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

doi:10.1016/j.nucmedbio.2009.05.004

« Previous Next »Nuclear Medicine and Biology
Volume 36, Issue 7 , Pages 759-770, October 2009

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
- Unit of Molecular Therapies, Department of Experimental Oncology and Laboratories, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy
Angela Coliva
- Department of Imaging and Nuclear Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy
Elena Luison
- Unit of Molecular Therapies, Department of Experimental Oncology and Laboratories, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy
Ettore Seregni
- Department of Imaging and Nuclear Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy
Emilio Bombardieri
- Department of Imaging and Nuclear Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy
Augusto Giussani
- Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
Mariangela Figini
- Unit of Molecular Therapies, Department of Experimental Oncology and Laboratories, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy
- M.F. and S.C. contributed equally to this work.
Silvana Canevari
- Unit of Molecular Therapies, Department of Experimental Oncology and Laboratories, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy
- Corresponding author. Tel.: +390223902567; fax: +390223903073.
- M.F. and S.C. contributed equally to this work.

Received 31 March 2009; received in revised form 13 May 2009; accepted 15 May 2009. published online 30 July 2009.

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.

Keywords: Ovarian cancer, Monoclonal antibody MOv18, Radioimmunotherapy, Radiometals, Folate Receptor