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

Els Kievit, Frank B. Van Gog, Hennie M M Schlüper, Guus A M S Van Dongen, Herbert M. Pinedo, Epie Boven

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: The radionuclide 186Re has favorable physical characteristics for use in radioimmunotherapy, including the emission of β- particles of a high-energy and a low-abundance of γ-emission. The γ- emission, in particular, is ideal for tumor imaging and poses less hazards to the patient and the medical personnel when compared with the γ-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.

Original languageEnglish (US)
Pages (from-to)813-823
Number of pages11
JournalInternational Journal of Radiation Oncology, Biology, Physics
Volume38
Issue number4
DOIs
StatePublished - Jul 1 1997
Externally publishedYes

Keywords

  • I
  • Re
  • MAb 323/A3
  • Ovarian cancer xenografts
  • Radioimmunotherapy

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

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