PT  - JOURNAL ARTICLE
AU  - Patricia M.R. Pereira
AU  - Jalen Norfleet
AU  - Jason S. Lewis
AU  - Freddy E. Escorcia
TI  - Immuno-PET Detects Changes in Multi-RTK Tumor Cell Expression Levels in Response to Targeted Kinase Inhibition
AID  - 10.2967/jnumed.120.244897
DP  - 2021 Mar 01
TA  - Journal of Nuclear Medicine
PG  - 366--371
VI  - 62
IP  - 3
4099  - http://jnm.snmjournals.org/content/62/3/366.short
4100  - http://jnm.snmjournals.org/content/62/3/366.full
SO  - J Nucl Med2021 Mar 01; 62
AB  - 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.