TAT-10: Preclinical Evaluation of Anti-HER2 2Rs15d Nanobody Labeled with Ac225

Kanazawa, Japan (UroToday.com) Human Epidermal Growth Factor Receptor type 2 (HER2) is over expressed in many types of human cancer such as breast, ovarian, and colorectal cancers. Whole monoclonal antibodies targeted to HER2 might seem like powerful vectors for radioimmunotherapy but their slow pharmacokinetics and normal tissue clearance are significant disadvantages.

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.
E-Newsletters

Newsletter subscription

Free Daily and Weekly newsletters offered by content of interest

The fields of GU Oncology and Urology are rapidly advancing. Sign up today for articles, videos, conference highlights and abstracts from peer-review publications by disease and condition delivered to your inbox and read on the go.

Subscribe