Preclinical evaluation of 18F-PF-05270430, a novel PET radioligand for the phosphodiesterase 2A enzyme

Journal of Nuclear Medicine

Volumn 57, Issue 9, 2016, Pages 1448-1453

  Chen, Laigao ^a   Nabulsi, Nabeel ^b   Naganawa, Mika ^b   Zasadny, Kenneth ^a   Skaddan, Marc B ^a   Zhang, Lei ^a   Najafzadeh, Soheila ^b   Lin, Shu Fei ^b   Helal, Christopher J ^a   Boyden, Tracey L ^a   Chang, Cheng ^a   Ropchan, Jim ^b   Carson, Richard E ^b   Villalobos, Anabella ^a   Huang, Yiyun ^b  

^a PFIZER INC   (United States)

^b YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Non human primates; Phosphodiesterase 2a; Positron emission tomography; Radioligand

Indexed keywords

4 (3 FLUOROAZETIDIN 1 YL) 7 METHYL 5 [1 METHYL 5 [4 (TRIFLUOROMETHYL)PHENYL] 1H PYRAZOL 4 YL]IMIDAZO [1,5 F] [1,2,4] TRIAZINE; RADIOPHARMACEUTICAL AGENT; SPLEEN EXONUCLEASE; SPLEEN EXONUCLEASE A; UNCLASSIFIED DRUG; 4-(3-FLUOROAZETIDIN-1-YL)-7-METHYL-5-(1-METHYL-5-(4-(TRIFLUOROMETHYL)PHENYL)-1H-PYRAZOL-4-YL)IMIDAZO(5,1-F)(1,2,4)TRIAZINE; AZABICYCLO DERIVATIVE; AZETIDINE DERIVATIVE; CYCLIC NUCLEOTIDE PHOSPHODIESTERASE 2;

ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DOSIMETRY; IMAGE ANALYSIS; ISOTOPE LABELING; MACACA FASCICULARIS; MALE; NONHUMAN; NUCLEOPHILICITY; PET SCANNER; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; RADIATION DOSE DISTRIBUTION; RADIATION SAFETY; RADIOISOTOPE DECAY; RADIOISOTOPE DISTRIBUTION; RADIOLOGICAL PARAMETERS; RAT; STANDARDIZED UPTAKE VOLUME; TEST RETEST RELIABILITY; ANIMAL; ANTIBODY SPECIFICITY; BRAIN; DIAGNOSTIC IMAGING; METABOLIC CLEARANCE RATE; METABOLISM; MOLECULAR IMAGING; PROCEDURES; REPRODUCIBILITY; RHESUS MONKEY; SENSITIVITY AND SPECIFICITY; SPECIES DIFFERENCE; SPRAGUE DAWLEY RAT; TISSUE DISTRIBUTION;

ANIMALS; AZABICYCLO COMPOUNDS; AZETIDINES; BRAIN; CYCLIC NUCLEOTIDE PHOSPHODIESTERASES, TYPE 2; MACACA MULATTA; MALE; METABOLIC CLEARANCE RATE; MOLECULAR IMAGING; ORGAN SPECIFICITY; POSITRON-EMISSION TOMOGRAPHY; RADIOPHARMACEUTICALS; RATS; RATS, SPRAGUE-DAWLEY; REPRODUCIBILITY OF RESULTS; SENSITIVITY AND SPECIFICITY; SPECIES SPECIFICITY; TISSUE DISTRIBUTION;

EID: 84989311692     PISSN: 01615505     EISSN: 2159662X     Source Type: Journal    
DOI: 10.2967/jnumed.115.171454     Document Type: Article

References (22)

1. Eaton WW, Chen CY. Epidemiology. In: Leiberman JA, Stroup TS, Perkins DO, eds. Textbook of Schizophrenia. Washington, D.C.: American Psychiatric Publishing; 2006:17-37.
2. Javitt DC, Laruelle M. Neurochemical theory. In: Lieberman JA, Stroup TS, Perkins DO, eds. Textbook of Schizophrenia. Washington D.C.: American Psychiatric Publishing; 2006:85-116.
3. Keefe RS, Harvey PD. Cognitive impairment in schizophrenia. Handb Exp Pharmacol. 2012;213:11-37.
4. Keefe RS, Bilder RM, Davis SM, et al. Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE Trial. Arch Gen Psychiatry. 2007;64:633-647.
5. Stroup TS, Kraus JE, Marder SR. Pharmacotherapies. In: Lieberman JA, Stroup TS, Perkins DO, eds. Textbook of Schizophrenia. Washington D.C.: American Psychiatric Publishing; 2006:303-325.
6. Stephenson DT, Coskran TM, Wilhelms MB, et al. Immunohistochemical localization of phosphodiesterase 2A in multiple mammalian species. J Histochem Cytochem. 2009;57:933-949.
7. Perez-Costas E, Melendez-Ferro M, Roberts RC. Basal ganglia pathology in schizophrenia: dopamine connections and anomalies. J Neurochem. 2010;113:287-302.
8. Coyle JT. Glutamate and schizophrenia: Beyond the dopamine hypothesis. Cell Mol Neurobiol. 2006;26:365-384.
9. Goff DC, Coyle JT. The emerging role of glutamate in the pathophysiology and treatment of schizophrenia. Am J Psychiatry. 2001;158:1367-1377.
10. Boess FG, Hendrix M, van der Staay FJ, et al. Inhibition of phosphodiesterase 2 increases neuronal cGMP, synaptic plasticity and memory performance. Neuropharmacology. 2004;47:1081-1092.
11. Helal CJ, Chappie TA, Humphrey JM, Verhoest PR, Yang E, inventors; Pfizer Inc., assignee. Preparation of imidazo[5, 1-f][1, 2, 4]triazines for the treatment of neurological disorders. USpatent20120214791A1. August 23, 2012.
12. Schröder S, Wenzel B, Deuther-Conrad W, et al. Synthesis, 18F-radiolabelling and biological characterization of novel fluoroalkylated triazine derivatives for in vivo imaging of phosphodiesterase 2A in brain via positron emission tomography. Molecules. 2015;20:9591-9615.
13. Zhang L, Villalobos A, Beck EM, et al. Design and selection parameters to accelerate the discovery of novel central nervous system positron emission tomography (PET) ligands and their application in the development of a novel phosphodiesterase 2A PET ligand. J Med Chem. 2013;56:4568-4579.
14. Naganawa M, Waterhouse RN, Nabulsi N, et al. First-in-human assessment of the novel PDE2A PET radiotracer 18F-PF-05270430. J Nucl Med. 2016;57:1388-1395.
15. Lim K, Labaree D, Li S, Huang Y. Preparation of the metabotropic glutamate receptor 5 (mGluR5) PET tracer [18F]FPEB for human use: An automated radiosynthesis and a novel one-pot synthesis of its radiolabeling precursor. Appl Radiat Isot. 2014;94:349-354.
16. Hilton J, Yokoi F, Dannals RF, Ravert HT, Szabo Z, Wong DF. Column-switching HPLC for the analysis of plasma in PET imaging studies. Nucl Med Biol. 2000;27:627-630.
17. Gandelman MS, Baldwin RM, Zoghbi SS, Zea-Ponce Y, Innis RB. Evaluation of ultrafiltration for the free-fraction determination of single photon emission computed tomography (SPECT) radiotracers: Beta-CIT, IBF, and iomazenil. J Pharm Sci. 1994;83:1014-1019.
18. Innis RB, Cunningham VJ, Delforge J, et al. Consensus nomenclature for in vivo imaging of reversibly binding radioligands. J Cereb Blood Flow Metab. 2007;27:1533-1539.
19. Ichise M, Toyama H, Innis RB, Carson RE. Strategies to improve neuroreceptor parameter estimation by linear regression analysis. J Cereb Blood Flow Metab. 2002;22:1271-1281.
20. Lammertsma AA, Hume SP. Simplified reference tissue model for PET receptor studies. Neuroimage. 1996;4:153-158.
21. Thomas N. Hypothesis testing and Bayesian estimation using a sigmoid Emax model applied to sparse dose-response designs. J Biopharm Stat. 2006;16:657-677.
22. Morgan P, Van Der Graaf PH, Arrowsmith J, et al. Can the flow of medicines be improved? Fundamental pharmacokinetic and pharmacological principles toward improving phase II survival. Drug Discov Today. 2012;17:419-424.