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Radioimmunotherapy

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https://www.readbyqxmd.com/read/28705917/curative-multi-cycle-radioimmunotherapy-monitored-by-quantitative-spect-ct-based-theranostics-using-bispecific-antibody-pretargeting-strategy-in-colorectal-cancer
#1
Sarah M Cheal, Edward K Fung, Miteshkumar V Patel, Blesida Punzalan, Hong Xu, Hong-Fen Guo, Pat B Zanzonico, Sebastien Monette, Karl Dane Wittrup, Nai-Kong Cheung, Steven M Larson
Radioimmunotherapy of solid tumors using antibody-targeted radionuclides has been limited by low therapeutic indices (TI). We recently reported a novel three-step pretargeted radioimmunotherapy (PRIT) strategy based on a glycoprotein A33 (GPA33)-targeting bispecific antibody (bsAb) and a small-molecule radioactive hapten, a complex of lutetium-177 ((177)Lu) and S-2-(4-aminobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid ((177)Lu-DOTA-Bn) that leads to high TIs for radiosensitive tissues such as blood (TI = 73) and kidney (TI = 12)...
July 13, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28675216/comparative-studies-on-the-therapeutic-benefit-of-targeted-%C3%AE-particle-radiation-therapy-for-the-treatment-of-disseminated-intraperitoneal-disease
#2
Diane E Milenic, Kwamena E Baidoo, Young-Seung Kim, Rachel Barkley, Martin W Brechbiel
Identification of the appropriate combination of radionuclide, target and targeting vehicle is critical for successful radioimmunotherapy. For the treatment of disseminated peritoneal diseases such as pancreatic or ovarian cancer, α-emitting radionuclides have been proposed for targeted radiation therapy. This laboratory has taken a systematic approach investigating targeted α-radiation therapy, allowing comparisons to now be made between (211)At, (227)Th, (213)Bi and (212)Pb. Herein, trastuzumab radiolabeled with (211)At and (227)Th was evaluated for therapeutic efficacy in the LS-174T i...
July 4, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28658304/validating-%C3%AE-particle-emission-from-211at-labeled-antibodies-in-single-cells-for-cancer-radioimmunotherapy-using-cr-39-plastic-nuclear-track-detectors
#3
Satoshi Kodaira, Huizi Keiko Li, Teruaki Konishi, Hisashi Kitamura, Mieko Kurano, Sumitaka Hasegawa
Recently, 211At has received increasing attention as a potential radionuclide for cancer radioimmunotherapy. It is a α-particle emitter, which is extremely effective against malignant cells. We demonstrate a method to verify the efficiency of 211At-labeled trastuzumab antibodies (211At-trastuzumab) against HER2 antigens, which has not been determined for radioimmunotherapy. A CR-39 plastic nuclear detector is used for measuring the position and the linear energy transfer (LET) of individual 211At α- particle tracks...
2017: PloS One
https://www.readbyqxmd.com/read/28599227/assessment-and-estimation-of-67-cu-production-yield-via-deuteron-induced-reactions-on-nat-zn-and-70-zn
#4
Seyedeh Fatemeh Hosseini, Mohammadreza Aboudzadeh, Mahdi Sadeghi, Ahmad Ahmadi Teymourlouy, Malihe Rostampour
(67)Cu radioisotope is a beta particle-emitting nuclide used in radioimmunotherapy (RIT) as well as for imaging, tracer kinetic studies and dosimetry. (67)Cu can be produced by bombarding (nat)Zn with deuterons. In this study, the physical yields of (67)Cu via (nat)Zn(d,x)(67)Cu reaction channel as well as via subreactions of (68)Zn(d,2pn)(67)Cu, (67)Zn(d,2p)(67)Cu, (70)Zn(d,2p3n)(67)Cu, (68)Zn(d,x)(67)Ni(T1/2=21s)→(67)Cu and (70)Zn(d,x)(67)Ni(T1/2=21s)→(67)Cu in the (nat)Zn target have been calculated by using the MCNPX-2...
May 31, 2017: Applied Radiation and Isotopes
https://www.readbyqxmd.com/read/28577439/targeted-%C3%AE-particle-radiation-therapy-of-her1-positive-disseminated-intraperitoneal-disease-an-investigation-of-the-human-anti-egfr-monoclonal-antibody-panitumumab
#5
Diane E Milenic, Kwamena E Baidoo, Young-Seung Kim, Rachel Barkley, Martin W Brechbiel
Identifying molecular targets and an appropriate targeting vehicle, i.e., monoclonal antibodies (mAb) and their various forms, for radioimmunotherapy (RIT) remains an active area of research. Panitumumab, a fully human and less immunogenic mAb that binds to the epidermal growth factor receptor (Erb1; HER1), was evaluated for targeted α-particle radiation therapy using (212)Pb, an in vivo α generator. A single dose of (212)Pb-panitumumab administered to athymic mice bearing LS-174T intraperitoneal (i.p.) tumor xenografts was found to have greater therapeutic efficacy when directly compared with (212)Pb-trastuzumab, which binds to HER2...
May 31, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28566329/venetoclax-synergizes-with-radiotherapy-for-treatment-of-b-cell-lymphomas
#6
Shyril O'Steen, Damian J Green, Ajay K Gopal, Johnnie J Orozco, Aimee L Kenoyer, Yukang Lin, D Scott Wilbur, Donald K Hamlin, Darrell R Fisher, Mark D Hylarides, Theodore A Gooley, Amelia Waltman, Brian G Till, Oliver W Press
Constitutive B-cell receptor signaling leads to overexpression of the antiapoptotic BCL-2 protein and is implicated in the pathogenesis of many types of B-cell non-Hodgkin lymphoma (B-NHL). The BCL-2 small-molecule inhibitor venetoclax shows promising clinical response rates in several lymphomas, but is not curative as monotherapy. Radiotherapy is a rational candidate for combining with BCL-2 inhibition, as DNA damage caused by radiotherapy increases the activity of pro-apoptotic BCL-2 pathway proteins, and lymphomas are exquisitely sensitive to radiation...
May 31, 2017: Cancer Research
https://www.readbyqxmd.com/read/28530668/radioimmunotherapy-augmented-beam-chemotherapy-vs-beam-alone-as-the-high-dose-regimen-for-autologous-stem-cell-transplantation-asct-in-relapsed-follicular-lymphoma-fl-a-retrospective-study-of-the-ebmt-lymphoma-working-party
#7
L Bento, A Boumendil, H Finel, S Le Gouill, S Amorim, H Monjanel, R Bouabdallah, J O Bay, E Nicolas-Virelizier, G McQuaker, G Rossi, R Johnson, A Huynh, P Ceballos, A Rambaldi, E Bachy, R Malladi, K Orchard, D Pohlreich, H Tilly, F Bonifazi, X Poiré, F Guilhot, A Haenel, C Crawley, B Metzner, J Gribben, N H Russell, G Damaj, K Thomson, P Dreger, S Montoto
Relapse remains the most common cause of treatment failure in patients receiving autologous stem cell transplantation (ASCT) for follicular lymphoma (FL). The aim of this study was to evaluate the effect of adding radioimmunotherapy or rituximab (R) to BEAM (carmustine, etoposide, ara-c, melphalan) high-dose therapy for ASCT in patients with relapsed FL. Using the European Society for Blood and Marrow Transplantation registry, we conducted a cohort comparison of BEAM (n=1973), Zevalin-BEAM (Z-BEAM) (n=207) and R-BEAM (n=179) and also a matched-cohort analysis of BEAM vs Z-BEAM including 282 and 154 patients, respectively...
May 22, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28521478/enhancement-of-antitumor-immunity-by-combination-of-anti-ctla-4-antibody-and-radioimmunotherapy-through-the-suppression-of-tregs
#8
Cheol-Hun Son, Jaeho Bae, Hong-Rae Lee, Kwangmo Yang, You-Soo Park
Cytotoxic T lymphocyte antigen-4 (CTLA-4) is expressed during cluster of differentiation (CD)4+ T-cell activation and terminates immune responses by interrupting CD28-enhanced activation. In addition, CTLA-4 is known to be constitutively expressed in regulatory T-cells (Tregs) and to contribute to immune suppression by enhancing the suppressive function of Tregs. However, the molecular mechanisms underlying CTLA-4-mediated Treg suppression remains incompletely understood. Furthermore, it is uncertain whether the in vivo immune suppressive functions of CTLA-4 are mediated only by a reduction in the level of conventional T-cell activity, or enhancement of Treg function...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28514062/locoregional-therapy-with-%C3%AE-emitting-trastuzumab-against-peritoneal-metastasis-of-her2-positive-gastric-cancer-in-mice
#9
Huizi Keiko Li, Yukie Morokoshi, Kotaro Nagatsu, Tadashi Kamada, Sumitaka Hasegawa
Peritoneal metastasis of gastric cancer (PMGC) is incurable and thus has an extremely poor prognosis. We have found however that locoregionally administered trastuzumab armed with a radionuclide astatine-211 ((211) At)-emitting α-particle ((211) At-trastuzumab) is effective against HER2-positive PMGC in a xenograft mouse model. We first observed that (211) At-trastuzumab can specifically bind and effectively kill NCI-N87 (N87) cells, which are HER2-positive human metastatic GC cells, both in vitro and in subcutaneous tumors...
May 17, 2017: Cancer Science
https://www.readbyqxmd.com/read/28504666/conditioning-regimens-for-allogeneic-hematopoietic-stem-cell-transplants-in-acute-myeloid-leukemia
#10
REVIEW
Y S Jethava, S Sica, B Savani, F Socola, M Jagasia, M Mohty, A Nagler, A Bacigalupo
AML is currently the first indication for allogeneic hematopoietic stem cell transplantation (allo-HSCT), as shown by international transplant registries. The conditioning regimens are classified as myeloablative conditioning, non-myeloablative or reduced intensity conditioning. Targeted radioimmunotherapy such as anti-CD45 antibody have also been added to the conditioning regimen in an attempt to improve tumor cell kill. Refinement of standard regimens has led to a reduction of non-relapse mortality, also in the older age group over 60 or 70 years of age...
May 15, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28498337/imaging-of-early-response-to-predict-prognosis-in-the-first-line-management-of-follicular-non-hodgkin-lymphoma-with-iodine-131-rituximab-radioimmunotherapy
#11
Murali Kesavan, Jan Boucek, William MacDonald, Andrew McQuillan, J Harvey Turner
The purpose of this study was to evaluate prediction of prognosis after first-line radioimmunotherapy (RIT) of advanced follicular non-Hodgkin lymphoma (FL), by imaging with fluorine-18-fluorodeoxyglucose positron emission tomography with computed tomography ((18)F-FDG-PET/CT) three months after induction treatment by Iodine-131-rituximab ((131)I-rituximab). Objective response was determined using the Deauville 5-point scale in 68 prospective clinical trial patients. Baseline (18)F-FDG-PET/CT studies were used to calculate total-metabolic-tumor-volume (TMTV)...
May 12, 2017: Diagnostics
https://www.readbyqxmd.com/read/28491264/priming-radioimmunotherapy-with-external-beam-radiation-in-patients-with-relapsed-low-grade-non-hodgkin-lymphoma
#12
Yazan Abuodeh, Kamran Ahmed, Michelle Echevarria, Arash Naghavi, G Daniel Grass, Timothy J Robinson, Michael Tomblyn, Bijal Shah, Julio Chavez, Celeste Bello, Ghassan El-Haddad, Louis Harrison, Sungjune Kim
BACKGROUND: The aim of this study was to evaluate the outcomes of priming salvage radioimmunotherapy (RIT) with a low dose of external beam radiotherapy (EBRT) in patients with relapsed low grade non-Hodgkin lymphoma (LG-NHL). METHODS: Patients who received salvage RIT with or without 2 × 2 Gy EBRT between March 2009 and February 2013 were retrospectively reviewed at a single institution. Planning target volume (PTV) for EBRT was created by adding a 1-2 cm expansion to the gross tumor volume depending on the anatomical location...
April 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28466487/risk-of-histological-transformation-and-therapy-related-myelodysplasia-acute-myeloid-leukaemia-in-patients-receiving-radioimmunotherapy-for-follicular-lymphoma
#13
Narendranath Epperla, Anthony Q Pham, Brian L Burnette, Gregory A Wiseman, Thomas M Habermann, William R Macon, Stephen M Ansell, David J Inwards, Ivana N Micallef, Patrick B Johnston, Svetomir N Markovic, Luis F Porrata, Joseph P Colgan, Kay M Ristow, Grzegorz S Nowakowski, Thomas E Witzig
Histological transformation (HT) of follicular lymphoma (FL) to an aggressive lymphoma after chemotherapy remains a key issue. The incidence of HT after radioimmunotherapy (RIT) is unknown. This single institution study analysed the risk of HT in FL after treatment with yttrium-90 ibritumomab tiuxetan in 115 consecutive patients treated during 1987-2012. RIT was administered for progressive FL in 111 (97%) patients and as first-line therapy in the remaining 4. 28% (n = 32) had HT, occurring at a median of 60 months from diagnosis and 20 months after RIT...
May 3, 2017: British Journal of Haematology
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
#14
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
#15
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...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28428282/whither-radioimmunotherapy-to-be-or-not-to-be
#16
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...
May 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28423546/tetraspanin-8-tspan-8-as-a-potential-target-for-radio-immunotherapy-of-colorectal-cancer
#17
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
#18
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
#19
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-225-ac-decay-chain-feasibility-studies
#20
A K H Robertson, C F Ramogida, C Rodríguez-Rodríguez, Stephan Blinder, Peter Kunz, Vesna Sossi, Paul Schaffer
Effective use of the [Formula: see text] decay chain in targeted internal radioimmunotherapy requires the retention of both [Formula: see text] 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 [Formula: see text] decay chain: [Formula: see text] (218 keV) and [Formula: see text] (440 keV)...
March 31, 2017: Physics in Medicine and Biology
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