The Variability of Translocator Protein Signal in Brain and Blood of Genotyped Healthy Humans using in vivo [123I]CLINDE-SPECT imaging – a test-retest study.

¹²³I-CLINDE is a radiotracer developed for single photon emission computed tomography (SPECT) and targets the 18 kDa Translocator protein (TSPO). TSPO is upregulated in glial cells and used as a measure of neuroinflammation in a variety of CNS diseases. The aim of this study was to examine the test-retest variability of ¹²³I-CLINDE binding in healthy subjects.

Methods SPECT-scans were acquired over 90 mins in sixteen healthy controls (nine females, eight mixed affinity binder (MAB) and eight high affinity binders (HAB) twice with an interval of 35±15 days. Arterial input functions were based on individual blood measurements in eight subjects, and a population-based approach in combination with individual whole-blood time activity curves (TACs) in the other eight subjects. Seven brain volumes of interest were extracted and quantified by standard uptake values (SUVs) and by two-tissue compartment modelling (2TCM) for calculation of distribution volumes (VT). Test-retest variability was measured by percentage difference (PD), the absolute PD, intraclass correlation coefficient (ICC) and coefficient of variation (COV).

Results The absolute PD of brain SUV and the VT had similar values. The ICC values were higher for VTs than for brain SUVs, which were both moderate to high, however, lower ICC values were observed when calculated separately for HABs and MABs. Test-retest reproducibility was higher in subjects with immediate centrifugation of blood samples. The population-based method efficiently recovered data with delayed centrifugation. The VT of a 49-year-old male HAB was 7.5±1.4 mL/cm3 compared to 4.6±1.4 mL/cm3 of a gender- and age- matched MAB. The SUV of a 49-year-old male HAB and MAB were 1.03±0.14 g/ml and 0.88±0.15 g/ml, respectively.

Conclusions The test-retest reproducibility of ¹²³I-CLINDE is comparable or better than that reported for commonly used PET TSPO tracers. Due to binding of ¹²³I-CLINDE to blood cells and peripheral tissues, SUV is not a sufficient surrogate of VT from 2TCM. The population-adjusted method has the potential to reduce the complexity of blood analyses of TSPO tracers.