From the Departments of Neurology (C.Q., K.M.), and Radiology (M.F.), University of Pennsylvania, Perelman School of Medicine, Philadelphia; ImaginAb (W.L., I.W.), Inc., Inglewood, CA; Department of Medicine (N.G.), Duke University School of Medicine, Durham, NC; Abcuro, Inc., Newton, MA; Department of Radiology (J.M.), University of Alabama at Birmingham, Heersink School of Medicine; and Department of Neurology (S.A.G.), Brigham and Women's Hospital and Boston Childrens Hospital, Harvard Medical School, MA.
Neurology. 2023 Sep 12;101(11):e1158-e1166. doi: 10.1212/WNL.0000000000207596. Epub 2023 Jul 24.
Inclusion body myositis (IBM) is a progressive autoimmune skeletal muscle disease in which cytotoxic CD8 T cells infiltrate muscle and destroy myofibers. IBM has required a muscle biopsy for diagnosis. Here, we administered to patients with IBM a novel investigational PET tracer Zr-Df-crefmirlimab for in vivo imaging of whole body skeletal muscle CD8 T cells. This technology has not previously been applied to patients with autoimmune disease.
Four patients with IBM received Zr-Df-crefmirlimab followed by PET/CT imaging 24 hours later, and the results were compared with similar imaging of age-matched patients with cancer. Mean standardized uptake value (SUVmean) was measured for reference tissues using spherical regions of interest (ROIs).
Zr-Df-crefmirlimab was safe and well-tolerated. PET imaging demonstrated diffusely increased uptake qualitatively and quantitatively in IBM limb musculature. Quantitation of Zr-Df-crefmirlimab intensity in ROIs demonstrated particularly increased CD8 T-cell infiltration in patients with IBM compared with patients with cancer in quadriceps (SUVmean 0.55 vs 0.20, < 0.0001), biceps brachii (0.62 vs 0.26, < 0.0001), triceps (0.61 vs 0.25, = 0.0005), and forearm finger flexors (0.71 vs 0.23, = 0.008).
Zr-Df-crefmirlimab uptake in muscles of patients with IBM was present at an intensity greater than the comparator population. The ability to visualize whole body in vivo cytotoxic T-cell tissue infiltration in the autoimmune disease IBM may hold utility as a biomarker for diagnosis, disease activity, and therapeutic development and potentially be applicable to other diseases with cytotoxic T-cell autoimmunity.
包涵体肌炎(IBM)是一种进行性自身免疫性骨骼肌疾病,其中细胞毒性 CD8 T 细胞浸润肌肉并破坏肌纤维。IBM 需要进行肌肉活检才能确诊。在此,我们向 IBM 患者给予一种新型研究性 PET 示踪剂 Zr-Df-crefmirlimab,以对全身骨骼肌 CD8 T 细胞进行体内成像。这项技术以前从未应用于自身免疫性疾病患者。
4 名 IBM 患者接受 Zr-Df-crefmirlimab 治疗,随后在 24 小时后进行 PET/CT 成像,并将结果与年龄匹配的癌症患者的类似成像进行比较。使用球形感兴趣区(ROI)测量参考组织的平均标准化摄取值(SUVmean)。
Zr-Df-crefmirlimab 安全且耐受良好。PET 成像定性和定量显示 IBM 肢体肌肉摄取明显增加。ROI 中 Zr-Df-crefmirlimab 强度的定量分析表明,与癌症患者相比,IBM 患者的 CD8 T 细胞浸润特别增加,股四头肌(SUVmean 0.55 比 0.20, < 0.0001)、肱二头肌(0.62 比 0.26, < 0.0001)、肱三头肌(0.61 比 0.25, = 0.0005)和前臂手指屈肌(0.71 比 0.23, = 0.008)。
IBM 患者肌肉中的 Zr-Df-crefmirlimab 摄取强度大于对照组。在 IBM 等自身免疫性疾病中,可视化全身体内细胞毒性 T 细胞组织浸润的能力可能作为诊断、疾病活动和治疗开发的生物标志物具有实用性,并且可能适用于其他具有细胞毒性 T 细胞自身免疫的疾病。