Radiopaque, Tumor-Targeted Nanoparticles for Improved Mammographic Detection of Breast Cancer

摘要

Despite the widespread use of X-ray mammography for routine breast cancer (BC) screening the technique suffers from a number of major limitations including a false-negative rate of at least 10-15% and a positive predictive value (PPV2) of only 25-40%. Accordingly a large number of patients either do not receive treatment when they should or are subjected to needless physical and emotional trauma. The weakness of X-ray mammography stems from its poor ability to (a) image small or noncalcified lesions particularly in patients with high breast density and (b) to distinguish between benign and malignant microcalcifications. A tumor-selective X-ray contrast agent would mitigate both of these limitations. This proposal was focused on developing radiopaque gold nanoparticles targeted to HER2 a BC-relevant antigen. Administered intravenously these conjugates should accumulate preferentially at tumors enhancing visualization due to the presence of the gold. Interpretation could be aided by subtraction imaging or comparison to a baseline mammogram performed prior to contrast injection. The major objective were (1) to determine the ability of nanogold clusters to detectably alter X-ray mammograms performed using plastic phantoms; (2) to develop nanogold conjugates using small engineered antibody fragments; and (3) to perform initial in vivo targeting studies with these conjugates.