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Radioimmunotherapy

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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
#1
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
https://www.readbyqxmd.com/read/28906259/radiation-and-immunotherapy-in-high-grade-gliomas-where-do-we-stand
#2
Elizabeth Reznik, Andrew W Smith, Shoshana Taube, Justin Mann, Menachem Z Yondorf, Bhupesh Parashar, A Gabriella Wernicke
High-grade glioma is the most common primary brain tumor, with glioblastoma multiforme (GBM) accounting for 52% of all brain tumors. The current standard of care (SOC) of GBM involves surgery followed by adjuvant fractionated radiotherapy and chemotherapy. However, little progress has been made in extending overall survival, progression-free survival, and quality of life. Attempts to characterize and customize treatment of GBM have led to mitigating the deleterious effects of radiotherapy using hypofractionated radiotherapy, as well as various immunotherapies as a promising strategy for the incurable disease...
September 12, 2017: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28893110/radioimmunotherapy-for-delivery-of-cytotoxic-radioisotopes-current-status-and-challenges
#3
Carlos Daniel Martins, Gabriela Kramer-Marek, Wim J G Oyen
Radioimmunotherapy (RIT) with monoclonal antibodies and their fragments labelled with radionuclides emitting α-particles, β-particles or Auger electrons have been used for many years in the development of anticancer strategies. While RIT has resulted in approved radiopharmaceuticals for the treatment of hematological malignancies, its use in solid tumors still remains challenging. Areas covered: In this review, we discuss the exciting progress towards elucidating the potential of current and novel radioimmunoconjugates and address the challenges for translation into clinical practice...
September 12, 2017: Expert Opinion on Drug Delivery
https://www.readbyqxmd.com/read/28869617/a-phase-1-trial-of-90-y-zevalin-radioimmunotherapy-with-autologous-stem-cell-transplant-for-multiple-myeloma
#4
A Dispenzieri, A D'Souza, M A Gertz, K Laumann, G Wiseman, M Q Lacy, B LaPlant, F Buadi, S R Hayman, S K Kumar, D Dingli, W J Hogan, S M Ansell, D A Gastineau, D J Inwards, I N Micallef, L F Porrata, P B Johnston, M R Litzow, T E Witzig
This phase 1 study (clinical trial NCT00477815) was conducted to determine the maximum tolerated dose (MTD) of yttrium-90 ibritumomab tiuxetan ((90)Y-Zevalin) with high dose melphalan (HDM) therapy in multiple myeloma (MM) patients undergoing autologous stem cell transplantation (ASCT). In a 3+3 trial design, 30 patients received rituximab 250 mg/m(2) with indium-111 ibritumomab tiuxetan ((111)In-Zevalin) for dosimetry (day -22); rituximab 250 mg/m(2) with escalating doses of (90)Y-Zevalin (day -14); melphalan 100 mg/m(2) (days -2,-1) followed by ASCT (day 0) and sargramostim (GM-CSF, day 0) until neutrophil engraftment...
September 4, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28821931/targeting-angiogenesis-for-radioimmunotherapy-with-a-177-lu-labeled-antibody
#5
Emily B Ehlerding, Saige Lacognata, Dawei Jiang, Carolina A Ferreira, Shreya Goel, Reinier Hernandez, Justin J Jeffery, Charles P Theuer, Weibo Cai
PURPOSE: Increased angiogenesis is a marker of aggressiveness in many cancers. Targeted radionuclide therapy of these cancers with angiogenesis-targeting agents may curtail this increased blood vessel formation and slow the growth of tumors, both primary and metastatic. CD105, or endoglin, has a primary role in angiogenesis in a number of cancers, making this a widely applicable target for targeted radioimmunotherapy. METHODS: The anti-CD105 antibody, TRC105 (TRACON Pharmaceuticals), was conjugated with DTPA for radiolabeling with (177)Lu (t 1/2 6...
August 18, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28816801/bevacizumab-associated-bowel-microperforation-in-a-patient-with-neuroblastoma
#6
Rachel Glincher, Anita P Price, Michael P LaQuaglia, Brian H Kushner, Shakeel Modak
The antivascular endothelial growth factor antibody, bevacizumab, is effective against several malignancies in adults but unproven in pediatric oncology. In early phase pediatric studies toxicities were similar to those in adults. Bowel perforation in adults is a rare but serious toxicity, but has not been hitherto reported in children. A 5-year-old boy with chemoresistant neuroblastoma treated with bevacizumab plus radioimmunotherapy developed acute abdominal pain. Computed tomography scan showed free abdominal air and pneumatosis coli...
August 14, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28777832/endless-research-ii-the-genomic-era-neohippocratic-medicine
#7
EDITORIAL
Philip C Grammaticos, Dimitrios E Antoniou
The great progress of genetics research, during 2015-2017, will certainly influence all medical specialties including nuclear medicine. In nuclear medicine there are still problems to solve as to differentiate between infection, inflammation and cancer etc. Furthermore, in dosimetry and radiation protection there are worldwide problems. It has been reported that (64) Cu-cetuximab immune-PET represented EGFR expression levels in ESCC tumors and that (177) Lu-cetuximab radioimmunotherapy effectively inhibited the tumor growth...
May 2017: Hellenic Journal of Nuclear Medicine
https://www.readbyqxmd.com/read/28767228/-89-zr-immuno-positron-emission-tomography-in-oncology-state-of-the-art-89-zr-radiochemistry
#8
Sandra Heskamp, René Raavé, Otto Boerman, Mark Rijpkema, Victor Goncalves, Franck Denat
Immuno-positron emission tomography (immunoPET) with (89)Zr-labeled antibodies has shown great potential in cancer imaging. It can provide important information about the pharmacokinetics and tumor-targeting properties of monoclonal antibodies and may help in anticipating on toxicity. Furthermore, it allows accurate dose planning for individualized radioimmunotherapy and may aid in patient selection and early-response monitoring for targeted therapies. The most commonly used chelator for (89)Zr is desferrioxamine (DFO)...
August 24, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28745238/effect-of-number-of-bifunctional-chelating-agents-on-the-pharmacokinetics-and-immunoreactivity-of-177lu-labeled-rituximab-a-systemic-study
#9
Mohini Guleria, Tapas Das, Chandan Kumar, Rohit Sharma, Jeyachitra Amirdhanayagam, Haladhar D Sarma, Ashutosh Dash
OBJECTIVE: Monoclonal antibodies (mAbs) have been radiolabeled with a variety of radioisotopes utilizing various kinds of bi-functional chelating agents (BFCAs) with an aim to develop suitable agents for radioimmunotherapy. The number of BFCA moieties present per antibody molecule plays a significant role in determining the pharmacokinetics and immunoreactivity exhibited by the radiolabeled antibodies. The objective of the present study is to evaluate the effect of number of BFCA moieties present per antibody molecule on the pharmacokinetics and immunoreactivity of the 177Lu-labeled Rituximab...
July 25, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28741052/applying-near-infrared-photoimmunotherapy-to-b-cell-lymphoma-comparative-evaluation-with-radioimmunotherapy-in-tumor-xenografts
#10
Yusri-Dwi Heryanto, Hirofumi Hanaoka, Takahito Nakajima, Aiko Yamaguchi, Yoshito Tsushima
OBJECTIVE: Radioimmunotherapy (RIT) has proven effective for patients with relapsed and refractory lymphoma. However, new types of therapy are strongly desired as B-cell lymphoma remains incurable for many patients. Photoimmunotherapy (PIT) is an emerging targeted cancer therapy that uses photosensitizer (IR700)-conjugated monoclonal antibodies (mAbs) to specifically kill cancer cells. To evaluate the usefulness and potential role of PIT for treating B-cell lymphoma in a comparison with RIT, we performed in vivo PIT and RIT studies with an IR700 or (90)Y-conjugated anti-CD20 mAb, NuB2...
July 24, 2017: Annals of Nuclear Medicine
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
#11
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
#12
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
#13
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
#14
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
#15
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...
August 2017: Translational Oncology
https://www.readbyqxmd.com/read/28566329/venetoclax-synergizes-with-radiotherapy-for-treatment-of-b-cell-lymphomas
#16
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...
July 15, 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
#17
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...
August 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
#18
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-human-epidermal-growth-factor-receptor-2-positive-gastric-cancer-in-mice
#19
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 astatine-211 ((211) At-trastuzumab) is effective against human epidermal growth factor receptor 2 (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 s.c...
August 2017: Cancer Science
https://www.readbyqxmd.com/read/28504666/conditioning-regimens-for-allogeneic-hematopoietic-stem-cell-transplants-in-acute-myeloid-leukemia
#20
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
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