We developed 11C-CPPC to image the macrophage colony-stimulating factor 1 receptor (CSF1R), which is expressed almost exclusively by microglia in the brain. However, relevant microglial targets such as 18 kDa translocator protein may be expressed on other cell types in human brain. Radiotracers developed for use with positron emission tomography (PET) can allow researchers to study microglia in their native tissue microenvironment, which has advantages since these resident immune cells assume different morphologies ex vivo. Imaging of microglia and their contribution to brain injury and repair across neuropsychiatric conditions has been widely pursued. Our results extend support for the use of 11C-CPPC with PET to study microglia in the human brain.

Total distribution volume ( V T) values computed from 1TCM aligned well with those from Logan graphical analysis ( t* = 30), with V T values relatively high in thalamus, striatum, and most cortical regions, and with relatively lower V T in hippocampus, total white matter, and cerebellar cortex. ResultsĬortical and subcortical tissue TACs peaked by 37.5 min post-injection of 11C-CPPC and then declined.

One- and two-tissue compartmental models (1TCM and 2TCM) as well as Logan graphical analysis were compared. Tissue time-activity curves (TACs) were generated using regions of interest identified from co-registered magnetic resonance imaging data. Arterial blood sampling was collected in order to generate a metabolite-corrected arterial input function. MethodsĮight healthy nonsmoker adults completed a 90-min dynamic PET scan that began with bolus injection of 11C-CPPC. Our prior work with 11C-CPPC demonstrated its high, specific uptake in brains of rodents and nonhuman primates with neuroinflammation, which supports the current first-in-human evaluation of its pharmacokinetic behavior in the brains of healthy individuals. 11C-CPPC was developed to image the macrophage colony-stimulating factor 1 receptor, a target that is expressed largely by microglia relative to other cell types in the brain. However, many relevant microglial imaging targets such as the 18 kDa translocator protein are also expressed on non-microglial cells, which can complicate the interpretation of PET findings. Imaging microglia with radiotracers developed for use with positron emission tomography (PET) allows researchers to study these cells in their native tissue microenvironment. Study of the contribution of microglia to onset and course of several neuropsychiatric conditions is challenged by the fact that these resident immune cells often take on different phenotypes and functions outside the living brain.

Almost Royalty by Courtney Hamilton