Intraperitoneal alpha-radioimmunotherapy in mice using different specific activities.

Abstract

PURPOSE:

The aim of this study was to investigate the therapeutic efficacy of the alpha-radioimmunotherapy of ovarian cancer in mice, using different specific activities. This study was performed by using the monoclonal antibody, MX35 F(ab')(2), labeled with the alpha-particle-emitter, 211At.

METHODS:

Animals were intraperitoneally inoculated with approximately 1 x 10(7) cells of the cell line, NIH:OVCAR-3. Four (4) weeks later, five groups of animals were given 400 kBq of 211At-MX35 F(ab')(2) with specific activities equal to 130, 65, 32, 16, or 4 kBq/microg, respectively (n = 18 in each group). As controls, animals were given unlabeled MX35 F(ab')(2) (n = 12). Eight (8) weeks after treatment, the animals were sacrificed and the presence of macro- and microscopic tumors and ascites was determined.

RESULTS:

The tumor-free fractions (TFFs) of the animals, defined as the fraction of animals with no macro- and microtumors and no ascites, were 0.67, 0.73, 0.50, 0.50, and 0.17 when treated as above. Only the TFF of 0.17, for the specific activity of 4 kBq/microg, was significantly less, compared to that of the specific activity of 130 kBq/microg. The TFF for the specific activity of 4 kBq/microg showed a significant lowering, compared to the specific activity of 130 kBq/microg (p < 0.05). Treatment with unlabeled MX35 F(ab')(2) resulted in a TFF of zero.

CONCLUSIONS:

A specific activity-dependent therapeutic outcome could not be shown in the interval of 130- to 16 kBq/mug. For lower specific activities (i.e., 4 kBq/microg), the therapeutic efficacy was significantly lowered.

• Authors: Jörgen Elgqvist, Håkan Andersson, Elin Haglund, Holger Jensen, Helena Kahu, Sture Lindegren, Elisabet Warnhammar, Ragnar Hultborn
• Journal: Cancer biotherapy & radiopharmaceuticals (Cancer Biother Radiopharm) Vol. 24 Issue 4 Pg. 509-13 (Aug 2009) ISSN: 1557-8852 [Electronic] United States
• PMID: 19694586 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal

Topics

• Alpha Particles
• Animals
• Antibodies, Monoclonal (administration & dosage, chemistry)
• Cell Line, Tumor
• Disease Models, Animal
• Female
• Infusions, Parenteral
• Mice
• Ovarian Neoplasms (immunology, radiotherapy)
• Radioimmunotherapy (methods)