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Carsten-O Sahlmann, Kia Homayounfar, Martin Niessner, Jerzy Dyczkowski, Lena-Christin Conradi, Friederike Braulke, Birgit Meller, Tim Beißbarth, B Michael Ghadimi, Johannes Meller, David M Goldenberg, Torsten Liersch
BACKGROUND: In previous work, a single administration of anticarcinoembryonic antigen (anti-CEA) (131) I-labetuzumab radioimmunotherapy (RIT) after complete resection of colorectal liver metastases was well tolerated and significantly improved survival compared with controls. In the current phase 2 trial, the authors studied repeated RIT in the same setting, examining safety, feasibility, and efficacy. METHODS: Sixty-three patients (median age, 64.5 years) received RIT at 40 to 50 millicuries/m(2) per dose...
October 20, 2016: Cancer
Ximena Camacho, Victoria Calzada, Marcelo Fernández, Omar Alonso, Roger Chammas, Eloisa Riva, Juan Pablo Gambini, Pablo Cabral
BACKGROUND: Vascular endothelial growth factor (VEGF) is one of the classic factors to tumor-induced angiogenesis in several types, including melanoma. Bevacizumab is a humanized monoclonal antibody directed against VEGF. OBJECTIVE: To radiolabel Bevacizumab with 177-Lutetium as a potential radioimmunotherapy agent for melanoma. METHODS: Bevacizumab was derivatized with DOTA-NHS-ester at 4 ºC for 18 h. DOTA-Bevacizumab was radiolabeled with 177LuCl3 (15 MBq/mg) at 37 ºC for 1 h...
October 10, 2016: Current Radiopharmaceuticals
David S Geller, Jonathan Morris, Ekaterina Revskaya, Mani Kahn, Wendong Zhang, Sajida Piperdi, Amy Park, Pratistha Koirala, Hillary Guzik, Charles Hall, Bang Hoang, Rui Yang, Michael Roth, Jonathan Gill, Richard Gorlick, Ekaterina Dadachova
INTRODUCTION: Osteosarcoma overall survival has plateaued around 70%, without meaningful improvements in over 30years. Outcomes for patients with overt metastatic disease at presentation or who relapse are dismal. In this study we investigated a novel osteosarcoma therapy utilizing radioimmunotherapy (RIT) targeted to IGF2R, which is widely expressed in OS. METHODS: Binding efficiency of the Rhenium-188((188)Re)-labeled IGF2R-specific monoclonal antibody (mAb) to IGF2R on OS17 OS cells was assessed with Scatchard plot analysis...
July 30, 2016: Nuclear Medicine and Biology
Dina Tsukrov, Alicia McFarren, Alfred Morgenstern, Frank Bruchertseifer, Eugene Dolce, Miroslaw K Gorny, Susan Zolla-Pazner, Joan W Berman, Ellie Schoenbaum, Barry S Zingman, Arturo Casadevall, Ekaterina Dadachova
Eliminating virally infected cells is an essential component of any HIV eradication strategy. Radioimmunotherapy (RIT), a clinically established method for killing cells using radiolabeled antibodies, was recently applied to target HIV-1 gp41 antigen expressed on the surface of infected cells. Since gp41 expression by infected cells is likely downregulated in patients on antiretroviral therapy (ART), we evaluated the ability of RIT to kill ART-treated infected cells using both in vitro models and lymphocytes isolated from HIV-infected subjects...
2016: Frontiers in Medicine
Malay Patra, Kristof Zarschler, Hans-Jürgen Pietzsch, Holger Stephan, Gilles Gasser
Tumour pretargeting is a promising strategy for cancer diagnosis and therapy allowing for the rational use of long circulating, highly specific monoclonal antibodies (mAbs) for both non-invasive cancer radioimmunodetection (RID) and radioimmunotherapy (RIT). In contrast to conventional RID/RIT where the radionuclides and oncotropic vector molecules are delivered as presynthesised radioimmunoconjugates, the pretargeting approach is a multistep procedure that temporarily separates targeting of certain tumour-associated antigens from delivery of diagnostic or therapeutic radionuclides...
September 27, 2016: Chemical Society Reviews
Jie Xiao, Xiaobo Xu, Xiao Li, Yanli Li, Guobing Liu, Hui Tan, Hua Shen, Hongcheng Shi, Dengfeng Cheng
The malignant behaviors of solid tumors such as growth, infiltration and metastasis are mainly nourished by tumor neovascularization. Thus, anti-angiogenic therapy is key to controlling tumor progression. Bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF) antibody, plus chemotherapy or biological therapy can prolong survival for cancer patients, but treatment-related mortality is a concern. To improve inhibitory effect and decrease side-effects on non-small-cell lung cancer (NSCLC), we used Re-188, which is a β emitting radionuclide, directly labeled with bevacizumab for radioimmunotherapy in a human A549 tumor model...
September 30, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Eun Jung Kim, Byoung Soo Kim, Dan Bee Choi, Sung-Gil Chi, Tae Hyun Choi
PURPOSE: Directly radioiodinated [(131)I]-rituximab has been developed as a radioimmunotherapeutic agent in patients with CD20-positive B cell non-Hodgkin's lymphoma. However, there are concerns over its in vivo catabolism and deiodination. A novel radioiodination linker, N-(4-isothiocyanatobenzyl)-2-(3-(tributylstannyl)phenyl) acetamide (IBPA), was synthesized for the preparation of stable radioiodinated proteins. METHODS: The authors evaluated the potential of IBPA as a stable radioiodinated linker for rituximab...
September 30, 2016: Cancer Biotherapy & Radiopharmaceuticals
Tom A Bäck, Nicolas Chouin, Sture Lindegren, Helena Kahu, Holger Jensen, Per Albertsson, Stig Palm
: The goal of this study was to investigate if targeted alpha therapy (TAT) could be used to successfully treat also macro tumors, in addition to its established role for treating micrometastatic and minimal disease. We used an intravenous (i.v.) fractionated regimen of alpha-radioimmunotherapy (α-RIT) in a subcutaneous (s.c.) tumor model in mice. We aimed at evaluating the absorbed dose levels required for tumor eradication and to monitor tumor growth, as well as the long-term survival after treatment...
September 29, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Y A Abuodeh, K A Ahmed, M Echevarria, A O Naghavi, G D Grass, M B Tomblyn, L B Harrison, S Kim
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
R F Meredith, J Torgue, T Rozgaja, E Banaga, P Bunch, M C Dobelbower, R Alvarez
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
Adeola Y Makinde, Iris Eke, Molykutty J Aryankalayil, Mansoor M Ahmed, C Norman Coleman
The dramatic changes in the technological delivery of radiation therapy, the repertoire of molecular targets for which pathway inhibitors are available, and the cellular and immunologic responses that can alter long-term clinical outcome provide a potentially unique role for using the radiation-inducible changes as therapeutic targets. Various mathematical models of dose and fractionation are extraordinarily useful in guiding treatment regimens. However, although the model may fit the clinical outcome, a deeper understanding of the molecular and cellular effect of the individual dose size and the adaptation to repeated exposure, called multifraction (MF) adaptation, may provide new therapeutic targets for use in combined modality treatments using radiochemotherapy and radioimmunotherapy...
October 2016: Seminars in Radiation Oncology
Yiming Wu, Hua Zhu, Bo Zhang, Fei Liu, Jingxian Chen, Yufei Wang, Yan Wang, Ziwei Zhang, Ling Wu, Longlong Si, Huan Xu, Tianzhuo Yao, Sulong Xiao, Qing Xia, Lihe Zhang, Zhi Yang, Demin Zhou
Radioimmunotherapy (RIT) delivers radioisotopes to antigen-expressing cells via mono-antibodies for the imaging of lesions or medical therapy. The chelates are typically conjugated to the antibody through cysteine or lysine residues, resulting in heterogeneous chelate to antibody ratios and various conjugation sites. To overcome this heterogeneity, we have developed an approach for site-specific radiolabeling of antibodies by combination of genetic code expansion and click chemistry. As a proof of concept study, model systems including anti-CD20 antibody rituximab, positron-emitting isotope 64Cu, and a newly synthesized bifunctional linker DIBO-DOTA were used...
September 12, 2016: Bioconjugate Chemistry
Damian J Green, Shani L Frayo, Yukang Lin, Donald K Hamlin, Darrell R Fisher, Sofia Hl Frost, Aimee L Kenoyer, Mark D Hylarides, Ajay K Gopal, Ted A Gooley, Johnnie J Orozco, Brian G Till, Shyril O'Steen, Kelly D Orcutt, D Scott Wilbur, K Dane Wittrup, Oliver W Press
Streptavidin (SA)-biotin pretargeted radioimmunotherapy (PRIT) that targets CD20 in non-Hodgkin lymphoma (NHL) exhibits remarkable efficacy in model systems, but SA immunogenicity and interference by endogenous biotin may complicate clinical translation of this approach. In this study, we engineered a bispecific fusion protein (FP) that evades the limitations imposed by this system. Briefly, one arm of the FP was an anti-human CD20 antibody (2H7) with the other arm of the FP an anti-chelated radiometal trap for a radiolabeled ligand (yttrium[Y]-DOTA) captured by a very high-affinity anti-Y-DOTA scFv antibody (C825)...
September 2, 2016: Cancer Research
Johan Blakkisrud, Ayca Løndalen, Jostein Dahle, Simon Turner, Harald Holte, Arne Kolstad, Caroline Stokke
: Red bone marrow (RM) is often the primary organ at risk in radioimmunotherapy; irradiation of marrow may induce short and long term hematological toxicity. (177)Lu-lilotomab satetraxetan is a novel anti-CD37 antibody-radionuclide-conjugate (ARC) currently in phase 1/2a. Two pre-dosing regimens have been investigated, one with 40 mg unlabeled lilotomab antibody (arm 1) and one without (arm 2). The aim of this work was to compare RM absorbed doses for the two arms and to correlate absorbed doses with hematological toxicity...
September 1, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Dong-Yeop Shin, Byung Hyun Byun, Kyeong Min Kim, Joo Hyun Kang, Ilhan Lim, Byung Il Kim, Seung-Sook Lee, Chang Woon Choi, Hye Jin Kang, Sang Moo Lim
PURPOSE: The aim of this study was to assess the clinical activity and toxicity of (131)I-rituximab as consolidation therapy for patients with diffuse large B-cell lymphoma (DLBCL) who were treated with R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisolone). METHODS: Patients who had been diagnosed with advanced stage (Ann Arbor III or IV) or bulky stage II DLBCL and achieved complete or partial response after six to eight cycles of R-CHOP were enrolled...
October 2016: Cancer Chemotherapy and Pharmacology
Urs B Hagemann, Katrine Wickstroem, Ellen Wang, Adam O Shea, Kristine Sponheim, Jenny Karlsson, Roger M Bjerke, Olav B Ryan, Alan S Cuthbertson
The clinical efficacy of the first approved alpha pharmaceutical, Xofigo (radium-223 dichloride, (223)RaCl2), has stimulated significant interest in the development of new alpha-particle emitting drugs in oncology. Unlike radium-223 ((223)Ra), the parent radionuclide thorium-227 ((227)Th) is able to form highly stable chelator complexes and is therefore amenable to targeted radioimmunotherapy. We describe the preparation and use of a CD33-targeted thorium-227 conjugate (CD33-TTC), which binds to the sialic acid receptor CD33 for the treatment of acute myeloid leukemia (AML)...
October 2016: Molecular Cancer Therapeutics
Tobias Weber, Benedikt Bötticher, Michaela A E Arndt, Walter Mier, Max Sauter, Evelyn Exner, Armin Keller, Susanne Krämer, Karin Leotta, Artjom Wischnjow, Ludger Grosse-Hovest, Dirk Strumberg, Dirk Jäger, Hermann-Josef Gröne, Uwe Haberkorn, Gottfried Brem, Jürgen Krauss
Radioimmunotherapy is considered as treatment option in recurrent and/or refractory B-cell non-Hodgkin lymphoma (B-NHL). To overcome the dose limiting bone marrow toxicity of IgG-based radioimmunoconjugates (RICs), we modified a humanized diabody with 5-, 10-, or 20-kDa polyethylene glycol (PEG) for CD22-targeted radioimmunotherapy using the low-energy β-emitter lutetium-177 ((177)Lu). A favorable pharmacokinetic profile was observed for the 10-kDa-PEG-diabody in nude mice being xenografted with subcutaneous human Burkitt lymphoma...
October 28, 2016: Cancer Letters
Dane Bergstrom, Jeffrey V Leyton, Arman Zereshkian, Conrad Chan, Zhongli Cai, Raymond M Reilly
INTRODUCTION: (111)In-DTPA-NLS-CSL360 radioimmunoconjugates (RIC) recognize the overexpression of the interleukin-3 receptor α-subchain (CD123) relative to the β-subchain (CD131) on leukemia stem cells (LSC). Our aim was to study Auger electron radioimmunotherapy (RIT) of acute myeloid leukemia (AML) with (111)In-DTPA-NLS-CSL360 in non-obese diabetic severe combined immunodeficiency (NOD/SCID) mice or NOD-Rag1(null)IL2rγ(null) (NRG) mice engrafted with CD123(+) human AML-5 cells. METHODS: The toxicity of three doses of (111)In-DTPA-NLS-CSL360 (3...
October 2016: Nuclear Medicine and Biology
Johan Blakkisrud, Ayca Løndalen, Anne Catrine Trægde Martinsen, Jostein Dahle, Jon Erik Holtedahl, Tore Bach-Gansmo, Harald Holte, Arne Kolstad, Caroline Stokke
: (177)Lu-lilotomab satetraxetan is a novel antibody radionuclide conjugate (ARC) currently tested in a phase 1/2a first-in-human dosage escalation trial for patients with relapsed CD37+ indolent non-Hodgkin's lymphoma. The aim of this work was to develop dosimetric methods and calculate tumor absorbed radiation doses for patients treated with (177)Lu-lilotomab satetraxetan. METHODS: Patients were treated at escalating injected activities (10, 15 and 20 MBq/kg) of (177)Lu-lilotomab satetraxetan and with different pre-dosing; with or without 40 mg unlabeled lilotomab...
August 4, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Jew Win Kuan, Chiong Soon Law, Xiang Qi Wong, Ching Tiong Ko, Zool Hilmi Awang, Lee Ping Chew, Kian Meng Chang
Radioimmunotherapy is an established treatment modality in Non-Hodgkin's lymphoma. The only two commercially available radioimmunotherapies - (90)Y-ibritumomab tiuxetan is expensive and (131)I-tositumomab has been discontinued from commercial production. In resource limited environment, self-labelling (131)I-rituximab might be the only viable practical option. We reported our pioneer experience in Malaysia on self-labelling (131)I-rituximab, substituting autologous haematopoietic stem cell transplantation (HSCT) and a patient, the first reported case, received high dose (131)I-rituximab (6000MBq/163mCi) combined with BEAM conditioning for autologous HSCT...
October 2016: Applied Radiation and Isotopes
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