TY - JOUR T1 - PD-L1 detection using <sup>89</sup>Zr-atezolizumab immuno-PET in renal cell carcinoma tumorgrafts from a patient with favorable nivolumab response JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer DO - 10.1186/s40425-019-0607-z VL - 7 IS - 1 SP - 144 AU - Joseph Vento AU - Aditi Mulgaonkar AU - Layton Woolford AU - Kien Nham AU - Alana Christie AU - Aditya Bagrodia AU - Alberto Diaz de Leon AU - Raquibul Hannan AU - Isaac Bowman AU - Renee M. McKay AU - Payal Kapur AU - Guiyang Hao AU - Xiankai Sun AU - James Brugarolas Y1 - 2019/12/01 UR - http://jitc.bmj.com/content/7/1/144.abstract N2 - Background Programmed death-ligand 1 (PD-L1) expression in metastatic renal cell carcinoma (RCC) correlates with a worse prognosis, but whether it also predicts responsiveness to anti-PD-1/PD-L1 therapy remains unclear. Most studies of PD-L1 are limited by evaluation in primary rather than metastatic sites, and in biopsy samples, which may not be representative. These limitations may be overcome with immuno–positron emission tomography (iPET), an emerging tool allowing the detection of cell surface proteins with radiolabeled antibodies. Here, we report iPET studies of PD-L1 in a preclinical tumorgraft model of clear cell RCC (ccRCC) from a patient who had a favorable response to anti-PD-1 therapy.Case presentation A 49-year-old man underwent a cytoreductive nephrectomy in 2017 of a right kidney tumor invading into the adrenal gland that was metastatic to the lungs and a rib. Histological analyses revealed a ccRCC of ISUP grade 4 with extensive sarcomatoid features. IMDC risk group was poor. Within two hours of surgery, a tumor sample was implanted orthotopically into NOD/SCID mice. Consistent with an aggressive tumor, a renal mass was detected 18 days post-implantation. Histologically, the tumorgraft showed sarcomatoid differentiation and high levels of PD-L1, similar to the patient’s tumor. PD-L1 was evaluated in subsequently transplanted mice using iPET and the results were compared to control mice implanted with a PD-L1-negative tumor. We labeled atezolizumab, an anti-PD-L1 antibody with a mutant Fc, with zirconium-89. iPET revealed significantly higher 89Zr-atezolizumab uptake in index than control tumorgrafts. The patient was treated with high-dose IL2 initially, and subsequently with pazopanib, with rapidly progressive disease, but had a durable response with nivolumab.Conclusions To our knowledge, this is the first report of non-invasive detection of PD-L1 in renal cancer using molecular imaging. This study supports clinical evaluation of iPET to identify RCC patients with tumors deploying the PD-L1 checkpoint pathway who may be most likely to benefit from PD-1/PD-L1 disrupting drugs.Joseph Vento, Aditi Mulgaonkar and Layton Woolford contributed equally to this work.Abbreviations:% ID/gPercent Injected Dose per gram89ZrZirconium-89ccRCCclear cell Renal Cell CarcinomaCTComputed Tomographyd.p.i.days post-injectionFcFragment crystallizablehhoursHD-IL2High-Dose Interleukin 2IHCImmunohistochemistryIL2Interleukin 2IMDCInternational Metastatic Database ConsortiumINDInvestigational New DrugiPETimmuno-PETirAE immune-related Adverse EventISUPInternational Society of Urological PathologyIVIntravenousMRMagnetic ResonanceNOD/SCIDNon-Obese Diabetic with Severe Combined ImmunodeficiencyPD-1Programmed Cell Death Protein 1PD-L1Programmed Death-Ligand 1PDXPatient-Derived XenograftPETPositron Emission TomographyPOOralPRPartial Responseqeveryqdevery dayRCCRenal Cell CarcinomaSABRStereotactic Ablative RadiotherapyTKITyrosine Kinase Inhibitor ER -