Translational Studies

Immuno-Positron Emission Tomography (iPET)

The specificity of monoclonal antibodies (mAb) combined with the high sensitivity of positron emission tomography makes iPET a highly effective, quantitative, non-invasive technique for disease diagnosis, prognosis, and response to therapy. Recent iPET advancements have allowed us to target immune cells and protein components of the immune system in real time using the specificity of mAb.

Renal cell carcinoma (RCC) is resistant to conventional therapy, but is responsive to hypofractionated radiation (HRT) and immunotherapy. Furthermore, HRT might synergize with immune checkpoint inhibitors (ICI). Despite the synergy, most patients progress because of therapeutic resistance. Adaptive resistance of increased programmed cell death ligand 1 (PD-L1) in response to PD-1/L1 directed therapy as well as HRT has been reported. However, this mechanism has not been verified in real time in vivo. Confirming this hypothesis will require multiple invasive biopsies of metastatic sites before and during therapy. Furthermore, due to inter- and intra-lesional heterogeneity of metastasis, we expect variable degrees of temporal and spatial adaptive resistance that may not be captured by biopsy. As a first step toward non-invasive real-time imaging of patients, we have reported the feasibility of immuno-positron emission tomography (iPET) with 89Zr labeled anti-PD-L1 mAb atezolizumab (ATZ) for tracking the dynamic changes in PD-L1 expression in vivo in response to HRT in RCC patient-derived xenograft (PDX) mouse models. In the future, our lab, in collaboration with other labs at UTSW, plan to implement this novel technique to detect the same or other proteins in similar PDX models with patient-derived tumors of different origins.

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Pet Imaging of Protein Expression

Figure legend: A schematic representing detection of target protein expression following targeted radiation of the tumor. Subcutaneous or flank model of tumors from different origins (kidney/breast/lung) expressing protein of interest in a suitable mouse model is injected with 89Zr labeled –antibody specific for the protein. PET imaging is done in different time points to detect protein expression levels in the tumor.