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

Abstract

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.

• Authors: Jörgen Elgqvist, Håkan Andersson, Peter Bernhardt, Tom Bäck, Ingela Claesson, Ragnar Hultborn, Holger Jensen, Bengt R Johansson, Sture Lindegren, Marita Olsson, Stig Palm, Elisabet Warnhammar, Lars Jacobsson
• Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 66 Issue 4 Pg. 1228-37 (Nov 15 2006) ISSN: 1879-355X [Electronic] United States
• PMID: 17145538 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Radiopharmaceuticals
• Astatine

Topics

• Animals
• Antibodies, Monoclonal (therapeutic use)
• Astatine (therapeutic use)
• Data Interpretation, Statistical
• Dose Fractionation, Radiation
• Female
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Ovarian Neoplasms (pathology, radiotherapy, secondary)
• Radiation Dosage
• Radioimmunotherapy (methods)
• Radiopharmaceuticals (therapeutic use)
• Treatment Outcome