Human biodistribution and dosimetry of 18F-JNJ42259152, a radioligand for phosphodiesterase 10A imaging

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• 作者：Koen Van Laere (1) (4)
  Rawaha U. Ahmad (1)
  Hendra Hudyana (1)
  Sofie Celen (3)
  Kristof Dubois (2)
  Mark E. Schmidt (2)
  Guy Bormans (3)
  Michel Koole (1)
  
• 关键词：Phosphodiesterase 10A ; 18F ; JNJ42259152 ; PET ; Dosimetry ; Biodistribution ; Brain kinetics
• 刊名：European Journal of Nuclear Medicine and Molecular Imaging
• 出版年：2013
• 出版时间：January 2013
• 年：2013
• 卷：40
• 期：2
• 页码：254-261
• 全文大小：482KB
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• 作者单位：Koen Van Laere (1) (4)
  Rawaha U. Ahmad (1)
  Hendra Hudyana (1)
  Sofie Celen (3)
  Kristof Dubois (2)
  Mark E. Schmidt (2)
  Guy Bormans (3)
  Michel Koole (1)
  
  1. Division of Nuclear Medicine, University Hospital Leuven and KU Leuven, Leuven, Belgium
  4. Division of Nuclear Medicine, University Hospital Leuven - Gasthuisberg, Herestraat 49, 3000, Leuven, Belgium
  3. Laboratory for Radiopharmacy, KU Leuven, Leuven, Belgium
  2. Janssen Research & Development, Division of Janssen Pharmaceuticals NV, Beerse, Belgium
  
• ISSN：1619-7089

文摘

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 23-7?years) underwent ten dynamic whole-body PET/CT scans over 6?h after bolus injection of 175.5?±-.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?±-.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.