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Radioimmunotherapy

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https://www.readbyqxmd.com/read/27908170/high-resolution-digital-autoradiographic-and-dosimetric-analysis-of-heterogeneous-radioactivity-distribution-in-xenografted-prostate-tumors
#1
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
#2
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
#3
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...
November 24, 2016: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/27844106/lymphoma-current-status-of-clinical-and-preclinical-imaging-with-radiolabeled-antibodies
#4
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...
November 14, 2016: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/27823646/radioimmunotherapy-in-non-hodgkin-lymphoma-prediction-and-assessment-of-response
#5
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
#6
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...
November 3, 2016: 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
#7
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
#8
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
https://www.readbyqxmd.com/read/27774435/combining-radiation-therapy-with-immune-checkpoint-blockade-for-central-nervous-system-malignancies
#9
Neil M D'Souza, Penny Fang, Jennifer Logan, Jinzhong Yang, Wen Jiang, Jing Li
Malignancies of the central nervous system (CNS), particularly glioblastoma and brain metastases from a variety of disease sites, are difficult to treat despite advances in multimodality approaches consisting of surgery, chemotherapy, and radiation therapy (RT). Recent successes of immunotherapeutic strategies including immune checkpoint blockade (ICB) via anti-PD-1 and anti-CTLA-4 antibodies against aggressive cancers, such as melanoma, non-small cell lung cancer, and renal cell carcinoma, have presented an exciting opportunity to translate these strategies for CNS malignancies...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27763687/repeated-adjuvant-anti-cea-radioimmunotherapy-after-resection-of-colorectal-liver-metastases-safety-feasibility-and-long-term-efficacy-results-of-a-prospective-phase-2-study
#10
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
https://www.readbyqxmd.com/read/27748184/177lu-dota-bevacizumab-radioimmunotherapy-agent-for-melanoma
#11
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
https://www.readbyqxmd.com/read/27744117/targeted-therapy-of-osteosarcoma-with-radiolabeled-monoclonal-antibody-to-an-insulin-like-growth-factor-2-receptor-igf2r
#12
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...
December 2016: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/27725930/combination-of-antiretroviral-drugs-and-radioimmunotherapy-specifically-kills-infected-cells-from-hiv-infected-individuals
#13
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
https://www.readbyqxmd.com/read/27722526/new-insights-into-the-pretargeting-approach-to-image-and-treat-tumours
#14
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...
November 21, 2016: Chemical Society Reviews
https://www.readbyqxmd.com/read/27706035/re-188-enhances-the-inhibitory-effect-of-bevacizumab-in-non-small-cell-lung-cancer
#15
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
https://www.readbyqxmd.com/read/27689933/improved-in-vivo-stability-of-radioiodinated-rituximab-using-an-iodination-linker-for-radioimmunotherapy
#16
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
https://www.readbyqxmd.com/read/27688477/cure-of-human-ovarian-carcinoma-solid-xenografts-by-fractionated-211at-alpha-radioimmunotherapy-influence-of-tumor-absorbed-dose-and-effect-on-long-term-survival
#17
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
https://www.readbyqxmd.com/read/27675684/priming-radioimmunotherapy-with-external-beam-radiation-in-patients-with-relapsed-low-grade-non-hodgkin-lymphoma
#18
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
https://www.readbyqxmd.com/read/27675549/completion-of-first-in-human-%C3%AE-emitter-radioimmunotherapy-trial-with-tumor-marker-analysis
#19
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
https://www.readbyqxmd.com/read/27619247/exploiting-gene-expression-kinetics-in-conventional-radiotherapy-hyperfractionation-and-hypofractionation-for-targeted-therapy
#20
REVIEW
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
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