Selective Chemistry Enables Simultaneous ImmunoPET and Radioimmunotherapy with a Dual-Labeled Probe

Area of Science:

• Oncology
• Nuclear Medicine
• Bioconjugation Chemistry

Background:

• Theranostics combines nuclear imaging and targeted radiotherapy.
• Current theranostic methods use separate agents, assuming identical pharmacokinetics.
• This limits precision and requires extensive probe development.

Purpose of the Study:

• To develop a modular platform for simultaneous PET imaging and radioimmunotherapy.
• To enable dual-radionuclide labeling on a single targeting vector.
• To validate the accuracy of PET-derived dosimetry for predicting therapeutic response.

Main Methods:

• Synthesis of a trifunctional reagent (TzAz-PODS) for versatile bioconjugation.
• Development of a dual-radionuclide (89Zr/177Lu) immunoconjugate targeting the A33 antigen.
• In vivo validation using PET imaging and biodistribution studies in a colorectal cancer mouse model.

Main Results:

• Successful synthesis and labeling of the dual-radionuclide immunoconjugate.
• Confirmation of tumor targeting and accurate PET-derived dosimetry for 177Lu.
• Radioimmunotherapy studies indicated PET imaging can predict treatment response.

Conclusions:

• The modular platform enables simultaneous PET imaging and radioimmunotherapy with dual-radionuclide labeling.
• PET-based dosimetry accurately reflects therapeutic radionuclide distribution.
• This approach enhances theranostic precision and may predict treatment outcomes.