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Purpose <p>Mitochondrial translocator protein 18&#xa0;kDa (TSPO), expressed by brain cells involved in immunity, has been a positron emission tomography (PET) target in numerous neurological and psychiatric studies. TSPO PET ligand binding is influenced by the single nucleotide polymorphism rs6971, dividing the population into three groups: high-affinity binders (HAB), mixed-affinity binders (MAB), and low-affinity binders (LAB). Unlike most “second generation” TSPO ligands, [<sup>11</sup>C]ER176 allows imaging of even LAB. This study examines the yet unstudied test-retest reproducibility of [<sup>11</sup>C]ER176 binding in all TSPO genotypes.</p> Methods <p>Twelve healthy participants were studied. Seven had two [<sup>11</sup>C]ER176 PET scans in the same day, morning and afternoon; five of these had a third PET scan on a separate morning. Five additional controls underwent two scans on separate mornings. Metabolite-corrected arterial input function (AIF) was used to calculate total distribution volume (<i>V</i><sub>T</sub>) with a two-tissue compartment model.</p> Results <p><i>V</i><sub>T</sub> showed showed excellent reproducibility for scans performed at the same time of day: for AM scans, whole-brain variability, excluding an outlier, was 12.4 ± 6.0%. The intraclass correlation coefficient was excellent, at 0.92. However, <i>V</i><sub>T</sub> showed a significant diurnal effect: [<sup>11</sup>C]ER176 parent SUV was higher in all subjects in AM compared to PM, while brain <i>V</i><sub>T</sub> was lower in AM. HABs and MABs showed greater <i>V</i><sub>T</sub> increases: whole-brain <i>V</i><sub>T</sub> variability for AM versus PM was 8.5 ± 5.8% <i>/</i> 28.4 ± 4.5% <i>/</i> 28.5 ± 8.0% for LAB/MAB/HAB.</p> Conclusion <p>[<sup>11</sup>C]ER176 brain <i>V</i><sub>T</sub> has good reproducibility across days for scans performed in the morning. However, <i>V</i><sub>T</sub> shows diurnal effects, which must be accounted for in study design.</p>

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TSPO circadian pattern: a test-retest study of [11C]ER176

  • 期刊论文

  • 发表日期：

    2025年7月4日

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  • Quentin Finn,
  • Paolo Zanotti-Fregonara,
  • Meixiang Yu,
  • Masahiro Fujita,
  • Joseph C. Masdeu,
  • Belen Pascual

摘要

Purpose

Mitochondrial translocator protein 18 kDa (TSPO), expressed by brain cells involved in immunity, has been a positron emission tomography (PET) target in numerous neurological and psychiatric studies. TSPO PET ligand binding is influenced by the single nucleotide polymorphism rs6971, dividing the population into three groups: high-affinity binders (HAB), mixed-affinity binders (MAB), and low-affinity binders (LAB). Unlike most “second generation” TSPO ligands, [11C]ER176 allows imaging of even LAB. This study examines the yet unstudied test-retest reproducibility of [11C]ER176 binding in all TSPO genotypes.

Methods

Twelve healthy participants were studied. Seven had two [11C]ER176 PET scans in the same day, morning and afternoon; five of these had a third PET scan on a separate morning. Five additional controls underwent two scans on separate mornings. Metabolite-corrected arterial input function (AIF) was used to calculate total distribution volume (VT) with a two-tissue compartment model.

Results

VT showed showed excellent reproducibility for scans performed at the same time of day: for AM scans, whole-brain variability, excluding an outlier, was 12.4 ± 6.0%. The intraclass correlation coefficient was excellent, at 0.92. However, VT showed a significant diurnal effect: [11C]ER176 parent SUV was higher in all subjects in AM compared to PM, while brain VT was lower in AM. HABs and MABs showed greater VT increases: whole-brain VT variability for AM versus PM was 8.5 ± 5.8% / 28.4 ± 4.5% / 28.5 ± 8.0% for LAB/MAB/HAB.

Conclusion

[11C]ER176 brain VT has good reproducibility across days for scans performed in the morning. However, VT shows diurnal effects, which must be accounted for in study design.