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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 10/2008

01-10-2008 | Original Article

Quantitative PET imaging of Met-expressing human cancer xenografts with 89Zr-labelled monoclonal antibody DN30

Authors: Lars R. Perk, Marijke Stigter-van Walsum, Gerard W. M. Visser, Reina W. Kloet, Maria J. W. D. Vosjan, C. René Leemans, Giuseppe Giaccone, Raffaella Albano, Paolo M. Comoglio, Guus A. M. S. van Dongen

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 10/2008

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Abstract

Purpose

Targeting the c-Met receptor with monoclonal antibodies (MAbs) is an appealing approach for cancer diagnosis and treatment because this receptor plays a prominent role in tumour invasion and metastasis. Positron emission tomography (PET) might be a powerful tool for guidance of therapy with anti-Met MAbs like the recently described MAb DN30 because it allows accurate quantitative imaging of tumour targeting (immuno-PET). We considered the potential of PET with either 89Zr-labelled (residualising radionuclide) or 124I-labelled (non-residualising radionuclide) DN30 for imaging of Met-expressing tumours.

Materials and methods

The biodistribution of co-injected 89Zr-DN30 and iodine-labelled DN30 was compared in nude mice bearing either the human gastric cancer line GLT-16 (high Met expression) or the head-and-neck cancer line FaDu (low Met expression). PET images were acquired in both xenograft models up to 4 days post-injection (p.i.) and used for quantification of tumour uptake.

Results

Biodistribution studies in GTL-16-tumour-bearing mice revealed that 89Zr-DN30 achieved much higher tumour uptake levels than iodine-labelled DN30 (e.g. 19.6%ID/g vs 5.3%ID/g, 5 days p.i.), while blood levels were similar, indicating internalisation of DN30. Therefore, 89Zr-DN30 was selected for PET imaging of GLT-16-bearing mice. Tumours as small as 11 mg were readily visualised with immuno-PET. A distinctive lower 89Zr uptake was observed in FaDu compared to GTL-16 xenografts (e.g. 7.8%ID/g vs 18.1%ID/g, 3 days p.i.). Nevertheless, FaDu xenografts were also clearly visualised with 89Zr-DN30 immuno-PET. An excellent correlation was found between PET-image-derived 89Zr tumour uptake and ex-vivo-assessed 89Zr tumour uptake (R 2 = 0.98).

Conclusions

The long-lived positron emitter 89Zr seems attractive for PET-guided development of therapeutic anti-c-Met MAbs.
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Metadata
Title
Quantitative PET imaging of Met-expressing human cancer xenografts with 89Zr-labelled monoclonal antibody DN30
Authors
Lars R. Perk
Marijke Stigter-van Walsum
Gerard W. M. Visser
Reina W. Kloet
Maria J. W. D. Vosjan
C. René Leemans
Giuseppe Giaccone
Raffaella Albano
Paolo M. Comoglio
Guus A. M. S. van Dongen
Publication date
01-10-2008
Publisher
Springer-Verlag
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 10/2008
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-008-0774-5

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