Site-specific 68Ga-labeled Annexin A5 as a PET imaging agent for apoptosis

Area of Science:

• Nuclear medicine
• Molecular imaging
• Radiopharmaceutical chemistry

Background:

• Annexin A5 is a protein that binds to phosphatidylserine, a marker of apoptosis.
• Gallium-68 is a positron-emitting radionuclide suitable for PET imaging.
• Developing novel radiotracers is crucial for advancing molecular imaging in oncology.

Purpose of the Study:

• To synthesize and evaluate two Gallium-68 labeled Annexin A5 variants (Cys2-AnxA5 and Cys165-AnxA5) as potential PET imaging agents.
• To assess the biological properties, including biodistribution and pharmacokinetics, of these novel radiotracers.
• To investigate their utility in detecting apoptosis and monitoring therapeutic response in preclinical cancer models.

Main Methods:

• Radiolabeling of Annexin A5 variants with Gallium-68.
• Biodistribution and pharmacokinetic studies in healthy mice and a hepatic apoptosis model using microPET (μPET).
• μPET/μMRI imaging in Daudi tumor-bearing mice before and after chemo-radiotherapy.

Main Results:

• The Gallium-68 labeled Annexin A5 variants exhibited rapid urinary clearance and minimal hepatobiliary excretion, with notable kidney retention.
• Liver uptake was significantly higher (3-8 fold) in animals treated with anti-Fas compared to healthy controls, indicating apoptosis detection.
• Tumor uptake of both tracers was low but showed a significant increase post-therapy, suggesting visualization of treatment-induced apoptosis.

Conclusions:

• Both (68)Ga-Cys2-AnxA5 and (68)Ga-Cys165-AnxA5 demonstrate specific binding to apoptotic cells.
• These Gallium-68 labeled Annexin A5 variants are promising radiotracers for the rapid assessment of cancer therapy efficacy.