Head-to-head comparison of 11C-PBR28 and 11C-ER176 for quantification of the translocator protein in the human brain

Eur J Nucl Med Mol Imaging. 2019 Aug;46(9):1822-1829. doi: 10.1007/s00259-019-04349-w. Epub 2019 May 31.

Abstract

Introduction: 11C-ER176 is a new PET tracer to quantify the translocator protein (TSPO), a biomarker for inflammation. The aim of this study was to perform a head-to-head comparison between 11C-ER176 and the widely used 11C-PBR28.

Methods: Seven healthy volunteers had a 90-min PET scan and metabolite-corrected arterial input function with 11C-PBR28 in the morning and 11C-ER176 in the afternoon. Binding was quantified at the regional level in terms of VT with a two-tissue compartmental model. By using VND values from the literature obtained with pharmacological blockade, we derived the binding potential BPND for both tracers.

Results: 11C-ER176 was more stable in arterial blood than 11C-PBR28 (the percentages of unmetabolized parent in plasma at 90 min were 29.0 ± 8.3% and 8.8 ± 2.9% respectively). The brain time-activity curves for both tracers were well fitted by the two-tissue model, but 11C-ER176 had higher VT values than 11C-PBR28 (5.74 ± 1.54 vs 4.43 ± 1.99 ml/cm3) and a lower coefficient of variation. The BPND of 11C-ER176 was more than 4 times larger than that of 11C-PBR28 for high-affinity binders, and more than 9 times larger for mixed-affinity binders.

Conclusion: 11C-ER176 displays a higher binding potential and a smaller variability of VT values. Thanks to these characteristics, clinical studies performed with 11C-ER176 are expected to have higher statistical power and thus require fewer subjects.

Keywords: 11C-ER176; 11C-PBR28; PET; TSPO.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Brain / diagnostic imaging*
  • Brain / metabolism*
  • Carbon Radioisotopes*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Positron-Emission Tomography / methods*
  • Pyrimidines*
  • Quinazolines*
  • Receptors, GABA / metabolism*

Substances

  • (11)C-ER176
  • (methyl-(11)C)N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine
  • Carbon Radioisotopes
  • Pyrimidines
  • Quinazolines
  • Receptors, GABA
  • TSPO protein, human