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, [ 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).
Competing Interests: Funding Support and Author Disclosures Support for this study was provided in part by the following grants from the National Institutes of Health: R01HL109448 (to Drs Caravan and Sosnovik), R01HL141563 (to Dr Sosnovik), R01HL131907 (to Dr Caravan), R01HL131635 (to Dr Mekkaoui), and R01CA218187 (to Dr Catana); and the following grants to the A. A. Martinos Center for Biomedical Imaging: S10RR022976, S10RR019933, P41EB015896. Dr Caravan is an inventor of [64Cu]FBP8, which is patented by Massachusetts General Hospital. Dr Caravan is a founder of and has financial interests in Collagen Medical, LLC, and Factor 1A, LLC, which are developing fibrin-targeted imaging probes. Factor 1A, LLC has a license to the patent covering the probe [64Cu]FBP8 that used in this study. Dr Caravan’s interests were reviewed and are managed by Massachusetts General Hospital and Mass General Brigham in accordance with their conflict of interest policies. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
(Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)