Comparison of therapeutic efficacy and biodistribution of 213Bi- and 211At-labeled monoclonal antibody MX35 in an ovarian cancer model.

Abstract

INTRODUCTION:

The purpose of this study was to compare the therapeutic efficacy and biodistribution of the monoclonal antibody MX35 labeled with either (213)Bi or (211)At, both α-emitters, in an ovarian cancer model.

METHODS:

One hundred female nude BALB/c (nu/nu) mice were inoculated intraperitoneally with human ovarian cancer cells (OVCAR-3). Two weeks later, 40 of these mice were injected intraperitoneally with ~2.7 MBq of (213)Bi-MX35 (n=20) or ~0.44 MBq of (211)At-MX35 (n=20). Four weeks after inoculation, 40 new OVCAR-3-inoculated mice were injected with the same activities of (213)Bi-MX35 (n=20) or (211)At-MX35 (n=20). Presence of tumors and ascites was investigated 8 weeks after therapy. Biodistributions of intraperitoneally injected (213)Bi-MX35 and (211)At-MX35 were studied in tumor-free nude BALB/c (nu/nu) mice (n=16).

RESULTS:

The animals injected with (213)Bi-MX35 or (211)At-MX35 2 weeks after cell inoculation had tumor-free fractions (TFFs) of 0.60 and 0.90, respectively. The untreated reference group had a TFF of 0.20. The groups treated with (213)Bi-MX35 or (211)At-MX35 4 weeks after inoculation both had TFFs of 0.25, and the reference animals all exhibited evidence of disease. The biodistributions of (213)Bi-MX35 and (211)At-MX35 were very similar to each other and displayed no alarming activity levels in the investigated organs.

CONCLUSIONS:

Micrometastatic growth of an ovarian cancer cell line was reduced in nude mice after treatment with (213)Bi-MX35or (211)At-MX35. Treatment with (211)At-MX35 provided a non-significantly better result for the chosen activity levels. The radiolabeled MX35 did not accumulate to a high extent in the investigated organs. No considerable signs of toxicity were observed.

• Authors: Anna M E Gustafsson, Tom Bäck, Jörgen Elgqvist, Lars Jacobsson, Ragnar Hultborn, Per Albertsson, Alfred Morgenstern, Frank Bruchertseifer, Holger Jensen, Sture Lindegren
• Journal: Nuclear medicine and biology (Nucl Med Biol) Vol. 39 Issue 1 Pg. 15-22 (Jan 2012) ISSN: 1872-9614 [Electronic] United States
• PMID: 21958859 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• 211At-labeled monoclonal antibody MX35
• 213Bi-cDTPA-9.2.27 monoclonal antibody
• Antibodies, Monoclonal
• Organometallic Compounds
• Radioisotopes

Topics

• Alpha Particles (therapeutic use)
• Animals
• Antibodies, Monoclonal (pharmacokinetics, therapeutic use)
• Female
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasms, Experimental
• Organometallic Compounds (pharmacokinetics, therapeutic use)
• Ovarian Neoplasms (metabolism, radiotherapy)
• Radioisotopes (pharmacokinetics, therapeutic use)
• Tissue Distribution
• Treatment Outcome