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Radioimmunotherapy

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https://www.readbyqxmd.com/read/29777377/radiolabeled-f-ab-2-cetuximab-for-theranostic-purposes-in-colorectal-and-skin-tumor-bearing-mice-models
#1
P-S Bellaye, M Moreau, O Raguin, A Oudot, C Bernhard, J-M Vrigneaud, L Dumont, D Vandroux, F Denat, A Cochet, F Brunotte, B Collin
PURPOSE: This study aimed to investigate theranostic strategies in colorectal and skin cancer based on fragments of cetuximab, an anti-EGFR mAb, labeled with radionuclide with imaging and therapeutic properties, 111 In and 177 Lu, respectively. METHODS: We designed F(ab')2 -fragments of cetuximab radiolabeled with 111 In and 177 Lu. 111 In-F(ab')2 -cetuximab tumor targeting and biodistribution were evaluated by SPECT in BalbC nude mice bearing primary colorectal tumors...
May 17, 2018: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/29777009/feasibility-of-cxcr4-directed-radioligand-therapy-in-advanced-diffuse-large-b-cell-lymphoma
#2
Constantin Lapa, Heribert Hänscheid, Malte Kircher, Andreas Schirbel, Gerd Wunderlich, Rudolf Werner, Samuel Samnick, Jörg Kotzerke, Hermann Einsele, Andreas Buck, Hans-Jürgen Wester, Götz Ulrich Grigoleit
We have recently reported on our experience with C-X-C-motif chemokine receptor 4- (CXCR4-) directed radioligand therapy (RLT) in multiple myeloma and acute leukemia. Methods: Six patients with heavily pre-treated relapsed diffuse large B cell lymphoma (DLBCL) (3 males, 3 females; aged, 54±8 years) underwent CXCR4-directed RLT in combination with conditioning chemotherapy and allogeneic stem cell transplantation (SCT). In 2 patients, radioimmunotherapy (RIT) targeting CD20 or CD66 was added to enhance anti-lymphoma activity...
May 18, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29733658/bevacizumab-radioimmunotherapy-rit-with-accelerated-blood-clearance-using-the-avidin-chase
#3
Ryan Yudistiro, Hirofumi Hanaoka, Natsumi Katsumata, Aiko Yamaguchi, Yoshito Tsushima
The overexpression of vascular endothelial growth factor (VEGF) in varying types of solid tumor renders radioimmunotherapy (RIT) with the anti-VEGF antibody bevacizumab (BV) a promising treatment. However, the slow blood clearance of BV, which may increase the occurrence risk of hematotoxicity, hinders the application of BV-RIT. Using the avidin chase is a long-known blood clearance enhancement strategy for biotinylated-mAb. To enhance RIT efficacy by increasing the radioactivity dose, we evaluated the ability of avidin to accelerate the blood clearance of yttrium-90 (90 Y)-labeled biotinylated BV (90 Y-Bt-BV) in a xenograft mouse model of triple-negative breast cancer (TNBC)...
May 7, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29719928/long-term-follow-up-of-2-patients-treated-with-90-y-rituximab-radioimmunotherapy-for-relapse-of-nodular-lymphocyte-predominant-hodgkin-lymphoma
#4
S Golstein, K Muylle, M Vercruyssen, C Spilleboudt, A de Wind, D Bron
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma (< 5% of Hodgkin's lymphomas) predominantly affecting the middle-aged man, with an indolent behavior. Given the rare occurrence of this lymphoma, there are currently no clear guidelines for initial treatment or relapse. In this report, we present the follow up of two patients treated by radioimmunotherapy for first relapse of their NLPHL. Both patients were initially treated with rituximab and relapsed 1 year after the end of their treatment...
May 2, 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29684714/microspect-imaging-of-triple-negative-breast-cancer-cell-tumor-xenografted-in-athymic-mice-with-radioiodinated-anti-icam-1-monoclonal-antibody
#5
Linyi You, Xiangyu Wang, Zhide Guo, Deliang Zhang, Pu Zhang, Jindian Li, Xinhui Su, Weimin Pan, Xianzhong Zhang
Intercellular adhesion molecule-1(ICAM-1) is a potential molecular target and biomarker for triple negative breast cancer (TNBC) therapy and diagnosis. In this study, aICAM-1 was radioiodinated with 125 I/131 I in high radiochemical yield and the probes for TNBC tumor targeting and radioimmunotherapy were evaluated in tumor-bearing mice. High and specific accumulation of 125 I-aICAM1 in TNBC MDA-MB-231 tumor was observed in SPECT imaging and the tumor grew was inhibited obviously by 131 I-aICAM1. Thus, the radioiodinated aICAM1 could serve as potential agents for TNBC theranostics...
April 4, 2018: Applied Radiation and Isotopes
https://www.readbyqxmd.com/read/29683132/correction-evaluation-of-tenascin-c-by-tenatumomab-in-t-cell-non-hodgkin-lymphomas-identifies-a-new-target-for-radioimmunotherapy
#6
Giuseppe Gritt, Andrea Gianatt, Fiorella Petronzeii, Rita De Santis, Chiara Pavoni, Riccardo Lorenzo Rossi, Laura Cattaneo, Luigi Giusto Spagnoli, Silvia Ferrar, Andrea Ross, Anna Maria Barbu, Alessandro Rambald
[This corrects the article DOI: 10.18632/oncotarget.23919.].
March 30, 2018: Oncotarget
https://www.readbyqxmd.com/read/29674421/anti-misrii-radiolabeled-antibodies-new-tools-for-a-theranostic-approach-in-ovarian-cancer
#7
Emmanuel Deshayes, Riad Ladjohounlou, Pierre Le Fur, Alexandre Pichard, Catherine Lozza, Vincent Boudousq, Samuel Sevestre, Marta Jarlier, Roxana Kashani, Joanna Koch, Jane Sosabowski, Julie Foster, Nicolas Chouin, Frank Bruchertseifer, Alfred Morgenstern, Pierre-Olivier Kotzki, Isabelle Navarro-Teulon, Jean-Pierre Pouget
We have developed the 16F12 mouse monoclonal antibody (mAb) that targets the MISRII receptor expressed by ovarian tumors. Here, we assessed in preclinical models the possibility to use radiolabeled 16F12 in a theranostic approach for small-volume ovarian peritoneal carcinomatosis, for instance after cytoreductive surgery. Methods: DOTA-, DTPA- or DFO-conjugated 16F12 mAb was radiolabeled with beta (177 Lu) or alpha (213 Bi) particle emitters for therapeutic use, and with 89 Zr for positron emission tomography (PET) imaging...
April 19, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29616868/frontline-treatment-of-diffuse-large-b-cell-lymphoma-in-elderly-a-systematic-review-of-clinical-trials-in-post-rituximab-era
#8
Sara Beygi, Santhosh Sadashiv, James B Reilly, Cyrus Khan, John Lister
Treatment of diffuse large B cell lymphoma (DLBCL) remains challenging in elderly population and systematic reviews are lacking in this area. Medline and Cochrane Register of Controlled Trials in addition to conference proceedings were searched for therapeutic clinical trials on frontline treatment of DLBCL in adults ≥60 in post-rituximab era. Forty-one out of 713 reviewed papers met our inclusion criteria. Six cycles of rituximab, cyclophosphamide, vincristine, prednisone (R-CHOP) administered every 21 d remain the standard treatment for fit elderly, with no role for maintenance rituximab...
April 4, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29615812/structure-function-analysis-and-therapeutic-efficacy-of-antibodies-to-fungal-melanin-for-melanoma-radioimmunotherapy
#9
J D Nosanchuk, A Jeyakumar, A Ray, E Revskaya, Z Jiang, R A Bryan, K J H Allen, R Jiao, M E Malo, B L Gómez, A Morgenstern, F Bruchertseifer, D Rickles, G B Thornton, A Bowen, A Casadevall, E Dadachova
Metastatic melanoma remains difficult to treat despite recent approvals of several new drugs. Recently we reported encouraging results of Phase I clinical trial of radiolabeled with188 Re murine monoclonal IgM 6D2 to melanin in patients with Stage III/IV melanoma. Subsequently we generated a novel murine IgG 8C3 to melanin. IgGs are more amenable to humanization and cGMP (current Good Manufacturing Practice) manufacturing than IgMs. We performed comparative structural analysis of melanin-binding IgM 6D2 and IgG 8C3...
April 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29571067/evaluation-of-177-lu-chx-a%C3%A2-dtpa-6a10-fab-as-a-radioimmunotherapy-agent-targeting-carbonic-anhydrase-xii
#10
L Fiedler, M Kellner, A Gosewisch, R Oos, G Böning, S Lindner, N Albert, P Bartenstein, H-J Reulen, R Zeidler, F J Gildehaus
INTRODUCTION: Due to their infiltrative growth behavior, gliomas have, even after surgical resection, a high recurrence tendency. The approach of intracavitary radioimmunotherapy (RIT) is aimed at inhibiting tumor re-growth by directly administering drugs into the resection cavity (RC). Direct application of the radioconjugate into the RC has the advantage of bypassing the blood-brain barrier, which allows the administration of higher radiation doses than systemic application. Carbonic anhydrase XII (CA XII) is highly expressed on glioma cells while being absent from normal brain and thus an attractive target molecule for RIT...
March 4, 2018: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/29569511/radioimmunotherapy-as-the-first-line-of-treatment-in-non-hodgkin-lymphoma
#11
Mahsa Eskian, MirHojjat Khorasanizadeh, Pier L Zinzani, Nima Rezaei
Non-Hodgkin lymphoma (NHL) is the most common hematologic malignancy. The estimated deaths and new cases of NHL in the USA in 2018 have reached 19,910 and 74,680, respectively, with 5-year survival rate of 71%. Therapeutic interventions for NHL consist of chemotherapy, radiation therapy and immunotherapy. Radioimmunotherapy (RIT) is a potential alternative treatment for NHL that is currently used in different lines of treatment. Studies show that nuclear medicine physicians and radiation oncologists are not yet certain about the proper line for administration of RIT...
March 23, 2018: Immunotherapy
https://www.readbyqxmd.com/read/29561763/-212-pb-labeled-antibody-225-28-targeted-to-chondroitin-sulfate-proteoglycan-4-for-triple-negative-breast-cancer-therapy-in-mouse-models
#12
Benjamin B Kasten, Patsy G Oliver, Harrison Kim, Jinda Fan, Soldano Ferrone, Kurt R Zinn, Donald J Buchsbaum
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a poor prognosis. There is a clinical need for effective, targeted therapy strategies that destroy both differentiated TNBC cells and TNBC cancer initiating cells (CICs), as the latter are implicated in the metastasis and recurrence of TNBC. Chondroitin sulfate proteoglycan 4 (CSPG4) is overexpressed on differentiated tumor cells and CICs obtained from TNBC patient specimens, suggesting that CSPG4 may be a clinically relevant target for the imaging and therapy of TNBC...
March 21, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29545376/penetrating-the-barriers-to-successful-alpha-radioimmunotherapy
#13
Sean D Carlin
No abstract text is available yet for this article.
March 15, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29537104/aligning-physics-and-physiology-engineering-antibodies-for-radionuclide-delivery
#14
Wen-Ting K Tsai, Anna M Wu
The exquisite specificity of antibodies and antibody fragments renders them excellent agents for targeted delivery of radionuclides. Radiolabeled antibodies and fragments have been successfully used for molecular imaging and radioimmunotherapy (RIT) of cell-surface targets in oncology and immunology. Protein engineering has been employed for antibody humanization essential for clinical applications, as well as optimization of important characteristics including pharmacokinetics, biodistribution, and clearance...
March 14, 2018: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/29524233/radioimmunotherapy-of-solid-tumors-approaches-on-the-verge-of-clinical-application
#15
Mark D Bartholomä
While radioimmunotherapy (RIT) for the treatment of hematological malignancies such as indolent B-cell lymphoma has proven quite successful, clinical results of RIT in solid tumors have only been moderate in the past. The reasons were manifold and can be mostly attributed to the different biological properties of solid tumors vs hematological cancers. Furthermore, the slow clearance of the radiolabelled antibody prevents the use of radiation doses necessary to achieve clinical responses. The long biological half-life of radioimmunoconjugates results in high background levels and is the main reason for radiation related toxicities...
March 9, 2018: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/29515769/evaluation-of-tenascin-c-by-tenatumomab-in-t-cell-non-hodgkin-lymphomas-identifies-a-new-target-for-radioimmunotherapy
#16
Giuseppe Gritti, Andrea Gianatti, Fiorella Petronzelli, Rita De Santis, Chiara Pavoni, Riccardo Lorenzo Rossi, Laura Cattaneo, Luigi Giusto Spagnoli, Silvia Ferrari, Andrea Rossi, Anna Maria Barbui, Alessandro Rambaldi
The clinical outcome of T-cell non-Hodgkin lymphoma (NHL) is poor and innovative treatments are needed. Tenascin-C is a large extracellular glycoprotein not expressed under physiological conditions, but overexpressed in cancer. Aim of the study was to evaluate tenascin-C expression within pathologic tissue of T-cell NHL and determine its clinical significance. We used an immunohistochemistry approach using the anti-tenascin-C monoclonal antibody Tenatumomab in 75 systemic T-cell NHL (including 72 mature and 3 precursor T-cell NHL), and 25 primary cutaneous T-cell NHL...
February 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29502416/click-mediated-pretargeted-radioimmunotherapy-of-colorectal-carcinoma
#17
Rosemery Membreno, Brendon E Cook, Kimberly Fung, Jason S Lewis, Brian M Zeglis
Pretargeted radioimmunotherapy (PRIT) based on the inverse electron demand Diels-Alder (IEDDA) reaction between tetrazine (Tz) and trans-cyclooctene (TCO) represents a promising strategy for leveraging the affinity and specificity of antibodies without their pharmacokinetic drawbacks. Herein, we present an investigation of the in vivo efficacy and dosimetry of a PRIT strategy for colorectal carcinoma based on the ligation between a 177 Lu-labeled Tz radioligand (177 Lu-DOTA-PEG7 -Tz) and a TCO-bearing immunoconjugate of the huA33 antibody (huA33-TCO)...
April 2, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29502411/evaluation-of-an-anti-her2-nanobody-labeled-with-225-ac-for-targeted-%C3%AE-particle-therapy-of-cancer
#18
Marek Pruszynski, Matthias D'Huyvetter, Frank Bruchertseifer, Alfred Morgenstern, Tony Lahoutte
Human epidermal growth factor receptor type 2 (HER2) is overexpressed in numerous carcinomas. Nanobodies (Nbs) are the smallest antibody-derived fragments with beneficial characteristics for molecular imaging and radionuclide therapy. Therefore, HER2-targeting nanobodies could offer a valuable platform for radioimmunotherapy, especially when labeled with α-particle emitters, which provide highly lethal and localized radiation to targeted cells with minimal exposure to surrounding healthy tissues. In this study, the anti-HER2 2Rs15d-nanobody was conjugated with 2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid ( p-SCN-Bn-DOTA) and radiolabeled with an α-emitter 225 Ac with a high yield (>90%) and a radiochemical purity above 95%...
April 2, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29500551/immune-modulatory-effects-of-radiotherapy-as-basis-for-well-reasoned-radioimmunotherapies
#19
REVIEW
Michael Rückert, Lisa Deloch, Rainer Fietkau, Benjamin Frey, Markus Hecht, Udo S Gaipl
BACKGROUND: Radiotherapy (RT) has been known for decades as a local treatment modality for malign and benign disease. In order to efficiently exploit the therapeutic potential of RT, an understanding of the immune modulatory properties of ionizing radiation is mandatory. These should be used for improvement of radioimmunotherapies for cancer in particular. METHODS: We here summarize the latest research and review articles about immune modulatory properties of RT, with focus on radiation dose and on combination of RT with selected immunotherapies...
March 2, 2018: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
https://www.readbyqxmd.com/read/29471300/yttrium-90-ibritumomab-tiuxetan-zevalin%C3%A2-radioimmunotherapy-after-cytoreduction-with-eshap-chemotherapy-in-patients-with-relapsed-follicular-non-hodgkin-lymphoma-final-results-of-a-phase-ii-study
#20
Soham D Puvvada, José M Guillén-Rodríguez, Jessica Yan, Lora Inclán, Kara Heard, Xavier I Rivera, Faiz Anwer, Daruka Mahadevan, Jonathan H Schatz, Daniel O Persky
BACKGROUND: Radioimmunotherapy (RIT) is effective in treating relapsed/refractory follicular lymphoma (FL), with durable remissions in first-line consolidation. We hypothesized that RIT with ibritumomab tiuxetan (Zevalin®) would result in durable remissions by eliminating minimal residual disease after cytoreduction. METHODS: Patients with FL received 2 cycles of ESHAP (etoposide, methylprednisolone, cytarabine, cisplatin) every 28 days, followed by Zevalin 4-6 weeks later if there was no disease progression and bone marrow biopsy showed < 25% involvement...
2018: Oncology
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