No abstract

This study assessed whether the newly developed PET radioligands C-PS13 andC-MC1 could image constitutive levels of cyclooxygenase (COX)-1 and COX-2, respectively, in rhesus monkeys. After intravenous injection of either radioligand, 24 whole-body PET scans were performed. To measure enzyme-specific uptake, scans of the 2 radioligands were also performed after administration of a nonradioactive drug preferential for either COX-1 or COX-2. Concurrent venous samples were obtained to measure parent radioligand concentrations. SUVs were calculated from 10 to 90 min. C-PS13 showed specific uptake in most organs, including spleen, gastrointestinal tract, kidneys, and brain, which was blocked by COX-1, but not COX-2, preferential inhibitors. Specific uptake ofC-MC1 was not observed in any organ except the ovaries and possibly kidneys. The findings suggest thatC-PS13 has adequate signal in monkeys to justify its extension to human subjects. In contrast, C-MC1 is unlikely to show significant signal in healthy humans, though it may be able to do so in inflammatory conditions.

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.