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

Abstract

BackgroundInclusion 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 tracer89Zr-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.MethodsFour patients with IBM received89Zr-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).Results89Zr-Df-crefmirlimab was safe and well tolerated. PET imaging demonstrated diffusely increased uptake qualitatively and quantitatively in IBM limb musculature. Quantitation of89Zr-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).Discussion89Zr-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.

Preliminary evidence of localizing CD8+ T-cell responses in COVID-19 patients with PET imaging

“…Biomarker technologies that allow early and quantitative assessment of changes in CD8+ T-cell distributions, e.g., from lymphoid compartments to mucosal linings, may provide alternative endpoints that can accelerate the development of effective vaccination approaches. Similarly, novel treatment strategies in immune-mediated inflammatory conditions that are dominated by CD8+ T-cells ( 26 ) or in which CD8+ T-cells are therapeutically targeted may benefit from non-invasive imaging approaches. The observations made in this case series highlight PET imaging with immune cell-specific tracers as an imaging biomarker that may complement current immunological assays with information on the spatiotemporal distributions of CD8+ T-cells on a whole-body scale, assessing yet another aspect of CD8+ T-cell biology ( 9 ).…”