Multiple target-specific molecular agents for detection and image analysis of breast cancer characteristics in mice.

Breast cancer is a heterogenetic tumor at the cellular level with multiple factors and components. The inconsistent expression of molecular markers during disease progression reduces the accuracy of diagnosis and efficacy of target-specific therapy. Single target-specific imaging agents can only provide limited tumor information at one time point. In contrast, multiple target-specific imaging agents can increase the accuracy of diagnosis. The aim of this study was to demonstrate the ability of multi-agent imaging to discriminate such differences in single tumor. Mice bearing human cancer cell xenografts were tested to determine individual differences under optimal experimental conditions. Neovasculature agent (RGD peptide), tumor stromal agent (matrix metalloproteinase), and tumor cell markers (epidermal growth factor, Her-2, interleukin 11) imaging agents were labeled with reporters. 18F-Fluorodeoxyglucose was used to evaluate the tumor glucose status. Optical, X-ray, positron emission tomography, and computer tomography imaging modalities were used to determine tumor characteristics. Tumor size and imaging data demonstrated that individual differences exist under optimal experimental conditions. The target-specific agents used in the study bind to human breast cancer cell lines in vitro and xenografts in vivo. The pattern of binding corresponds to that of tumor markers. Multi-agent imaging had complementary effects in tumor detection. Multiple noninvasive imaging agents and modalities are complementary in the interrogation of unique biological information from each individual tumor. Such multi-agent approaches provide methods to study several disease components simultaneously. In addition, the imaging results provide information on disease status at the molecular level.

Ascorbic acid prevents beta-amyloid-induced intracellular calcium increase and cell death in PC12 cells.

Characteristics of Alzheimer's disease include loss of brain neurons associated with the deposit of beta-amyloid protein (A beta) which is thought to be toxic to neurons possibly via induction of intracellular calcium and generation of free radicals. On this basis, we have determined the effect of ascorbic acid on the cell death and calcium increase induced by A beta in PC12 cells. We found that ascorbic acid completely abolished A beta-induced calcium increase and cell death in PC12 cells, indicating that calcium elevation and cell death are associated phenomena induced by A beta that can be rescued by antioxidants. These results are important to understand the mechanisms by which A beta is toxic to neurons and suggest that antioxidants may be part of future treatments for Alzheimer's disease.