A Dendrimer based Contrast Agent for MR Imaging of Her-2/neu Receptors by a Three-step Pretargeting Approach
Zhu W, Okollie B, Bhujwalla Z, Artemov D
Johns Hopkins University
Herceptin, an FDA approved humanized MAb for the treatments of Her-2/neu positive breast cancer, is also used to selectively deliver anticancer or image agents to Her-2/neu overexpressing tumor cells. Pretargeting approaches that separate the delivery of antibody and anticancer or imaging agents may further reduce toxicity by avoiding the long half-life of the antibody while an avidin/streptavidin-biotin system is used to link the antibody and agents. We have prepared a PAMAM dendrimer generation 4 based DTPA-Gd conjugate for MRI studies. MR enhancement by a three-step pretargeting approach of Her-2/neu positive BT-474 breast tumors in vitro and in vivo are shown.