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European Journal of Nuclear Medicine and Molecular Imaging

Erschienen in:

01.11.2005 | Original Article

In vitro evaluation of the astatinated chimeric monoclonal antibody U36, a potential candidate for treatment of head and neck squamous cell carcinoma

verfasst von: M. Nestor, M. Persson, G. A. M. S. van Dongen, H. J. Jensen, H. Lundqvist, M. Anniko, V. Tolmachev

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 11/2005

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Abstract

Purpose

The purpose of this study was to analyse the properties of the astatinated chimeric MAb (cMAb) U36 as a conjugate to selectively target and eradicate head and neck squamous cell carcinoma (HNSCC).

Methods

cMAb U36 was labelled with ²¹¹At via the linker N-succinimidyl 4-(trimethylstannyl)benzoate (SPMB). The quality of the conjugate was extensively evaluated for binding and internalisation capacity, and compared with ¹²⁵I-SPMB-cMAb U36. The cellular toxicity of the astatinated conjugate was assessed in two types of in vitro growth assay and compared with ¹³¹I-labelled cMAb U36 (directly labelled).

Results

Comparisons between ²¹¹At-cMAb U36 and ¹²⁵I-cMAb U36 demonstrated an optimal functional capacity of the labelled products. Immunoreactivity and affinity assays showed high immunoreactive fractions (>93%), and an affinity in good agreement between the astatinated and iodinated antibodies. For both conjugates, specific binding to HNSCC cells could be demonstrated, as well as some internalisation. Retention of the astatinated conjugate was just slightly lower than for the iodinated conjugate and still reasonable for therapeutic use (31±2% vs 42.6±1.0% at 22 h), demonstrating no adverse effects from astatination of the antibody. Studies on cellular toxicity demonstrated a dose-dependent and antigen-specific cellular toxicity for ²¹¹At-cMAb U36, with about 10% cell survival at 50 decays per cell. The ¹³¹I-labelled conjugate was not as efficient, with a surviving cell fraction of about 50% at 55 decays per cell.

Conclusion

These results indicate that ²¹¹At-cMAb U36 might be a promising future candidate for eradicating HNSCC micrometastases in vivo.

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Titel: In vitro evaluation of the astatinated chimeric monoclonal antibody U36, a potential candidate for treatment of head and neck squamous cell carcinoma
verfasst von: M. Nestor
M. Persson
G. A. M. S. van Dongen
H. J. Jensen
H. Lundqvist
M. Anniko
V. Tolmachev
Publikationsdatum: 01.11.2005
Verlag: Springer-Verlag
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 11/2005
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-005-1848-2

Live-Webinar "Chronische Unterbauch- und Viszeralschmerzen in der Praxis managen"

Springer Medizin

In vitro evaluation of the astatinated chimeric monoclonal antibody U36, a potential candidate for treatment of head and neck squamous cell carcinoma

Abstract

Purpose

Methods

Results

Conclusion

Live-Webinar "Chronische Unterbauch- und Viszeralschmerzen in der Praxis managen"

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

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