Abstract
1290
Objectives: Translocator protein (TSPO) is a mitochondrial membrane protein known to be highly expressed in macrophages. In patients with rheumatoid arthritis (RA), TSPO is also highly expressed in Fibroblast like synoviocytes (FLS) [1]. We performed PET imaging studies to quantitatively assess the uptake of the TSPO radioligand, [11C]PBR28 in Inflammatory Joint disease (IJD) and evaluated its specific binding by performing a blocking study.
Methods: Dynamic [11C]PBR28 PET-CT scans of both knees were performed in 10 subjects with RA or Psoriatic arthritis (PA). Eight subjects had a single scan. Two subjects had dual scans, before oral administration of the TSPO blocking agent XBD90 and two hours afterwards. Subjects with genetic polymorphisms demonstrating high or medium affinity for TSPO binding (HAB and MAB) were included. Radial arterial blood was sampled throughout the dynamic PET scan (90 min) and evaluated for blood radioactivity and radioactive metabolites. Synovial regions were delineated on CT images, identifying non-bone tissue regions in the knee joint space via a semi-automated threshold based algorithm. Standardized uptake value (SUV) and SUV normalized to blood (SUVR) between 50 and 70 minutes were calculated and compartmental modelling was performed to obtain the partition co-efficient (VT).
Results: Four male and six female subjects (six MABs and four HABs) aged between 37 and 71 years took part in the study. Mean [11C]PBR28 radioactivity of 364 MBq (range 291 - 389 MBq) was administered and all subjects completed their scans. Data are presented in Table 1. Overall a higher uptake was observed in HABs compared to MABs. The mean baseline scan SUV50-70 and SUVR50-70 in the knees (10 subjects; 20 knees) was 0.91 (range 0.34 - 2.21) and 5.76 (range 2.25 - 15.37), respectively. A two tissue compartmental model fitted the data well in all but one knee in each of two subjects, as in those knees the time activity curve had not reached equilibrium by the end of the scan. The mean VT in 18 knees at baseline was 5.58 (range 3.47 - 10.23) ml.cm-3. In the two subjects who also had a blocking scan, although a decrease in SUV after blocking of TSPO was not observed in both subjects, a decrease in SUVR and VT was observed with the decrease in VT being 33% and 56% for the first and second subjects, respectively, confirming specific binding of [11C]PBR28 to TSPO. Table 1:
Conclusions: The uptake and specific binding of [11C]PBR28 to TSPO demonstrates its utility in imaging IJD, suggesting that [11C]PBR28 PET-CT may have a role in investigating novel therapeutics that target FLS and macrophages.