First treatment with Hsp90 inhibitor PDE Inhibitor in clinical trials with PET imaging with Gallium-68 F2 fragments labeled trastuzumab. They found a reduction in tumor uptake of 70% in BT474 breast tumor xenografts. The reduced absorption was not until 5 days after treatment. Her2 levels were not determined ex-vivo imaging studies were performed only. Oude Munnink and colleagues used PET imaging with a compl Length of 89 zirconium labeled trastuzumab for downregulation of Her2 after treatment with an Hsp90 inhibitor in SKOV contributed 3 ovarian tumor xenografts measured. They reported a decrease in tumor uptake of 41%. Immunohistochemistry best CONFIRMS the reduction in ex vivo expression of HER2 in a qualitative way only. Kramer and colleagues Marek measured Ver changes In expression after 17 DMAG treatment HER2 Affibody with the same we used in our study, but instead of using digital image processing, they are labeled with fluorine-18 made for Affibody PET imaging, and only one pre- and post-processing analysis. They reported a reduction of33% transfected into MCF7 cells with HER2 and 71% in BT474 breast tumor xenografts. Her2 downregulation was best ex vivo using Western blot and ELISA CONFIRMS. Both Munnink Oude Kamer and colleagues, and Marek and his colleagues compared a Ma Exception after treatment with a single treatment. Her2 expression was not pursued over a long period of time. The St strength Our study is that we each mouse was followed for 10 days, which allows us to see lower levels of HER2 after treatment and recovery after cessation of treatment.
This suggests that we are the molecular Ver Noninvasive monitoring changes over time with our strategy of optical imaging, w While we are not significant Ver Changes in tumor volume w Have observed during the study. Our in vivo results of the signal reduction of 22.5%, in agreement with previous reports, taking into account that different cell lines that were used for tumor xenografts and the imaging was used was also different. In addition, the correlation of the optical signal in vivo imaging with ex vivo Her2 levels by Western blot supports our results. Although tumor volume has not promising after 17 DMAG treatment changed, In 2 of 17 treated M Mice tumors DMAG B clone fell to very small volumes on day 9 To ensure that Best term changes in the optical imaging signal, Were caused due to decreased levels of HER2 expression and not by other non-specific anti-tumor effects of the drug, we have correlated the in vivo optical imaging with the Expression of Her2 not only ex vivo mice on day 9, but on day 3 in a subset of 8 M. In this group also monitored by ultrasound, the tumor volume measurements on day 3 and best Firmed that there is no decrease in tumor volume after treatment. The results show that the measured changes Ver In the optical imaging signal Ver Changes in HER2 expression after drug to Reflect se treatment. An important advantage of the optical imaging compared with PET imaging is that it is not radioactive components or ionizing radiation and can therefore h Be used more often. An additionally Tzlicher advantage is that optical contrast agents are easier and much cheaper than PET tracers. In contrast to Ans UPRIGHTS In which radionuclide imaging over time disappears, the imaging signal T as a result of natural decay and more clear.