School of Biomedical Engineering and Imaging Sciences, Department of Imaging Chemistry and Biology, King's College London, UK; Institute of Bioengineering and Bioimaging, Agency for Science, Technology, and Research (A⁎ STAR), 11 Biopolis Way, #01-02 Helios, Singapore 138667, Singapore; Clinical Imaging Research Centre, 14 Medical Drive, #B01-01 Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore; Minerva Imaging ApS, Lyshøjvej 21, Ølstykke 3650, Denmark.
Institute of Bioengineering and Bioimaging, Agency for Science, Technology, and Research (A⁎ STAR), 11 Biopolis Way, #01-02 Helios, Singapore 138667, Singapore.
Biomed Pharmacother. 2024 Nov;180:117617. doi: 10.1016/j.biopha.2024.117617. Epub 2024 Oct 30.
F-interleukin-2 based PET imaging of activated T cells serves as a potential tool for non-invasive response prediction, treatment evaluation, and patient stratification in cancer immune checkpoint therapy. Herein, we report the radiolabelling of interleukin-2 (IL-2) with a novel arginine selective bioconjugation reagent, 4-[F]fluorophenylglyoxal ([F]FPG). Good non-decay corrected bioconjugation efficiencies of 29 ± 4 % (n = 5) were obtained for the [F]FPG-IL-2. [F]FPG-IL-2 uptake by the phytohemagglutinin-activated Jurkat cells (50.5 ± 1.2 %, n = 3) was significantly higher compared to the non-activated Jurkat cells (12.9 ± 1.1 %, n = 3). The [F]FPG-IL-2 uptake was blocked by the pre-treatment of activated Jurkat cells with excess native IL-2 (22.3 ± 2.2 %, n = 3). Dynamic PET imaging and ex vivo biodistribution study of [F]FPG-IL-2 in healthy and CT26 tumour bearing mice demonstrated hepatobiliary and renal clearance with minimal uptake in other organs and CT26 tumours. [F]FPG-IL-2 PET imaging was applied to non-invasively monitor immune checkpoint therapy in CT26 tumour bearing mice, treated with IgG (control), ⍺PD-1 (monotherapy), and ⍺PD-1+⍺CTLA-4 (combination therapy). Significant uptake was observed in the spleens and tumours of the mice in the combination therapy group, which was associated with increased cytotoxic CD8+ T-cell infiltration and reduced tumour volumes. [F]FPG-IL-2 based PET imaging has the potential to monitor immune checkpoint therapy.
基于 F-白细胞介素-2 的正电子发射断层扫描成像可作为癌症免疫检查点治疗中无创性反应预测、治疗评估和患者分层的潜在工具。在此，我们报告了用新型精氨酸选择性生物偶联试剂 4-[F]氟苯乙二醛 ([F]FPG) 标记白细胞介素-2 (IL-2)。[F]FPG-IL-2 的非衰变校正生物偶联效率为 29±4%（n=5）。植物血凝素激活的 Jurkat 细胞摄取 [F]FPG-IL-2（50.5±1.2%，n=3）明显高于未激活的 Jurkat 细胞（12.9±1.1%，n=3）。用过量天然 IL-2 预处理激活的 Jurkat 细胞可阻断 [F]FPG-IL-2 的摄取（22.3±2.2%，n=3）。[F]FPG-IL-2 在健康和 CT26 荷瘤小鼠中的动态 PET 成像和体外生物分布研究显示，其具有肝胆和肾脏清除作用，其他器官和 CT26 肿瘤摄取较少。[F]FPG-IL-2 PET 成像用于非侵入性监测 CT26 荷瘤小鼠的免疫检查点治疗，这些小鼠分别用 IgG（对照）、αPD-1（单药治疗）和 αPD-1+αCTLA-4（联合治疗）治疗。组合治疗组的小鼠脾脏和肿瘤观察到明显摄取，与细胞毒性 CD8+T 细胞浸润增加和肿瘤体积减少相关。基于 [F]FPG-IL-2 的 PET 成像具有监测免疫检查点治疗的潜力。
