Detection and Characterization of Thrombosis in Humans Using Fibrin-Targeted Positron Emission Tomography and Magnetic Resonance

利用纤维蛋白靶向正电子发射断层扫描和磁共振技术检测和表征人体血栓形成

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Abstract

OBJECTIVES: The authors present a novel technique to detect and characterize LAA thrombus in humans using combined positron emission tomography (PET)/cardiac magnetic resonance (CMR) of a fibrin-binding radiotracer, [(64)Cu]FBP8. BACKGROUND: The detection of thrombus in the left atrial appendage (LAA) is vital in the prevention of stroke and is currently performed using transesophageal echocardiography (TEE). METHODS: The metabolism and pharmacokinetics of [(64)Cu]FBP8 were studied in 8 healthy volunteers. Patients with atrial fibrillation and recent TEEs of the LAA (positive n = 12, negative n = 12) were injected with [(64)Cu]FBP8 and imaged with PET/CMR, including mapping the longitudinal magnetic relaxation time (T(1)) in the LAA. RESULTS: [(64)Cu]FBP8 was stable to metabolism and was rapidly eliminated. The maximum standardized uptake value (SUV(Max)) in the LAA was significantly higher in the TEE-positive than TEE-negative subjects (median of 4.0 [interquartile range (IQR): 3.0-6.0] vs 2.3 [IQR: 2.1-2.5]; P < 0.001), with an area under the receiver-operating characteristic curve of 0.97. An SUV(Max) threshold of 2.6 provided a sensitivity of 100% and specificity of 84%. The minimum T(1) (T(1Min)) in the LAA was 970 ms (IQR: 780-1,080 ms) vs 1,380 ms (IQR: 1,120-1,620 ms) (TEE positive vs TEE negative; P < 0.05), with some overlap between the groups. Logistic regression using SUV(Max) and T(1Min) allowed all TEE-positive and TEE-negative subjects to be classified with 100% accuracy. CONCLUSIONS: PET/CMR of [(64)Cu]FBP8 is able to detect acute as well as older platelet-poor thrombi with excellent accuracy. Furthermore, the integrated PET/CMR approach provides useful information on the biological properties of thrombus such as fibrin and methemoglobin content. (Imaging of LAA Thrombosis; NCT03830320).

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