Aligning physics and physiology: Engineering antibodies for radionuclide delivery

Area of Science:

• Biomedical engineering
• Radiopharmaceutical science
• Oncology

Background:

• Antibodies and fragments are highly specific for targeted delivery of radionuclides.
• Radiolabeled antibodies are used in molecular imaging and radioimmunotherapy (RIT) for cell surface targets.
• Protein engineering optimizes antibody characteristics for clinical use.

Purpose of the Study:

• To review the use of engineered antibodies and fragments for radionuclide delivery.
• To discuss the alignment of radionuclide properties with antibody/fragment characteristics.
• To highlight advances in engineered antibodies and fragments for imaging and therapy.

Main Methods:

• Review of literature on radiolabeled antibodies and fragments.
• Discussion of protein engineering for antibody optimization.
• Analysis of radionuclide properties (positron, gamma, beta, alpha, Auger emitters).

Main Results:

• Engineered fragments offer reduced serum half-life and improved clearance compared to intact antibodies.
• Radiolabeled fragments and pretargeting strategies enhance image contrast and reduce RIT toxicity.
• Antibody fragments can be engineered for specific clearance pathways (hepatic or renal).

Conclusions:

• Engineered antibodies and fragments are valuable tools for targeted radionuclide delivery in oncology and immunology.
• Optimizing antibody/fragment properties and radionuclide selection enhances imaging and therapeutic efficacy.
• Advances in engineered antibodies and fragments show promise in preclinical and clinical development.