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https://www.readbyqxmd.com/read/28439844/therapeutic-efficacy-of-%C3%AE-radioimmunotherapy-with-different-activity-levels-of-the-213-bi-labeled-monoclonal-antibody-mx35-in-an-ovarian-cancer-model
#1
Anna Gustafsson-Lutz, Tom Bäck, Emma Aneheim, Ragnar Hultborn, Stig Palm, Lars Jacobsson, Alfred Morgenstern, Frank Bruchertseifer, Per Albertsson, Sture Lindegren
BACKGROUND: The aim of this study was to compare the therapeutic efficacy of two different activity levels of the (213)Bi-labeled monoclonal antibody MX35 in an ovarian cancer model. Sixty female BALB/c (nu/nu) mice were inoculated intraperitoneally with human ovarian cancer cells (OVCAR-3). Two weeks later, 40 mice were injected intraperitoneal (i.p.) with 1 ml of (213)Bi-MX35, 3 MBq/mL (n = 20), or 9 MBq/mL (n = 20). An additional 20 mice received unlabeled MX35. Incidence of tumors and ascites was investigated 8 weeks after therapy...
December 2017: EJNMMI Research
https://www.readbyqxmd.com/read/28430648/radioimmunotherapy-for-cd133-colonic-cancer-stem-cells-inhibits-tumor-development-in-nude-mice
#2
Dinghu Weng, Xueyan Jin, Saimei Qin, Xiaoli Lan, Chong Chen, Xun Sun, Xianliang She, Changling Dong, Rui An
Accumulating evidence indicates that cancer stem cells (CSCs) are the cause of tumor drug/radio-resistance or distant metastasis; therefore, it is essential to eliminate CSCs to cure cancer completely. The purpose of this study was to utilize radioimmunotherapy (RIT) to target CD133(+) colonic CSCs and observe whether this prevented tumor development, by assessing the maximum tolerated dose (MTD) of HCT116 tumor-bearing nude mice with escalating doses of 131I-AC133.1 monoclonal antibody (mAb), and determining the therapeutic efficacy of RIT with 131I-AC133...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28428282/whither-radioimmunotherapy-to-be-or-not-to-be
#3
Damian J Green, Oliver W Press
Therapy of cancer with radiolabeled monoclonal antibodies has produced impressive results in preclinical experiments and in clinical trials conducted in radiosensitive malignancies, particularly B-cell lymphomas. Two "first-generation," directly radiolabeled anti-CD20 antibodies, (131)iodine-tositumomab and (90)yttrium-ibritumomab tiuxetan, were FDA-approved more than a decade ago but have been little utilized because of a variety of medical, financial, and logistic obstacles. Newer technologies employing multistep "pretargeting" methods, particularly those utilizing bispecific antibodies, have greatly enhanced the therapeutic efficacy of radioimmunotherapy and diminished its toxicities...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28423546/tetraspanin-8-tspan-8-as-a-potential-target-for-radio-immunotherapy-of-colorectal-cancer
#4
Aurelie Maisonial-Besset, Tiffany Witkowski, Isabelle Navarro-Teulon, Odile Berthier-Vergnes, Giovanna Fois, Yingying Zhu, Sophie Besse, Olivia Bawa, Arnaud Briat, Mercedes Quintana, Alexandre Pichard, Mathilde Bonnet, Eric Rubinstein, Jean-Pierre Pouget, Paule Opolon, Lydia Maigne, Elisabeth Miot-Noirault, Jean-Michel Chezal, Claude Boucheix, Françoise Degoul
Tetraspanin 8 (TSPAN8) overexpression is correlated with poor prognosis in human colorectal cancer (CRC). A murine mAb Ts29.2 specific for human TSPAN8 provided significant efficiency for immunotherapy in CRC pre-clinical models. We therefore evaluate the feasability of targeting TSPAN8 in CRC with radiolabeled Ts29.2. Staining of tissue micro-arrays with Ts29.2 revealed that TSPAN8 espression was restricted to a few human healthy tissues. DOTA-Ts29.2 was radiolabeled with 111In or 177Lu with radiochemical purities >95%, specific activity ranging from 300 to 600 MBq/mg, and radioimmunoreactive fractions >80%...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413681/phase-2-study-of-chop-r-14-followed-by-90-y-ibritumomab-tiuxetan-in-patients-with-previously-untreated-diffuse-large-b-cell-lymphoma
#5
Reem Karmali, Melissa L Larson, Jamile M Shammo, Stephanie A Gregory, Teresa O'Brien, Parameswaran Venugopal
The aim of this open-label, single-center, phase 2 study was to assess the efficacy and safety of dose-dense CHOP-R-14 followed by (90)Y-ibritumomab radioimmunotherapy (RIT) in patients with previously untreated diffuse large B-cell lymphoma (DLBCL). A total of 20 patients, the majority presenting with high-risk characteristics, were enrolled to receive dose-dense cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab every 14 days (CHOP-R-14), followed by (90)Y-ibritumomab tiuxetan consolidation...
April 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28381167/cytokine-evaluation-in-untreated-and-radioimmunotherapy-treated-tumors-in-an-immunocompetent-rat-model
#6
Erika Elgström, Tomas G Ohlsson, Sophie E Eriksson
The tumor microenvironment can act so as to stimulate or reject tumor cells. Among the determining factors are cytokines produced, for example, by infiltrating immune cells, tumor cells, and fibroblasts. External radiotherapy has been shown to be able to activate an immune response against tumor cells with cytokine signaling as an important part of the activation. The aim of this study was to evaluate the cytokines present in the tumor microenvironment and whether the cytokine profile changed during tumor regression induced by radioimmunotherapy with the beta emitter (177)Lu...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28362640/multi-isotope-spect-imaging-of-the-sup-225-sup-ac-decay-chain-feasibility-studies
#7
Andrew K H Robertson, Caterina Ramogida, Cristina Rodriguez-Rodriguez, Stephan Blinder, Peter Kunz, Vesna Sossi, Paul Schaffer
<b>Purpose:</b> Effective use of the <sup>225</sup>Ac decay chain in targeted internal radioimmunotherapy requires the retention of both <sup>225</sup>Ac and progeny isotopes at the target site. Imaging-based pharmacokinetic tests of these pharmaceuticals must therefore separately yet simultaneously image multiple isotopes that may not be colocalized despite being part of the same decay chain. This work presents feasibility studies demonstrating the ability of a microSPECT/CT scanner equipped with a high energy collimator to simultaneously image two components of the <sup>225</sup>Ac decay chain: <sup>221</sup>Fr (218 keV) and <sup>213</sup>Bi (440 keV)...
March 31, 2017: Physics in Medicine and Biology
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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