Positron Emission Tomography of CD47/SIRPα Axis and Image-Informed Therapeutic Design

Area of Science:

• Immunology
• Radiochemistry
• Oncology

Background:

• The CD47/SIRPα immune axis is a key target for innate cancer immunotherapy.
• Current antibody therapies face challenges like dose-limiting side effects and anemia.
• Improved understanding of CD47/SIRPα dynamics is needed for better therapeutic strategies.

Purpose of the Study:

• To develop and evaluate anti-CD47 and anti-SIRPα radiotracers for in vivo imaging.
• To investigate the whole-body biodistribution of these radiotracers in healthy and tumor-bearing mice.
• To assess the impact of low-dose radiotherapy and antibody PEGylation on biodistribution.

Main Methods:

• Development of anti-CD47 and anti-SIRPα radiotracers.
• Biodistribution studies in healthy and CT26 colorectal cancer allograft mouse models.
• Evaluation of low-dose radiotherapy and PEGylation on tracer pharmacokinetics.

Main Results:

• Radiotracers demonstrated good yields and stability, with consistent whole-body biodistribution.
• Significant uptake observed in the liver and spleen, alongside tumor accumulation.
• Low-dose radiotherapy showed minimal impact on overall biodistribution.
• PEGylation of anti-SIRPα tracer reduced splenic uptake and altered distribution.

Conclusions:

• In vivo molecular imaging is vital for evaluating therapeutic designs targeting the CD47/SIRPα axis.
• SIRPα-targeted agents may benefit from combination therapies and optimized drug delivery systems.
• These findings provide insights for developing safer and more effective cancer immunotherapies.