Cerebral [18F]AIF-FAPI-42-based PET imaging of fibroblast activation protein for non-invasive quantification of fibrosis after ischaemic stroke

Abstract The development of fibrosis after injury to the brain or spinal cord limits the regeneration of the central nervous system in adult mammals. However, the extent of fibrosis in the injured brain has not been systematically investigated in mammals in vivo. This study aimed to assess whether [18F]AlF-FAPI-42-based cerebral positron emission tomography (PET) can be utilized to assess the extent of fibrosis in ischaemic regions of the brain in vivo. Sprague-Dawley rats underwent permanent occlusion of the right middle cerebral artery (MCAO) or sham surgery (control). On days 3, 7, 14, and 21 post-MCAO, the uptake of [18F]AlF-FAPI-42 in the ischaemic region of the brain in the MCAO groups surpassed that in the control group. Specificity to FAP was confirmed through immunofluorescence staining. Histopathological analysis revealed higher collagen deposition in the ischaemic hemisphere of the rats in the MCAO group than the control level. [18F]AlF-FAPI-42 intensity correlated with the density of collagen fibres in the ischaemic hemisphere (p < 0.001). [18F]AlF-FAPI-42 PET/CT imaging revealed high FAP in the infarct zone of ischemic stroke patients. PET imaging by using [18F]AlF-FAPI-42 offers a promising non-invasive method for monitoring the progression of cerebral fibrosis caused by ischaemic stroke and may facilitate the clinical management of stroke patients. Trial registration: chictr.org.cn ChiCTR2200059004. Registered April 22, 2022.