Imaging With PET/CT of Diffuse CD8 T-Cell Infiltration of Skeletal Muscle in Patients With Inclusion Body Myositis.

Abstract

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 89Zr-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 89Zr-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). 89Zr-Df-crefmirlimab was safe and well-tolerated. PET imaging demonstrated diffusely increased uptake qualitatively and quantitatively in IBM limb musculature. Quantitation of 89Zr-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, p < 0.0001), biceps brachii (0.62 vs 0.26, p < 0.0001), triceps (0.61 vs 0.25, p = 0.0005), and forearm finger flexors (0.71 vs 0.23, p = 0.008). 89Zr-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.