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

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

Research output: Contribution to journalArticle

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 (R2=0.98). Conclusions: The long-lived positron emitter 89Zr seems attractive for PET-guided development of therapeutic anti-c-Met MAbs.

Original languageEnglish
Pages (from-to)1857-1867
Number of pages11
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume35
Issue number10
DOIs
Publication statusPublished - Oct 2008

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Heterografts
Positron-Emission Tomography
Monoclonal Antibodies
Neoplasms
Iodine
Injections
Head and Neck Neoplasms
Nude Mice
Radioisotopes
Radionuclide Imaging
Stomach Neoplasms
Therapeutics
Electrons
Neoplasm Metastasis

Keywords

  • DN30
  • Immuno-PET
  • Met receptor
  • Molecular imaging
  • Zirconium-89

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Perk, L. R., Stigter-Van Walsum, M., Visser, G. W. M., Kloet, R. W., Vosjan, M. J. W. D., Leemans, C. R., ... Van Dongen, G. A. M. S. (2008). Quantitative PET imaging of Met-expressing human cancer xenografts with 89Zr-labelled monoclonal antibody DN30. European Journal of Nuclear Medicine and Molecular Imaging, 35(10), 1857-1867. https://doi.org/10.1007/s00259-008-0774-5

Quantitative PET imaging of Met-expressing human cancer xenografts with 89Zr-labelled monoclonal antibody DN30. / Perk, Lars R.; Stigter-Van Walsum, Marijke; Visser, Gerard W M; Kloet, Reina W.; Vosjan, Maria J W D; Leemans, C. René; Giaccone, Giuseppe; Albano, Raffaella; Comoglio, Paolo M.; Van Dongen, Guus A M S.

In: European Journal of Nuclear Medicine and Molecular Imaging, Vol. 35, No. 10, 10.2008, p. 1857-1867.

Research output: Contribution to journalArticle

Perk, LR, Stigter-Van Walsum, M, Visser, GWM, Kloet, RW, Vosjan, MJWD, Leemans, CR, Giaccone, G, Albano, R, Comoglio, PM & Van Dongen, GAMS 2008, 'Quantitative PET imaging of Met-expressing human cancer xenografts with 89Zr-labelled monoclonal antibody DN30', European Journal of Nuclear Medicine and Molecular Imaging, vol. 35, no. 10, pp. 1857-1867. https://doi.org/10.1007/s00259-008-0774-5
Perk, Lars R. ; Stigter-Van Walsum, Marijke ; Visser, Gerard W M ; Kloet, Reina W. ; Vosjan, Maria J W D ; Leemans, C. René ; Giaccone, Giuseppe ; Albano, Raffaella ; Comoglio, Paolo M. ; Van Dongen, Guus A M S. / Quantitative PET imaging of Met-expressing human cancer xenografts with 89Zr-labelled monoclonal antibody DN30. In: European Journal of Nuclear Medicine and Molecular Imaging. 2008 ; Vol. 35, No. 10. pp. 1857-1867.
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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 (R2=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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AU - Stigter-Van Walsum, Marijke

AU - Visser, Gerard W M

AU - Kloet, Reina W.

AU - Vosjan, Maria J W D

AU - Leemans, C. René

AU - Giaccone, Giuseppe

AU - Albano, Raffaella

AU - Comoglio, Paolo M.

AU - Van Dongen, Guus A M S

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N2 - 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 (R2=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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