Abstract | PURPOSE: 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 for non-invasive in vivo evaluation of HER2 expression. 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 for HER2 (Ka = 3.1 ± 0.6 nM) in SKOV3. In subcutaneous tumors, PET imaging revealed tumor uptake 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-expressing ovarian cancer. CONCLUSIONS: 64Cu-NOTA-pertuzumab is an effective PET tracer for the non-invasive imaging of HER2 expression in vivo, rendering it a potential tracer for treatment monitoring and improved patient stratification.
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Authors | Dawei Jiang, Hyung-Jun Im, Haiyan Sun, Hector F Valdovinos, Christopher G England, Emily B Ehlerding, Robert J Nickles, Dong Soo Lee, Steve Y Cho, Peng Huang, Weibo Cai |
Journal | European journal of nuclear medicine and molecular imaging
(Eur J Nucl Med Mol Imaging)
Vol. 44
Issue 8
Pg. 1296-1305
(Aug 2017)
ISSN: 1619-7089 [Electronic] Germany |
PMID | 28265738
(Publication Type: Journal Article)
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Chemical References |
- Antibodies, Monoclonal, Humanized
- Copper Radioisotopes
- Copper-64
- Heterocyclic Compounds, 1-Ring
- 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
- ERBB2 protein, human
- Receptor, ErbB-2
- pertuzumab
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Topics |
- Animals
- Antibodies, Monoclonal, Humanized
(chemistry, metabolism, pharmacokinetics)
- Cell Line, Tumor
- Cell Transformation, Neoplastic
- Copper Radioisotopes
- Female
- Gene Expression Regulation, Neoplastic
- Heterocyclic Compounds, 1-Ring
(chemistry)
- Humans
- Isotope Labeling
- Mice
- Ovarian Neoplasms
(diagnostic imaging, metabolism, pathology)
- Positron-Emission Tomography
(methods)
- Radiometry
- Receptor, ErbB-2
(metabolism)
- Tissue Distribution
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