Novel Radiopharmaceuticals for Radioguided Surgery of Ductal Carcinoma In Situ of the Breast
Abstract
Ductal carcinoma in situ (DCIS) is an early stage of breast cancer treated by surgery and local radiotherapy. The surgeon has difficulty however in accurately defining the disease margins which may lead to re-excision or recurrent DCIS. Our objective is to develop novel radiopharmaceuticals for radioguided surgery (ROS) of DCIS to improve its surgical management. In the 2nd year, monoclonal antibodies (mAbs) cc49 and trastuzumab (Herceptin) were tested for reactivity with DCIS specimens which demonstrated 60% and 20% reactivity respectively. We also completed preclinical testing of trastuzumab Pab labeled with indium-111 in mice implanted with human breast cancer xenografts which showed high and specific radiopharmaceutical tumor accumulation achieving tumor/blood ratios of >25:1 at %2 hours p.i. A gamma detecting surgical guidance system (C-Trak) was purchased and evaluated for sensitivity and spatial resolution using a framework to move the probe accurately in the x, y and z directions over phantom models of simulated DCIS lesions. Finally, an expression vector was constructed to produce a novel recombinant cc49 Fab fragment containing an integrated radiometal binding site for technetium-99m. Studies are continuing in the 3rd year and a Phase I trial is planned for the 4th year of the project.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2002
- Accession Number
- ADA410858
Entities
People
- Raymond M. Reilly
Organizations
- Toronto General Hospital