The following is a summary of “ImmunoPET Imaging with 89Zr-Labeled Atezolizumab Enables In Vivo Evaluation of PD-L1 in Tumorgraft Models of Renal Cell Carcinoma” published in the November 2022 issue of Clinical Cancer by Mulgaonkar et al.
The standard of care for patients with advanced stages of renal cell carcinoma (RCC) has shifted dramatically thanks to the development of immune checkpoint inhibitors (ICI) that target the programmed cell death protein 1 and its ligand (PD-1/PD-L1). However, there is a lack of prognostic biomarkers, and response rates to ICIs as single agents or in combination vary substantially. Possibly due to the heterogeneity and dynamic nature of PD-L1 expression, tissue-based approaches have yet to demonstrate much value. Non-invasive, all-inclusive, and real-time PD-L1 detection may be possible with immuno-positron emission tomography (immunoPET). In this study, we compared the efficacy of immunoPET against immunohistochemistry (IHC) for detecting PD-L1 in a tumorgraft (TG) platform obtained from patients with renal cell carcinoma.
ImmunoPET was used to analyze the activity of eight separate RCC TGs spanning a wide range of PD-L1 expression (0% to 85%). Double-blind analyses compared tumor PD-L1 expression with uptake of [89Zr]Zr-labeled atezolizumab ([89Zr]Zr-DFO-ATZ). Clinical outcomes of ICI-treated patients whose TGs were assessed were analyzed to determine the clinical role of immunoPET in RCC. The correlation between PD-L1 IHC tests and [89Zr]Zr-DFO-ATZ immunoPET scans on days 6/7 postinjection was statistically significant (P=0.0014; PXY =0.78).
Furthermore, immunoPET can be employed to analyze the heterogeneous distribution of PD-L1 expression. Studies in matched patients (n=4) also demonstrate that PD-L1 signal may affect ICI responsiveness. ImmunoPET using [89Zr]Zr-DFO-ATZ may offer a complete and dynamic assessment of PD-L1 across areas of illness. In a current clinical trial, researchers are examining whether immunoPET may accurately predict ICI response in RCC (NCT04006522).