EXPRESS: Kinetic modeling of the Tropomyosin Receptor Kinases radioligand [ ¹⁸ F]TRACK in human brain with high-resolution positron emission tomography

Tropomyosin receptor kinases family members TrkA, TrkB and TrkC mediate critical processes, such as neuronal growth, survival, and synaptic plasticity, and have been implicated in neuropsychiatric disorders. In this work, we characterized the pharmacokinetics of the novel positron emission tomography (PET) radioligand [ 18 F]TRACK for in vivo quantification of TrkB/C in the human brain. Seven healthy volunteers (3 men; 20–61 years) underwent a 90 min PET scan following an intravenous bolus injection of [ 18 F]TRACK. Arterial blood sampling was performed throughout image acquisition. [ 18 F]TRACK was slowly metabolized, accounting for 60% of the plasma activity at 90 min, with two more polar radiometabolites observed. Regional time-activity curves (TACs) showed moderate uptake (SUV: 1-2) and good reversibility in gray matter regions. Across regions, the two-tissue compartment model (2TCM) yielded superior fits than the 1TCM for 98% of extra-striatal gray-matter TACs, whereas it improved fits for only 52% of striatal TACs. Total distribution volume (VT) ranged from 2.49±0.30 ml/cm 3 (thalamus) to 1.94±0.21 ml/cm 3 (hippocampus) showing good identifiability (%SE: 1–5%) and low inter-subject variability (%CoV<14%). Transient equilibrium between [ 18 F]TRACK in tissue and plasma was reached at approximately 70 min. Shortening the scan duration to 60 min preserved VT accuracy and precision.