Imaging high-risk atherothrombosis using a novel fibrin-binding positron emission tomography probe Articles uri icon

authors

  • IZQUIERDO GARCÍA, DAVID
  • DIYABALANAGE, HIMASHINIE
  • RAMSAY, IAN A.
  • ROTILE, NICHOLAS J.
  • MAUSKAPF, ADAM
  • CHOI, JI-KYUNG
  • WITZEL, THOMAS
  • HUMBLET, VALERIE
  • JAFFER, FAROUC A.
  • BROWNELL, ANNA-LIISA
  • TAWAKOL, AHMED
  • CATANA, CIPRIAN
  • CONRAD, MARK F.
  • CARAVAN, PETER
  • AY, ILKNUR

published in

publication date

  • February 2022

start page

  • 595

end page

  • 604

issue

  • 2

volume

  • 53

International Standard Serial Number (ISSN)

  • 0039-2499

Electronic International Standard Serial Number (EISSN)

  • 1524-4628

abstract

  • Background and Purpose: High-risk atherosclerosis is an underlying cause of cardiovascular events, yet identifying the specific patient population at immediate risk is still challenging. Here, we used a rabbit model of atherosclerotic plaque rupture and human carotid endarterectomy specimens to describe the potential of molecular fibrin imaging as a tool to identify thrombotic plaques.
    Methods: Atherosclerotic plaques in rabbits were induced using a high-cholesterol diet and aortic balloon injury (N=13). Pharmacological triggering was used in a group of rabbits (n=9) to induce plaque disruption. Animals were grouped into thrombotic and nonthrombotic plaque groups based on gross pathology (gold standard). All animals were injected with a novel fibrin-specific probe 68Ga-CM246 followed by positron emission tomography (PET)/magnetic resonance imaging 90 minutes later. 68Ga-CM246 was quantified on the PET images using tissue-to-background (back muscle) ratios and standardized uptake value.
    Results: Both tissue-to-background (back muscle) ratios and standardized uptake value were significantly higher in the thrombotic versus nonthrombotic group (P<0.05). Ex vivo PET and autoradiography of the abdominal aorta correlated positively with in vivo PET measurements. Plaque disruption identified by 68Ga-CM246 PET agreed with gross pathology assessment (85%). In ex vivo surgical specimens obtained from patients undergoing elective carotid endarterectomy (N=12), 68Ga-CM246 showed significantly higher binding to carotid plaques compared to a D-cysteine nonbinding control probe.
    Conclusions: We demonstrated that molecular fibrin PET imaging using 68Ga-CM246 could be a useful tool to diagnose experimental and clinical atherothrombosis. Based on our initial results using human carotid plaque specimens, in vivo molecular imaging studies are warranted to test 68Ga-CM246 PET as a tool to stratify risk in atherosclerotic patients.

subjects

  • Biology and Biomedicine

keywords

  • aorta, abdominal; atherosclerosis; fibrin; positron emission tomography; thrombosis