Targeting of a head and neck squamous cell carcinoma xenograft model using the chimeric monoclonal antibody U36 radioiodinated with a closo-dodecaborate-containing linker.
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.


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.


CONCLUSIONS
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.
Cheng
Junping
J
Division of Biomedical Radiation Sciences Uppsala University Uppsala. Junping.Chen@ent.uu.se
Persson
Mikael
M
Tolmachev
Vladimir
V
Siavaev
Igor
I
Orlova
Anna
A
Kairemo
Kalevi
K
Anniko
Matti
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D001896:Boron Compounds / Q000493:pharmacokinetics; D045744:Cell Line, Tumor / Q000528:radiation effects; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D018307:Neoplasms, Squamous Cell / Q000378:metabolism / Q000532:radiotherapy*; D016499:Radioimmunotherapy / Q000379:methods*; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D001896:Boron Compounds; D007457:Iodine Radioisotopes