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European Journal of Nuclear Medicine and Molecular Imaging

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01.09.2007 | Original article

Immuno-PET of undifferentiated thyroid carcinoma with radioiodine-labelled antibody cMAb U36: application to antibody tumour uptake studies

verfasst von: Marc-André Fortin, Alexei V. Salnikov, Marika Nestor, Nils-Erik Heldin, Kristofer Rubin, Hans Lundqvist

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 9/2007

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Abstract

Purpose

We tested the suitability of the chimeric monoclonal anti-human CD44 splice version 6 antibody (cMAb U36) for targeting and visualising human anaplastic thyroid carcinoma with PET. We also performed experiments aimed at elucidating the relation between tumour interstitial fluid pressure (TIFP) and the tumour uptake of antibodies.

Methods

The affinity and specificity of the cMAb U36 for KAT-4 cells were evaluated in vitro, as was the Na⁺/I⁻ symporter (NIS) expression. Biodistribution studies were performed on KAT-4 carcinoma-bearing mice injected with ¹²⁴I-cMAb U36 or free iodine. Biodistribution studies were also performed in animals treated with the specific TGF-β1 and -β3 inhibitor Fc:TβRII, which lowers TIFP. Treated and non-treated animals were scanned by microPET.

Results

Cultured human undifferentiated/anaplastic thyroid carcinoma KAT-4 cells expressed low levels of NIS and uptake of free iodine was insignificant. The cMAb U36 expressed an affinity (K _D) of 11 ± 2 nM. Tumour radioactivity uptake reached maximum values 48 h after injection of ¹²⁴I-cMAb U36 (∼22%IA/g). KAT-4 carcinomas were readily identified in all ¹²⁴I-immuno-PET images. Radioactivity tumour uptake in Fc:TβRII-treated animals was significantly lower at 24 and 48 h after injection, and five times higher thyroid uptake was also noted.

Conclusion

We successfully used ¹²⁴I-cMAb U36 to visualise CD44v6-expressing human anaplastic thyroid carcinoma. Given the lack of NIS expression in KAT-4, tumour visualisation is not due to free iodine uptake. Lowering the TIFP in KAT-4 carcinomas did not increase the uptake of mAbs into tumour tissue.

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Titel: Immuno-PET of undifferentiated thyroid carcinoma with radioiodine-labelled antibody cMAb U36: application to antibody tumour uptake studies
verfasst von: Marc-André Fortin
Alexei V. Salnikov
Marika Nestor
Nils-Erik Heldin
Kristofer Rubin
Hans Lundqvist
Publikationsdatum: 01.09.2007
Verlag: Springer-Verlag
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 9/2007
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-006-0346-5

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

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