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European Journal of Nuclear Medicine and Molecular Imaging

Erschienen in:

01.10.2008 | Original Article

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

verfasst von: 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

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 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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Titel: Quantitative PET imaging of Met-expressing human cancer xenografts with 89Zr-labelled monoclonal antibody DN30
verfasst von: 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
Publikationsdatum: 01.10.2008
Verlag: Springer-Verlag
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 10/2008
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-008-0774-5

Springer Medizin

Abstract

Purpose

Materials and methods

Results

Conclusions

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