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

Abstract

¹²³I-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 ¹²³I-CLINDE binding in healthy subjects. Methods: 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 (V_T). Test-retest variability was measured by percentage difference (PD), the absolute PD, intraclass correlation coefficient (ICC), and coefficient of variation. Results: The absolute PD of brain SUV and the V_T had similar values. The ICC values were higher for V_Ts 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 V_T of a 49-y-old male HAB was 7.5 ± 1.4 mL/cm³ compared with 4.6 ± 1.4 mL/cm³ 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. Conclusion: The test-retest reproducibility of ¹²³I-CLINDE is comparable or better than that reported for commonly used PET TSPO tracers. Because of the binding of ¹²³I-CLINDE to blood cells and peripheral tissues, SUV is not a sufficient surrogate of V_T from 2-tissue-compartment modeling. The population-adjusted method has the potential to reduce the complexity of blood analyses of TSPO tracers.

Keywords: TSPO imaging; polymorphism; second-generation TSPO tracer; variability.