Administered activity and metastatic cure probability during radioimmunotherapy of ovarian cancer in nude mice with 211At-MX35 F(ab')2.
Journal article, 2006

PURPOSE: To elucidate the therapeutic efficacy of alpha-radioimmunotherapy of ovarian cancer in mice. This study: (i) estimated the minimum required activity (MRA), giving a reasonable high therapeutic efficacy; and (ii) calculated the specific energy to tumor cell nuclei and the metastatic cure probability (MCP) using various assumptions regarding monoclonal-antibody (mAb) distribution in measured tumors. The study was performed using the alpha-particle emitter Astatine-211 (211At) labeled to the mAb MX35 F(ab')2. METHODS AND MATERIALS: Animals were inoculated intraperitoneally with approximately 1 x 10(7) cells of the cell line NIH:OVCAR-3. Four weeks later animals were treated with 25, 50, 100, or 200 kBq 211At-MX35 F(ab')2 (n = 74). Another group of animals was treated with a nonspecific mAb: 100 kBq 211At-Rituximab F(ab')2 (n = 18). Eight weeks after treatment the animals were sacrificed and presence of macro- and microscopic tumors and ascites was determined. An MCP model was developed and compared with the experimentally determined tumor-free fraction (TFF). RESULTS: When treatment was given 4 weeks after cell inoculation, the TFFs were 25%, 22%, 50%, and 61% after treatment with 25, 50, 100, or 200 kBq (211)At-MX35 F(ab')2, respectively, the specific energy to irradiated cell nuclei varying between approximately 2 and approximately 400 Gy. CONCLUSION: As a significant increase in the therapeutic efficacy was observed between the activity levels of 50 and 100 kBq (TFF increase from 22% to 50%), the conclusion was that the MRA is approximately 100 kBq (211)At-MX35 F(ab')2. MCP was most consistent with the TFF when assuming a diffusion depth of 30 mum of the mAbs in the tumors.

Statistical

Female

Antibodies

Data Interpretation

Treatment Outcome

Dose Fractionation

therapeutic use

secondary

Mice

Astatine

radiotherapy

Mice

Nude

therapeutic use

therapeutic use

Radiation Dosage

Ovarian Neoplasms

Inbred BALB C

Mice

methods

pathology

Radiopharmaceuticals

Monoclonal

Animals

Radioimmunotherapy

Author

Jörgen Elgqvist

University of Gothenburg

Håkan Andersson

University of Gothenburg

Peter Bernhardt

University of Gothenburg

Tom Bäck

University of Gothenburg

Ingela Claesson

University of Gothenburg

Ragnar Hultborn

University of Gothenburg

Holger Jensen

Bengt R Johansson

University of Gothenburg

Sture Lindegren

University of Gothenburg

Marita Olsson

Chalmers, Mathematical Sciences, Mathematical Statistics

University of Gothenburg

Stig Palm

University of Gothenburg

Elisabet Warnhammar Finnborg

University of Gothenburg

Lars Jacobsson

University of Gothenburg

International journal of radiation oncology, biology, physics

1879-355X (ISSN)

Vol. 66 4 1228-37

Subject Categories

Cell and Molecular Biology

DOI

10.1016/j.ijrobp.2006.07.003

PubMed

17145538

More information

Created

10/6/2017