Herceptin Research Today is a free monthly online journal that collates and summarizes the latest research about Herceptin, including details on side-effects, breast cancer, treatment, therapy.

In Vitro Evaluation of Two Polyhedral Boron Anion Derivatives as Linkers for Attachment of Radioiodine to the Anti-HER2 Monoclonal Antibody Trastuzumab.

Persson M, Sivaev I, Winberg KJ, Gedda L, Malmström PU, Tolmachev V

Unit of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden., Unit of Experimental Urology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.

Improving intracellular retention is important for the use of radiohalogens in radionuclide therapy using internalizing antibodies. Two putative linkers for residualization of radioiodine labels, 7-(4-isothiocyanato-phenyl)undecahydro-7,8-dicarba-nido-undecaborate(1-) ion (NBI) and (4-isothiocyanato-benzylammonio)undecahydro-closo-dodecaborate(1-) (DABI), were analyzed. The anti-HER-2 antibody, trastuzumab, was labeled with iodine-125 using NBI and DABI linkers, and, for comparison, with the para-[(125)I]iodobenzoate (PIB), and Chloramine-T((R)) (CAT) methods. The different labels were tested for residualizing properties using the HER-2 overexpressing SKBR-3 cells. The cellular radioactivity retention showed that DABI provided a 55% better retention than CAT and was 42% better than PIB after 20 hours. NBI did not improve retention. Accumulation tests up to 21 hours showed that the HER-2-specific accumulation of radioactivity delivered with DABI was, on average, 33% higher than with the use of PIB. These DABI-dependent improvements could, with high probability, be attributed to the good residualizing properties of DABI. The affinity of DABI-labeled trastuzumab to SKBR-3 cells was not better than the affinity of the PIB labeled (3.2 +/- 1.9 nM and 0.77 +/- 0.39 nM, respectively). In conclusion, the use of the DABI linker improved intracellular retention in vitro in comparison with the other labeling methods.

Published 5 November 2007 in Cancer Biother Radiopharm, 22(5): 585-96.
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