ArticleEuropean journal of nuclear medicine and molecular imaging2010
In vitro experimental (211)At-anti-CD33 antibody therapy of leukaemia cells overcomes cellular resistance seen in vivo against gemtuzumab ozogamicin.
Article in European journal of nuclear medicine and molecular imaging, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 27 citations in OpenAlex.
- Recent advances in the development ofAnalytical sciences : the international journal of the Japan Society for Analytical Chemistry · 2024Review
- ImmunoPET: Concept, Design, and Applications.Chemical reviews · 2020Review
- Targeted and Nontargeted α-Particle Therapies.Annual review of biomedical engineering · 2018Review
- Automated astatination of biomolecules--a stepping stone towards multicenter clinical trials.Scientific reports · 2015Article
- Successful radioimmunotherapy of established syngeneic rat colon carcinoma with 211At-mAb.EJNMMI research · 2013Article
- Targeted alpha-therapy using [Bi-213]anti-CD20 as novel treatment option for radio- and chemoresistant non-Hodgkin lymphoma cells.Oncotarget · 2013Article
- Molecular pathways: targeted α-particle radiation therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013Review
- Production of [(211)At]-astatinated radiopharmaceuticals and applications in targeted α-particle therapy.Cancer biotherapy & radiopharmaceuticals · 2013Review
- What happened to anti-CD33 therapy for acute myeloid leukemia?Current hematologic malignancy reports · 2012Review
- Applications of 211At and 223Ra in targeted alpha-particle radiotherapy.Current radiopharmaceuticals · 2011Review
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeMonoclonal anti-CD33 antibodies conjugated with toxic calicheamicin derivative (gemtuzumab ozogamicin, GO) are a novel therapy option for acute myeloid leukaemia (AML). Key prognostic factors for patients with AML are high CD33 expression on the leukaemic cells and the ability to overcome mechanisms of resistance to cytotoxic chemotherapies, including drug efflux or other mechanisms decreasing apoptosis. Alpha particle-emitting radionuclides overwhelm such anti-apoptotic mechanisms by producing numerous DNA double-stranded breaks (DSBs) accompanied by decreased DNA repair.
methodsWe labelled anti-CD33 antibodies with the alpha-emitter (211)At and compared survival of leukaemic HL-60 and K-562 cells treated with the (211)At-labelled antibodies, GO or unlabelled antibodies as controls. We also measured caspase-3/7 activity, DNA fragmentation and necrosis in HL-60 cells after treatment with the different antibodies or with free (211)At.
resultsThe mean labelling ratio of (211)At-labelled antibodies was 1:1,090 +/- 364 (range: 1:738-1:1,722) in comparison to 2-3:1 for GO. Tumour cell binding of (211)At-anti-CD33 was high in the presence of abundant CD33 expression and could be specifically blocked by unlabelled anti-CD33. (211)At-anti-CD33 decreased survival significantly more than did GO at comparable dilution (1:1,000). No significant differences in induction of apoptosis or necrosis or DNA DSB or in decreased survival were observed after (211)At-anti-CD33 (1:1,090) versus GO (1:1) treatment.
conclusionOur results suggest that (211)At is a promising, highly cytotoxic radioimmunotherapy in CD33-positive leukaemia and kills tumour cells more efficiently than does calicheamicin-conjugated antibody. Labelling techniques leading to higher chemical yield and specific activities must be developed to increase (211)At-anti-CD33 therapeutic effects.
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