Preclinical evaluation of a P2X7 receptor-selective radiotracer: PET studies in a rat model with local overexpression of the human p2x7 receptor and in nonhuman primates

Journal of Nuclear Medicine

Volumn 57, Issue 9, 2016, Pages 1436-1441

  Ory, Dieter ^a,b   Celen, Sofie ^a   Gijsbers, Rik ^b,c   Haute, Chris Van Den ^a,c   Postnov, Andrey ^d   Koole, Michel ^d   Vandeputte, Caroline ^d   Andrés, José Ignacio ^e   Alcazar, Jesus ^e   Angelis, Meri De ^e   Langlois, Xavier ^e   Bhattacharya, Anindya ^e   Schmidt, Mark ^e   Letavic, Michael A ^e   Vanduffel, Wim ^f   Laere, Koen Van ^d   Verbruggen, Alfons ^a   Debyser, Zeger ^b   Bormans, Guy ^a  

^a UNIVERSITY OF LEUVEN   (Belgium)

^b DEPARTMENT OF PHARMACEUTICAL AND PHARMACOLOGICAL SCIENCES   (Belgium)

^c KU LEUVEN   (Belgium)

^d UNIVERSITY HOSPITALS LEUVEN   (Belgium)

^e JANSSEN RESEARCH AND DEVELOPMENT   (Belgium)

^f KU LEUVEN UNIVERSITY OF LEUVEN   (Belgium)

Author keywords

Neuroinflammation; Non human primate; P2x7 receptor; Pet; Viral vector

Indexed keywords

DRUG METABOLITE; ENHANCED GREEN FLUORESCENT PROTEIN; JNJ 54173717 C 11; PURINERGIC P2X7 RECEPTOR; TRACER; UNCLASSIFIED DRUG; VIRUS VECTOR; P2XR RECEPTOR, HUMAN; RADIOPHARMACEUTICAL AGENT;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; AUTORADIOGRAPHY; BINDING AFFINITY; BLOOD BRAIN BARRIER; BRAIN REGION; CONTROLLED STUDY; CORPUS STRIATUM; DEGENERATIVE DISEASE; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG PENETRATION; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG STRUCTURE; HISTOPATHOLOGY; HUMAN; IC50; MALE; MEMBRANE BINDING; NONHUMAN; PET SCANNER; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN EXPRESSION; RAT; RAT MODEL; RHESUS MONKEY; ANIMAL; ANTIBODY SPECIFICITY; BRAIN; DIAGNOSTIC IMAGING; FEMALE; METABOLIC CLEARANCE RATE; METABOLISM; MOLECULAR IMAGING; PROCEDURES; REPRODUCIBILITY; SENSITIVITY AND SPECIFICITY; TISSUE DISTRIBUTION; TRANSGENIC RAT; UPREGULATION; WISTAR RAT;

ANIMALS; BRAIN; FEMALE; HUMANS; MACACA MULATTA; MALE; METABOLIC CLEARANCE RATE; MOLECULAR IMAGING; ORGAN SPECIFICITY; POSITRON-EMISSION TOMOGRAPHY; RADIOPHARMACEUTICALS; RATS; RATS, TRANSGENIC; RATS, WISTAR; RECEPTORS, PURINERGIC P2X7; REPRODUCIBILITY OF RESULTS; SENSITIVITY AND SPECIFICITY; TISSUE DISTRIBUTION; UP-REGULATION;

EID: 84989329051     PISSN: 01615505     EISSN: 2159662X     Source Type: Journal    
DOI: 10.2967/jnumed.115.169995     Document Type: Article

References (25)

1. Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH. Mechanisms underlying inflammation in neurodegeneration. Cell. 2010;140:918-934.
2. Chen M-K, Guilarte TR. Translocator protein 18 kDa (TSPO): molecular sensor of brain injury and repair. Pharmacol Ther. 2008;118:1-17.
3. Jacobs AH, Tavitian B. Noninvasive molecular imaging of neuroinflammation. J Cereb Blood Flow Metab. 2012;32:1393-1415.
4. Eggen BJL, Raj D, Hanisch U-K, Boddeke HWGM. Microglial phenotype and adaptation. J Neuroimmune Pharmacol. 2013;8:807-823.
5. Rudin M, Weissleder R. Molecular imaging in drug discovery and development. Nat Rev Drug Discov. 2003;2:123-131.
6. Owen DR, Yeo AJ, Gunn RN, et al. An 18-kDa translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28. J Cereb Blood Flow Metab. 2012;32:1-5.
7. Ohara K, Shimizu K, Matsuura S, et al. Toll-like receptor 4 signaling in trigeminal ganglion neurons contributes tongue-referred pain associated with tooth pulp inflammation. J Neuroinflammation. 2013;10:139-149.
8. Skaper SD, Debetto P, Giusti P. The P2X7 purinergic receptor: from physiology to neurological disorders. FASEB J. 2010;24:337-345.
9. Parvathenani LK, Tertyshnikova S, Greco CR, Roberts SB, Robertson B, Posmantur R. P2X7 mediates superoxide production in primary microglia and is up-regulated in a transgenic mouse model of Alzheimer's disease. J Biol Chem. 2003;278:13309-13317.
10. Sanz JM, Chiozzi P, Ferrari D, et al. Activation of microglia by amyloid b requires P2X7 receptor expression. J Immunol. 2009;182:4378-4385.
11. Takenouchi T, Sekiyama K, Sekigawa A, et al. P2X7 receptor signaling pathway as a therapeutic target for neurodegenerative diseases. Arch Immunol Ther Exp (Warsz). 2010;58:91-96.
12. Ory D, Celen S, Verbruggen A, Bormans G. PET radioligands for in vivo visualization of neuroinflammation. Curr Pharm Des. 2014;20:5897-5913.
13. Able SL, Fish RL, Bye H, et al. Receptor localization, native tissue binding and ex vivo occupancy for centrally penetrant P2X7 antagonists in the rat. Br J Pharmacol. 2011;162:405-414.
14. Bhattacharya A, Wang Q, Ao H, et al. Pharmacological characterization of a novel centrally permeable P2X7 receptor antagonist: JNJ-47965567. Br J Pharmacol. 2013;170:624-640.
15. Lord B, Aluisio L, Shoblock JR, et al. Pharmacology of a novel central nervous system-penetrant P2X7 antagonist JNJ-42253432. J Pharmacol Exp Ther. 2014;351:628-641.
16. Donnelly-Roberts DL, Jarvis MF. Discovery of P2X7 receptor-selective antagonists offers new insights into P2X7 receptor function and indicates a role in chronic pain states. Br J Pharmacol. 2007;151:571-579.
17. Gunosewoyo H, Coster MJ, Kassiou M. Molecular probes for P2X7 receptor studies. Curr Med Chem. 2007;14:1505-1523.
18. Donnelly-Roberts DL, Namovic MT, Surber B, et al. [3H]A-804598 ([3H]2-cyano- 1-[(1S)-1-phenylethyl]-3-quinolin-5-ylguanidine) is a novel, potent, and selective antagonist radioligand for P2X7 receptors. Neuropharmacology. 2009;56:223-229.
19. Van der Perren A, Toelen J, Carlon M, et al. Efficient and stable transduction of dopaminergic neurons in rat substantia nigra by rAAV 2/1, 2/2, 2/5, 2/6.2, 2/7, 2/8 and 2/9. Gene Ther. 2011;18:517-527.
20. Savall BM, Wu D, De Angelis M, et al. Synthesis, SAR, and pharmacological characterization of brain penetrant P2X7 receptor antagonists. ACS Med Chem Lett. 2015;6:671-676.
21. Rudolph DA, Alcazar J, Ameriks MK, et al. Novel methyl substituted 1-(5, 6- dihydro-[1, 2, 4]triazolo[4, 3-A]pyrazin-7(8H)-yl)methanones are P2X7 antagonists. Bioorg Med Chem Lett. 2015;25:3157-3163.
22. Casteels C, Vermaelen P, Nuyts J, et al. Construction and evaluation of multitracer small-Animal PET probabilistic atlases for voxel-based functional mapping of the rat brain. J Nucl Med. 2006;47:1858-1866.
23. Lammertsma AA, Hume SP. Simplified reference tissue model for PET receptor studies. Neuroimage. 1996;4:153-158.
24. Janssen B, Vugts DJ, Funke U, et al. Synthesis and initial preclinical evaluation of the P2X7 receptor antagonist [11C]A-740003 as a novel tracer of neuroinflammation. J Labelled Comp Radiopharm. 2014;57:509-516.
25. Salinas CA, Searle GE, Gunn RN. The simplified reference tissue model: model assumption violations and their impact on binding potential. J Cereb Blood Flow Metab. 2015;35:304-311.