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

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 (V_T) was found to be 1.2-fold higher in HABs across all brain regions. Additionally, the polymorphism plot estimated nondisplaceable uptake (V_ND) as 1.40 mL · cm⁻³, which generated a specific-to-nondisplaceable ratio (BP_ND) of 1.6 ± 0.6 in HABs and 1.1 ± 0.6 in MABs. V_T increased significantly with age in nearly all regions and was well estimated with radio-HPLC measurements from six arterial samples. However, V_T 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.