ArticlePloS one2013
Therapeutic efficacy of c-kit-targeted radioimmunotherapy using 90Y-labeled anti-c-kit antibodies in a mouse model of small cell lung cancer.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21 citing papers in PubMed, 31 citations in OpenAlex.
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- Quantitative Radionuclide Imaging Analysis of Enhanced Drug Delivery Induced by Photoimmunotherapy.International journal of molecular sciences · 2021Article
- Radiolabeled Human Monoclonal Antibody 067-213 has the Potential for Noninvasive Quantification of CD73 Expression.International journal of molecular sciences · 2020Article
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- Preclinical Evaluation of the Acute Radiotoxicity of the α-Emitting Molecular-Targeted Therapeutic AgentTranslational oncology · 2019Article
- Therapeutic efficacy evaluation of radioimmunotherapy withCancer science · 2019Article
- Prognostic significance of CD117 expression andOncology letters · 2018Article
- A Novel Theranostic Combination of Near-infrared Fluorescence Imaging and Laser Irradiation Targeting c-KIT for Gastrointestinal Stromal Tumors.Theranostics · 2018Article
- Molecular imaging using an anti-human tissue factor monoclonal antibody in an orthotopic glioma xenograft model.Scientific reports · 2017Article
- Radioimmunotherapy of pancreatic cancer xenografts in nude mice using 90Y-labeled anti-α6β4 integrin antibody.Oncotarget · 2016Article
- Expression profiling of receptor tyrosine kinases in high-grade neuroendocrine carcinoma of the lung: a comparative analysis with adenocarcinoma and squamous cell carcinoma.Journal of cancer research and clinical oncology · 2015Article
- Neutralization of KIT Oncogenic Signaling in Leukemia with Antibodies Targeting KIT Membrane Proximal Domain 5.Molecular cancer therapeutics · 2015Article
- Enhanced EJ Cell Killing of (125)I Radiation by Combining with Cytosine Deaminase Gene Therapy Regulated by Synthetic Radio-Responsive Promoter.Cancer biotherapy & radiopharmaceuticals · 2015Article
- Article
- 90Y-Labeled Anti-ROBO1 Monoclonal Antibody Exhibits Antitumor Activity against Small Cell Lung Cancer Xenografts.PloS one · 2015Article
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Authors and funding
8 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
unlabelledSmall cell lung cancer (SCLC) is an aggressive tumor and prognosis remains poor. Therefore, the development of more effective therapy is needed. We previously reported that high levels of an anti-c-kit antibody (12A8) accumulated in SCLC xenografts. In the present study, we evaluated the efficacy of two antibodies (12A8 and 67A2) for radioimmunotherapy (RIT) of an SCLC mouse model by labeling with the (90)Y isotope.
methods(111)In- or (125)I-labeled antibodies were evaluated in vitro by cell binding, competitive inhibition and cellular internalization assays in c-kit-expressing SY cells and in vivo by biodistribution in SY-bearing mice. Therapeutic efficacy of (90)Y-labeled antibodies was evaluated in SY-bearing mice upto day 28 and histological analysis was conducted at day 7.
results[(111)In]12A8 and [(111)In]67A2 specifically bound to SY cells with high affinity (8.0 and 1.9 nM, respectively). 67A2 was internalized similar to 12A8. High levels of [(111)In]12A8 and [(111)In]67A2 accumulated in tumors, but not in major organs. [(111)In]67A2 uptake by the tumor was 1.7 times higher than for [(111)In]12A8. [(90)Y]12A8, but not [(90)Y]67A2, suppressed tumor growth in a dose-dependent manner. Tumors treated with 3.7 MBq of [(90)Y]12A8, and 1.85 and 3.7 MBq of [(90)Y]67A2 (absorbed doses were 21.0, 18.0 and 35.9 Gy, respectively) almost completely disappeared approximately 2 weeks after injection, and regrowth was not observed except for in one mouse treated with 1.85 MBq [(90)Y]67A2. The area of necrosis and fibrosis increased depending on the RIT effect. Apoptotic cell numbers increased with increased doses of [(90)Y]12A8, whereas no dose-dependent increase was observed following [(90)Y]67A2 treatment. Body weight was temporarily reduced but all mice tolerated the RIT experiments well.
conclusionTreatment with [(90)Y]12A8 and [(90)Y]67A2 achieved a complete therapeutic response when SY tumors received an absorbed dose greater than 18 Gy and thus are promising RIT agents for metastatic SCLC cells at distant sites.
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