Interleukin-2 PET imaging in patients with metastatic melanoma before and during immune checkpoint inhibitor therapy

Purpose immune checkpoint inhibitors can induce a T cell-mediated anti-tumor immune response in patients with melanoma. Visualizing T cell activity using positron emission tomography (PET) might allow early insight into treatment efficacy. Activated tumor-infiltrating T cells express the high-affinity interleukin-2 receptor (IL-2R). Therefore, we performed a pilot study, using fluorine-18-labeled IL-2 ([F-18]FB-1L2 PET), to evaluate whether a treatment-induced immune response can be detected. Methods Patients with metastatic melanoma received similar to 200 MBq [F-18]FB-IL2 intravenously, followed by a PET/CT scan before and during immune checkpoint inhibitor therapy. [F-18]FB-IL2 uptake was measured as standardized uptake value in healthy tissues (SUVmean) and tumor lesions (SUVmax). Response to therapy was assessed using RECIST v1.1. Archival tumor tissues were used for immunohistochemical analyses of T cell infiltration. Results Baseline [F-18]FB-IL2 PET scans were performed in 13 patients. SUVmean at baseline was highest in the kidneys (14.2, IQR: 11.6-18.0) and liver (10.6, IQR: 8.6-13.4). In lymphoid tissues, uptake was highest in spleen (10.9, IQR: 8.8-12.4) and bone marrow (2.5, IQR: 2.1-3.0). SUVmax in tumor lesions (n = 41) at baseline was 1.9 (IQR: 1.7-2.3). In 11 patients, serial imaging was performed, three at week 6, seven at week 2, and one at week 4. Median [F-18]FB-IL2 tumor uptake decreased from 1.8 (IQR: 1.7-2.1) at baseline to 1.7 (IQR: 1.4-2.1) during treatment (p = 0.043). Changes in [F-18]FB-11.2 tumor uptake did not correlate with response. IL-2R expression in four archival tumor tissues was low and did not correlate with baseline [F-18]FB-IL2 uptake. No [F-18]FB-IL2-related side effects occurred. Conclusion PET imaging of the IL-2R, using [F-18]FB-IL2, is safe and feasible. In this small patient group, serial [F-18]FB-IL2-PEr imaging did not detect a treatment-related immune response.