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Radioimmunotherapy

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https://www.readbyqxmd.com/read/28301261/a-radiolabeled-fully-human-antibody-to-human-aspartyl-asparaginyl-%C3%AE-hydroxylase-is-a-promising-agent-for-imaging-and-therapy-of-metastatic-breast-cancer
#1
Ekaterina Revskaya, Zewei Jiang, Alfred Morgenstern, Frank Bruchertseifer, Muctarr Sesay, Susan Walker, Steven Fuller, Michael S Lebowitz, Claudia Gravekamp, Hossein A Ghanbari, Ekaterina Dadachova
There is a need for novel effective and safe therapies for metastatic breast cancer based on targeting tumor-specific molecular markers of cancer. Human aspartyl (asparaginyl) β-hydroxylase (HAAH) is a highly conserved enzyme that hydroxylates epidermal growth factor-like domains in transformation-associated proteins and is overexpressed in a variety of cancers, including breast cancer. A fully human monoclonal antibody (mAb) PAN-622 has been developed to HAAH. In this study, they describe the development of PAN-622 mAb as an agent for imaging and radioimmunotherapy of metastatic breast cancer...
March 2017: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28299759/optimizing-the-benefit-of-cns-radiation-therapy-in-the-pediatric-population-part-2-novel-methods-of-radiation-delivery
#2
REVIEW
Lindsay S Rowe, Andra V Krauze, Holly Ning, Kevin A Camphausen, Aradhana Kaushal
Newer approaches in the field of radiation therapy have raised the bar in the treatment of central nervous system (CNS) malignancies, with recognized advances that have aimed to increase the therapeutic index by improving conformality of the radiation dose to the planned target volume. Beyond these advances, the continued evolution of more effective systems for delivery of radiation to the CNS may offer further benefit not only to adults but also to pediatric patients, a cohort of the population that may be more sensitive to the long-term effects of radiation...
March 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28260607/preclinical-evaluation-of-131-i-bevacizumab-a-prospective-agent-for-radioimmunotherapy-in-vegf-expressing-cancers
#3
Mythili Kameswaran, Haladhar Dev Sarma, Ashutosh Dash
This study focuses on preparation and evaluation of (131)I-bevacizumab by Iodogen method for targeting VEGF over-expressing cancers for therapy. (131)I-Bevacizumab exhibited radiochemical purity of 98.0±0.7%. In vitro stability of (131)I-Bevacizumab was retained at >85% in both saline and serum at 37°C upto 5 days post iodination. In vitro cell studies showed good immunoreactivity and uptake by VEGF expressing tumor cells. Uptake and retention of (131)I-Bevacizumab in tumor with reduction in uptake in presence of cold Bevacizumab confirmed its specificity to VEGF...
February 16, 2017: Applied Radiation and Isotopes
https://www.readbyqxmd.com/read/28254528/candidate-immune-biomarkers-for-radioimmunotherapy
#4
REVIEW
Antonin Levy, Giulia Nigro, Philippe J Sansonetti, Eric Deutsch
Newly available immune checkpoint blockers (ICBs), capable to revert tumor immune tolerance, are revolutionizing the anticancer armamentarium. Recent evidence also established that ionizing radiation (IR) could produce antitumor immune responses, and may as well synergize with ICBs. Multiple radioimmunotherapy combinations are thenceforth currently assessed in early clinical trials. Past examples have highlighted the need for treatment personalization, and there is an unmet need to decipher immunological biomarkers that could allow selecting patients who could benefit from these promising but expensive associations...
February 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28191976/preloading-with-unlabeled-ca19-9-targeted-human-monoclonal-antibody-leads-to-improved-pet-imaging-with-89-zr-5b1
#5
Jacob L Houghton, Dalya Abdel-Atti, Wolfgang W Scholz, Jason S Lewis
CA19.9 is one of the most commonly occurring and highest density antigens in >90% of pancreatic cancers, making it an excellent target for monoclonal antibody (mAb)-based imaging and therapy applications. Preloading of unlabeled antibodies to enhance targeting of a radiolabeled mAb has been previously described both for imaging and radioimmunotherapy studies for other targets. We investigated the effect of preloading with the unmodified anti-CA19.9 antibody 5B1 on the uptake and contrast of the PET tracer (89)Zr-5B1 in subcutaneous and orthotopic murine models of pancreatic cancer utilizing Capan-2 xenografts, known to both express CA19...
March 6, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28181275/preparation-of-clinical-scale-177-lu-rituximab-optimization-of-protocols-for-conjugation-radiolabeling-and-freeze-dried-kit-formulation
#6
Mohini Guleria, Tapas Das, Chandan Kumar, Jeyachitra Amirdhanayagam, Haladhar D Sarma, Sharmila Banerjee
Rituximab is a monoclonal chimeric antibody which has been approved by US FDA for immunotherapy of Non-Hodgkins' lymphoma (NHL). Bexxar and Zevalin are the two other approved radiolabeled antibodies for radioimmunotherapy of NHL; however the fact that they are of murine origin reduces their treatment efficacy. To circumvent this, efforts have been made to radiolabel Rituximab with various therapeutic radioisotopes. In the present study, an effort has been made to optimize the conjugation (BFCA and antibody) and radiolabeling procedures for the preparation of clinical-scale (177) Lu-labeled Rituximab...
February 8, 2017: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28104527/b7-h3-targeted-212-pb-radioimmunotherapy-of-ovarian-cancer-in-preclinical-models
#7
Benjamin B Kasten, Rebecca C Arend, Ashwini A Katre, Harrison Kim, Jinda Fan, Soldano Ferrone, Kurt R Zinn, Donald J Buchsbaum
INTRODUCTION: Novel therapies that effectively kill both differentiated cancer cells and cancer initiating cells (CICs), which are implicated in causing chemotherapy-resistance and disease recurrence, are needed to reduce the morbidity and mortality of ovarian cancer. These studies used monoclonal antibody (mAb) 376.96, which recognizes a B7-H3 epitope expressed on ovarian cancer cells and CICs, as a carrier molecule for targeted α-particle radioimmunotherapy (RIT) in preclinical models of human ovarian cancer...
April 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28068509/erratum-to-reduced-intensity-conditioning-combined-with-188-rhenium-radioimmunotherapy-before-allogeneic-hematopoietic-stem-cell-transplantation-in-elderly-patients-with-acute-myeloid-leukemia-the-role-of-in-vivo-t-cell-depletion-biol-blood-marrow-transplant
#8
Sebastian Schneider, Annette Strumpf, Johannes Schetelig, Gerd Wunderlich, Gerhard Ehninger, Jörg Kotzerke, Martin Bornhäuser
No abstract text is available yet for this article.
January 6, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28062708/establishment-of-the-in-vivo-efficacy-of-pretargeted-radioimmunotherapy-utilizing-inverse-electron-demand-diels-alder-click-chemistry
#9
Jacob L Houghton, Rosemery Membreno, Dalya Abdel-Atti, Kristen M Cunanan, Sean Carlin, Wolfgang W Scholz, Pat B Zanzonico, Jason S Lewis, Brian M Zeglis
The pretargeting system based on the inverse electron demand Diels-Alder reaction (IEDDA) between trans-cyclooctene (TCO) and tetrazine (Tz) combines the favorable pharmacokinetic properties of radiolabeled small molecules with the affinity and specificity of antibodies. This strategy has proven to be an efficient method for the molecularly targeted delivery of pharmaceuticals, including isotopes for radiological imaging. Despite encouraging results from in vivo PET imaging studies, this promising system has yet to be thoroughly evaluated for pretargeted radioimmunotherapy (PRIT)...
January 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28036044/immuno-pet-for-clinical-theranostic-approaches
#10
REVIEW
Clément Bailly, Pierre-François Cléry, Alain Faivre-Chauvet, Mickael Bourgeois, François Guérard, Ferid Haddad, Jacques Barbet, Michel Chérel, Françoise Kraeber-Bodéré, Thomas Carlier, Caroline Bodet-Milin
Recent advances in molecular characterization of tumors have allowed identification of new molecular targets on tumor cells or biomarkers. In medical practice, the identification of these biomarkers slowly but surely becomes a prerequisite before any treatment decision, leading to the concept of personalized medicine. Immuno-positron emission tomography (PET) fits perfectly with this approach. Indeed, monoclonal antibodies (mAbs) labelled with radionuclides represent promising probes for theranostic approaches, offering a non-invasive solution to assess in vivo target expression and distribution...
December 28, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27964867/consolidation-anti-cd22-fractionated-radioimmunotherapy-with-90-y-epratuzumab-tetraxetan-following-r-chop-in-elderly-patients-with-diffuse-large-b-cell-lymphoma-a-prospective-single-group-phase-2-trial
#11
Françoise Kraeber-Bodere, Amandine Pallardy, Hervé Maisonneuve, Loïc Campion, Anne Moreau, Isabelle Soubeyran, Steven Le Gouill, Olivier Tournilhac, Etienne Daguindau, Henry Jardel, Nadine Morineau, Krimo Bouabdallah, Emmanuel Gyan, Marie-Pierre Moles, Remy Gressin, Christian Berthou, Sophie Sadot, Philippe Moreau, Bénédicte Deau, Caroline Bodet-Milin, Anne-Laure Cazeau, Etienne Garin, Pierre-Yves Salaun, Jean-Philippe Vuillez, Valérie Gouilleux-Gruart, Jacques Barbet, William A Wegener, David M Goldenberg, Thierry Lamy, Pierre Soubeyran
BACKGROUND: Radioimmunotherapy represents a potential option as consolidation after chemoimmunotherapy in patients with diffuse large B-cell lymphoma who are not candidates for transplantation. We aimed to assess activity and toxicity of fractionated radioimmunotherapy using anti-CD22 (90)Y-epratuzumab tetraxetan as consolidation after front-line induction chemoimmunotherapy in untreated elderly patients with diffuse large B-cell lymphoma. METHODS: We did a prospective, single-group, phase 2 trial at 28 hospitals in France, with patients recruited from 17 hospitals...
January 2017: Lancet Haematology
https://www.readbyqxmd.com/read/27964866/radioimmunotherapy-of-lymphoma-an-underestimated-therapy-option
#12
Karin Hohloch
No abstract text is available yet for this article.
January 2017: Lancet Haematology
https://www.readbyqxmd.com/read/27908170/high-resolution-digital-autoradiographic-and-dosimetric-analysis-of-heterogeneous-radioactivity-distribution-in-xenografted-prostate-tumors
#13
Oskar V Timmermand, Jenny Nilsson, Sven-Erik Strand, Jörgen Elgqvist
PURPOSE: The first main aim of this study was to illustrate the absorbed dose rate distribution from (177)Lu in sections of xenografted prostate cancer (PCa) tumors using high resolution digital autoradiography (DAR) and compare it with hypothetical identical radioactivity distributions of (90)Y or 7 MeV alpha-particles. Three dosimetry models based on either dose point kernels or Monte Carlo simulations were used and evaluated. The second and overlapping aim, was to perform DAR imaging and dosimetric analysis of the distribution of radioactivity, and hence the absorbed dose rate, in tumor sections at an early time point after injection during radioimmunotherapy using (177)Lu-h11B6, directed against the human kallikrein 2 antigen...
December 2016: Medical Physics
https://www.readbyqxmd.com/read/27906723/safety-and-outcome-measures-of-first-in-human-intraperitoneal-%C3%AE-radioimmunotherapy-with-212pb-tcmc-trastuzumab
#14
Ruby F Meredith, Julien J Torgue, Tania A Rozgaja, Eileen P Banaga, Patty W Bunch, Ronald D Alvarez, J Michael Straughn, Michael C Dobelbower, Andrew M Lowy
PURPOSE: One-year monitoring of patients receiving intraperitoneal (IP) Pb-TCMC-trastuzumab to provide long-term safety and outcome data. A secondary objective was to study 7 tumor markers for correlation with outcome. METHODS: Eighteen patients with relapsed intra-abdominal human epidermal growth factor receptor-2 expressing peritoneal metastases were treated with a single IP infusion of Pb-TCMC-trastuzumab, delivered <4 h after 4 mg/kg IV trastuzumab. Seven tumor markers were studied for correlation with outcome...
November 30, 2016: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/27885456/-intravesical-radioimmunotherapy-of-carcinoma-in-situ-of-the-urinary-bladder-after-bcg-failure
#15
M E Autenrieth, T Horn, F Kurtz, K Nguyen, A Morgenstern, F Bruchertseifer, M Schwaiger, M Blechert, C Seidl, R Senekowitsch-Schmidtke, J E Gschwend, K Scheidhauer
BACKGROUND: In failure to respond to bacillus Calmette-Guérin (BCG) in patients with carcinoma in situ (CIS) of the urinary bladder, radical cystectomy remains the mainstay after BCG failure. OBJECTIVES: The aim of this pilot study was to evaluate tolerability and safety of the α‑emitter radioimmunoconjugate instillation in patients after BCG failure. MATERIALS AND METHODS: Nine patients were included. After emptying the bladder via a transurethral catheter, Bi-213-anti-EGFR-mAb was instilled...
January 2017: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/27844106/lymphoma-current-status-of-clinical-and-preclinical-imaging-with-radiolabeled-antibodies
#16
REVIEW
Christopher G England, Lixin Rui, Weibo Cai
Lymphoma is a complex disease that arises from cells of the immune system with an intricate pathology. While lymphoma may be classified as Hodgkin or non-Hodgkin, each type of tumor is genetically and phenotypically different and highly invasive tissue biopsies are the only method to investigate these differences. Noninvasive imaging strategies, such as immunoPET, can provide a vital insight into disease staging, monitoring treatment response in patients, and dose planning in radioimmunotherapy. ImmunoPET imaging with radiolabeled antibody-based tracers may also assist physicians in optimizing treatment strategies and enhancing patient stratification...
March 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/27823646/radioimmunotherapy-in-non-hodgkin-lymphoma-prediction-and-assessment-of-response
#17
REVIEW
Mahsa Eskian, MirHojjat Khorasanizadeh, Francoise Kraeber-Bodere, Nima Rezaei
Non-Hodgkin lymphoma (NHL) is one of the most common malignancies and a major cause of morbidity and mortality. Radioimmunotherapy (RIT) is a novel modality for treating NHL which offers the combined use of monoclonal antibodies for specific targeting of malignant cells and radiation for killing these cells. Despite the promising results favoring RIT in several clinical studies in different target populations and NHL types, Food and Drug Administration (FDA) approval for RIT agents is restricted to a limited number of indications and agents, maybe because of several ambiguities that still exist in the field...
November 2016: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/27813061/development-of-lu-177-trastuzumab-for-radioimmunotherapy-of-her2-expressing-breast-cancer-and-its-feasibility-assessment-in-breast-cancer-patients
#18
Priya Bhusari, Rakhee Vatsa, Gurpreet Singh, Madan Parmar, Amanjit Bal, Devinder K Dhawan, Bhagwant R Mittal, Jaya Shukla
HER2/neu is over expressed in 20-25% of breast cancers. HER2 breast cancers are aggressive and are associated with poor prognosis. The aim of this study was to develop the clinical grade Lu-177-trastuzumab and its preliminary evaluation for specific tumor targeting in HER2 positive breast cancer patients. Trastuzumab was conjugated to bifunctional chelator, DOTA, and characterized for integrity and the number of molecules conjugated. Radiolabeling of DOTA-conjugated trastuzumab was optimized using Lu-177. Quality control parameters including radiochemical purity, stability, sterility, pyrogenicity and immunoreactivity were assessed...
February 15, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27798787/initial-experience-with-tositumomab-and-i-131-labeled-tositumomab-for-treatment-of-relapsed-refractory-hodgkin-lymphoma
#19
Heather Jacene, John Crandall, Yvette L Kasamon, Richard F Ambinder, Steven Piantadosi, Donna Serena, Wayne Kasecamp, Richard L Wahl
PURPOSE: To determine the maximum tolerated dose (MTD) of [(131)I]tositumomab in patients with refractory/recurrent Hodgkin lymphoma (HL) and to preliminarily determine if [(131)I]tositumomab has activity against HL and if positron emission tomography (PET) with 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]DG) performed 6 weeks post-therapy predicted 12-week response. PROCEDURES: Separate dose-finding studies were performed for patients with and without prior transplant...
October 31, 2016: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/27776176/evaluation-of-cd146-as-target-for-radioimmunotherapy-against-osteosarcoma
#20
Sara Westrøm, Tina B Bønsdorff, Nasir Abbas, Øyvind S Bruland, Thora J Jonasdottir, Gunhild M Mælandsmo, Roy H Larsen
BACKGROUND: Osteosarcoma is a rare form of cancer but with a substantial need for new active drugs. There is a particular need for targeted therapies to combat metastatic disease. One possible approach is to use an antibody drug conjugate or an antibody radionuclide conjugate to target the osteosarcoma metastases and circulating tumor cells. Herein we have evaluated a radiolabeled monoclonal antibody targeting CD146 both in vitro and in vivo. METHODS AND RESULTS: A murine monoclonal anti-CD146 IgG1 isotype antibody, named OI-3, was developed along with recombinant chimeric versions with human IgG1 or human IgG3 Fc sequences...
2016: PloS One
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