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

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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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Acknowledgments

This project was financially supported by the Dutch Technology Foundation (grant VBC.6120) and by the Associazione Italiana per la Ricerca sul Cancro. We thank the technical staff of BV Cyclotron and the Radionuclide Center for supplying and processing of 89Zr, Floris van Velden for PET analyses and Otto Hoekstra for providing PET imaging facilities and for reviewing the manuscript.

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Authors and Affiliations

  1. Department of Otolaryngology–Head and Neck Surgery, VU University Medical Centre, De Boelelaan 1117, P.O. Box 7057, Amsterdam, 1007 MB, The Netherlands

    Lars R. Perk, Marijke Stigter-van Walsum, Maria J. W. D. Vosjan, C. René Leemans & Guus A. M. S. van Dongen

  2. Nuclear Medicine and PET Research, VU University Medical Centre, Amsterdam, The Netherlands

    Gerard W. M. Visser, Reina W. Kloet & Guus A. M. S. van Dongen

  3. Medical Oncology Branch CCR, National Cancer Institute, Bethesda, MD, USA

    Giuseppe Giaccone

  4. Division of Molecular Oncology, Institute for Cancer Research and Treatment (IRCC), University of Turin Medical School, Turin, Italy

    Raffaella Albano & Paolo M. Comoglio

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  1. Lars R. Perk
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  2. Marijke Stigter-van Walsum
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  3. Gerard W. M. Visser
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  5. Maria J. W. D. Vosjan
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  6. C. René Leemans
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  9. Paolo M. Comoglio
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  10. Guus A. M. S. van Dongen
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Correspondence to Guus A. M. S. van Dongen.

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Perk, L.R., Stigter-van Walsum, M., Visser, G.W.M. et al. Quantitative PET imaging of Met-expressing human cancer xenografts with 89Zr-labelled monoclonal antibody DN30. Eur J Nucl Med Mol Imaging 35, 1857–1867 (2008). https://doi.org/10.1007/s00259-008-0774-5

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  • DOI: https://doi.org/10.1007/s00259-008-0774-5

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