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

Abstract

Translocator protein 18 kDa (TSPO) has been widely imaged as a marker of neuroinflammation using several radioligands, including [C]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 [C]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 ( V) was found to be 1.2-fold higher in HABs across all brain regions. Additionally, the polymorphism plot estimated nondisplaceable uptake ( V) as 1.40 mL · cm, which generated a specific-to-nondisplaceable ratio ( BP) of 1.6 ± 0.6 in HABs and 1.1 ± 0.6 in MABs. V increased significantly with age in nearly all regions and was well estimated with radio-HPLC measurements from six arterial samples. However, V did not correlate with body mass index and was not affected by sex. These results underscore which patient characteristics should be accounted for during [C]PBR28 studies and suggest ways to perform such studies more easily and with fewer blood samples.

Neuroinflammation in frontotemporal lobar degeneration revealed by 11C‐PBR28 PET

“…Four patients who met criteria for one of the clinical FTLD syndromes were recruited. 2 Twenty-two cognitively normal subjects from a previously described database 11 were retrospectively demographically matched with the FTLD patients to serve as a control group; subjects with significant comorbid medical or psychiatric illnesses were excluded. TSPObinding affinity was determined by in vitro receptor binding to TSPO on leukocyte membranes, 12 and low-affinity binders were excluded.…”

“…18 F-FDG PET scans were obtained in all four patients with FTLD, and 11 C-Pittsburgh Compound B (PIB) PET scans were obtained in three of the four FTLD patients. 11 C-PIB PET data were also available for all healthy controls older than 45 years (N = 15), and were confirmed to be "PIB-negative" using a dichotomizing method adapted from Jack and colleagues. 13 Brain MRI, 18 F-FDG, 11 C-PIB, and 11 C-PBR28 PET procedures and preprocessing steps were performed as previously described.…”

“…11 C-PIB PET data were also available for all healthy controls older than 45 years (N = 15), and were confirmed to be "PIB-negative" using a dichotomizing method adapted from Jack and colleagues. 13 Brain MRI, 18 F-FDG, 11 C-PIB, and 11 C-PBR28 PET procedures and preprocessing steps were performed as previously described. 10 For region-of-interest (ROI)-based analysis of 11 C-PBR28 PET images, the realigned PET images were coregistered to the MR images using SPM8 software (Wellcome Center for Human Neuroimaging, London, UK).…”

“…Data were also analyzed using a simplified ratio method as previously described, with cerebellum as a pseudoreference region. 16 For visual comparison of TSPO distribution in the FTLD patients and two representative healthy controls, 11 C-PBR28 parametric images where each voxel represents V T /f Pwere generated using the Logan plot and arithmetic tools in PMOD.…”

“…One used the prototypical TSPO radioligand 11 C-(R)-PK11195 in patients with FTLD 5 and the second used 11 C-DAA1106 in presymptomatic carriers of the FTLD genetic mutation. 6 However, 11 C-(R)-PK11195 has been shown to have low specific-to-nonspecific binding, 7 and further studies using improved radioligands have not yet been performed in symptomatic FTLD patients.…”