First-In-Human Study of [ 64 Cu]Cu-DOTATATE PET/CT in Infective Endocarditis: A Prospective Head-to-Head Comparison With [ 18 F]FDG

BACKGROUND: Infective endocarditis (IE) can be challenging to diagnose. Positron emission tomography/computed tomography (PET/CT) with 2-deoxy-2-[ 18 F]-fluoro- d -glucose ([ 18 F]FDG) is recommended as a diagnostic tool in the guidelines, but holds limitations. The aim of this study was to compare the tracer uptake between the novel [ 64 Cu]Cu-DOTATATE, which has low cardiac uptake and does not require fasting or dietary restrictions, and [ 18 F]FDG in patients with IE and examine the sensitivity and specificity. METHODS: The CuDOS study (Cu-Dotatate Positron Emissions Tomography in Infective Endocarditis) was a prospective study including 20 patients with IE (10 with prosthetic valve endocarditis and 10 with native valve endocarditis) and 20 controls. All participants underwent [ 64 Cu]Cu-DOTATATE and [ 18 F]FDG PET/CT. Scans were read blinded to clinical data. Tracer uptakes were measured as maximum standardized uptake values in each heart valve. Differences were tested with Wilcoxon rank tests. RESULTS: The median age of the cases and controls was 68 years (interquartile range [IQR], 55.0–75.5) and 61 years (IQR, 57.0–69.5), respectively. [ 64 Cu]Cu-DOTATATE uptake (median maximum standardized uptake value [IQR]) in patients with IE was higher than in controls (2.34 [1.40–3.23] versus 1.44 [1.21–1.60]; P =0.008), although this difference was mainly driven by prosthetic valve endocarditis cases (3.23 [2.02–3.86]; P <0.001) and not between native valve endocarditis cases and controls (1.51 [1.23–2.58]; P =0.428). The sensitivity of [ 64 Cu]Cu-DOTATATE and [ 18 F]FDG PET/CT in 20 cases versus 20 controls were equal, and the specificity was 90% and 75%, respectively. The analysis of prosthetic valve endocarditis versus the 20 controls showed equal sensitivity (80%), and a specificity of 90% and 75%, respectively ( P =0.38). In addition, a greater proportion of scans achieved diagnostic certainty with [ 64 Cu]Cu-DOTATATE PET/CT compared with [ 18 F]FDG PET/CT for native valve endocarditis, prosthetic valve endocarditis, and controls. CONCLUSIONS: [ 64 Cu]Cu-DOTATATE PET/CT showed uptake in the infected valve in patients with IE, and has major advantage as it does not require any preparation compared with [ 18 F]FDG. [ 64 Cu]Cu-DOTATATE had a numerically higher specificity than [ 18 F]FDG, although the difference was not statistically significant. Both tracers were limited in the detection of native valve endocarditis. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05432427. www.clinicaltrialsregister.eu ; Unique identifier: 2021-005501-27.