Exploring [11C]CPPC as a CSF1R-targeted PET Imaging Marker for Early Parkinson's Disease Severity.

Neuroinflammation through enhanced innate immunity is thought play a role in the pathogenesis of Parkinson's disease (PD). Methods for monitoring neuroinflammation in living patients with PD are currently limited to positron emission tomography (PET) ligands that lack specificity in labeling immune cells in the nervous system. The colony stimulating factor 1 receptor (CSF1R) plays a crucial role in microglial function, an important cellular contributor to the nervous system's innate immune response. Using immunologic methods, we show that CSF1R in human brain is colocalized with the microglial marker, ionized calcium binding adaptor molecule 1 (Iba1). In PD, CSF1R immunoreactivity is significantly increased in PD across multiple brain regions, with the largest differences in the midbrain versus controls. Autoradiography revealed significantly increased [3H]JHU11761 binding in the inferior parietal cortex of PD patients. PET imaging demonstrated that higher [11C]CPPC binding in the striatum was associated with greater motor disability in PD. Furthermore, increased [11C]CPPC binding in various regions correlated with more severe motor disability and poorer verbal fluency. This study finds that CSF1R expression is elevated in PD and that [11C]CPPC-PET imaging of CSF1R is indicative of motor and cognitive impairments in the early stages of the disease. Moreover, the study underscores the significance of CSF1R as a promising biomarker for neuroinflammation in Parkinson's disease, suggesting its potential use for non-invasive assessment of disease progression and severity, leading to earlier diagnosis and targeted interventions.

Pilot imaging of the colony stimulating factor 1 receptor in the brains of virally-suppressed individuals with HIV.

OBJECTIVE: Neuroimmune activation is a putative driver of cognitive impairment in people with HIV (PWH), even in the age of modern antiretroviral therapy. Nevertheless, imaging of the microglial marker, the 18 kDa translocator protein (TSPO), with positron emission tomography (PET) in treated PWH has yielded inconclusive findings. One potential reason for the varied TSPO results is a lack of cell-type specificity of the TSPO target. DESIGN: [ 11 C]CPPC, 5-cyano- N -(4-(4-[ 11 C]methylpiperazin-1-yl)-2-(piperidin-1-yl)phenyl) furan-2-carboxaminde, is a radiotracer for use with PET to image the colony stimulating factor 1 receptor (CSF1R). The CSF1R is expressed on microglia and central nervous system macrophages, with little expression on other cell types. We used [ 11 C]CPPC PET in virally-suppressed- (VS)-PWH and HIV-uninfected individuals to estimate the effect sizes of higher CSF1R in the brains of VS-PWH. METHODS: Sixteen VS-PWH and 15 HIV-uninfected individuals completed [ 11 C]CPPC PET. [ 11 C]CPPC binding (V T ) in nine regions was estimated using a one-tissue compartmental model with a metabolite-corrected arterial input function, and compared between groups. RESULTS: Regional [ 11 C]CPPC V T did not significantly differ between groups after age- and sex- adjustment [unstandardized beta coefficient ( B ) = 1.84, standard error (SE) = 1.18, P  = 0.13]. The effect size was moderate [Cohen's d  = 0.56, 95% confidence interval (CI) -0.16, 1.28), with strongest trend of higher V T in VS-PWH in striatum and parietal cortex (each P  = 0.04; Cohen's d  = 0.71 and 0.72, respectively). CONCLUSIONS: A group difference in [ 11 C]CPPC V T was not observed between VS-PWH and HIV-uninfected individuals in this pilot, although the observed effect sizes suggest the study was underpowered to detect regional group differences in binding.