Department of Radiology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Molecules. 2020 Jul 7;25(13):3102. doi: 10.3390/molecules25133102.
The human immune system is a complex system which protects against invaders and maintains tissue homeostasis. It is broadly divided into the innate and adaptive branches. Granzyme B is serine protease that plays an important role in both and can serve as a biomarker for cellular activation. Because of this, a granzyme B PET agent (GZP) has recently been developed and has been shown to be able to monitor response to immunotherapy. Here, we evaluated the utility of granzyme B PET imaging to assess the innate immune response. We subcutaneously administered LPS to mice to induce inflammation and performed granzyme B PET imaging after 24 and 120 h. We dissected out tissue in the region of injection and performed granzyme B immunofluorescence (IF) to confirm specificity of the GZP radiotracer. Granzyme B PET imaging demonstrated increased uptake in the region of LPS injection after 24 h, which normalized at 120 h. Granzyme B immunofluorescence showed specific staining in tissue from the 24 h time point compared to the PBS-injected control. These findings support the use of granzyme B PET for imaging innate immunity. In certain clinical contexts, the use of GZP PET imaging may be superior to currently available agents, and we therefore suggest further preclinical studies with the ultimate goal of translation to clinical use.
人体免疫系统是一个复杂的系统，可抵御外来入侵并维持组织内环境稳定。它大致可分为先天免疫和适应性免疫分支。颗粒酶 B 是一种丝氨酸蛋白酶，在这两个分支中都发挥着重要作用，并且可以作为细胞活化的生物标志物。正因为如此，最近开发了一种颗粒酶 B PET 示踪剂（GZP），并已证明它能够监测免疫治疗的反应。在这里，我们评估了颗粒酶 B PET 成像在评估先天免疫反应中的效用。我们通过皮下注射 LPS 诱导炎症，并在 24 小时和 120 小时后进行颗粒酶 B PET 成像。我们从注射部位取出组织，并进行颗粒酶 B 免疫荧光（IF）以确认 GZP 放射性示踪剂的特异性。24 小时后，LPS 注射部位的颗粒酶 B PET 成像显示摄取增加，120 小时后恢复正常。颗粒酶 B 免疫荧光显示与 PBS 注射对照相比，在 24 小时的时间点组织有特异性染色。这些发现支持使用颗粒酶 B PET 进行先天免疫成像。在某些临床情况下，使用 GZP PET 成像可能优于目前可用的药物，因此我们建议进行更多的临床前研究，最终目标是转化为临床应用。
