The Variability of Translocator Protein Signal in Brain and Blood of Genotyped Healthy Humans Using In Vivo I-CLINDE SPECT Imaging: A Test-Retest Study.

I-CLINDE is a radiotracer developed for 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 central nervous system diseases. The aim of this study was to examine the test-retest variability of I-CLINDE binding in healthy subjects. SPECT scans were acquired over 90 min in 16 healthy controls (9 women, 8 mixed-affinity binders [MABs] and 8 high-affinity binders [HABs] twice with an interval of 35 ± 15 d). Arterial input functions were based on individual blood measurements in 8 subjects and a population-based approach in combination with individual whole-blood time-activity curves in the other 8 subjects. Seven brain volumes of interest were extracted and quantified by SUVs and by 2-tissue-compartment modeling for calculation of distribution volumes (). Test-retest variability was measured by percentage difference (PD), the absolute PD, intraclass correlation coefficient (ICC), and coefficient of variation. The absolute PD of brain SUV and the had similar values. The ICC values were higher for s 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 of a 49-y-old male HAB was 7.5 ± 1.4 mL/cm compared with 4.6 ± 1.4 mL/cm of a sex- and age-matched MAB. The SUVs of a 49-y-old male HAB and MAB were 1.03 ± 0.14 and 0.88 ± 0.15 g/mL, respectively. The test-retest reproducibility of I-CLINDE is comparable or better than that reported for commonly used PET TSPO tracers. Because of the binding of I-CLINDE to blood cells and peripheral tissues, SUV is not a sufficient surrogate of from 2-tissue-compartment modeling. The population-adjusted method has the potential to reduce the complexity of blood analyses of TSPO tracers.