A universally applicable 68Ga-labeling technique for proteins

Area of Science:

• Radiochemistry
• Bioconjugation Chemistry
• Molecular Imaging

Background:

• Protein-based Positron Emission Tomography (PET) imaging agents are crucial for future diagnostics.
• Current methods for labeling complex biomolecules with PET radionuclides are often challenging and inefficient.

Purpose of the Study:

• To develop a straightforward and efficient chemistry for labeling proteins with the radionuclide Gallium-68 (68Ga).
• To enable a rapid kit-labeling procedure for 68Ga-labeled proteins without the need for post-labeling purification.

Main Methods:

• Introduced a novel chelating agent, NODA-GA-T, for 68Ga attachment to proteins pre-processed with sulfo-SMCC.
• Developed a one-step kit-labeling procedure for 68Ga-protein conjugates.
• Performed small-animal PET imaging studies using 68Ga-rat serum albumin and 68Ga-annexin V.

Main Results:

• Proteins were successfully modified with 1.2-1.7 labeling sites per molecule.
• High radiochemical yields (>95%) were achieved in under 10 minutes at room temperature.
• Labeled proteins exhibited high specific activities (20-45 GBq/μmol) and demonstrated successful in vivo imaging in animal models.

Conclusions:

• The developed kit labeling technique allows for the preparation of 68Ga-labeled proteins with high yields and recovery rates.
• Pre-processed protein precursors are stable for long-term storage, facilitating on-demand radiolabeling.
• The method is proven effective for in vivo applications, paving the way for new PET tracer development.