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Research Article

Synthesis and In Vitro Evaluation of New Translocator Protein Ligands Designed for Positron Emission Tomography

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Pages 539-550 | Received 03 Sep 2018, Accepted 10 Jan 2019, Published online: 19 Mar 2019

References

  • Papadopoulos V Baraldi M Guilarte TR et al. Translocator protein (18 kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function . Trends Pharmacol. Sci.27 ( 8 ), 402 – 409 ( 2006 ).
  • Braestrup C Squires RF . Specific benzodiazepine receptors in rat brain characterized by high-affinity (3H)diazepam binding . Proc. Natl Acad. Sci. USA74 ( 9 ), 3805 – 3809 ( 1977 ).
  • Liu G-J Middleton RJ Hatty CR et al. The 18 kDa translocator protein, microglia and neuroinflammation . Brain Pathol.24 ( 6 ), 631 – 653 ( 2014 ).
  • Veenman L Gavish M . The peripheral-type benzodiazepine receptor and the cardiovascular system. Implications for drug development . Pharmacol. Ther.110 ( 3 ), 503 – 524 ( 2006 ).
  • Kunduzova OR Escourrou G De La Farge F et al. Involvement of peripheral benzodiazepine receptor in the oxidative stress, death-signaling pathways, and renal injury induced by ischemia-reperfusion . J. Am. Soc. Nephrol. JASN15 ( 8 ), 2152 – 2160 ( 2004 ).
  • Jordà EG Jiménez A Verdaguer E et al. Evidence in favour of a role for peripheral-type benzodiazepine receptor ligands in amplification of neuronal apoptosis . Apoptosis Int. J. Program. Cell Death10 ( 1 ), 91 – 104 ( 2005 ).
  • Zhao AH Tu LN Mukai C et al. Mitochondrial translocator protein (TSPO) function is not essential for heme biosynthesis . J. Biol. Chem.291 ( 4 ), 1591 – 1603 ( 2016 ).
  • Papadopoulos V Fan J Zirkin B . Translocator protein (18 kDa): an update on its function in steroidogenesis . J. Neuroendocrinol.30 ( 2 ), e12500 ( 2018 ).
  • Denora N Natile G . An Updated view of translocator protein (TSPO) . Int. J. Mol. Sci.18 ( 12 ), 2640 – 2644 ( 2017 ).
  • Bonsack F Alleyne CH Sukumari-Ramesh S . Augmented expression of TSPO after intracerebral hemorrhage: a role in inflammation?J. Neuroinflammation13 , 151 – 164 ( 2016 ).
  • Tu LN Zhao AH Hussein M Stocco DM Selvaraj V . Translocator protein (TSPO) affects mitochondrial fatty acid oxidation in steroidogenic cells . Endocrinology157 ( 3 ), 1110 – 1121 ( 2016 ).
  • Di Grigoli G Monterisi C Belloli S et al. Radiosynthesis and preliminary biological evaluation of [18F]VC701, a radioligand for translocator protein . Mol. Imaging14 , 1535 – 3508 ( 2015 ).
  • Cagnin A Kassiou M Meikle SR Banati RB . Positron emission tomography imaging of neuroinflammation . Neurother. J. Am. Soc. Exp. Neurother.4 ( 3 ), 443 – 452 ( 2007 ).
  • Rupprecht R Papadopoulos V Rammes G et al. Translocator protein (18 kDa) (TSPO) as a therapeutic target for neurological and psychiatric disorders . Nat. Rev. Drug Discov.9 ( 12 ), 971 – 988 ( 2010 ).
  • O'Brien ER Kersemans V Tredwell M et al. Glial activation in the early stages of brain metastasis: TSPO as a diagnostic biomarker . J. Nucl. Med. Off. Publ. Soc. Nucl. Med.55 ( 2 ), 275 – 280 ( 2014 ).
  • Dupont A-C Largeau B Santiago Ribeiro MJ Guilloteau D Tronel C Arlicot N . Translocator protein-18 kDa (TSPO) positron emission tomography (PET) Imaging and its clinical impact in neurodegenerative diseases . Int. J. Mol. Sci.18 ( 4 ), 785 – 821 ( 2017 ).
  • Shah F Hume SP Pike VW Ashworth S McDermott J . Synthesis of the enantiomers of [N-methyl-11C]PK 11195 and comparison of their behaviours as radioligands for PK binding sites in rats . Nucl. Med. Biol.21 ( 4 ), 573 – 581 ( 1994 ).
  • Bird JLE Izquierdo-Garcia D Davies JR et al. Evaluation of translocator protein quantification as a tool for characterising macrophage burden in human carotid atherosclerosis . Atherosclerosis210 ( 2 ), 388 – 391 ( 2010 ).
  • Kobayashi M Jiang T Telu S et al. 11C-DPA-713 has much greater specific binding to translocator protein 18 kDa (TSPO) in human brain than 11C-( R)-PK11195 . J. Cereb. Blood Flow Metab.38 ( 3 ), 393 – 403 ( 2018 ).
  • Fujita M Kobayashi M Ikawa M et al. Comparison of four 11C-labeled PET ligands to quantify translocator protein 18 kDa (TSPO) in human brain: (R)-PK11195, PBR28, DPA-713, and ER176-based on recent publications that measured specific-to-non-displaceable ratios . EJNMMI Res.7 ( 1 ), 84 – 88 ( 2017 ).
  • Kreisl WC Fujita M Fujimura Y et al. Comparison of [11C]-(R)-PK 11195 and [11C]PBR28, two radioligands for translocator protein (18 kDa) in human and monkey: implications for positron emission tomographic imaging of this inflammation biomarker . Neuroimage49 ( 4 ), 2924 – 2932 ( 2010 ).
  • Vivash L O'Brien TJ . Imaging microglial activation with TSPO PET: lighting up neurologic diseases?J. Nucl. Med.57 ( 2 ), 165 – 168 ( 2016 ).
  • Lockhart A Davis B Matthews JC et al. The peripheral benzodiazepine receptor ligand PK11195 binds with high affinity to the acute phase reactant alpha1-acid glycoprotein: implications for the use of the ligand as a CNS inflammatory marker . Nucl. Med. Biol.30 ( 2 ), 199 – 206 ( 2003 ).
  • Guo Q Owen DR Rabiner EA Turkheimer FE Gunn RN . Identifying improved TSPO PET imaging probes through biomathematics: the impact of multiple TSPO binding sites in vivo . Neuroimage60 ( 2 ), 902 – 910 ( 2012 ).
  • Wilson AA Garcia A Parkes J et al. Radiosynthesis and initial evaluation of [18F]-FEPPA for PET imaging of peripheral benzodiazepine receptors . Nucl. Med. Biol.35 ( 3 ), 305 – 314 ( 2008 ).
  • James ML Fulton RR Henderson DJ et al. Synthesis and in vivo evaluation of a novel peripheral benzodiazepine receptor PET radioligand . Bioorg. Med. Chem.13 ( 22 ), 6188 – 6194 ( 2005 ).
  • Boutin H Prenant C Maroy R et al. [18F]DPA-714: Direct Comparison with [11C]PK11195 in a model of cerebral ischemia in rats . PLoS ONE8 ( 2 ), e56441 ( 2013 ).
  • Imaizumi M Kim H-J Zoghbi SS et al. PET imaging with [11C]PBR28 can localize and quantify upregulated peripheral benzodiazepine receptors associated with cerebral ischemia in rat . Neurosci. Lett.411 ( 3 ), 200 – 205 ( 2007 ).
  • Fujita M Imaizumi M Zoghbi SS et al. Kinetic analysis in healthy humans of a novel positron emission tomography radioligand to image the peripheral benzodiazepine receptor, a potential biomarker for inflammation . NeuroImage40 ( 1 ), 43 – 52 ( 2008 ).
  • Owen DRJ Gunn RN Rabiner EA et al. Mixed-affinity binding in humans with 18-kDa translocator protein ligands . J. Nucl. Med.52 ( 1 ), 24 – 32 ( 2011 ).
  • 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.32 ( 1 ), 1 – 5 ( 2012 ).
  • Owen DR Guo Q Rabiner EA Gunn RN . The impact of the rs6971 polymorphism in TSPO for quantification and study design . Clin. Transl. Imaging3 ( 6 ), 417 – 422 ( 2015 ).
  • Zanotti-Fregonara P Zhang Y Jenko KJ et al. Synthesis and evaluation of translocator 18 kDa protein (TSPO) positron emission tomography (PET) radioligands with low binding sensitivity to human single nucleotide polymorphism rs6971 . ACS Chem. Neurosci.5 ( 10 ), 963 – 971 ( 2014 ).
  • Brouwer C Jenko K Zoghbi SS Innis RB Pike VW . Development of N-Methyl-(2-arylquinolin-4-yl)oxypropanamides as Leads to PET Radioligands for Translocator Protein (18 kDa) . J. Med. Chem.57 ( 14 ), 6240 – 6251 ( 2014 ).
  • Castellano S Taliani S Milite C et al. Synthesis and biological evaluation of 4-phenylquinazoline-2-carboxamides designed as a novel class of potent ligands of the translocator protein . J. Med. Chem.55 ( 9 ), 4506 – 4510 ( 2012 ).
  • Ikawa M Lohith TG Shrestha S et al. 11C-ER176, a radioligand for 18-kDa translocator protein, has adequate sensitivity to robustly image all three affinity genotypes in human brain . J. Nucl. Med.58 ( 2 ), 320 – 325 ( 2017 ).
  • Tiwari AK Ji B Yui J et al. [18F]FEBMP: Positron emission tomography imaging of TSPO in a model of neuroinflammation in rats, and in vitro autoradiograms of the human brain . Theranostics5 ( 9 ), 961 – 969 ( 2015 ).
  • Tiwari AK Yui J Fujinaga M et al. Characterization of a novel acetamidobenzoxazolone-based PET ligand for translocator protein (18 kDa) imaging of neuroinflammation in the brain . J. Neurochem.129 ( 4 ), 712 – 720 ( 2014 ).
  • Fujinaga M Luo R Kumata K et al. Development of a 18F-labeled radiotracer with improved brain kinetics for positron emission tomography imaging of translocator protein (18 kDa) in ischemic brain and glioma . J. Med. Chem.60 ( 9 ), 4047 – 4061 ( 2017 ).
  • Milenkovic VM Bader S Sudria-Lopez D et al. Effects of genetic variants in the TSPO gene on protein structure and stability . PLoS ONE13 ( 4 ), e0195627 ( 2018 ).
  • Mokrov GV Deeva OA Gudasheva TA Yarkov SA Yarkova MA Seredenin SB . Design, synthesis and anxiolytic-like activity of 1-arylpyrrolo[1,2-a]pyrazine-3-carboxamides . Bioorg. Med. Chem.23 ( 13 ), 3368 – 3378 ( 2015 );
  • Giri R Goodell JR Xing C et al. Synthesis and cancer cell cytotoxicity of substituted xanthenes . Bioorg. Med. Chem.18 ( 4 ), 1456 – 1463 ( 2010 ).
  • Andreu R C Ronda J . Synthesis of 3,4-Dihydro-2H-1,3-benzoxazines by condensation of 2-hydroxyaldehydes and primary amines: application to the synthesis of hydroxy-substituted and deuterium-labeled compounds . Synth. Commun.38 (14) , 2316 – 2329 ( 2008 ).
  • Ayedi MA Le Bigot Y Ammar H Abid S El Gharbi R Delmas M . Synthesis of primary amines by one-pot reductive amination of aldehydes . Synth. Commun.43 ( 6 ), 2127 – 2133 ( 2013 ).
  • Zou Q Duan H Ning M et al. 4-Benzofuranyloxynicotinamide derivatives are novel potent and orally available TGR5 agonists . Eur. J. Med. Chem.82 , 1 – 15 ( 2014 ).
  • Stevenson L Pimlott SL Sutherland A . A novel approach for the synthesis of the peripheral benzodiazepine receptor ligand, PK11195 . Tetrahedron Lett.48 ( 40 ), 7137 – 7139 ( 2007 ).
  • Tucker SC Brown JM Oakes J Thornthwaite D . Resolution and coupling of 1-(2′-hydroxy-1′-naphthyl)isoquinolines . Tetrahedron57 ( 13 ), 2545 – 2554 ( 2001 ).
  • Shah P Westwell AD . The role of fluorine in medicinal chemistry . J. Enzyme Inhib. Med. Chem.22 ( 5 ), 527 – 540 ( 2007 ).
  • Briard E Zoghbi SS Imaizumi M et al. Synthesis and evaluation in monkey of two sensitive 11C-Labeled aryloxyanilide ligands for imaging brain peripheral benzodiazepine receptors in vivo . J. Med. Chem.51 ( 1 ), 17 – 30 ( 2008 ).
  • Vraka C Nics L Wagner K-H Hacker M Wadsak W Mitterhauser M . LogP, a yesterday's value?Nucl. Med. Biol.50 ( Supplement C ), 1 – 10 ( 2017 ).
  • Cremer JE Hume SP Cullen BM et al. The distribution of radioactivity in brains of rats given [N-methyl-11C]PK 11195 in vivo after induction of a cortical ischaemic lesion . Int. J. Rad. Appl. Instrum. B.19 ( 2 ), 159 – 166 ( 1992 ).
  • Council of Europe . Radiopharmaceutical preparations . In : Europäisches Arzneibuch (European Pharmacopoeia) (8th ed.) . Verlag ÖsterreichGmbH ( Ed. ). Vienna, Austria , 995 ( 2008 ).
  • Council of Europe . Raclopride ([11C]methoxy) injection . In : European Pharmacopoeia (7.0) , European Pharmacopoeia Commission , Strasbourg, France , 988 – 90 ( 2010 ).
  • Jia L Liu X . The conduct of drug metabolism studies considered good practice (II): in vitro experiments . Curr. Drug Metab.8 ( 8 ), 822 – 829 ( 2007 ).
  • Eberl S Katsifis A Peyronneau MA et al. Preclinical in vivo and in vitro comparison of the translocator protein PET ligands [18F]PBR102 and [18F]PBR111 . Eur. J. Nucl. Med. Mol. Imaging.44 ( 2 ), 296 – 307 ( 2017 ).
  • Lee Y-S Siméon FG Briard E Pike VW . Solution structures of the prototypical 18 kDa translocator protein ligand, PK 11195, elucidated with 1H/13C NMR spectroscopy and quantum chemistry . ACS Chem. Neurosci.3 ( 4 ), 325 – 335 ( 2012 ).

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