PET imaging of colony-stimulating factor 1 receptor: A head-to-head comparison of a novel radioligand, 11 C-GW2580, and 11 C-CPPC, in mouse models of acute and chronic neuroinflammation and a rhesus monkey

• Published in: Journal of cerebral blood flow and metabolism 2021-09, Vol.41 (9), p.2410-2422
• Main Authors: Zhou, Xiaoyun, Ji, Bin, Seki, Chie, Nagai, Yuji, Minamimoto, Takafumi, Fujinaga, Masayuki, Zhang, Ming-Rong, Saito, Takashi, Saido, Takaomi C, Suhara, Tetsuya, Kimura, Yasuyuki, Higuchi, Makoto
• Format: Article
• Language: English
• Subjects: Acute Disease; Animals; Disease Models, Animal; Inflammation - diagnostic imaging; Inflammation - pathology; Macaca mulatta; Macrophage Colony-Stimulating Factor - metabolism; Mice; Positron-Emission Tomography - methods; Radioligand Assay - methods
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1177/0271678X211004146

Colony-stimulating factor 1 receptor (CSF1R) is a specific biomarker for microglia. In this study, we developed a novel PET radioligand for CSF1R, C-GW2580, and compared it to a reported CSF1R tracer, C-CPPC, in mouse models of acute and chronic neuroinflammation and a rhesus monkey. Dynamic C-GW2580- and C-CPPC-PET images were quantified by reference tissue-based models and standardized uptake value ratio. Both tracers exhibited increased uptake in the lesioned striata of lipopolysaccharide-injected mice and in the forebrains of -knock-in mice, spatially in agreement with an increased 18-kDa translocator protein radioligand retention. Moreover, C-GW2580 captured changes in CSF1R availability more sensitively than C-CPPC, with a larger dynamic range and a smaller inter-individual variability, in these model animals. PET imaging of CSF1R in a rhesus monkey displayed moderate-to-high tracer retention in the brain at baseline. Homologous blocker (i. e. unlabeled tracer) treatment reduced the uptake of C-GW2580 by ∼30% in all examined brain regions except for centrum semi-ovale white matter, but did not affect the retention of C-CPPC. In summary, our results demonstrated that C-GW2580-PET captured inflammatory microgliosis in the mouse brain with higher sensitivity than a reported radioligand, and displayed saturable binding in the monkey brain, potentially providing an imaging-based quantitative biomarker for reactive microgliosis.