Comparison of the biodistribution and the efficacy of monoclonal antibody 323/A3 labeled with either 131I or 186Re in human ovarian cancer xenografts.

Abstract

PURPOSE:

The radionuclide 186Re has favorable physical characteristics for use in radioimmunotherapy, including the emission of beta-particles of a high-energy and a low-abundance of gamma-emission. The gamma-emission, in particular, is ideal for tumor imaging and poses less hazards to the patient and the medical personnel when compared with the gamma-emission of the widely used radionuclide 131I. In the present study, we determined whether 186Re-labeled monoclonal antibody 323/A3 may be better suited for the treatment of ovarian cancer than 131I-323/A3.

METHODS AND MATERIALS:

We compared the biodistribution and the efficacy of 186Re- and 131I-labeled 323/A3 in nude mice bearing s.c. the human ovarian cancer xenografts FMa, OVCAR-3 and Ov.Pe. 186Re was conjugated to 323/A3 with the use of the S-benzoylmercaptoacetyltriglycine (S-benzoyl-MAG3) chelate.

RESULTS:

A molar ratio of Re-MAG3:323/A3 of 3:1 did not affect the integrity and the pharmacokinetic behaviour of the MAb. The tumor uptake and the retention of 186Re- and 131I-labeled 323/A3 were comparable, but the cumulative absorbed radiation dose in the tumor delivered by 186Re-323/A3 was 1.3-fold higher than that of 131I-323/A3. When mice were treated with equivalent radionuclide doses, the tumor growth inhibition induced by 186Re-323/A3 was similar or slightly better when compared with the efficacy of 131I-323/A3. When mice were treated with radionuclide doses that were adjusted to obtain equal cumulative absorbed radiation doses in the tumor for both conjugates, 131I-323/A3 was slightly more effective in the inhibition of the growth of FMa and OVCAR-3 xenografts.

CONCLUSIONS:

The favorable physical characteristics of 186Re as well as its efficacy when conjugated to a MAb indicate 186Re as an attractive radionuclide in radioimmunotherapy of ovarian cancer patients.

• Authors: E Kievit, F B van Gog, H M Schlüper, G A van Dongen, H M Pinedo, E Boven
• Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 38 Issue 4 Pg. 813-23 (Jul 01 1997) ISSN: 0360-3016 [Print] United States
• PMID: 9240651 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Iodine Radioisotopes
• Organotechnetium Compounds
• Radioisotopes
• Radiopharmaceuticals
• technetium-99m-MAG3-dsFV
• Rhenium

Topics

• Animals
• Antibodies, Monoclonal (pharmacokinetics, therapeutic use)
• Female
• Humans
• Iodine Radioisotopes (pharmacokinetics, therapeutic use)
• Mice
• Mice, Nude
• Organotechnetium Compounds (pharmacokinetics, therapeutic use)
• Ovarian Neoplasms (metabolism, radiotherapy)
• Radioimmunotherapy (methods)
• Radioisotopes (pharmacokinetics, therapeutic use)
• Radiopharmaceuticals (pharmacokinetics, therapeutic use)
• Radiotherapy Dosage
• Rhenium (pharmacokinetics, therapeutic use)
• Tissue Distribution
• Transplantation, Heterologous
• Tumor Cells, Cultured