Epidermal Growth Factor Receptor Overexpression as a Target for Auger Electron Radiotherapy of Breast Cancer
Abstract
EGFR%R 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, (111)In-hEGF to breast cancer cells for treatment of the disease. (111)In-hECF 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. (111)In-hEGF was >100-400 fold more cytotoxic to MDA-NB-46B cells than chemotherapeutic agents (IC50 70 pM vs. 6-30 nM) and low concentrations to (70 pM) of 1111n-hECE produced the same growth inhibition as 4 Gy of 7- radiation. The cytotoxicity was amplified (IC50 15 pM) by conjugation of hEGE with ESA and derivatization with multiple DTPA metal chelators for (111)In. Mice implanted with MDA-MB-468 tumors treated with 5 doses of 500 muCi of (111)In-hEGE exhibited tumor growth arrest. There was no evidence of normal tissue toxicity as measured by 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 WEC and platelets. Our results are highly promising for the development of (111)In-hEGF as a novel treatment for breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2001
- Accession Number
- ADA398068
Entities
People
- Raymond M. Reilly
Organizations
- Toronto General Hospital