Abstract
PURPOSE: The 18 kDa translocator protein (TSPO) has been a central molecular target for imaging inflammation in the preclinical and clinical research settings across a plethora of applications, including neuroinflammation, cardiovascular inflammation and cancer. Recently, we reported the development of [(18)F]LW223 as a third-generation TSPO positron emission tomography (PET) radiotracer with binding to human TSPO independent of the rs6971 genetic polymorphism. This study reports the first whole-body human analysis, including biodistribution and dosimetry calculations, following intravenous administration of [(18)F]LW223. METHODS: Whole-body PET images were acquired over 250 min after intravenous bolus injection of 184.3 ± 20.2 MBq of [(18)F]LW223 in healthy adult human volunteers. Volumes of interest (VOIs) in different source organs were manually delineated by three independent observers, then time-activity curves were generated for residency times calculations for subsequent quantification of radiation equivalent and effective doses using OLINDA/EXM 2.2 software. RESULTS: The radiotracer biodistribution in humans recapitulated known TSPO expression in various tissues. The main elimination route was found to be hepatobiliary, and the critical organ was the intestine. The cumulated radioactivity excreted by the kidneys was < 10% over the measurement period and no bone uptake suggestive of in vivo defluorination was observed in any of the study subjects. The effective dose ranged between 11.8 ± 0.9 and 12.5 ± 0.9 µSv/MBq. Inter-observer VOI variability had no impact on estimated organ and whole-body effective doses. CONCLUSION: [(18)F]LW223 is predominantly excreted by the hepatobiliary route with no evidence of in vivo defluorination but demonstrates marked uptake into tissues with known TSPO expression. It complies with radiation limits and guidelines recommended by regulatory authorities and is in line with previously reported [(18)F]-labelled radiotracers, such as [(18)F]fluorodeoxyglucose. [(18)F]LW223 is suitable for translation into human clinical studies.