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https://www.readbyqxmd.com/read/29348316/evaluation-of-next-generation-anti-cd20-antibodies-labeled-with-zirconium-89-in-human-lymphoma-xenografts
#1
Jason T Yoon, Mark S Longtine, Bernadette V Marquez-Nostra, Richard L Wahl
Radioimmunotherapies with monoclonal antibodies (mAbs) to the B-lymphocyte antigen 20 (CD20) are effective treatments for B-cell lymphomas, but United States Food and Drug Administration (FDA)-approved radioimmunotherapies exclusively use radiolabeled murine antibodies, potentially limiting re-dosing. The FDA recently approved two unlabeled anti-CD20 monoclonal antibodies, obinutizumab and ofatumumab, termed "next generation" as they are humanized (obinituzumab) or fully human (ofatumumab), thus potentially allowing a greater potential for re-dosing than with previous generation anti-CD20 antibodies, including rituximab (chimeric) and tositumumab (murine) which contain more murine peptide sequences...
January 18, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29335856/abscopal-effects-of-radiotherapy-and-combined-mrna-based-immunotherapy-in-a-syngeneic-ova-expressing-thymoma-mouse-model
#2
Lucas Basler, Aleksandra Kowalczyk, Regina Heidenreich, Mariola Fotin-Mleczek, Savas Tsitsekidis, Daniel Zips, Franziska Eckert, Stephan M Huber
BACKGROUND: Tumor metastasis and immune evasion present major challenges of cancer treatment. Radiotherapy can overcome immunosuppressive tumor microenvironments. Anecdotal reports suggest abscopal anti-tumor immune responses. This study assesses abscopal effects of radiotherapy in combination with mRNA-based cancer vaccination (RNActive®). METHODS: C57BL/6 mice were injected with ovalbumin-expressing thymoma cells into the right hind leg (primary tumor) and left flank (secondary tumor) with a delay of 4 days...
January 16, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29314858/panitumumab-modified-with-metal-chelating-polymers-mcp-complexed-to-111in-and-177lu-an-egfr-targeted-theranostic-for-pancreatic-cancer
#3
Sadaf Aghevlian, Yijie Lu, Mitchell A Winnik, David W Hedley, Raymond M Reilly
A metal-chelating polymer (MCP) with a polyglutamide (PGlu) backbone presenting on average 13 DOTA (tetraazacyclododecane-1,4,7,10-tetraacetic acid) chelators for complexing 111In or 177Lu and 10 polyethylene glycol (PEG) chains to minimize liver and spleen uptake was conjugated to anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb), panitumumab. Since panitumumab-MCP may be dual-labeled with 111In and 177Lu for SPECT, or radioimmunotherapy (RIT) exploiting the Auger electrons or β-particle emissions, respectively, we propose that panitumumab-MCP could be a useful theranostic agent EGFR-positive PnCa...
January 9, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29247459/131-i-radiolabeled-immune-albumin-nanospheres-loaded-with-doxorubicin-for-in-vivo-combinatorial-therapy
#4
Anping Ji, Yuanchao Zhang, Gaochao Lv, Jianguo Lin, Ning Qi, Faquan Ji, Minghua Du
For the purpose of providing a new insights for high-efficiency radiochemotherapy of hepatoma, a radioimmunotherapy and chemotherapy combinatorial therapy albumin nanospheres 131 I-antiAFPMcAb-DOX-BSA-NPs was designed and prepared. It was obtained in a high radiolabeling yield (RLY) about 65% with the radiochemical purity (RCP) of over 98%. The transmission electron microscope (TEM) showed that the nanospheres obtained in good monodispersion with a diameter of approximately 230 nm. The doxorubicin (DOX) loading capacity of the DOX-BSA-NPs nanoparticles was determined to about 180 μg/mg and 95...
December 16, 2017: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/29239276/radiolabeled-anti-adenosine-triphosphate-synthase-monoclonal-antibody-as-a-theragnostic-agent-targeting-angiogenesis
#5
Bok-Nam Park, Su Jin Lee, Jung Hyun Roh, Kyung-Han Lee, Young-Sil An, Joon-Kee Yoon
INTRODUCTION: The potential of a radioiodine-labeled, anti-adenosine triphosphate synthase monoclonal antibody (ATPS mAb) as a theragnostic agent for simultaneous cancer imaging and treatment was evaluated. METHODS: Adenosine triphosphate synthase monoclonal antibody was labeled with radioiodine, then radiotracer uptake was measured in 6 different cancer cell lines. In vivo biodistribution was evaluated 24 and 48 hours after intravenous injection of 125I-ATPS mAb into MKN-45 tumor-bearing mice (n = 3)...
January 2017: Molecular Imaging
https://www.readbyqxmd.com/read/29230857/chemical-aspects-of-metal-ion-chelation-in-the-synthesis-and-application-antibody-based-radiotracers
#6
Eszter Boros, Jason P Holland
Radiometals are becoming increasingly accessible and are utilized frequently in the design of radiotracers for imaging and therapy. Nuclear properties ranging from the emission of γ-ray and ®+ -particles (imaging) to Auger electron, ®- and α-particles (therapy) in combination with long half-lives are ideally matched with the relatively long biological half-life of monoclonal antibodies in vivo. Radiometal labelling of antibodies requires the incorporation of a metal chelate onto the monoclonal antibody...
December 12, 2017: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/29204055/combined-treatment-of-pancreatic-cancer-xenograft-with-90y-itga6b4-mediated-radioimmunotherapy-and-pi3k-mtor-inhibitor
#7
Winn Aung, Atsushi B Tsuji, Hitomi Sudo, Aya Sugyo, Yoshinori Ukai, Katsushi Kouda, Yoshikazu Kurosawa, Takako Furukawa, Tsuneo Saga, Tatsuya Higashi
AIM: To investigate the therapeutic effect of combined integrin α6β4-targeted radioimmunotherapy (RIT) and PI3K/mTOR inhibitor BEZ235 in a pancreatic cancer model. METHODS: Phosphorylation of Akt, mTOR, the downstream effectors eukaryotic initiation factor 4E binding protein 1 (4EBP1) and S6 ribosomal protein (S6) were evaluated in BxPC-3 human pancreatic cancer cells treated with Yttrium-90 (90Y) labeled anti-integrin α6β4 antibody (ITGA6B4) and BEZ235 by western blotting...
November 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29190900/immuno-pet-imaging-based-radioimmunotherapy-in-head-and-neck-squamous-cell-carcinoma-model
#8
In Ho Song, Youn Noh, Junhye Kwon, Jae Ho Jung, Byung Chul Lee, Kwang Il Kim, Yong Jin Lee, Joo Hyun Kang, Chae Seo Rhee, Chul Hee Lee, Tae Sup Lee, Ik Joon Choi
The epidermal growth factor receptor (EGFR) is one of the most comprehensively studied molecular targets in head and neck squamous cell carcinoma (HNSCC). However, inherent and acquired resistance are serious problems and are responsible for limited clinical efficacy and tumor recurrence. In this study, we evaluated the feasibility of immuno-positron emission tomography (PET) imaging and radioimmunotherapy (RIT) with 64Cu-/177Lu-PCTA-cetuximab in cetuximab-resistant SNU-1066 HNSCC xenografted model. The cellular uptake of 64Cu/177Lu-3,6,9,15-tetraazabicyclo[9...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29158362/cd38-bispecific-antibody-pretargeted-radioimmunotherapy-for-multiple-myeloma-and-other-b-cell-malignancies
#9
Damian J Green, Shyril O'Steen, Yukang Lin, Melilssa L Comstock, Aimee L Kenoyer, Donald K Hamlin, D Scott Wilbur, Darrell R Fisher, Margaret Nartea, Mark D Hylarides, Ajay K Gopal, Theodore A Gooley, Johnnie J Orozco, Brian G Till, Kelly D Orcutt, K Dane Wittrup, Oliver W Press
Pretargeted radioimmunotherapy (PRIT) has demonstrated remarkable efficacy targeting tumor antigens, but immunogenicity and endogenous biotin blocking may limit clinical translation. We describe a new PRIT approach for the treatment of Multiple Myeloma (MM) and other B cell malignancies, for which we developed an anti-CD38 bispecific fusion protein that eliminates endogenous biotin interference and immunogenic elements. In murine xenograft models of MM and non-Hodgkin lymphoma (NHL), the CD38 bispecific construct demonstrated excellent blood clearance and tumor targeting...
November 20, 2017: Blood
https://www.readbyqxmd.com/read/29129050/metal-free-cycloaddition-chemistry-driven-pretargeted-radioimmunotherapy-using-%C3%AE-particle-radiation
#10
Manan Shah, Xiuli Zhang, Raffaella Rossin, Marc S Robillard, Darrell Fisher, Tyler Bueltmann, Freek J M Hoeben, Thomas Quinn
The pretargeted radioimmunotherapy approach (PRIT) decouples the administration of tumor targeting monoclonal antibodies (mAb) from that of the radiolabeled ligand. This multi-step strategy allows delivery of high doses of radiation to tumor cells while minimizing non-specific normal tissue irradiation. In this study, we evaluated the potential of pretargeted α-particle radioimmunotherapy based on inverse electron demand Diels-Alder reaction (IEDAA) between trans-cyclooctene (TCO) and tetrazine (Tz). Two tetrazine based chelators, DOTA-Tz and TCMC-Tz, were synthesized and compared for their radiolabeling efficiency with 212Pb, radiochemical stability and in-vivo pharmacokinetics...
November 12, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29097747/antibody-pegylation-in-bioorthogonal-pretargeting-with-trans-cyclooctene-tetrazine-cycloaddition-in-vitro-and-in-vivo-evaluation-in-colorectal-cancer-models
#11
Aurélie Rondon, Nancy Ty, Jean-Baptiste Bequignat, Mercedes Quintana, Arnaud Briat, Tiffany Witkowski, Bernadette Bouchon, Claude Boucheix, Elisabeth Miot-Noirault, Jean-Pierre Pouget, Jean-Michel Chezal, Isabelle Navarro-Teulon, Emmanuel Moreau, Françoise Degoul
Bioorthogonal chemistry represents a challenging approach in pretargeted radioimmunotherapy (PRIT). We focus here on mAb modifications by grafting an increase amount of trans-cyclooctene (TCO) derivatives (0 to 30 equivalents with respect to mAb) bearing different polyethylene glycol (PEG) linkers between mAb and TCO (i.e. PEG0 (1), PEG4 (2) and PEG12 (3)) and assessing their functionality. We used colorectal xenograft (HT29/Ts29.2) and peritoneal carcinomatosis (A431-CEA-Luc/35A7) as tumor cells/mAbs models and fluorescent tetrazines (TZ)...
November 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29083933/beyond-dose-using-pretherapy-biomarkers-to-improve-dose-prediction-of-outcomes-for-radioimmunotherapy-of-non-hodgkin-lymphoma
#12
Peter L Roberson, Lauren B Smith, Meredith A Morgan, Matthew J Schipper, Scott J Wilderman, Anca M Avram, Mark S Kaminski, Yuni K Dewaraja
INTRODUCTION: Non-Hodgkin Lymphoma patients respond differently to therapy according to inherent biological variations. Pretherapy biomarkers may improve dose-response prediction. MATERIALS AND METHODS: Hybrid single-photon emission computed tomography (SPECT)/computed tomography (CT) three-dimensional imaging at multiple time points plus follow-up positron emission tomography (PET)/CT or CT at 2 and 6 months post therapy were used to fit tumor response to combined biological effect and cell clearance models from which three biological effect response parameters (radiosensitivity, cold effect sensitivity, and proliferation potential) were determined per patient...
November 2017: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/29054987/theranostic-radiolabeled-anti-cd20-sdab-for-targeted-radionuclide-therapy-of-non-hodgkin-lymphoma
#13
Ahmet Krasniqi, Matthias D'Huyvetter, Catarina Xavier, Kevin Van der Jeught, Serge Muyldermans, José Van Der Heyden, Tony Lahoutte, Jan Tavernier, Nick Devoogdt
Anti-CD20 radioimmunotherapy is an effective approach for therapy of relapsed or refractory CD20pos lymphomas, but faces limitations due to poor tumor penetration and undesirable pharmacokinetics of full antibodies. Camelid single-domain Ab fragments (sdAbs) might circumvent some of the limitations of radiolabeled full antibodies. In this study, a set of hCD20-targeting sdAbs was generated and their capacity to bind hCD20 was evaluated in vitro and in vivo. A lead sdAb, sdAb 9079, was selected based on its specific tumor targeting and significant lower kidney accumulation compared to other sdAbs...
October 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29033288/the-therapeutic-antibody-lm609-selectively-inhibits-ligand-binding-to-human-%C3%AE-v%C3%AE-3-integrin-via-steric-hindrance
#14
Andrew J Borst, Zachary M James, William N Zagotta, Mark Ginsberg, Felix A Rey, Frank DiMaio, Marija Backovic, David Veesler
The LM609 antibody specifically recognizes αVβ3 integrin and inhibits angiogenesis, bone resorption, and viral infections in an arginine-glycine-aspartate-independent manner. LM609 entered phase II clinical trials for the treatment of several cancers and was also used for αVβ3-targeted radioimmunotherapy. To elucidate the mechanisms of recognition and inhibition of αVβ3 integrin, we solved the structure of the LM609 antigen-binding fragment by X-ray crystallography and determined its binding affinity for αVβ3...
November 7, 2017: Structure
https://www.readbyqxmd.com/read/28979315/development-of-dota-rituximab-to-be-labeled-with-90-y-for-radioimmunotherapy-of-b-cell-non-hodgkin-lymphoma
#15
Fariba Johari Doha, Siyavash Rahmani, Pedram Rikhtechi, Samira Rasaneh, Zahra Sheikholislam, Soraya Shahhosseini
NHL is the most common hematologic cancer in adults. Rituximab is the FDA approved treatment of relapsed or refractory low grade B-cell Non-Hodgkin Lymphoma (NHL). But patients eventually become resistant to rituximab. Since lymphocytes and lymphoma cells are highly radiosensitive, low grade NHL that has relapsed or refractory to standard therapy is treated by RIT in which a beta-emitting radionuclide coupled to anti-CD20 antibody. The association of beta emitter radionuclide to rituximab enhances its therapeutic efficacy...
2017: Iranian Journal of Pharmaceutical Research: IJPR
https://www.readbyqxmd.com/read/28971764/recent-research-trends-on-bismuth-compounds-in-cancer-chemo-and-radiotherapy
#16
Mateusz Kowalik, Joanna Masternak, Barbara Barszcz
The application of coordination chemistry in the light of nanotechnology is a rapidly developing research field in medicine. Bismuth complexes have been widely and willingly used in biomedicine with satisfactory therapeutic effects, mostly in Helicobacter pylori eradication, but also as potential anti-microbial and anti-leishmanial agents. Additionally, in recent years, an application of bismuth-based compounds as potent anticancer drugs has also been studied extensively. Therefore, in this review, we want to highlight a number current problems connected with: (1) characterization of bismuth complexes based on thiosemicarbazone, hydrazone, and dithiocarbamate classes of ligands as potential chemotherapeutics, (2) pioneering research on application of bismuth-based nanoparticles and nanodots for radiosensitization, and (3) research challenges in using bismuth radionuclides in targeted radioimmunotherapy...
October 3, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28951872/monoclonal-antibodies-radiolabeling-with-rhenium-188-for-radioimmunotherapy
#17
REVIEW
Licia Uccelli, Petra Martini, Micol Pasquali, Alessandra Boschi
Rhenium-188, obtained from an alumina-based tungsten-188/rhenium-188 generator, is actually considered a useful candidate for labeling biomolecules such as antibodies, antibody fragments, peptides, and DNAs for radiotherapy. There is a widespread interest in the availability of labeling procedures that allow obtaining (188)Re-labeled radiopharmaceuticals for various therapeutic applications, in particular for the rhenium attachment to tumor-specific monoclonal antibodies (Mo)Abs for immunotherapy. Different approaches have been developed in order to obtain (188)Re-radioimmunoconjugates in high radiochemical purity starting from the generator eluted [(188)Re]ReO4(-)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28940863/a-phase-ii-study-of-radioimmunotherapy-with-intraventricular-131-i-3f8-for-medulloblastoma
#18
Kim Kramer, Neeta Pandit-Taskar, John L Humm, Pat B Zanzonico, Sofia Haque, Ira J Dunkel, Suzanne L Wolden, Maria Donzelli, Debra A Goldman, Jason S Lewis, Serge K Lyashchenko, Yasmin Khakoo, Jorge A Carrasquillo, Mark M Souweidane, Jeffrey P Greenfield, David Lyden, Kevin D De Braganca, Stephen W Gilheeney, Steven M Larson, Nai-Kong V Cheung
BACKGROUND: High-risk and recurrent medulloblastoma (MB) is associated with significant mortality. The murine monoclonal antibody 3F8 targets the cell-surface disialoganglioside GD2 on MB. We tested the efficacy, toxicity, and dosimetry of compartmental radioimmunotherapy (cRIT) with intraventricular (131) I-labeled 3F8 in patients with MB on a phase II clinical trial. METHODS: Patients with histopathologically confirmed high-risk or recurrent MB were eligible for cRIT...
September 22, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28928164/immunopet-of-malignant-and-normal-b-cells-with-89-zr-and-124-i-labeled-obinutuzumab-antibody-fragments-reveals-differential-cd20-internalization-in-vivo
#19
Kirstin A Zettlitz, Richard Tavaré, Scott M Knowles, Kristopher K Steward, John M Timmerman, Anna M Wu
Purpose: The B-cell antigen CD20 provides a target for antibody-based positron emission tomography (immunoPET). We engineered antibody fragments targeting human CD20 and studied their potential as immunoPET tracers in transgenic mice (huCD20TM) and in a murine lymphoma model expressing human CD20.Experimental Design: Anti-CD20 cys-diabody (cDb) and cys-minibody (cMb) based on rituximab and obinutuzumab (GA101) were radioiodinated and used for immunoPET imaging of a murine lymphoma model. Pairwise comparison of obinutuzumab-based antibody fragments labeled with residualizing ((89)Zr) versus non-residualizing ((124)I) radionuclides by region of interest analysis of serial PET images was conducted both in the murine lymphoma model and in huCD20TM to assess antigen modulation in vivoResults:(124)I-GAcDb and (124)I-GAcMb produced high-contrast immunoPET images of B-cell lymphoma and outperformed the respective rituximab-based tracers...
September 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28910150/phase-i-ii-trial-of-anticarcinoembryonic-antigen-radioimmunotherapy-gemcitabine-and-hepatic-arterial-infusion-of-fluorodeoxyuridine-postresection-of-liver-metastasis-for-colorectal-carcinoma
#20
Benjamin Cahan, Lucille Leong, Lawrence Wagman, David Yamauchi, Stephen Shibata, Sharon Wilzcynski, Lawrence E Williams, Paul Yazaki, David Colcher, Paul Frankel, Anna Wu, Andrew Raubitschek, John Shively, Jeffrey Y C Wong
OBJECTIVES: Report the feasibility, toxicities, and long-term results of a Phase I/II trial of (90)Y-labeled anticarcinoembryonic antigen (anti-CEA) (cT84.66) radioimmunotherapy (RIT), gemcitabine, and hepatic arterial infusion (HAI) of fluorodeoxyuridine (FUdR) after maximal hepatic resection of metastatic colorectal cancer to the liver. METHODS: Patients with metastatic colorectal cancer to the liver postresection or ablation to minimum disease were eligible. Each cohort received HAI of FUdR for 14 days on a dose escalation schedule...
September 2017: Cancer Biotherapy & Radiopharmaceuticals
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