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European Journal of Nuclear Medicine and Molecular Imaging

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01-10-2014 | Original Article

Anti-L1CAM radioimmunotherapy is more effective with the radiolanthanide terbium-161 compared to lutetium-177 in an ovarian cancer model

Authors: Jürgen Grünberg, Dennis Lindenblatt, Holger Dorrer, Susan Cohrs, Konstantin Zhernosekov, Ulli Köster, Andreas Türler, Eliane Fischer, Roger Schibli

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 10/2014

Abstract

Purpose

The L1 cell adhesion molecule (L1CAM) is considered a valuable target for therapeutic intervention in different types of cancer. Recent studies have shown that anti-L1CAM radioimmunotherapy (RIT) with ⁶⁷Cu- and ¹⁷⁷Lu-labelled internalising monoclonal antibody (mAb) chCE7 was effective in the treatment of human ovarian cancer xenografts. In this study, we directly compared the therapeutic efficacy of anti-L1CAM RIT against human ovarian cancer under equitoxic conditions with the radiolanthanide ¹⁷⁷Lu and the potential alternative ¹⁶¹Tb in an ovarian cancer therapy model.

Methods

Tb was produced by neutron bombardment of enriched ¹⁶⁰Gd targets. ¹⁶¹Tb and ¹⁷⁷Lu were used for radiolabelling of DOTA-conjugated antibodies. The in vivo behaviour of the radioimmunoconjugates (RICs) was assessed in IGROV1 tumour-bearing nude mice using biodistribution experiments and SPECT/CT imaging. After ascertaining the maximal tolerated doses (MTD) the therapeutic impact of 50 % MTD of ¹⁷⁷Lu- and ¹⁶¹Tb-DOTA-chCE7 was evaluated in groups of ten mice by monitoring the tumour size of subcutaneous IGROV1 tumours.

Results

The average number of DOTA ligands per antibody was 2.5 and maximum specific activities of 600 MBq/mg were achieved under identical radiolabelling conditions. RICs were stable in human plasma for at least 48 h. ¹⁷⁷Lu- and ¹⁶¹Tb-DOTA-chCE7 showed high tumour uptake (37.8–39.0 %IA/g, 144 h p.i.) with low levels in off-target organs. SPECT/CT images confirmed the biodistribution data. ¹⁶¹Tb-labelled chCE7 revealed a higher radiotoxicity in nude mice (MTD: 10 MBq) than the ¹⁷⁷Lu-labelled counterpart (MTD: 12 MBq). In a comparative therapy study with equitoxic doses, tumour growth inhibition was better by 82.6 % for the ¹⁶¹Tb-DOTA-chCE7 than the ¹⁷⁷Lu-DOTA-chCE7 RIT.

Conclusions

Our study is the first to show that anti-L1CAM ¹⁶¹Tb RIT is more effective compared to ¹⁷⁷Lu RIT in ovarian cancer xenografts. These results suggest that ¹⁶¹Tb is a promising candidate for future clinical applications in combination with internalising antibodies.

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Title: Anti-L1CAM radioimmunotherapy is more effective with the radiolanthanide terbium-161 compared to lutetium-177 in an ovarian cancer model
Authors: Jürgen Grünberg
Dennis Lindenblatt
Holger Dorrer
Susan Cohrs
Konstantin Zhernosekov
Ulli Köster
Andreas Türler
Eliane Fischer
Roger Schibli
Publication date: 01-10-2014
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 10/2014
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-014-2798-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Anti-L1CAM radioimmunotherapy is more effective with the radiolanthanide terbium-161 compared to lutetium-177 in an ovarian cancer model

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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