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Sequential radioimmunotherapy with 177Lu- and 211At-labeled monoclonal antibody BR96 in a syngeneic rat colon carcinoma model

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DOI

  1. Shelf-life of ɛ-lysyl-3-(trimethylstannyl)benzamide immunoconjugates, precursors for 211At labeling of antibodies

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  2. Comparison of (211)At-PRIT and (211)At-RIT of Ovarian Microtumors in a Nude Mouse Model

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  3. Evaluation of effects on the peritoneum after intraperitoneal α-radioimmunotherapy with (211)At

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  4. Intraperitoneal alpha-radioimmunotherapy in mice using different specific activities

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  5. Various functions of PBMC from colon cancer patients are not decreased compared to healthy blood donors.

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  1. Extraction of 211At from nitric acid solutions into various organic solvents for use as an α-source for radiation chemistry studies

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  2. Synthesis and Evaluation of Astatinated N-[2-(Maleimido)ethyl]-3-(trimethylstannyl)benzamide Immunoconjugates

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  3. Absorbed Doses and Risk Estimates of (211)At-MX35 F(ab')2 in Intraperitoneal Therapy of Ovarian Cancer Patients

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  4. N-[2-(maleimido)ethyl]-3-(trimethylstannyl)benzamide, a molecule for radiohalogenation of proteins and peptides

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  • Sophie E Eriksson
  • Erika Elgström
  • Tom Bäck
  • Tomas Ohlsson
  • Holger Jensen
  • Rune Nilsson
  • Sture Lindegren
  • Jan Tennvall
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UNLABELLED: Alpha-particle emitters, such as astatine-211 (211At), are generally considered suitable for the treatment of small cell clusters due to their short path length, while beta-particle emitters, for example, Lutetium-177 (177Lu), have a longer path length and are considered better for small, established tumors. A combination of such radionuclides may be successful in regimens of radioimmunotherapy. In this study, rats were treated by sequential administration of first a 177Lu-labeled antibody, followed by a 211At-labeled antibody 25 days later.

METHODS: Rats bearing solid colon carcinoma tumors were treated with 400 MBq/kg body weight 177Lu-BR96. After 25 days, three groups of animals were given either 5 or 10 MBq/kg body weight of 211At-BR96 simultaneously with or without a blocking agent reducing halogen uptake in normal tissues. Control animals were not given any 211At-BR96. Myelotoxicity, body weight, tumor size, and development of metastases were monitored for 120 days.

RESULTS: Tumors were undetectable in 90% of the animals on day 25, independent of treatment. Additional treatment with 211At-labeled antibodies did not reduce the proportion of animals developing metastases. The rats suffered from reversible myelotoxicity after treatment.

CONCLUSIONS: Sequential administration of 177Lu-BR96 and 211At-BR96 resulted in tolerable toxicity providing halogen blocking but did not enhance the therapeutic effect.

Original languageEnglish
JournalCancer Biotherapy & Radiopharmaceuticals
Volume29
Issue number6
Pages (from-to)238-46
Number of pages9
ISSN1084-9785
DOIs
Publication statusPublished - Aug 2014

ID: 45005718