Activated Coagulation FXII: A Unique Target for In Vivo Molecular Imaging

Area of Science:

• Biomedical Imaging
• Molecular Imaging
• Thrombosis Research

Background:

• Current clinical imaging of thromboembolic diseases is often indirect, potentially delaying diagnosis and treatment.
• Factor XIIa (FXIIa) initiates coagulation and inflammatory responses, making it an ideal molecular target for thrombosis detection.
• FXIIa is dispensable for hemostasis, allowing for targeted diagnostic and therapeutic strategies without compromising normal blood clotting.

Purpose of the Study:

• To develop a molecular imaging tool for rapid, specific, and direct visualization of thrombi.
• To target the activated form of factor XII (FXIIa) for enhanced thrombosis detection.
• To evaluate the potential of FXIIa-targeting for both diagnostic and therapeutic applications in thromboembolic diseases.

Main Methods:

• Conjugated an FXIIa-specific antibody (3F7) to a near-infrared (NIR) fluorophore.
• Utilized 3D fluorescence emission computed tomography/computed tomography and 2D fluorescence imaging for detection.
• Demonstrated ex vivo imaging of carotid thrombosis, pulmonary embolism, and FXIIa in human thrombi.

Main Results:

• Significant increase in NIR signal detected in carotid thrombosis models using the 3F7-NIR probe compared to controls (P=0.002).
• Elevated NIR signal observed in lungs with pulmonary embolism (P=0.0008) and in FXIIa-positive human thrombi.
• Demonstrated specific binding and imaging of FXIIa in both arterial and venous thrombosis models.

Conclusions:

• FXIIa targeting is highly suitable for specific detection of venous and arterial thrombi.
• This approach enables direct, specific, and early imaging of thrombosis using preclinical modalities.
• The developed tool may facilitate monitoring of antithrombotic treatment in vivo.