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

Aidan P G Walsh1,2,3, Eefang Yu1,2,3, James D McFadyen2,3,4,5

  • 1Molecular Imaging and Theranostics Laboratory (A.P.G.W., E.Y., V.B., X.W.), Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.

Arteriosclerosis, Thrombosis, and Vascular Biology
|April 20, 2023
PubMed
Summary
This summary is machine-generated.

Researchers developed a new molecular imaging tool targeting FXIIa (factor XIIa) for direct and specific detection of blood clots (thrombi). This FXIIa-targeting approach shows promise for early diagnosis and monitoring of thromboembolic diseases.

Keywords:
blood coagulationfactor XIIhumanslungthrombosis

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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.