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

Autor: van de Donk PP; Department of Medical Oncology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands., Wind TT; Department of Medical Oncology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands., Hooiveld-Noeken JS; Department of Medical Oncology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands., van der Veen EL; Department of Medical Oncology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands., Glaudemans AWJM; Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University Medical Center Groningen, Groningen, The Netherlands., Diepstra A; Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Jalving M; Department of Medical Oncology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands., de Vries EGE; Department of Medical Oncology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands., de Vries EFJ; Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University Medical Center Groningen, Groningen, The Netherlands., Hospers GAP; Department of Medical Oncology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands. g.a.p.hospers@umcg.nl.
Jazyk: angličtina
Zdroj: European journal of nuclear medicine and molecular imaging [Eur J Nucl Med Mol Imaging] 2021 Dec; Vol. 48 (13), pp. 4369-4376. Date of Electronic Publication: 2021 Jun 02.
DOI: 10.1007/s00259-021-05407-y
Abstrakt: 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 ([ 18 F]FB-IL2 PET), to evaluate whether a treatment-induced immune response can be detected.
Methods: Patients with metastatic melanoma received ~ 200 MBq [ 18 F]FB-IL2 intravenously, followed by a PET/CT scan before and during immune checkpoint inhibitor therapy. [ 18 F]FB-IL2 uptake was measured as standardized uptake value in healthy tissues (SUV mean ) and tumor lesions (SUV max ). Response to therapy was assessed using RECIST v1.1. Archival tumor tissues were used for immunohistochemical analyses of T cell infiltration.
Results: Baseline [ 18 F]FB-IL2 PET scans were performed in 13 patients. SUV mean 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). SUV max 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 [ 18 F]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 [ 18 F]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 [ 18 F]FB-IL2 uptake. No [ 18 F]FB-IL2-related side effects occurred.
Conclusion: PET imaging of the IL-2R, using [ 18 F]FB-IL2, is safe and feasible. In this small patient group, serial [ 18 F]FB-IL2-PET imaging did not detect a treatment-related immune response.
Trial Registration: Clinicaltrials.gov : NCT02922283; EudraCT: 2014-003387.20.
(© 2021. The Author(s).)
Databáze: MEDLINE
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