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trastuzumab lutetium

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https://www.readbyqxmd.com/read/25937783/activity-estimation-in-radioimmunotherapy-using-magnetic-nanoparticles
#1
Samira Rasaneh, Hossein Rajabi, Fariba Johari Daha
OBJECTIVE: Estimation of activity accumulated in tumor and organs is very important in predicting the response of radiopharmaceuticals treatment. In this study, we synthesized (177)Lutetium ((177)Lu)-trastuzumab-iron oxide nanoparticles as a double radiopharmaceutical agent for treatment and better estimation of organ activity in a new way by magnetic resonance imaging (MRI). METHODS: (177)Lu-trastuzumab-iron oxide nanoparticles were synthesized and all the quality control tests such as labeling yield, nanoparticle size determination, stability in buffer and blood serum up to 4 d, immunoreactivity and biodistribution in normal mice were determined...
April 2015: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
https://www.readbyqxmd.com/read/25192223/what-a-difference-a-carbon-makes-h%C3%A2-octapa-vs-h%C3%A2-c3octapa-ligands-for-in-111-and-lu-177-radiochemistry
#2
Eric W Price, Brian M Zeglis, Jacqueline F Cawthray, Jason S Lewis, Michael J Adam, Chris Orvig
The acyclic ligands H4C3octapa and p-SCN-Bn-H4C3octapa were synthesized for the first time, using nosyl protection chemistry. These new ligands were compared to the previously studied ligands H4octapa and p-SCN-Bn-H4octapa to determine the extent to which the addition of a single carbon atom to the backbone of the ligand would affect metal coordination, complex stability, and, ultimately, utility for in vivo radiopharmaceutical applications. Although only a single carbon atom was added to H4C3octapa and the metal donor atoms and denticity were not changed, the solution chemistry and radiochemistry properties were drastically altered, highlighting the importance of careful ligand design and radiometal-ligand matching...
October 6, 2014: Inorganic Chemistry
https://www.readbyqxmd.com/read/24883121/targeted-radionuclide-therapy-with-a-177lu-labeled-anti-her2-nanobody
#3
Matthias D'Huyvetter, Cécile Vincke, Catarina Xavier, An Aerts, Nathalie Impens, Sarah Baatout, Hendrik De Raeve, Serge Muyldermans, Vicky Caveliers, Nick Devoogdt, Tony Lahoutte
RIT has become an attractive strategy in cancer treatment, but still faces important drawbacks due to poor tumor penetration and undesirable pharmacokinetics of the targeting vehicles. Smaller radiolabeled antibody fragments and peptides feature highly specific target accumulation, resulting in low accumulation in healthy tissue, except for the kidneys. Nanobodies are the smallest (MW<15 kDa) functional antigen-binding fragments that are derived from heavy chain-only camelid antibodies. Here, we show that the extend of kidney retention of nanobodies is predominantly dictated by the number of polar residues in the C-terminal amino acid tag...
2014: Theranostics
https://www.readbyqxmd.com/read/24104523/h6phospa-trastuzumab-bifunctional-methylenephosphonate-based-chelator-with-89zr-111in-and-177lu
#4
Eric W Price, Brian M Zeglis, Jason S Lewis, Michael J Adam, Chris Orvig
The acyclic chelator H6phospa and the bifunctional derivative p-SCN-Bn-H6phospa have been synthesized using nosyl protection chemistry and evaluated with (89)Zr, (111)In, and (177)Lu. The p-SCN-Bn-H6phospa derivative was successfully conjugated to trastuzumab with isotopic dilution assays indicating 3.3 ± 0.1 chelates per antibody and in vitro cellular binding assays indicating an immunoreactivity value of 97.9 ± 2.6%. Radiolabeling of the H6phospa-trastuzumab immunoconjugate was achieved with (111)In in 70-90% yields at room temperature in 30 minutes, while (177)Lu under the same conditions produced more inconsistent yields of 40-80%...
January 7, 2014: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/23901833/h-4-octapa-trastuzumab-versatile-acyclic-chelate-system-for-111in-and-177lu-imaging-and-therapy
#5
Eric W Price, Brian M Zeglis, Jacqueline F Cawthray, Caterina F Ramogida, Nicholas Ramos, Jason S Lewis, Michael J Adam, Chris Orvig
A bifunctional derivative of the versatile acyclic chelator H4octapa, p-SCN-Bn-H4octapa, has been synthesized for the first time. The chelator was conjugated to the HER2/neu-targeting antibody trastuzumab and labeled in high radiochemical purity and specific activity with the radioisotopes (111)In and (177)Lu. The in vivo behavior of the resulting radioimmunoconjugates was investigated in mice bearing ovarian cancer xenografts and compared to analogous radioimmunoconjugates employing the ubiquitous chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)...
August 28, 2013: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/22918766/-177-lu-90-y-intermediate-affinity-monoclonal-antibodies-targeting-egfr-and-her2-c-neu-preparation-and-preclinical-evaluation
#6
Denis R Beckford Vera, Sebastian Eigner, Katerina Eigner Henke, Rene Leyva Montaña, Frantisek Melichar, Milos Beran
The epidermal growth factor receptor (EGFR) is a rational target of anticancer therapies due to its overexpression in a variety of malignant epithelial tumors. Nevertheless, this antigen is also present in normal tissues. Consequently, monoclonal antibodies which selectively bind to EGFR-overexpressing tumors will be choice drug candidates for development of radioimmunoconjugates (RIC). Nimotuzumab (h-R3) and trastuzumab are monoclonal antibodies (mAbs) which would preferentially target tissues with EGFR and HER2 overexpression, respectively...
2013: Recent Results in Cancer Research
https://www.readbyqxmd.com/read/22881720/synthesis-and-preclinical-evaluation-of-bifunctional-ligands-for-improved-chelation-chemistry-of-90y-and-177lu-for-targeted-radioimmunotherapy
#7
Chi Soo Kang, Xiang Sun, Fang Jia, Hyun A Song, Yunwei Chen, Michael Lewis, Hyun-Soon Chong
We report a practical and high-yield synthesis of a bimodal bifunctional ligand 3p-C-NETA-NCS containing the isothiocyanate group for conjugation to a tumor targeting antibody. 3p-C-NETA-NCS was conjugated to a tumor-targeting antibody, trastuzumab, and the corresponding 3p-C-NETA-trastuzumab conjugate was evaluated and compared to trastuzumab conjugates of the known bifunctional ligands C-DOTA, C-DTPA, and 3p-C-DEPA for radiolabeling kinetics with (90)Y and (177)Lu. 3p-C-NETA-trastuzumab conjugate exhibited extremely rapid complexation kinetics with (90)Y and (177)Lu...
September 19, 2012: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/22643311/preclinical-evaluation-of-227th-labeled-and-177lu-labeled-trastuzumab-in-mice-with-her-2-positive-ovarian-cancer-xenografts
#8
COMPARATIVE STUDY
Nasir Abbas, Øyvind Sverre Bruland, Ellen Mengshoel Brevik, Jostein Dahle
OBJECTIVE: The aim of the present study was to compare the biodistribution, normal tissue toxicity, and therapeutic effect of two low-dose rate radioimmunoconjugates (RICs) in mice with HER2-expressing ovarian cancer xenografts: the α-particle-emitting (227)Th-trastuzumab and the β-particle-emitting (177)Lu-trastuzumab. MATERIALS AND METHODS: Trastuzumab (Herceptin), conjugated to DOTA and radiolabeled with (227)Th or (177)Lu, was injected intravenously into mice bearing SKOV-3 xenografts...
August 2012: Nuclear Medicine Communications
https://www.readbyqxmd.com/read/20537546/toxicity-of-trastuzumab-labeled-177lu-on-mcf7-and-skbr3-cell-lines
#9
Samira Rasaneh, Hossein Rajabi, Mohammad Hossein Babaei, Fariba Johari Daha
In this study, we labeled trastuzumab with (177)Lu to synthesize a new radiopharmaceutical for therapy of breast cancer and at the first stage investigated its therapeutic effects on SKBr3 and MCF7 breast cancer cell lines. Trastuzumab-(177)Lu showed very good in-vitro characteristics such as high radiochemical purity (91+/-0.9%), good stability in PBS buffer (86+/-2.3%) and blood serum (81+/-2.7%) up to 96 h, appropriate immunoreactivity (85.4+/-1.1%) and high cytotoxicity in HER2 expression cells. 5 fold increase in toxicity of trastuzumab-(177)Lu was observed when compared with unlabeled trastuzumab on SKBr3 cells...
October 2010: Applied Radiation and Isotopes
https://www.readbyqxmd.com/read/19423003/radiolabeling-of-trastuzumab-with-177lu-via-dota-a-new-radiopharmaceutical-for-radioimmunotherapy-of-breast-cancer
#10
Samira Rasaneh, Hossein Rajabi, Mohammad Hossein Babaei, Fariba Johari Daha, Mojtaba Salouti
AIM: Trastuzumab is a monoclonal antibody that is used in treating breast cancer. We labeled this monoclonal antibody with lutetium-177 and performed in vitro quality control tests as a first step in the production of a new radiopharmaceutical. MATERIAL AND METHODS: Trastuzumab was labeled with lutetium-177 using DOTA as chelator. Radiochemical purity and stability in buffer and human blood serum were determined using thin layer chromatography. Immunoreactivity and toxicity of the complex were tested on MCF7 breast cancer cell line...
May 2009: Nuclear Medicine and Biology
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