In vivo MPI of HER2-targeted tumor SPIO uptake is hindered by its current dynamic signal range

Trastuzumab (Tz, herceptin) is a clinically approved monoclonal antibody targeting HER2 on tumor cells, making it an attractive bioligand for specific tumor targeting of superparamagnetic iron oxide (SPIO) nanoparticles. We investigated if Tz-conjugated SPIO could be used for MPI of HER2+ breast tumors. Successful conjugation and preservation of specific HER2-binding of Tz after SPIO conjugation was confirmed in vitro by immunostaining and MPI. Following intravenous injection of Tz-SPIO in a transgenic (spontaneously orthotopic) HER2+ breast cancer mouse model, in vivo MPI was unable to show a distinguishable tumor signal due to the close anatomical proximity of high-signal organs (i.e., liver, spleen, and lungs) to the thoracic tumor, unlike in subcutaneous models. The pulmonary signal disappeared by day 3, indicating SPIO redistribution and/or clearance. However, ex vivo MPI confirmed that tumor accumulation of Tz-SPIO was approximately 1.7- to 3.7-fold higher than that for IgG1-SPIO and unconjugated-SPIO controls, respectively. We conclude that the limited dynamic range of the current MPI technology prevents successful in vivo tumor visualization at low tumor to non-tumor tissue ratios, which was 1:8 to 1:15 in our studies. While antibody-mediated SPIO tumor targeting works in principle, there is an urgent need to develop methods for increasing the dynamic range of MPI.