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

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, [⁶⁴Cu]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 [⁶⁴Cu]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 [⁶⁴Cu]FBP8 and imaged with PET/CMR, including mapping the longitudinal magnetic relaxation time (T₁) in the LAA.

Results: [⁶⁴Cu]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 T₁ (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 [⁶⁴Cu]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).