Immune checkpoint immunotherapies (ICIs) that target PD-L1 have rapidly become an essential part of the management of many cancers, including non-small cell lung cancer (NSCLC). Although expression of PD-L1 on a single biopsy can help select patients for ICI, the biopsy material obtained may not be representative of the biopsied lesion itself or of other lesions in anatomically different sites. Furthermore, many patients fail to respond to ICIs, some have discordant responses and most patients who do respond eventually relapse. New methods for understanding the clinical biology of PD-L1 in individual lesions over time, in the whole bodies of living patients, are urgently needed. Valuable information could potentially be obtained from sequential whole body imaging of PD-L1.
Our group has developed a novel PET tracer by linking 89Zr to durvalumab, an anti-PD-L1 monoclonal antibody used in cancer immunotherapy, with a DFO-squaramide ester chelator molecule. The resulting radiopharmaceutical was validated in vitro and in xenograft models of human PD-L1 positive and negative tumours. The tracer has so far been used for PET/CT imaging in two patients, both with PD-L1 positive stage IV NSCLC. No toxicity has been observed and in both patients uptake of tracer was observed in all known sites of disease that were apparent on contemporaneous FDG-PET scans. Our first patient, whose biopsy showed 92% PD-L1 positivity, had bone and brain metastases and had recently undergone radiotherapy to some of her metastatic lesions. Tracer uptake was most intense in recently irradiated lesions. The known brain lesions which had been treated with stereotactic radiosurgery were clearly imaged with the new tracer. The second patient had uptake of the tracer in the viable rim of a necrotic adrenal metastasis.
Conclusion: This novel PET tracer appears to be safe and capable of imaging known sites of disease in patients with PD-L1 positive NSCLC.