Abstract
Purpose
Phosphodiesterase 10A (PDE10A) is a cAMP/cGMP-hydrolysing enzyme with a central role in striatal signalling and implicated in neuropsychiatric disorders such as Huntington’s disease, Parkinson’s disease, schizophrenia and addiction. We have developed a novel PDE10A PET ligand, 18F-JNJ42259152, and describe here its human dynamic biodistribution, safety and dosimetry.
Methods
Six male subjects (age range 23–67 years) underwent ten dynamic whole-body PET/CT scans over 6 h after bolus injection of 175.5 ± 9.4 MBq 18F-JNJ42259152. Source organs were delineated on PET/CT and individual organ doses and effective dose were determined using the OLINDA software.
Results
F-JNJ42259152 was readily taken up by the brain and showed exclusive retention in the brain, especially in the striatum with good washout starting after 20 min. The tracer was cleared through both the hepatobiliary and the urinary routes. No defluorination was observed. Organ absorbed doses were largest for the gallbladder (239 μSv/MBq) and upper large intestine (138 μSv/MBq). The mean effective dose was 24.9 ± 4.1 μSv/MBq. No adverse events were encountered.
Conclusion
In humans, 18F-JNJ42259152 has an appropriate distribution, brain kinetics and safety. The estimated effective dose was within WHO class IIb with low interindividual variability. Therefore, the tracer is suitable for further kinetic evaluation in humans.
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Acknowledgments
The precursor for on-site synthesis of the tracer used in this study was kindly donated by Janssen Pharmaceuticals.
Conflicts of interest
K.D. and M.S. are employees of Janssen Pharmaceuticals. No industry sponsored grant was received for conducting the study. The authors declare no conflicts of interest.
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Supplementary Figure 1
Time–activity curve of 18F-JNJ42259152 in cortical bone (distal radius), indicating absence of a cumulative defluorination effect. Error bars represent the standard deviations for the mean values from the six subjects investigated. Activity is expressed as SUVs normalized to the injected activity per unit weight. (JPEG 64 kb)
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Van Laere, K., Ahmad, R.U., Hudyana, H. et al. Human biodistribution and dosimetry of 18F-JNJ42259152, a radioligand for phosphodiesterase 10A imaging. Eur J Nucl Med Mol Imaging 40, 254–261 (2013). https://doi.org/10.1007/s00259-012-2270-1
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DOI: https://doi.org/10.1007/s00259-012-2270-1