Immuno-PET detects changes in multi-RTK tumor cell expression levels in response to targeted kinase inhibition Journal Article
| Authors: | Pereira, P. M. R.; Norfleet, J.; Lewis, J. S.; Escorcia, F. E. |
| Article Title: | Immuno-PET detects changes in multi-RTK tumor cell expression levels in response to targeted kinase inhibition |
| Abstract: | Receptor tyrosine kinase (RTK) coexpression facilitates tumor resistance due to redundancies in the phosphatidylinositol-3'-kinase/protein kinase B and KRAS/extracellular-signal-regulated kinase signaling pathways, among others. Crosstalk between the oncogenic RTK hepatocyte growth factor receptor (MET), epidermal growth factor receptor (EGFR), and human epidermal growth factor receptor 2 (HER2) are involved in tumor resistance to RTK-targeted therapies. Methods: In a relevant renal cell carcinoma patient-derived xenograft model, we use the 89Zr-labeled anti-RTK antibodies (immuno-PET) onartuzumab, panitumumab, and trastuzumab to monitor MET, EGFR, and HER2 protein levels, respectively, during treatment with agents to which the model was resistant (cetuximab) or sensitive (INC280 and trametinib). Results: Cetuximab treatment resulted in continued tumor growth, as well as an increase in all RTK protein levels at the tumor in vivo on immuno-PET and ex vivo at the cellular level. Conversely, after dual MET/mitogen-activated protein kinase inhibition, tumor growth was significantly blunted and corresponded to a decrease in RTK levels. Conclusion: These data show the utility of RTK-targeted immuno-PET to annotate RTK changes in protein expression and inform tumor response to targeted therapies. © 2021 by the Society of Nuclear Medicine and Molecular Imaging. |
| Keywords: | molecular imaging; oncology; theranostics; kinases; immuno-pet |
| Journal Title: | Journal of Nuclear Medicine |
| Volume: | 62 |
| Issue: | 3 |
| ISSN: | 0161-5505 |
| Publisher: | Society of Nuclear Medicine |
| Date Published: | 2021-03-01 |
| Start Page: | 366 |
| End Page: | 371 |
| Language: | English |
| DOI: | 10.2967/jnumed.120.244897 |
| PUBMED: | 32646879 |
| PROVIDER: | scopus |
| PMCID: | PMC8049345 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 April 2021 -- Source: Scopus |
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