These disadvantages can be overcome by using only a fragment of the mAb, sometimes referred to as a nanobody (Nb). For example, the small size of a Nb (~ 15kDa) allows penetration well into the volume of the tumor. The aim of this study is to develop an anti-HER2-Nb labeled with Ac225. The full vector Ac225-DOTA-2Rs15d-Nb was assembled with the DOTA chelating agent attached to anti-HER2 2Rs15d-Nb. In vivo studies were carried out in female nud Crl:U-Foxn1e mice zenografted with SKOV-3 and MDA-M-231 tumors.
SKOV-3 tumor uptake was high and showed significant cytotoxicity for Ac225-DOTA-2Rs15d-Nb compared to bare Ac225-DOTA as a control. By contrast, MDA-MB-221 tumor uptake was below 0.5% after 1 hour post injection. Nor significant cytotoxicity was observed in MDA-MB-221 for Ac225-DOTA-2Rs15d-Nb compared to Ac225-DOTA.
Kidney accumulation could be reduced 3-fold by injecting 150 mg/kg Gelofusine with the Ac225-DOTA-2Rs15d-Nb
Presented By: Marek Pruszynski from Institute of Nuclear Chemistry and Technology, Warsaw, Poland
Written By: William Carithers, Lawrence Berkeley National Laboratory
at the 10th International Symposium on Targeted Alpha Therapy (TAT-10) May 31 - June 1, 2017 - Kanazawa, Japan.