{"doi":"10.1161/strokeaha.121.035638","title":"Imaging High-Risk Atherothrombosis Using a Novel Fibrin-Binding Positron Emission Tomography Probe","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 68 Ga-CM246 followed by positron emission tomography (PET)/magnetic resonance imaging 90 minutes later. 68 Ga-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 68 Ga-CM246 PET agreed with gross pathology assessment (85%). In ex vivo surgical specimens obtained from patients undergoing elective carotid endarterectomy (N=12), 68 Ga-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 68 Ga-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 68 Ga-CM246 PET as a tool to stratify risk in atherosclerotic patients.","journal":"Stroke","year":2021,"id":196376,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9486,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":769658,"name":"Himashinie Diyabalanage","orcid":null,"position":1,"is_corresponding":false},{"id":467020,"name":"Ian Ramsay","orcid":"0000-0003-1896-4337","position":2,"is_corresponding":false},{"id":345135,"name":"Nicholas J. Rotile","orcid":"0000-0001-6568-9927","position":3,"is_corresponding":false},{"id":329875,"name":"Adam Mauskapf","orcid":"0009-0009-2470-898X","position":4,"is_corresponding":false},{"id":433531,"name":"Ji‐Kyung Choi","orcid":"0000-0003-1842-8825","position":5,"is_corresponding":false},{"id":263268,"name":"Thomas Witzel","orcid":"0000-0002-5806-4897","position":6,"is_corresponding":false},{"id":345140,"name":"Valérie Humblet","orcid":"0000-0003-4428-9304","position":7,"is_corresponding":false},{"id":329880,"name":"Farouc A. Jaffer","orcid":"0000-0001-7980-384X","position":8,"is_corresponding":false},{"id":406506,"name":"Anna‐Liisa Brownell","orcid":"0000-0002-3814-868X","position":9,"is_corresponding":false},{"id":233339,"name":"Ahmed Tawakol","orcid":"0000-0002-9211-5483","position":10,"is_corresponding":false},{"id":308505,"name":"Ciprian Catana","orcid":"0000-0002-3249-5971","position":11,"is_corresponding":false},{"id":380767,"name":"Mark F. Conrad","orcid":"0000-0001-6625-8889","position":12,"is_corresponding":false},{"id":334441,"name":"Peter Caravan","orcid":"0000-0002-3179-6537","position":13,"is_corresponding":false},{"id":467021,"name":"İlknur Ay","orcid":"0000-0001-9558-742X","position":14,"is_corresponding":false},{"id":308503,"name":"David Izquierdo‐Garcia","orcid":"0000-0003-0763-8827","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-18T23:50:15.704473Z","pmid":"34965737","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}