Utility of [11C]PBR28 PET in the imaging of inflammatory arthritis

Background

PET is a cellular imaging modality that uses radionuclides targeted to a molecule of interest. Since macrophages have a crucial role in synovitis, PET targeted to translocator protein (TSPO), a mitochondrial protein upregulated in macrophages, is postulated to be a sensitive and specific means of imaging synovitis. We aimed to ascertain whether the TSPO tracer [¹¹C]PBR28 can detect and quantify synovitis in a proof-of-principle study.

Methods

Ten participants with clinical evidence of synovitis in one or both knees (five with rheumatoid arthritis, five with psoriatic arthritis), and four age-matched healthy volunteers, were included. Patients underwent clinical examination, ultrasound scanning, and PET-CT of both knees, as well as synovial biopsy of one knee over 10 days, in addition to routine blood tests. Synovial tissue from biopsy was stained for TSPO, and for the macrophage markers CD68 and CD163, and scored semiquantitatively. All knees were scored according to semiquantitative synovitis severity scores on clinical examination and ultrasound by two independent assessors.

Findings

A significant difference was observed between average tracer uptake in knees of different synovitis severity scores on both clinical examination and ultrasound (p<0·0001, ANOVA); knees with lowest synovitis scores on examination or ultrasonography had the least tracer uptake, and those with highest synovitis scores had the most tracer uptake. TSPO staining score on histology likewise positively correlated with tracer uptake from the biopsy compartment (r=0·67, p=0·02). A positive correlation was observed between C-reactive protein and average tracer uptake in both knees (r=0·81, p=0·03).

Interpretation

To our knowledge, this is the first study to indicate that [¹¹C]PBR28 PET can detect and quantify synovitis in patients with arthritis. The correlation between TSPO staining and tracer uptake implies that tracer uptake is the result of target expression and not due to confounding factors such as blood flow, but awaits confirmation with an in-vivo blocking study. Larger studies with [¹¹C]PBR28 before and after initiation of therapy will help ascertain its sensitivity as a tool for assessing response to treatment for inflammatory arthritis.

Funding

Imanova Academic Centre for Imaging Sciences (IMPETUS grant).