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 journalArticle

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

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antibodies
Heterografts
Radioisotopes
Ovarian Neoplasms
radioactive isotopes
tumors
cancer
Monoclonal Antibodies
Radioimmunotherapy
mice
dosage
Neoplasms
medical personnel
Radiation
radiation
Growth
chelates
Nude Mice
integrity
hazards

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

Cite this

Comparison of the biodistribution and the efficacy of monoclonal antibody 323/A3 labeled with either 131I or 186Re in human ovarian cancer xenografts. / Kievit, Els; Van Gog, Frank B.; Schlüper, Hennie M M; Van Dongen, Guus A M S; Pinedo, Herbert M.; Boven, Epie.

In: International Journal of Radiation Oncology, Biology, Physics, Vol. 38, No. 4, 01.07.1997, p. 813-823.

Research output: Contribution to journalArticle

Kievit, Els ; Van Gog, Frank B. ; Schlüper, Hennie M M ; Van Dongen, Guus A M S ; Pinedo, Herbert M. ; Boven, Epie. / Comparison of the biodistribution and the efficacy of monoclonal antibody 323/A3 labeled with either 131I or 186Re in human ovarian cancer xenografts. In: International Journal of Radiation Oncology, Biology, Physics. 1997 ; Vol. 38, No. 4. pp. 813-823.
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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.",
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T1 - Comparison of the biodistribution and the efficacy of monoclonal antibody 323/A3 labeled with either 131I or 186Re in human ovarian cancer xenografts

AU - Kievit, Els

AU - Van Gog, Frank B.

AU - Schlüper, Hennie M M

AU - Van Dongen, Guus A M S

AU - Pinedo, Herbert M.

AU - Boven, Epie

PY - 1997/7/1

Y1 - 1997/7/1

N2 - 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.

AB - 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.

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KW - Ovarian cancer xenografts

KW - Radioimmunotherapy

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