Early distribution of18 F‐labeled AAV9 vectors in the cerebrospinal fluid after intracerebroventricular or intracisternal magna infusion in non‐human primates

Background The delivery of adeno‐associated virus (AAV) vectors via the cerebrospinal fluid (CSF) has emerged as a valuable method for widespread transduction in the central nervous system. Although infusion into the cerebral ventricles is a common protocol in preclinical studies of small animals, the cisterna magna has been recognized as an alternative target for clinical studies because it can be reached in a less invasive manner using an intrathecal catheter via the subarachnoid space from a lumbar puncture. Methods We evaluated the early distribution of fluorine‐18‐labeled AAV9 vectors infused into the lateral ventricle or cisterna magna of four non‐human primates using positron emission tomography. The expression of the green fluorescent protein was immunohistochemically determined. Results In both approaches, the labeled vectors diffused into the broad arachnoid space around the brain stem and cervical spinal cord within 30 min. Both infusion routes efficiently transduced neurons in the cervical spinal cord. Conclusions For gene therapy that primarily targets the cervical spinal cord and brainstem, such as amyotrophic lateral sclerosis, cisterna magna infusion would be a feasible and effective administration method. Early distribution of [18F]fluorobenzoate‐labeled AAV9 vectors infused into the cisterna magna of non‐human primates was evaluated using positron emission tomography. The vectors diffused into the broad arachnoid space around the brain stem and cervical spinal cord. The cisterna magna infusion would be an effective administration method for gene therapy.