Visualization of intrathecal delivery by PET-imaging

Area of Science:

• Neuroscience
• Pharmacology
• Medical Imaging

Background:

• Intrathecal (IT) drug delivery is crucial for both research and clinical applications targeting the central nervous system (CNS).
• Existing methods for IT administration can be invasive, potentially impacting neurological evaluations and increasing surgical risks.
• A need exists for safer, more effective methods to distribute substances within the cerebrospinal fluid (CSF).

Purpose of the Study:

• To evaluate a new, minimally invasive route for intrathecal (IT) drug delivery to the subarachnoid space (SAS).
• To assess the distribution patterns of radiotracers administered via this novel IT route using positron emission tomography (PET).
• To demonstrate the feasibility of continuous infusion and intracranial pressure (ICP) monitoring during IT administration.

Main Methods:

• A novel catheter placement in the cisterna magna of anesthetized pigs allowed for IT administration of a ¹¹C-labeled PET-tracer.
• Substances were infused using artificial CSF (aCSF) under continuous ICP monitoring.
• PET/CT scanning was performed to visualize and quantify tracer distribution within the SAS, with catheter access via externalization or a subcutaneous port.

Main Results:

• Positron emission tomography/computed tomography (PET/CT) imaging confirmed even distribution of the tracer throughout the SAS.
• Continuous ICP monitoring allowed for precise adjustment of infusion rates, maintaining safe pressure levels.
• The use of a subcutaneous port facilitated potential for future survival studies.

Conclusions:

• This minimally invasive technique provides a reliable method for assessing drug distribution within the CNS in large animal models.
• The approach is suitable for evaluating PET-tracers, antibiotics, chemotherapeutics, and other CNS-targeting agents.
• This method holds promise for future translation to human clinical trials for targeted drug delivery.