Epidermal Growth Factor Receptor Overexpression as a Target for Auger Electron Radiotherapy of Breast Cancer
Abstract
EGFR are overexpressed in the majority of ER-negative, hormone-resistant and poor prognosis breast cancers. Our goal is to exploit EGFR overexpression to selectively target the Auger electron-emitting radiopharmaceutical, 1111n-hEGF to breast cancer cells for treatment of the disease. 1111n-hEGF was highly radiotoxic in vitro to MDA-MB-468 breast cancer cells overexpressing EGFR (1-2 X 106 receptors/cell) but not to MCF-7 breast cancer cells with a 100-fold lower level of EGFR. 1111n-hEGF was >85-500 fold more cytotoxic to MDA-MB-468 cells than chemotherapeutic agents (IC50 70 pM vs. 6-30 nM) and low concentrations (70 pM) of 1111n-hEGF produced the same growth inhibition as 4 Gy of gamma- radiation. The radiopharmaceutical exhibited dose-related and strong selective anti-tumor effects against MDA-MB-468 tumors overexpressing EGFR implanted into mice. There were no changes in body weight, histopathological examination of liver and kidneys and serum ALT and Cr levels. There was a slight but not significant decrease in WBC and platelets. The radiopharmaceutical was most effective against small, non-established tumors. Our results are highly promising for the development of 1111n-hEGF as a novel treatment for breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2002
- Accession Number
- ADA407381
Entities
People
- Raymond M. Reilly
Organizations
- Toronto General Hospital