Targeting of a Head and Neck Squamous Cell Carcinoma Xenograft Model Using the Chimeric Monoclonal Antibody U36 Radioiodinated with a closo-Dodecaborate-containing Linker

Abstract

Objective —High rates of local recurrence and distant metastases following surgery of high-grade head and neck squamous cell carcinoma (HNSCC) necessitate the use of adjuvant systemic treatment. Radioimmunotargeting might be a possible treatment modality in this case. The nuclear properties of ¹³¹I make it a suitable isotope for treatment of minimal residual disease and small metastases, but the conventional radioiodine label has poor cellular retention and its radiocatabolites accumulate in the thyroid. We attempted to overcome these problems by using closo-dodecaborate derivatives for attachment of radioiodine.

Material and Methods —We investigated the feasibility of targeting an SCC25 HNSCC xenograft in vivo using a benzylisothiocyanate derivative of closo-dodecaborate (DABI) as radioiodine linker and the chimeric anti-CD44v6 antibody U36. ¹²⁵I was used in biodistribution studies.

Results —The use of DABI enabled tumor targeting and decreased the radioactivity uptake of the thyroid.

Conclusion —Tumor localization of DABI-labeled U36 was similar to its para-iodobenzoate-labeled counterpart, presumably due to the strong dependence of targeting efficiency on tumor size.

• chimeric antibody U36
• head and neck
• 125I radionuclide labeling
• squamous cell carcinoma

Cheng J, Persson M, Tolmachev V, Siavaev I, Orlova A, Kairemo K, Anniko M. Targeting of a head and neck squamous cell carcinoma xenograft model using the chimeric monoclonal antibody U36 radioiodinated with a closo-dodecaborate-containing linker. Acta Otolaryngol 2004; 124: 1078–1085.

Cheng J, Persson M, Tolmachev V, Siavaev I, Orlova A, Kairemo K, Anniko M. Targeting of a head and neck squamous cell carcinoma xenograft model using the chimeric monoclonal antibody U36 radioiodinated with a closo-dodecaborate-containing linker. Acta Otolaryngol 2004; 124: 1078–1085.