Comparison of [ 11 C]TZ1964B and [ 18 F]MNI659 for PET imaging brain PDE10A in nonhuman primates
- Department of Radiology Washington University School of Medicine St. Louis Missouri
- Department of Neurology Washington University School of Medicine St. Louis Missouri
- Molecular NeuroImaging LLC New Haven Connecticut
- Department of Radiology Washington University School of Medicine St. Louis Missouri, Department of Neurology Washington University School of Medicine St. Louis Missouri, Department of Neuroscience Physical Therapy and Occupational Therapy Washington University School of Medicine St. Louis Missouri
Abstract Phosphodiesterase 10A ( PDE 10A) inhibitors show therapeutic effects for diseases with striatal pathology. PET radiotracers have been developed to quantify in vivo PDE 10A levels and target engagement for therapeutic interventions. The aim of this study was to compare two potent and selective PDE 10A radiotracers, [ 11 C] TZ 1964B and [ 18 F] MNI 659 in the nonhuman primate ( NHP ) brain. Double scans in the same cynomolgus monkey on the same day were performed after injection of [ 11 C] TZ 1964B and [ 18 F] MNI 659. Specific uptake was determined in two ways: nondisplaceable binding potential ( BP ND ) was calculated using cerebellum as the reference region and the PDE ‐10A enriched striatum as the target region of interest ( ROI ); the area under the time–activity curve ( AUC ) for the striatum to cerebellum ratio was also calculated. High‐performance liquid chromatography ( HPLC ) analysis of solvent‐extracted NHP plasma identified the percentage of intact tracer versus radiolabeled metabolites samples post injection of each radiotracer. Both radiotracers showed high specific accumulation in NHP striatum. [ 11 C] TZ 1964B has higher striatal retention and lower specific striatal uptake than [ 18 F] MNI 659. The BP ND estimates of [ 11 C] TZ 1964B were 3.72 by Logan Reference model (Logan REF ) and 4.39 by simplified reference tissue model ( SRTM ); the BP ND estimates for [ 18 F] MNI 659 were 5.08 (Logan REF ) and 5.33 ( SRTM ). AUC ratios were 5.87 for [ 11 C] TZ 1964B and 7.60 for [ 18 F] MNI 659. Based on BP ND values in NHP striatum, coefficients of variation were ~10% for [ 11 C] TZ 1964B and ~30% for [ 18 F] MNI 659. Moreover, the metabolism study showed the percentage of parent compounds were ~70% for [ 11 C] TZ 1964B and ~50% for [ 18 F] MNI 659 60 min post injection. These data indicate that either [ 11 C] TZ 1964B or [ 18 F] MNI 659 could serve as suitable PDE 10A PET radiotracers with distinguishing features for particular clinical application.
- Research Organization:
- Washington Univ., St. Louis, MO (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
- Grant/Contract Number:
- DESC0008432; DESC0012737; SC0008432
- OSTI ID:
- 1307790
- Alternate ID(s):
- OSTI ID: 1328252; OSTI ID: 1629771
- Journal Information:
- Pharmacology Research & Perspectives, Journal Name: Pharmacology Research & Perspectives Vol. 4 Journal Issue: 5; ISSN 2052-1707
- Publisher:
- Wiley Blackwell (John Wiley & Sons)Copyright Statement
- Country of Publication:
- United Kingdom
- Language:
- English
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