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

Int J Radiat Oncol Biol Phys. 1997 Jul 1;38(4):813-23. doi: 10.1016/s0360-3016(97)00007-2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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