Building a database for brain 18 kDa translocator protein imaged using [ 11 C]PBR28 in healthy subjects

J Cereb Blood Flow Metab. 2019 Jun;39(6):1138-1147. doi: 10.1177/0271678X18771250. Epub 2018 May 11.

Abstract

Translocator protein 18 kDa (TSPO) has been widely imaged as a marker of neuroinflammation using several radioligands, including [11C]PBR28. In order to study the effects of age, sex, and obesity on TSPO binding and to determine whether this binding can be accurately assessed using fewer radio high-performance liquid chromatography (radio-HPLC) measurements of arterial blood samples, we created a database of 48 healthy subjects who had undergone [11C]PBR28 scans (23 high-affinity binders (HABs) and 25 mixed-affinity binders (MABs), 20 F/28 M, age: 40.6 ± 16.8 years). After analysis by Logan plot using 23 metabolite-corrected arterial samples, total distribution volume ( VT) was found to be 1.2-fold higher in HABs across all brain regions. Additionally, the polymorphism plot estimated nondisplaceable uptake ( VND) as 1.40 mL · cm-3, which generated a specific-to-nondisplaceable ratio ( BPND) of 1.6 ± 0.6 in HABs and 1.1 ± 0.6 in MABs. VT increased significantly with age in nearly all regions and was well estimated with radio-HPLC measurements from six arterial samples. However, VT did not correlate with body mass index and was not affected by sex. These results underscore which patient characteristics should be accounted for during [11C]PBR28 studies and suggest ways to perform such studies more easily and with fewer blood samples.

Trial registration: ClinicalTrials.gov NCT01547780 NCT00526916 NCT01322555 NCT01851356 NCT02233868 NCT00613119.

Keywords: Translocator protein; [C]PBR28; distribution volume; high-affinity binder; mixed-affinity binder.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Intramural

MeSH terms

  • Acetamides
  • Adult
  • Age Factors
  • Body Mass Index
  • Brain / diagnostic imaging*
  • Brain / metabolism
  • Carbon Radioisotopes
  • Female
  • Healthy Volunteers
  • Humans
  • Male
  • Middle Aged
  • Pyridines
  • Radionuclide Imaging / methods
  • Radionuclide Imaging / standards
  • Radiopharmaceuticals / chemistry
  • Radiopharmaceuticals / metabolism
  • Receptors, GABA / analysis*
  • Sex Factors
  • Young Adult

Substances

  • Acetamides
  • Carbon Radioisotopes
  • N-(2-methoxybenzyl)-N-(4-phenoxypyridin-3-yl)acetamide
  • Pyridines
  • Radiopharmaceuticals
  • Receptors, GABA
  • TSPO protein, human

Associated data

  • ClinicalTrials.gov/NCT01547780
  • ClinicalTrials.gov/NCT00526916
  • ClinicalTrials.gov/NCT01322555
  • ClinicalTrials.gov/NCT01851356
  • ClinicalTrials.gov/NCT02233868
  • ClinicalTrials.gov/NCT00613119