Cytarabine and Alpha-Particle Immunotherapy with Bismuth-213 (213Bi)-Labeled-HuM195 (Lintuzumab) for Acute Myeloid Leukemia (AML)." Blood 112, no. 11 (2008): 2983. http://dx.doi.org/10.1182/blood.v112.11.2983.2983.

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Abstract HuM195, a humanized anti-CD33 monoclonal antibody, targets myeloid leukemia cells and has single-agent activity against acute myeloid leukemia (AML). To enhance the potency of native HuM195 and avoid nonspecific cytotoxicity seen with β-emitting radioimmunoconjugates, the α-emitting radiometal 213Bi was conjugated to HuM195. The feasibility, safety, and antileukemic activity of 213Bi-HuM195 were shown in a phase I trial (Jurcic et al. Blood 2002). Because of the short-range (50–80 μm) and high linear energy transfer (8400 keV) of α particles, radioimmunotherapy with 213Bi is ideally suited for the treatment of residual disease. To determine the effects of 213Bi-HuM195 against cytoreduced disease, we treated 31 patients (median age, 67 years; range, 37–80) with cytarabine 200 mg/m2/day for 5 days followed by 213Bi-HuM195 in a phase I/II trial. Thirteen patients had untreated AML (5 with de novo AML; 8 with secondary AML). Eight patients had AML in untreated first relapse, and ten patients had heavily pretreated relapsed AML (n=7) or primary refractory AML (n=3). Nine patients had poor-risk cytogenetics. During the phase I portion of the study, cohorts of 3–6 patients were treated with 18.5, 27.75, 37, and 46.25 MBq/kg. Prolonged myelosuppression with grade 4 leukopenia &gt; 35 days was the most common dose-limiting toxicity. The maximum tolerated dose (MTD) was 37 MBq/kg. Extramedullary toxicity was primarily limited to ≤ grade 2 events, including infusion-related reactions; however, grade 3/4 liver function abnormalities were seen in four patients (13%). Treatment-related deaths occurred in two of 21 patients (10%) who received the MTD. Significant reductions in marrow blasts were seen at all dose levels, and clinical responses were observed in 6 of the 25 patients (24%) who received doses of at least 37 MBq/kg (2 CR, 2 CRp, 2 PR). The median response duration was 7.7 months (range, 2–12). Pharmacokinetic and biodistribution studies suggested that saturation of all available CD33 sites by 213Bi-HuM195 was possible after cytoreduction with cytarabine. Sequential administration of cytarabine and 213Bi-HuM195 is tolerable and can produce complete remissions in patients with AML.

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Zhang, Meili, Zhengsheng Yao, Kayhan Garmestani та ін. "Pretargeting radioimmunotherapy of a murine model of adult T-cell leukemia with the α-emitting radionuclide, bismuth 213". Blood 100, № 1 (2002): 208–16. http://dx.doi.org/10.1182/blood-2002-01-0107.

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Abstract We used a pretargeting technique to treat a nonobese diabetic/severe combined immunodeficient murine model of human adult T-cell leukemia with an anti-Tac antibody-streptavidin (HAT-SA) conjugate, which recognizes CD25, followed by bismuth 213 (213Bi)-1,4,7,10-tetraazacyclododecane-N,N′,N′′,N′′′-tetraacetic acid (DOTA)- biotin. In the 3-step pretargeting radioimmunotherapy protocol, HAT-SA (140 or 400 μg) was administered intravenously (i.v.) to bind to the interleukin 2 receptor α (IL-2Rα; CD25)–expressing tumor cells. After 24 hours, 100 μg of a synthetic clearing agent was administered i.v. to remove unbound circulating HAT-SA conjugate from the circulation. Four hours later,213Bi–DOTA-biotin was administered i.v. for therapy. Tumor growth was significantly inhibited in 3 trials by using 250 μCi (9.25 MBq) of 213Bi–DOTA-biotin with a pretargeting technique as monitored by serum levels of soluble IL-2Rα and/or human β-2-microglobulin (P &lt; .05, t test) and by survival of tumor-bearing mice in the treatment groups (P &lt; .02, log rank test) as compared with the control groups. No prolongation of survival was observed with a nonspecific antibody-SA conjugate or in the absence of the radionuclide. Additionally, no prolongation of survival resulted from administration of 213Bi directly linked to intact HAT. Furthermore, there was no prolongation of survival when the β-emitting radionuclide yttrium 90 instead of the α-emitting radionuclide213Bi was used. The pretargeting approach with213Bi inhibited tumor growth more effectively than did immunotherapy with unmodified HAT. The best results were obtained with combination therapy that involved 213Bi–DOTA-biotin with a pretargeting technique supplemented by 4 weekly doses of HAT. The findings of this study support the use of this combination approach in a clinical trial in patients with IL-2Rα–expressing leukemias.

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31

Bethge, Wolfgang A., D. Scott Wilbur, Rainer Storb, et al. "Radioimmunotherapy with Bismuth-213 as Conditioning for Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation in Dogs: A Dose Deescalation Study." Transplantation 78, no. 3 (2004): 352–59. http://dx.doi.org/10.1097/01.tp.0000128853.62545.b2.

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32

Bethge, Wolfgang A., D. Scott Wilbur, Rainer Storb та ін. "Selective T-cell ablation with bismuth-213–labeled anti-TCRαβ as nonmyeloablative conditioning for allogeneic canine marrow transplantation". Blood 101, № 12 (2003): 5068–75. http://dx.doi.org/10.1182/blood-2002-12-3867.

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Abstract Two major immunologic barriers, the host-versus-graft (HVG) and graft-versus-host (GVH) reactions, have to be overcome for successful allogeneic hematopoietic cell transplantation. T cells were shown to be primarily involved in these barriers in the major histocompatibility complex identical setting. We hypothesized that selective ablation of T cells using radioimmunotherapy together with postgrafting immunosuppression would suffice to ensure stable allogeneic engraftment. We had described a canine model of nonmyeloablative marrow transplantation in which host immune reactions were impaired by a single dose of 200 cGy total body irradiation (TBI), and both GVH and residual HVG reactions were controlled by postgrafting immunosuppression with mycophenolate mofetil (MMF) and cyclosporine (CSP). Here, we substituted the α-emitter bismuth-213 (213Bi) linked to a monoclonal antibody (mAb) against T-cell receptor (TCR) αβ, using the metal-binding chelate diethylenetriaminepentaacetic acid (DTPA) derivative cyclohexyl–(CHX)-A″, for 200 cGy TBI. Biodistribution studies using a γ-emitting indium-111–labeled anti-TCRαβ mAb showed uptake primarily in blood, marrow, lymph nodes, spleen, and liver. Four dogs were treated with 0.13 to 0.46 mg/kg TCRαβ mAb labeled with 3.7 to 5.6 mCi/kg (137-207 MBq/kg) 213Bi. The treatment was administered in 6 injections on days –3 and –2 followed by transplantation of dog leukocyte antigen-identical marrow on day 0 and postgrafting immunosuppression with MMF/CSP. The therapy was well tolerated except for elevations of transaminases that were transient in all but one of the dogs. No other organ toxicities or signs of graft-versus-host disease were noted. The dogs had prompt allogeneic hematopoietic engraftment and achieved stable mixed donor-host hematopoietic chimerism with donor contributions ranging from 5% to 55% after more than 30 weeks of follow up.

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33

Nakamae, Hirohisa, D. Scott Wilbur, Donald K. Hamlin та ін. "Biodistributions, Myelosuppression, and Toxicities in Mice Treated with an Anti-CD45 Antibody Labeled with the α-Emitting Radionuclides Bismuth-213 or Astatine-211". Cancer Research 69, № 6 (2009): 2408–15. http://dx.doi.org/10.1158/0008-5472.can-08-4363.

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Schwartz, J., J. S. Jaggi, J. A. O’Donoghue, et al. "Renal uptake of bismuth-213 and its contribution to kidney radiation dose following administration of actinium-225-labeled antibody." Physics in Medicine and Biology 56, no. 3 (2011): 721–33. http://dx.doi.org/10.1088/0031-9155/56/3/012.

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Rizvi, Syed M. Abbas, Yong Li, Emma YanJun Song, et al. "Preclinical studies of bismuth-213 labeled plasminogen activator inhibitor type 2 (PAI2) in a prostate cancer nude mouse xenograft model." Cancer Biology & Therapy 5, no. 4 (2006): 386–93. http://dx.doi.org/10.4161/cbt.5.4.2478.

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Radchenko, Valery, Paul Schaffer, and F. F. Knapp. "The Evolving Clinical Role of Actinium-225 and Bismuth-213 for Targeted Alpha Therapy (TAT) - Production, Radiopharmaceutical Development and Clinical Applications." Current Radiopharmaceuticals 11, no. 3 (2018): 154–55. http://dx.doi.org/10.2174/187447101103180911115600.

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Ranson, M., Z. Tian, N. M. Andronicos, S. Rizvi, and B. J. Allen. "In Vitro Cytotoxicity of Bismuth-213 (213bi)-Labeled-Plasminogen Activator Inhibitor Type 2 (Alpha-PAI-2) on Human Breast Cancer Cells." Breast Cancer Research and Treatment 71, no. 2 (2002): 149–59. http://dx.doi.org/10.1023/a:1013850107791.

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38

Park, Steven I., Jaideep Shenoi, John M. Pagel, et al. "Conventional and pretargeted radioimmunotherapy using bismuth-213 to target and treat non-Hodgkin lymphomas expressing CD20: a preclinical model toward optimal consolidation therapy to eradicate minimal residual disease." Blood 116, no. 20 (2010): 4231–39. http://dx.doi.org/10.1182/blood-2010-05-282327.

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Abstract Radioimmunotherapy (RIT) with α-emitting radionuclides is an attractive approach for the treatment of minimal residual disease because the short path lengths and high energies of α-particles produce optimal cytotoxicity at small target sites while minimizing damage to surrounding normal tissues. Pretargeted RIT (PRIT) using antibody-streptavidin (Ab-SA) constructs and radiolabeled biotin allows rapid, specific localization of radioactivity at tumor sites, making it an optimal method to target α-emitters with short half-lives, such as bismuth-213 (213Bi). Athymic mice bearing Ramos lymphoma xenografts received anti-CD20 1F5(scFv)4SA fusion protein (FP), followed by a dendrimeric clearing agent and [213Bi]DOTA-biotin. After 90 minutes, tumor uptake for 1F5(scFv)4SA was 16.5% ± 7.0% injected dose per gram compared with 2.3% ± .9% injected dose per gram for the control FP. Mice treated with anti-CD20 PRIT and 600 μCi [213Bi]DOTA-biotin exhibited marked tumor growth delays compared with controls (mean tumor volume .01 ± .02 vs. 203.38 ± 83.03 mm3 after 19 days, respectively). The median survival for the 1F5(scFv)4SA group was 90 days compared with 23 days for the control FP (P < .0001). Treatment was well tolerated, with no treatment-related mortalities. This study demonstrates the favorable biodistribution profile and excellent therapeutic efficacy attainable with 213Bi-labeled anti-CD20 PRIT.

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Supiot, Stephane, Alain Faivre-Chauvet, Olivier Couturier, et al. "Comparison of the biologic effects of MA5 and B-B4 monoclonal antibody labeled with iodine-131 and bismuth-213 on multiple myeloma." Cancer 94, S4 (2002): 1202–9. http://dx.doi.org/10.1002/cncr.10286.

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Song, Yan J., Chang F. Qu, Syed M. A. Rizvi, et al. "Cytotoxicity of PAI2, C595 and Herceptin vectors labeled with the alpha-emitting radioisotope Bismuth-213 for ovarian cancer cell monolayers and clusters." Cancer Letters 234, no. 2 (2006): 176–83. http://dx.doi.org/10.1016/j.canlet.2005.03.060.

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Nakamae, Hirohisa, D. Scott Wilbur, Donald K. Hamlin, et al. "Evaluation of Toxicity and Tissue Radiation Doses Obtained in Mice with An Anti-CD45 Monoclonal Antibody (mAb) Labeled with the Alpha-Emitting Radionuclides, Astatine-211 or Bismuth-213." Blood 112, no. 11 (2008): 3270. http://dx.doi.org/10.1182/blood.v112.11.3270.3270.

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Abstract Background: One strategy to decrease toxicity of conditioning regimens for hematopoietic cell transplantation (HCT) has been the use of radiation targeted systemically with radionuclide-labeled mAbs. While mAb labeled with β-emitting radionuclides have shown some efficacy, a more promising alternative is the use of α-particle emitters. In contrast to β-emitting radionuclides, the high linear energy transfer and short particle range of α-particles makes them particularly attractive for killing hematopoietic cells in the blood and marrow. We initially investigated bismuth-213 (213Bi)-labeled anti-CD45 mAb to replace total body irradiation (TBI) as nonmyeloablative conditioning for HCT. This conditioning successfully allowed sustained engraftment of allogeneic marrow in a canine model. However, the limited availability, very short t1/2 of 46 min, and cost to produce 213Bi place limitations in using this for clinical trials. Therefore, in this study we evaluated whether astatine-211 (211At), which has a longer half-life (t1/2 = 7.2 h) than 213Bi, gave comparable results when targeting hematopoietic cells in mice. Methods: After injecting with either 213Bi- or 211At-labeled rat anti-murine CD45 mAb 30F11, we evaluated myelosuppression and non-hematological toxicity with varying quantities of radioactivity (2, 10, 20, and 50 μCi) on 10 μg of 30F11 and 20 μCi of radioactivity on various quantities of 30F11 (2, 10 and 40 μg). We also evaluated biodistribution with 20 μCi on various quantities of 30F11. Results: In the biodistribution studies, the highest concentrations of radioactivity were seen in the spleen. The 211At concentrations ranged from 167–417 % injected dose/gram (% ID/g) at 24 h post injection while the 213Bi concentrations ranged from 45–166 % ID/g at 3 h post injection. This result suggested that the longer half-life of 211At might allow higher quantities of labeled mAb to reach the spleen before decay. Importantly, the longer half-life and higher spleen concentrations of 211At resulted in much higher radiation doses to that tissue (e.g. 29,450 cGy/50 mCi 211At administered vs. 1165 cGy/50 mCi 213Bi when 10 mg of mAb was employed). Significant cytopenias were not observed in any of the 213Bi groups. In contrast, lethal and irreversible myelosuppression was observed in the mice receiving 20 μCi 211At on 40 μg of 30F11 and 50 μCi 211At on 10 μg of 30F11 (minimal WBC counts 0.21 x 103 and 0.12 x 103/mm3, Plt counts 1.2 x 104 and 0.3 x 104/mm3, Hb levels 1.5 and 4.2 g/dl, respectively). In the mice receiving 20 μCi 211At on 10 μg of 30F11, significant but reversible pancytopenia was observed, with a nadir of 2 weeks after injection (minimal WBC count 0.45 x 103/mm3, Plt count 3.3 x 104/mm3, Hb level 9.9 g/dl). The pancytopenia resolved at 3 weeks after injection. The second highest concentrations both in 211At studies (18–50% ID/g) and 213Bi studies (19–33%ID/g) were observed in the liver. Reversible but severe acute hepatic toxicity (maximal AST 1329 IU/L and ALT 928 IU/L) occurred 3h after 50 μCi 213Bi but not after 50 μCi 211At injection. This was surprising given the fact that the estimated radiation dose given to liver after 50 mCi 213Bi injection was ~200 cGy whereas the liver dose ranged from 1350–2600 cGy for 50 mCi 211At (depending on the amount of labeled mAb). No significant renal toxicity was observed with either 211At or 213Bi labeled 30F11 during 8 weeks follow-up period. Conclusion: The study results suggest that we may be able to replace low dose TBI in nonmyeloablative conditioning regimens with much lower (mCi) quantities of 211At-labeled anti-CD45 mAb without major non-hematological toxicities compared to the same mAb labeled with 213Bi.

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Pagel, John M., Aimee L. Kenoyer, Tom Bäck, et al. "Anti-CD45 pretargeted radioimmunotherapy using bismuth-213: high rates of complete remission and long-term survival in a mouse myeloid leukemia xenograft model." Blood 118, no. 3 (2011): 703–11. http://dx.doi.org/10.1182/blood-2011-04-347039.

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Abstract Pretargeted radioimmunotherapy (PRIT) using an anti-CD45 antibody (Ab)–streptavidin (SA) conjugate and DOTA-biotin labeled with β-emitting radionuclides has been explored as a strategy to decrease relapse and toxicity. α-emitting radionuclides exhibit high cytotoxicity coupled with a short path length, potentially increasing the therapeutic index and making them an attractive alternative to β-emitting radionuclides for patients with acute myeloid leukemia. Accordingly, we have used 213Bi in mice with human leukemia xenografts. Results demonstrated excellent localization of 213Bi-DOTA-biotin to tumors with minimal uptake into normal organs. After 10 minutes, 4.5% ± 1.1% of the injected dose of 213Bi was delivered per gram of tumor. α-imaging demonstrated uniform radionuclide distribution within tumor tissue 45 minutes after 213Bi-DOTA-biotin injection. Radiation absorbed doses were similar to those observed using a β-emitting radionuclide (90Y) in the same model. We conducted therapy experiments in a xenograft model using a single-dose of 213Bi-DOTA-biotin given 24 hours after anti-CD45 Ab-SA conjugate. Among mice treated with anti-CD45 Ab-SA conjugate followed by 800 μCi of 213Bi- or 90Y-DOTA-biotin, 80% and 20%, respectively, survived leukemia-free for more than 100 days with minimal toxicity. These data suggest that anti-CD45 PRIT using an α-emitting radionuclide may be highly effective and minimally toxic for treatment of acute myeloid leukemia.

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Suthiram, Janine, Thomas Ebenhan, Biljana Marjanovic-Painter, Mike M. Sathekge, and Jan Rijn Zeevaart. "Towards Facile Radiolabeling and Preparation of Gallium-68-/Bismuth-213-DOTA-[Thi8, Met(O2)11]-Substance P for Future Clinical Application: First Experiences." Pharmaceutics 13, no. 9 (2021): 1326. http://dx.doi.org/10.3390/pharmaceutics13091326.

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Substance P (SP) is a small peptide commonly known as a preferential endogenous ligand for the transmembrane neurokinin-1 receptor. Nuclear Medicine procedures currently involve radiolabeled SP derivatives in peptide radioligand endotherapy of inoperable glioblastoma. Promising clinical results sparked the demand for facile production strategies for a functionalized 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-[Thi8, Met(O2)11]-SP to allow for rapid Gallium-68 or Bismuth-213 complexation. Therefore, we provide a simple kit-like radiotracer preparation method that caters for the gallium-68 activity eluted from a SnO2 generator matrix as well as preliminary results on the adaptability to produce [213Bi]Bi-DOTA-[Thi8, Met(O2)11]SP from the same vials containing the same starting material. Following a phase of radioanalysis for complexation of gallium-68 to DOTA-[Thi8, Met(O2)11]SP and assessing the radiolabeling parameters, the vials containing appropriate kit-prototype material were produced in freeze-dried batches. The facile radiolabeling performance was tested and parameters for future human application were calculated to meet the criteria for theranostic loco-regional co-administration of activity doses comprising [68Ga]Ga-DOTA-[Thi8, Met(O2)11]SP mixed with [213Bi]Bi-DOTA-[Thi8, Met(O2)11]SP. [68Ga]Ga-DOTA-[Thi8, Met(O2)11]SP was prepared quantitatively from lyophilized starting material within 25 min providing the required molar activity (18 ± 4 GBq/µmol) and activity concentration (98 ± 24 MBq/mL), radiochemical purity (>95%) and sustained radiolabeling performance (4 months at >95% LE) as well as acceptable product quality (>95% for 120 min). Additionally, vials of the same starting materials were successfully adapted to a labeling strategy available for preparation of [213Bi]Bi-DOTA-[Thi8, Met(O2)11]SP providing sufficient activity for 1–2 human doses. The resultant formulation of [68Ga]Ga-/[213Bi]Bi-DOTA-[Thi8, Met(O2)11]SP activity doses was considered of adequate radiochemical quality for administration. This investigation proposes a simple kit-like formulation of DOTA-[Thi8, Met(O2)11]SP—a first-line investigation into a user friendly, straightforward tracer preparation that would warrant efficient clinical investigations in the future. Quantitative radiolabeling was accomplished for [68Ga]Ga-DOTA-[Thi8, Met(O2)11]SP and [213Bi]Bi-DOTA-[Thi8, Met(O2)11]SP preparations; a key requirement when addressing the specific route of catheter-assisted co-injection directly into the intratumoral cavities.

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Jurcic, Joseph G., and Todd L. Rosenblat. "Targeted Alpha-Particle Immunotherapy for Acute Myeloid Leukemia." American Society of Clinical Oncology Educational Book, no. 34 (May 2014): e126-e131. http://dx.doi.org/10.14694/edbook_am.2014.34.e126.

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Because alpha-particles have a shorter range and a higher linear energy transfer (LET) compared with beta-particles, targeted alpha-particle immunotherapy offers the potential for more efficient tumor cell killing while sparing surrounding normal cells. To date, clinical studies of alpha-particle immunotherapy for acute myeloid leukemia (AML) have focused on the myeloid cell surface antigen CD33 as a target using the humanized monoclonal antibody lintuzumab. An initial phase I study demonstrated the safety, feasibility, and antileukemic effects of bismuth-213 (213Bi)-labeled lintuzumab. In a subsequent study, 213Bi-lintuzumab produced remissions in some patients with AML after partial cytoreduction with cytarabine, suggesting the utility of targeted alpha-particle therapy for small-volume disease. The widespread use of 213Bi, however, is limited by its short half-life. Therefore, a second-generation construct containing actinium-225 (225Ac), a radiometal that generates four alpha-particle emissions, was developed. A phase I trial demonstrated that 225Ac-lintuzumab is safe at doses of 3 μCi/kg or less and has antileukemic activity across all dose levels studied. Fractionated-dose 225Ac-lintuzumab in combination with low-dose cytarabine (LDAC) is now under investigation for the management of older patients with untreated AML in a multicenter trial. Preclinical studies using 213Bi- and astatine-211 (211At)-labeled anti-CD45 antibodies have shown that alpha-particle immunotherapy may be useful as part conditioning before hematopoietic cell transplantation. The use of novel pretargeting strategies may further improve target-to-normal organ dose ratios.

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Jian, Gang, Fei Xue, Yuhang Guo, and Chao Yan. "Orientation Dependence of Elastic and Piezoelectric Properties in Rhombohedral BiFeO3." Materials 11, no. 12 (2018): 2441. http://dx.doi.org/10.3390/ma11122441.

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Through a coordinate transformation approach, crystal orientation dependences of elastic and piezoelectric properties at room temperature have been investigated in a three-dimensional space for rhombohedral bismuth ferrite (BiFeO3). Elastic constants (stiffnesses) c11′, c12′, c13′ and piezoelectric constants d15′, d31′, d33′ along arbitrary orientations were obtained based on crystalline asymmetry characteristics of 3m point group BiFeO3. Parameters along specific orientations obtaining the largest values were presented. The max c11′ = 213 × 109 N/m2 could be achieved in planes with ϕ = 0° and 90°. The max c12′ = c13′ = 132.2 × 109 N/m2 could be achieved along directions at θ = 13° and θ = 77° inside three mirror planes, respectively. The max d15′ = 27.6 × 10−12 C/N and the max d31′ = 12.67 × 10−12 C/N could be both obtained along directions at θ = 69° inside mirror planes. The max d33′ = 18 × 10−12 C/N could be obtained at θ = 0°, along the spontaneous polarization axis. By adopting optimal directions, the elastic and piezoelectric parameters of BiFeO3 could be significantly enhanced which shows applications for the growth of BeFeO3 films with preferred orientations and enhanced properties.

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Martinez, L. R., R. A. Bryan, C. Apostolidis, A. Morgenstern, A. Casadevall, and E. Dadachova. "Antibody-Guided Alpha Radiation Effectively Damages Fungal Biofilms." Antimicrobial Agents and Chemotherapy 50, no. 6 (2006): 2132–36. http://dx.doi.org/10.1128/aac.00120-06.

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ABSTRACT The use of indwelling medical devices—pacemakers, prosthetic joints, catheters—is rapidly growing and is often complicated by infections with biofilm-forming microbes that are resistant to antimicrobial agents and host defense mechanisms. We investigated for the first time the use of microbe-specific monoclonal antibodies (MAbs) as delivery vehicles for targeting biofilms with cytocidal radiation. MAb 18B7 (immunoglobulin G1 [IgG1]), which binds to capsular polysaccharides of the human pathogenic fungus Cryptococcus neoformans, penetrated cryptococcal biofilms, as shown by confocal microscopy. When the alpha radiation-emitter 213-Bismuth (213Bi) was attached to MAb 18B7 and the radiolabeled MAb was added to C. neoformans biofilms, there was a 50% reduction in biofilm metabolic activity. In contrast, when the IgM MAb 13F1 labeled with 213Bi was used there was no penetration of the fungal biofilm and no damage. Unlabeled 18B7, 213Bi-labeled nonspecific MAbs, and gamma and beta types of radiation did not have an effect on biofilms. The lack of efficacy of gamma and beta radiation probably reflects the radioprotective properties of polysaccharide biofilm matrix. Our results indicate that C. neoformans biofilms are susceptible to treatment with antibody-targeted alpha radiation, suggesting a novel option for the prevention or treatment of microbial biofilms on indwelling medical devices.

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Park, Steven I., Jaideep Shenoi, John M. Pagel, et al. "Conventional and Pretargeted Radioimmunotherapy with Bismuth-213 to Target and Treat CD20-Expressing Non-Hodgkin Lymphoma: A Preclinical Model for Consolidation Therapy to Eradicate Minimal Residual Disease." Blood 114, no. 22 (2009): 2705. http://dx.doi.org/10.1182/blood.v114.22.2705.2705.

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Abstract Abstract 2705 Poster Board II-681 Conventional radioimmunotherapy (RIT) with directly radiolabeled anti-B cell antibodies (Ab) induces remissions in 50 to 80% of patients with relapsed or refractory indolent non-Hodgkin lymphomas (NHL). Although administering RIT as consolidation after chemotherapy improves response rates and produces long-term durable remissions in treatment-naïve patients, the β-emitting radionuclides used in current RIT schemes may not be ideal for irradiating the microscopic tumors and the isolated tumor cells present in the setting of minimal residual disease (MRD). RIT with α-emitting radionuclides may be advantageous in the treatment of MRD because the short path length and high energies of α-particles produce optimal cytotoxicity at small target sites while minimizing damage to the surrounding normal tissues. Our group has successfully demonstrated that pretargeted RIT (PRIT) using streptavidin (SA)-Ab and radiolabeled biotin allows rapid specific localization of radioactivity at tumor sites. PRIT using α-emitting radionuclides may be particularly attractive since the most promising α-emitting radionuclides in clinical settings, such as 213Bi (t½ = 46 min), have short half-lives and pretargeting allows the delivery of radioactivity to tumor sites before the activity decays. We therefore performed in vivo studies to evaluate the biodistribution of 213Bi with PRIT. Athymic mice with B-cell NHL (Ramos) xenografts received a tetravalent anti-CD20 (1F5) single-chain (scFv)4SA fusion protein (FP) or a CC49 (scFv)4SA FP (non-binding negative control) followed by an N-acetyl galactosamine clearing agent (CA) and subsequent 213Bi-DOTA-biotin infusion. Tumors, blood, and major organs were collected to determine the percent injected dose per gram (%ID/g) at various time points within ∼3 half-lives of 213Bi. Maximal tumor uptake for 1F5 (scFv)4SA FP was 16.5 ± 7.0 %ID/g at 90 minutes vs. 2.3 ± 0.9 %ID/g for the control FP (p = 0.0001). Biodistributions of 213Bi using a conventional RIT scheme with directly labeled Ab were also evaluated. Athymic mice with Ramos xenografts received 213Bi labeled 1F5 Ab or 213Bi labeled HB8181 Ab (a murine isotype matched nonbinding control). Maximum tumor uptake for 1F5 Ab was 3.0 ± 0.9 %ID/g at 180 minutes vs. 2.3 ± 0.7 %ID/g for the control Ab (p = 0.171). There were no significant differences in tumor uptake and normal organ distribution between the two Ab within 180 minutes of radiolabeled Ab injection presumably due to the protracted circulating half-life of radiolabeled Abs. These results were concordant with our previous experiments using other radionuclides, showing that maximal targeting of radiolabeled Ab occurs between 20 to 24 hours; well beyond the effective half-life of 213Bi. When the results of PRIT and RIT studies were directly compared, tumor-to-blood ratios were 58 to 426-fold higher with PRIT than with conventional RIT. Tumor-to-normal organ ratios of nearly 100:1 were observed with PRIT compared to 3:1 or less with conventional RIT. Using the most favorable PRIT schemes defined in the biodistribution experiments, the therapeutic efficacy of 213Bi was evaluated. Mice treated with PRIT using 1F5 (scFv)4SA FP followed by a CA and 600 μCi 213Bi-DOTA-biotin experienced significant delays in tumor growth. The 1F5 (scFv)4SA FP treated animals had a mean tumor volume of 0.01 ± 0.02 vs. 203.38 ± 83.03 mm3 for the CC49 control group at 19 days (p = 0.0006). The median survival for 1F5 group was not reached after 90 days; whereas, the median survival was 23 days for the CC49 group (p = 0.0019) and 16 days for untreated mice (p = 0.0023). The treatment was well tolerated, with no treatment-related mortalities in any group. These data demonstrate that PRIT using 213Bi has a favorable biodistribution profile and excellent therapeutic efficacy. This model may be particularly effective in MRD settings and further studies are ongoing. Disclosures: No relevant conflicts of interest to declare.

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Miederer, Matthias, Christof Seidl, Gerd-Jürgen Beyer, et al. "Comparison of the Radiotoxicity of Two Alpha-Particle-Emitting Immunoconjugates, Terbium-149 and Bismuth-213, Directed against a Tumor-Specific, Exon 9 Deleted (d9) E-Cadherin Adhesion Protein." Radiation Research 159, no. 5 (2003): 612–20. http://dx.doi.org/10.1667/0033-7587(2003)159[0612:cotrot]2.0.co;2.

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Helal, Muath, Kevin J. H. Allen, Hilary Burgess та ін. "Safety Evaluation of an Alpha-Emitter Bismuth-213 Labeled Antibody to (1→3)-β-Glucan in Healthy Dogs as a Prelude for a Trial in Companion Dogs with Invasive Fungal Infections". Molecules 25, № 16 (2020): 3604. http://dx.doi.org/10.3390/molecules25163604.

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Background: With the limited options available for therapy to treat invasive fungal infections (IFI), radioimmunotherapy (RIT) can potentially offer an effective alternative treatment. Microorganism-specific monoclonal antibodies have shown promising results in the experimental treatment of fungal, bacterial, and viral infections, including our recent and encouraging results from treating mice infected with Blastomyces dermatitidis with 213Bi-labeled antibody 400-2 to (1→3)-β-glucan. In this work, we performed a safety study of 213Bi-400-2 antibody in healthy dogs as a prelude for a clinical trial in companion dogs with acquired invasive fungal infections and later on in human patients with IFI. Methods: Three female beagle dogs (≈6.1 kg body weight) were treated intravenously with 155.3, 142.5, or 133.2 MBq of 213Bi-400-2 given as three subfractions over an 8 h period. RBC, WBC, platelet, and blood serum biochemistry parameters were measured periodically for 6 months post injection. Results: No significant acute or long-term side effects were observed after RIT injections; only a few parameters were mildly and transiently outside reference change value limits, and a transient atypical morphology was observed in the circulating lymphocyte population of two dogs. Conclusions: These results demonstrate the safety of systemic 213Bi-400-2 administration in dogs and provide encouragement to pursue evaluation of RIT of IFI in companion dogs.

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Liu, Haitao, Weiqing Chen, Wenying Li, and Yanchong Yu. "Solubility of Bismuth in Liquid Bi-S Based Free Cutting Steel." High Temperature Materials and Processes 33, no. 2 (2014): 187–91. http://dx.doi.org/10.1515/htmp-2013-0047.

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AbstractSolubility of bismuth in liquid Bi-S based free cutting steel was measured using a vapor-liquid equilibration method at 1540–1600 °C, and the recovery rate of bismuth in the steel with different temperatures under an atmospheric pressure was also measured. The results showed that the solubility of bismuth in liquid Bi-S based free cutting steel from experiment under a constant volume at 1540, 1560, 1580, and 1600 °C were 0.174, 0.181, 0.205, and 0.220 mass%, respectively, and the relationship of bismuth solubility vs. temperature could be expressed as lg[%Bi] = −6049/T + 2.572. Meanwhile, the solubility of bismuth increased with the increase of Mn content, but decreased with the increase of C content. The recovery of bismuth in this experiment reached a maximum when the temperature was at bismuth boiling point or so, and then it was decreased with the increase of temperature when the temperature was above 1560 °C, which might be attributed to the accelerating of bismuth evaporation that were caused by the increase of bismuth equilibrium partial pressure above the surface of the molten steel with increasing temperature.

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