Cerebral [¹⁸F]AIF-FAPI-42-Based PET Imaging of Fibroblast Activation Protein for Non-invasive Quantification of Fibrosis After Ischemic Stroke

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 ischemic regions of the brain in vivo. Sprague–Dawley rats underwent permanent occlusion of the right middle cerebral artery (MCAO). On days 3, 7, 14, and 21 after MCAO, the uptake of [¹⁸F]AlF-FAPI-42 in the ischemic region of the brain in the MCAO groups surpassed that in the control group (day 0). The specific expression of fibroblast activation protein-α (FAP) in ischemic regions of the brain was also confirmed in immunohistofluorescence experiments in vitro. [¹⁸F]AlF-FAPI-42 intensity correlated with the density of collagen deposition in the ischemic hemisphere (p < 0.001). [¹⁸F]AlF-FAPI-42 PET/CT imaging demonstrated a specific uptake of radioactivity in the infarcted area in an ischemic stroke patient. PET imaging by using [¹⁸F]AlF-FAPI-42 offers a promising non-invasive method for monitoring the progression of cerebral fibrosis caused by ischemic stroke and may facilitate the clinical management of stroke patients. Trial registration: chictr.org.cn ChiCTR2200059004. Registered April 22, 2022.