Assessment of 18F-PBR-111 in the Cuprizone Mouse Model of Multiple Sclerosis

Abstract

The study aims to assess site assessment of the performance of 18F-PBR-111 as a neuroinflammation marker in the cuprizone mouse model of multiple sclerosis (MS). 18F-PBR-111 PET imaging has not been well evaluated in multiple sclerosis applications both in preclinical and clinical research. This study will help establish the potential utility of 18F-PBR-111 PET in preclinical MS research and future animal and future human applications.18F-PBR-111 PET/CT was conducted at 3.5 weeks (n = 7) and 5.0 weeks (n = 7) after cuprizone treatment or sham control (n = 3) in the mouse model. A subgroup of mice underwent autoradiography with cryosectioned brain tissue. T2 weighted MRI was performed to obtain the brain structural data of each mouse. 18F-PBR-111 uptake was assessed in multiple brain regions with PET and autoradiography images. The correlation between autoradiography and immunofluorescence staining of neuroinflammation (F4/80 and CD11b) was measured. Compared to control mice, significant 18F-PBR-111 uptake in the corpus callosum (p < 0.001), striatum (caudate and internal capsule, p < 0.001), and hippocampus (p < 0.05) was identified with PET images at both 3.5 weeks and 5.0 weeks, and validated with autoradiography. No significant uptake differences were detected between 3.5 weeks and 5.0 weeks assessing these regions as a whole, although there was a trend of increased uptake at 5.0 weeks compared to 3.5 weeks in the CC. High 18F-PBR-111 uptake regions correlated with microglial/ macrophage locations by immunofluorescence staining with F4/80 and CD11b antibodies. 18F-PBR-111 uptake in anatomic locations correlated with activated microglia at histology in the cuprizone mouse model of MS suggests that 18F-PBR-111 has potential for in vivo evaluation of therapy response and potential for use in MS patients and animal studies.

Editorial of Special Issue “Multiple Sclerosis: From Diagnostic Biomarkers to Imaging and Clinical Predictors”

“…Lastly, the work by Jewells et al utilizes novel in vivo detection of microglia through PET detection of 18-kDa translocator protein (TSPO) radiotracer in demyelinating mice model of MS [ 13 ]. TSPO, also called the peripheral benzodiazepine receptor (PBR), is highly expressed in activated microglia and a known prognostic factor in MS pathology.…”

“…TSPO, also called the peripheral benzodiazepine receptor (PBR), is highly expressed in activated microglia and a known prognostic factor in MS pathology. For this purpose, the Authors develop a specific 18F-PBR-111 radiotracer and demonstrated significant uptake after demyelination that was spatially correlated with positive histopathological staining of CD11b (activated microglia) and F4/80 (macrophages) [ 13 ]. This increase in uptake was greater when compared to control mice and located in the corpus callosum and striatum [ 13 ].…”

“…For this purpose, the Authors develop a specific 18F-PBR-111 radiotracer and demonstrated significant uptake after demyelination that was spatially correlated with positive histopathological staining of CD11b (activated microglia) and F4/80 (macrophages) [ 13 ]. This increase in uptake was greater when compared to control mice and located in the corpus callosum and striatum [ 13 ]. Therefore, PET 18F-PBR-111 could have potential as an in vivo imaging biomarker for MS neuroinflammation and an assessment of microglial activity.…”