Abstract
PurposeImmune 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 ([18F]FB-IL2 PET), to evaluate whether a treatment-induced immune response can be detected.MethodsPatients with metastatic melanoma received ~ 200 MBq [18F]FB-IL2 intravenously, followed by a PET/CT scan before and during immune checkpoint inhibitor therapy. [18F]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.ResultsBaseline [18F]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 [18F]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 [18F]FB-IL2 tumor uptake did not correlate with response. IL-2R expression in four archival tumor tissues was low and did not correlate with baseline [18F]FB-IL2 uptake. No [18F]FB-IL2-related side effects occurred.ConclusionPET imaging of the IL-2R, using [18F]FB-IL2, is safe and feasible. In this small patient group, serial [18F]FB-IL2-PET imaging did not detect a treatment-related immune response.Trial registrationClinicaltrials.gov: NCT02922283; EudraCT: 2014-003387.20
Highlights
This article is part of the Topical Collection on Oncology – GeneralImmune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy for the treatment of multiple tumor types, including melanoma [1,2,3,4,5,6,7]
These monoclonal antibody– based therapies exert their effect by blocking inhibitory ligand-receptor interactions of immune checkpoints, such as cytotoxic T lymphocyte–associated antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1) receptor, or its ligand (PD-L1) [8]
We developed N-(4-18F-fluorobenzoyl)-interleukin-2 ([18F]FB-IL2), a clinical-grade fluorine-18-labeled IL-2 positron emission tomography (PET) tracer [10]
Summary
Immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy for the treatment of multiple tumor types, including melanoma [1,2,3,4,5,6,7]. These monoclonal antibody– based therapies exert their effect by blocking inhibitory ligand-receptor interactions of immune checkpoints, such as cytotoxic T lymphocyte–associated antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1) receptor, or its ligand (PD-L1) [8]. The presence of tumor-specific T cells in the tumor microenvironment is a key predictive factor for response to ICI therapy [9] Visualizing these T cells could provide valuable insight into the anti-tumor immune response. We developed N-(4-18F-fluorobenzoyl)-interleukin-2 ([18F]FB-IL2), a clinical-grade fluorine-18-labeled IL-2 PET tracer [10]
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