PT - JOURNAL ARTICLE AU - Ling Feng AU - Per Jensen AU - Gerda Thomsen AU - Agnete Dyssegaard AU - Claus Svarer AU - Lars V. Knudsen AU - Kirsten Møller AU - Carsten Thomsen AU - Jens D. Mikkelsen AU - Denis Guilloteau AU - Gitte M. Knudsen AU - Lars H. Pinborg TI - The Variability of Translocator Protein Signal in Brain and Blood of Genotyped Healthy Humans Using In Vivo <sup>123</sup>I-CLINDE SPECT Imaging: A Test–Retest Study AID - 10.2967/jnumed.116.183202 DP - 2017 Jun 01 TA - Journal of Nuclear Medicine PG - 989--995 VI - 58 IP - 6 4099 - http://jnm.snmjournals.org/content/58/6/989.short 4100 - http://jnm.snmjournals.org/content/58/6/989.full SO - J Nucl Med2017 Jun 01; 58 AB - 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 (VT). 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 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-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 VT from 2-tissue-compartment modeling. The population-adjusted method has the potential to reduce the complexity of blood analyses of TSPO tracers.