Abstract
Background 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 IBM patients 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.
Methods Four patients with IBM received 89Zr-Df-crefmirlimab followed by PET/CT imaging 24 hours later and 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).
Results 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 to 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).
Discussion 89Zr-Df-crefmirlimab uptake in IBM patient muscles 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.
- Received December 2, 2022.
- Accepted in final form May 12, 2023.
- © 2023 American Academy of Neurology
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