Lohmann Philipp, Schäfer Laura, Krause Sandra, Altunay Betül, Willuweit Antje, Werner Jan-Michael, Galldiks Norbert, Langen Karl-Josef, Mottaghy Felix M, Lütje Susanne
Institute of Neuroscience and Medicine (INM-3, INM-4), Research Center Juelich, Juelich, Germany.
Department of Nuclear Medicine, RWTH Aachen University Hospital, Aachen, Germany.
Neurooncol Adv. 2025 Aug 4;7(1):vdaf176. doi: 10.1093/noajnl/vdaf176. eCollection 2025 Jan-Dec.
Glioblastoma is known for its highly immunosuppressive microenvironment, hindering the efficacy of immunotherapies. Noninvasive imaging like immuno-positron emission tomography (PET) offers the potential for visualizing immune dynamics within glioblastoma, potentially aiding in patient selection and treatment monitoring. This systematic review evaluates immuno-PET tracers currently under investigation for the noninvasive visualization of the immune environment in glioblastoma.
A literature search was conducted in PubMed and Web of Science up to March 2025, using keywords related to glioblastoma, immuno-PET, immune compartments, and specific tracers. Studies were screened based on predefined inclusion and exclusion criteria, focusing on the development, characterization, or application of immuno-PET tracers targeting immune cells or immune checkpoint molecules in glioblastoma.
Nineteen studies met the inclusion criteria, exploring tracers targeting immune checkpoints and immune cell populations. Full-length antibodies demonstrated higher tumor specificity and retention compared to smaller fragments but showed longer circulation times. Peptide-based tracers and affibodies offered improved pharmacokinetics with rapid clearance and lower nonspecific uptake but encountered hurdles in ensuring adequate tumor targeting and retention. Advancements included dual-modal tracers combining PET and near-infrared fluorescence imaging for enhanced diagnostic and intraoperative applications.
Significant progress has been made in developing immuno-PET tracers for noninvasive visualization of immune reactions in glioblastoma. Challenges persist in clinical translation due to issues like blood-brain barrier permeability and safety profiles. Continued research and clinical evaluations are essential to harness the potential of immuno-PET in improving glioblastoma diagnosis, assessment of treatment response, and guiding personalized immunotherapy strategies, ultimately aiming to enhance patient outcomes.
胶质母细胞瘤以其高度免疫抑制的微环境而闻名，这阻碍了免疫疗法的疗效。免疫正电子发射断层扫描（PET）等非侵入性成像技术为可视化胶质母细胞瘤内的免疫动态提供了潜力，可能有助于患者选择和治疗监测。本系统评价评估了目前正在研究的用于胶质母细胞瘤免疫环境非侵入性可视化的免疫PET示踪剂。
截至2025年3月，在PubMed和Web of Science上进行了文献检索，使用了与胶质母细胞瘤、免疫PET、免疫区室和特定示踪剂相关的关键词。根据预先定义的纳入和排除标准对研究进行筛选，重点关注针对胶质母细胞瘤中免疫细胞或免疫检查点分子的免疫PET示踪剂的开发、表征或应用。
19项研究符合纳入标准，探索了针对免疫检查点和免疫细胞群体的示踪剂。与较小片段相比，全长抗体表现出更高的肿瘤特异性和滞留率，但循环时间更长。基于肽的示踪剂和亲和体具有改善的药代动力学，清除迅速且非特异性摄取较低，但在确保足够的肿瘤靶向性和滞留方面遇到障碍。进展包括结合PET和近红外荧光成像的双模态示踪剂，用于增强诊断和术中应用。
在开发用于胶质母细胞瘤免疫反应非侵入性可视化的免疫PET示踪剂方面取得了重大进展。由于血脑屏障通透性和安全性等问题，临床转化中仍存在挑战。持续的研究和临床评估对于利用免疫PET在改善胶质母细胞瘤诊断、治疗反应评估和指导个性化免疫治疗策略方面的潜力至关重要，最终目标是改善患者预后。
