Visualization of intrathecal delivery by PET-imaging

Background: Intrathecal (IT) delivery is useful in both basic research and clinical treatments. Here we aim to test a new minimally invasive distribution route to the subarachnoid space (SAS) and the flow of IT administrations. We placed a radioligand into SAS during positron emission tomography (PET) scanning as a proof of concept. New method: We injected a C-11-labeled PET-tracer using a surgically placed catheter in the cisterna magna of anesthetized female pigs. The pigs were scanned for 1.5-2 hours in a PET/CT-scanner. The pressure from continuous infusion of artificial CSF (aCSF) promoted distribution of the tracer. The procedure was done under continuous intracranial pressure (ICP) monitoring. The catheter was made accessible both by externalization through the skin and through a subcutaneously placed sterile titanium port connected to the catheter. After image reconstruction, we used PMOD software to assess the tracer distribution throughout SAS. Internalisation of the catheter to a port enables survival studies. Previous studies performing ventriculography have placed a catheter trough brain cortex and parenchyma; such procedures may affect any behavioural or neurological evaluation, and have an increased risk of bleeding per- and post-operatively (Kaiser & Fruhauf, 2007). Results: The PET-CT visualized tracer was evenly distributed in the SAS. Furthermore, the ICP measurement made it possible to adjust infusion speed within acceptable pressure levels. Conclusion: This new method can be useful for testing distribution of PET-tracers, antibiotics, chemotherapeutics and a wide range of other pharmaceuticals targeting the CNS and spinal cord in large animal models, and potentially later in human.