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Imaging of enzyme replacement therapy using PET.

Christopher P Phenix¹, Brian P Rempel, Karen Colobong

¹Tri-University Meson Facility, 4004 Wesbrook Mall, Vancouver, BC, Canada.

Proceedings of the National Academy of Sciences of the United States of America

|June 11, 2010

Summary

Researchers developed a novel method to track enzyme replacement therapy (ERT) distribution using fluorine-18 labeling and PET imaging. This technique allows real-time monitoring of enzyme levels and half-life, improving treatment for Gaucher disease and other genetic disorders.

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Area of Science:

Biochemistry
Medical Imaging
Pharmacology

Background:

Enzyme replacement therapy (ERT) is used for rare genetic lysosomal storage diseases.
Current ERT effectiveness is limited by questions about dosing, enzyme half-life, and tissue distribution.
Gaucher disease is a primary example of a condition treated with ERT.

Purpose of the Study:

To develop a method for in vivo imaging of enzyme distribution and pharmacokinetics for ERT.
To utilize fluorine-18 (18F) labeled substrate analogs for tracking recombinant enzymes.
To assess the utility of Positron Emission Tomography (PET) for monitoring ERT in a murine model.

Main Methods:

Developed an 18F-labeled substrate analog to tag acid beta-glucocerebrosidase (GCase).
Administered the tagged enzyme to a murine model and used micro-PET imaging to track distribution.
Correlated PET imaging data with direct tissue 18F counts and monitored pharmacokinetic changes.

Main Results:

Successfully imaged the tissue distribution of injected GCase in a murine model using PET.
Demonstrated a correlation between PET data and actual tissue 18F counts.
Showed that PET imaging can effectively monitor pharmacokinetic changes, including those induced by receptor blocking.

Conclusions:

18F-labeling of GCase provides a powerful tool for in vivo monitoring of enzyme distribution and tissue half-life.
This PET imaging technique offers immediate clinical applications for Gaucher disease.
The method has a clear pathway for application to other enzyme replacement therapies.