Radiolabeling antibodies with holmium-166

Area of Science:

• Nuclear Medicine
• Radiochemistry
• Immunoconjugation

Background:

• Development of targeted radiopharmaceuticals is crucial for effective cancer therapy.
• Holmium-166 (166Ho) offers promising beta-emitting properties for radionuclide therapy.
• Efficient methods for radiolabeling antibodies with 166Ho are needed.

Purpose of the Study:

• To report preliminary results on the radiolabeling of chelate-conjugated antibodies with 166Ho.
• To optimize the separation and purification of 166Ho for antibody conjugation.
• To assess the efficiency, specific activity, and stability of the resulting 166Ho-antibody conjugates.

Main Methods:

• Production of 166Ho via beta(-)-decay of 166Dy.
• Separation of 166Ho from Dy target using reverse-phase ion-exchange chromatography (HPLC) with alpha-HIBA eluent.
• Radiolabeling of CHX-B-DTPA conjugated 135-14 monoclonal antibodies with purified 166Ho.

Main Results:

• 166Ho was successfully separated and purified using cation exchange HPLC.
• Radiolabeling of monoclonal antibodies with 166Ho achieved approximately 80% efficiency.
• Resulting 166Ho-antibody conjugates exhibited a specific activity of 3-4 mCi/mg and were stable for 50 hours.
• Iron (Fe3+) impurities in the alpha-HIBA eluent were found to interfere with the labeling process.

Conclusions:

• Preliminary results demonstrate a viable method for producing and radiolabeling antibodies with 166Ho.
• The developed method yields stable 166Ho-antibody conjugates with high efficiency and specific activity.
• Controlling impurities, such as Fe3+, is critical for successful radiolabeling.