Breast Tumor Detection and Treatment Using Tarvacin Labeled with Arsenic Radionuclides
Abstract
We will generate a novel approach for detection and therapy of advanced disseminated breast cancer based on three fundamentally novel discoveries and concepts. The first critical component exploits the discovery of a novel antibody, which targets phosphatidylserine (PS), expressed on tumor vasculature and stimulates recruitment of host defense cells to attack the vasculature. In collaboration with Peregrine Pharmaceuticals, this agent has been chimerized and is being developed for clinical trials as bavituximab (formerly named TarvacinTM). Normally, PS exclusively resides on the cytosolic leaflet of the plasma membrane. However, in tumors PS becomes externalized and provides a viable target. The agent not only targets various tumors, but also induces vascular damage and tumor regression with minimal accompanying toxicity. The second key component is the identification of diverse arsenic radionuclides suitable for imaging based on positron emission tomography (PET; 72As, 74As) and radio immunotherapy; 77As). Of equal significance was the discovery that antibodies derivatized with Nsuccinimidyl- S-acetylthioacetate (SATA) could be effectively labeled forming viable products of high specific radiochemical and biological activity. Thirdly, bringing together the pharmacological and radiochemical expertise and identifying animal tumor models and imaging instrumentation to facilitate collaboration, progress, and synergy. This project will permit a single agent (bavituximab) to serve as the foundation for tumor detection, dosimetry, and therapy based on differential properties of arsenic radionuclides, but exploiting a single chemistry.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2009
- Accession Number
- ADA511296
Entities
People
- Ralph P. Mason
Organizations
- University of Texas at Dallas