177Lu- labeled MOv18 as compared to 131I- or 90Y-labeled MOv18 has the better therapeutic effect in eradication of alpha folate receptor-expressing tumor xenografts

Alberto Zacchetti, Angela Coliva, Elena Luison, Ettore Seregni, Emilio Bombardieri, Augusto Giussani, Mariangela Figini, Silvana Canevari

Research output: Contribution to journalArticle

Abstract

Introduction: The mouse monoclonal antibody MOv18, directed against the α-isoform of folate receptor (FR), was investigated to identify the optimal radioconjugate for radioimmunotherapy of minimal residual disease in ovarian cancer. Methods: Pharmacokinetics, biodistribution, long-term therapeutic efficacy and toxicity of MOv18, labeled with the beta-emitters 131I, 90Y and 177Lu, were compared in a xenografted mouse model, composed by two cell lines, A431FR and A431MK, differing only for FR expression. Results: A shorter blood clearance and a higher tumor uptake were observed for 90Y- and 177Lu- compared to 131I-MOv18, and a shorter blood pharmacokinetics was recorded in A431FR-bearing animals. At equitoxic maximum tolerable doses, the general irradiation by 131I- and 90Y-MOv18 gives rise to strong targeted effects on A431FR and nontargeted effects on A431MK tumors, while 177Lu-MOv18 was able to eradicate small size tumor masses expressing the antigen of interest exerting only mild non-targeted effects. Conclusion: 177Lu-MOv18 at the maximal tolerated dose is the immunoradioconjugate with the best therapeutic window in experimental conditions of small tumor volume.

Original languageEnglish
Pages (from-to)759-770
Number of pages12
JournalNuclear Medicine and Biology
Volume36
Issue number7
DOIs
Publication statusPublished - Oct 2009

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Folate Receptor 1
Therapeutic Uses
Heterografts
Folic Acid
Pharmacokinetics
Radioimmunotherapy
Neoplasms
Maximum Tolerated Dose
Residual Neoplasm
Tumor Burden
Ovarian Neoplasms
Protein Isoforms
Antigens
Cell Line
Therapeutics

Keywords

  • Monoclonal antibody MOv18
  • Ovarian cancer
  • Radioimmunotherapy
  • Radiometals, Folate Receptor

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging

Cite this

177Lu- labeled MOv18 as compared to 131I- or 90Y-labeled MOv18 has the better therapeutic effect in eradication of alpha folate receptor-expressing tumor xenografts. / Zacchetti, Alberto; Coliva, Angela; Luison, Elena; Seregni, Ettore; Bombardieri, Emilio; Giussani, Augusto; Figini, Mariangela; Canevari, Silvana.

In: Nuclear Medicine and Biology, Vol. 36, No. 7, 10.2009, p. 759-770.

Research output: Contribution to journalArticle

Zacchetti, Alberto ; Coliva, Angela ; Luison, Elena ; Seregni, Ettore ; Bombardieri, Emilio ; Giussani, Augusto ; Figini, Mariangela ; Canevari, Silvana. / 177Lu- labeled MOv18 as compared to 131I- or 90Y-labeled MOv18 has the better therapeutic effect in eradication of alpha folate receptor-expressing tumor xenografts. In: Nuclear Medicine and Biology. 2009 ; Vol. 36, No. 7. pp. 759-770.
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abstract = "Introduction: The mouse monoclonal antibody MOv18, directed against the α-isoform of folate receptor (FR), was investigated to identify the optimal radioconjugate for radioimmunotherapy of minimal residual disease in ovarian cancer. Methods: Pharmacokinetics, biodistribution, long-term therapeutic efficacy and toxicity of MOv18, labeled with the beta-emitters 131I, 90Y and 177Lu, were compared in a xenografted mouse model, composed by two cell lines, A431FR and A431MK, differing only for FR expression. Results: A shorter blood clearance and a higher tumor uptake were observed for 90Y- and 177Lu- compared to 131I-MOv18, and a shorter blood pharmacokinetics was recorded in A431FR-bearing animals. At equitoxic maximum tolerable doses, the general irradiation by 131I- and 90Y-MOv18 gives rise to strong targeted effects on A431FR and nontargeted effects on A431MK tumors, while 177Lu-MOv18 was able to eradicate small size tumor masses expressing the antigen of interest exerting only mild non-targeted effects. Conclusion: 177Lu-MOv18 at the maximal tolerated dose is the immunoradioconjugate with the best therapeutic window in experimental conditions of small tumor volume.",
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AU - Luison, Elena

AU - Seregni, Ettore

AU - Bombardieri, Emilio

AU - Giussani, Augusto

AU - Figini, Mariangela

AU - Canevari, Silvana

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