(-)-5-18F-fluoroethoxybenzovesamicol (18F-FEOBV) is a vesamicol derivative that binds selectively to the vesicular acetylcholine transporter (VAChT) and has been used in preclinical studies to quantify presynaptic cholinergic nerve terminals. This study presents, to our knowledge, the first-in-human experience with 18F-FEOBV, including radiation dosimetry, biodistribution, tolerability and safety in human subjects, and brain kinetics and methods for quantitative analysis of 18F-FEOBV. Methods: Whole-body 18F-FEOBV scans were obtained in 3 healthy human volunteers. Seven additional subjects underwent dynamic brain imaging 0-120, 150-180, and 210- 240 min after bolus injection of 18F-FEOBV. Arterial blood sampling was performed with chromatographic identification of authentic 18FFEOBV to determine the arterial plasma input function. Analysis methods included nonlinear least-squares fitting of a 2-tissuecompartmental model, reference tissue modeling, and late singlescan imaging. Results: No pharmacologic or physiologic changes were observed after intravenous administration of up to 1.3 μg of 18F-FEOBV. Radiation dosimetry estimates indicate that more than 400 MBq may be administered without exceeding regulatory radiation dose limits. Kinetic analysis showed brain uptake to be relatively high with single-pass extraction of 25%-35%. VAChT binding estimates varied by a factor of greater than 30 between the striatum and cortex. Coefficients of variation in k3 estimates varied from 15% to 30%. Volume of distribution measures yielded a dynamic range of approximately 15 but with little reduction in variability. Reference tissue approaches yielded more stable estimates of the distribution volume ratio (1 1 BPND), with coefficients of variation ranging from 20% in the striatum to 6%-12% in cortical regions. The late static distribution of 18F-FEOBV correlated highly with the distribution volume ratio estimates from reference tissue models (r = 0.993). Conclusion: 18F-FEOBV PET confirms that the tracer binds to VAChT with the expected in vivo human brain distribution. Both reference tissue modeling and late static scanning approaches provide a robust index of VAChT binding.
ASJC Scopus subject areas
- Radiology Nuclear Medicine and imaging