Radiolabeled pertuzumab for imaging of human epidermal growth factor receptor 2 expression in ovarian cancer

Abstract

Purpose Human epidermal growth factor receptor 2 (HER2) is overexpressed in over 30% of ovarian cancer cases, playing essential roles in tumorigenesis and metastasis. Non-invasive imaging of HER2 is of great interest for physicians to better detect and monitor the progression of ovarian cancer. In this study, HER2 was assessed as a biomarker for ovarian cancer imaging using 64Cu-labeled pertuzumab for immunoPET imaging. Methods HER2 expression and binding were examined in three ovarian cancer cell lines (SKOV3, OVCAR3, Caov3) using in vitro techniques, including Western blot and saturation binding assays. PET imaging and biodistribution studies in subcutaneous models of ovarian cancer were performed to non-invasively evaluate HER2 expression in vivo. Additionally, orthotopic models were employed to further validate the imaging capability of 64Cu-NOTA-pertuzumab. Results HER2 expression was highest in SKOV3 cells, while OVCAR3 and Caov3 displayed lower HER2 expression. 64Cu-NOTA-pertuzumab showed high specificity to HER2 (Ka = 3.1 ± 0.6 nM) in SKOV3. In subcutaneous tumors, PET imaging revealed tumor uptakes of 41.8 ± 3.8, 10.5 ± 3.9, and 12.1 ± 2.3 %ID/g at 48 h post-injection for SKOV3, OVCAR3, and Caov3, respectively (n=3). In orthotopic models, PET imaging with 64Cu-NOTA-pertuzumab allowed for rapid and clear delineation of both primary and small peritoneal metastases in HER2-overexpressing ovarian cancer. Conclusion 64Cu-NOTA-pertuzumab is an effective PET tracer for the non-invasive imaging of HER2-expression in vivo, making it a potential tracer for treatment monitoring and improved patient stratification in the future.

Ovarian Cancer Targeted Theranostics

“…Radiolabeled trastuzumab, 89 Zr-trastuzumab, has demonstrated HER2 specific uptake in patients with metastatic breast cancer (26). Similarly, 89 Zrpertuzumab, another HER2 targeted antibody that inhibits dimerization of HER2, has shown promise in detecting HER2 positive tumors in preclinical models and in patients with metastatic disease (28)(29)(30). The optimal image contrast times for those intact antibodies are in days, which could potentially limit their routine use in the clinic.…”

Imaging of Preclinical Endometrial Cancer Models for Monitoring Tumor Progression and Response to Targeted Therapy

“…89 Zr-labeled pertuzumab ( 89 Zr-pertuzumab) has been used to detect HER2-positive breast cancer in small human cohorts [42,43] and to delineate tumors and show treatment effects from trastuzumab-emtansine (T-DM1) in HER2-positive breast cancer xenografts [44]. Similarly, PET-CT with radiolabeled pertuzumab ( 64 Cu-NOTA-pertuzumab) was used for non-invasive detection and monitoring of HER2 tumor expression, enabling the detection of primary tumors and peritoneal metastases in both subcutaneous and orthotopic models of ovarian cancer [45].…”

“…High specificity to HER2 expression and delineation of tumor and metastases in orthotopic and subcutaneous ovarian cancer xenografts [45].…”

European research trends in nuclear medicine

“…Non-invasive imaging of HER2 expression can allow physicians to monitor HER2-directed therapies in patients and can also be of assistance in patient stratification. Jiang et al [ 16 ] showed the usefulness of 64 Cu-labeled pertuzumab for in vivo imaging of HER2-positive ovarian cancer. In this study 64 Cu-NOTA-pertuzumab showed high specificity in an ovarian cancer cell line with high HER2 expression.…”