Abstract 109: PET imaging of 89Zr-labeled Pertuzumab in HER2-positive breast cancer xenografts

Abstract

Abstract The sensitivity and quantitative properties of Positron Emission Tomography (PET) imaging combined with the selectivity and high affinity of radiolabeled monoclonal antibodies (mAbs) make a powerful tool in molecular imaging of diseases including breast cancer. Radiolabeling mAbs with the positron-emitting 89Zr has recently been useful in clinical trials due to its relatively long half-life (t1/2 = 3.3 days), which matches the pharmacokinetic properties of mAbs. Pertuzumab (Perjeta™) is an FDA-approved mAb for the treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer, in combination with Trastuzumab (Herceptin™) and chemotherapy. Herein, we evaluated 89Zr-labeled Pertuzumab as a PET imaging agent in transgenic mice-bearing human breast cancer. The 89Zr chelator, p-isothiocyanatobenzyl-desferrioxamine, was conjugated to Pertuzumab and subsequently radiolabeled with 89Zr. The immunoreactivity and specificity of 89Zr-Pertuzumab for HER2-expressing cells were determined in vitro and showed retention of 89Zr-Pertuzumab immunoreactivity and specific binding to HER2-expressing cells. Human breast cancer cells were inoculated subcutaneously in severely immunocompromised NOG mice, a model which allows for the growth of HER2-positive tumors without exogenous stimuli. 89Zr-Pertuzumab was injected via tail vein and imaged and 5 and 7 days post-injection (p.i.) followed by biodistribution studies. Optimal contrast was achieved at 5 days p.i., with higher tumor uptake in the HER2-positive xenograft than the HER2-negative model. Immunohistochemical analysis of these tumors is in agreement with PET imaging analysis. These results illustrate that 89Zr-Pertuzumab may be beneficial for the noninvasive assessment of HER2 expression. Citation Format: Bernadette V. Marquez, Oluwatayo F. Ikotun, Brian Wright, Alexander Zheleznyak, Pierce Richard, Suzanne E. Lapi. PET imaging of 89Zr-labeled Pertuzumab in HER2-positive breast cancer xenografts. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 109. doi:10.1158/1538-7445.AM2014-109