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 Chemical Neuroscience

Volumn 5, Issue 10, 2014, Pages 963-971

  Zanotti Fregonara, Paolo ^a   Zhang, Yi ^a   Jenko, Kimberly J ^a   Gladding, Robert L ^a   Zoghbi, Sami S ^a   Fujita, Masahiro ^a   Sbardella, Gianluca ^b   Castellano, Sabrina ^b   Taliani, Sabrina ^c   Martini, Claudia ^c   Innis, Robert B ^a   Da Settimo, Federico ^c   Pike, Victor W ^a  

^a NATIONAL INSTITUTE OF MENTAL HEALTH   (United States)

^b UNIVERSITY OF SALERNO   (Italy)

^c UNIVERSITY OF PISA   (Italy)

Author keywords

brain; carbon 11; imaging; PET; radioligand; TSPO

Indexed keywords

4 PHENYLQUINAZOLINE 2 CARBOXAMIDE C 11; MEMBRANE PROTEIN; RADIOLIGAND; TRANSLOCATOR 18 KDA PROTEIN; UNCLASSIFIED DRUG; 4 AMINOBUTYRIC ACID RECEPTOR; CARBON; GABAERGIC RECEPTOR AFFECTING AGENT; QUINAZOLINE DERIVATIVE; RADIOPHARMACEUTICAL AGENT; TSPO PROTEIN, HUMAN;

ARTICLE; GENOTYPE; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; ISOTOPE LABELING; LIPOPHILICITY; NEUROIMAGING; NONHUMAN; PLASMA PROTEIN BINDING; POSITRON EMISSION TOMOGRAPHY; PROTEIN SYNTHESIS; SENSITIVITY ANALYSIS; SINGLE NUCLEOTIDE POLYMORPHISM; ANIMAL; BRAIN; EVALUATION STUDY; GENETICS; LEUKOCYTE; MALE; METABOLISM; PRECLINICAL STUDY; RHESUS MONKEY; SCINTISCANNING; SYNTHESIS;

ANIMALS; BRAIN; CARBON RADIOISOTOPES; DRUG EVALUATION, PRECLINICAL; GABA AGENTS; HUMANS; LEUKOCYTES; MACACA MULATTA; MALE; POLYMORPHISM, SINGLE NUCLEOTIDE; POSITRON-EMISSION TOMOGRAPHY; QUINAZOLINES; RADIOPHARMACEUTICALS; RECEPTORS, GABA;

EID: 84908022420     PISSN: None     EISSN: 19487193     Source Type: Journal    
DOI: 10.1021/cn500138n     Document Type: Article

References (51)

1. Papadopoulos, V., Baraldi, M., Guilarte, T. R., Knudsen, T. B., Lacapere, J. J., Lindemann, P., Norenberg, M. D., Nutt, D., Weizman, A., Zhang, M., and Gavish, M. (2006) Translocator protein (18 kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function Trends Pharmacol. Sci. 27, 402-409
2. Doble, A., Malgouris, C., Daniel, M., Daniel, N., Imbault, F., Basbaum, A., Uzan, A., Guérémy, C., and Le Fur, G. (1987) Labelling of peripheral-type benzodiazepine binding sites in human brain with [3H]PK 11195: anatomical and subcellular distribution Brain Res. Bull. 18, 49-61
3. Casellas, P., Galiegue, S., and Basile, A. S. (2002) Peripheral benzodiazepine receptors and mitochondrial function Neurochem. Int. 40, 475-486
4. Papadopoulos, V., Lecanu, L., Brown, R. C., Han, Z., and Yao, Z.-X. (2006) Peripheral-type benzodiazepine receptor in neurosteroid biosynthesis, neuropathology and neurological disorders Neuroscience 138, 749-756
5. Rone, M. B., Ran, J., and Papadopoulos, V. (2009) Cholesterol transport in steroid biosynthesis: role of protein-protein interactions and implications in disease states Biochim. Biophys. Acta 1791, 646-658
6. Veenman, L. and Gavish, M. (2000) Peripheral benzodiazepine receptors: their implication in brain disease Drug Dev. Res. 50, 355-370
7. Cagnin, A., Brooks, D. J., Kennedy, A. M., Gunn, R. N., Myers, R., Turkheimer, F. E., Jones, T., and Banati, R. B. (2001) In-vivo measurement of activated microglia in dementia Lancet 358, 461-467
8. Ouchi, Y., Yoshikawa, E., Sekine, Y., Futatsubashi, M., Kanno, T., Ogusu, T., and Torizuka, T. (2005) Microglial activation and dopamine terminal loss in early Parkinson's disease Ann. Neurol. 57, 168-175
9. Debruyne, J. C., Versijpt, J., Van Laere, K. J., De Vos, F., Keppens, J., Strijckmans, K., Achten, E., Slegers, G., Dierckx, R. A., Korf, J., and De Reuck, J. L. (2003) PET visualization of microglia in multiple sclerosis patients using [11C]PK11195 Eur. J. Neurol. 10, 257-264
10. Chelli, B., Pini, S., Abelli, M., Cardini, A., Lari, L., Muti, M., Gesi, C., Cassano, G. B., Lucacchini, A., and Martini, C. (2008) Platelet 18 kDa translocator protein density is reduced in depressed patients with adult separation anxiety Eur. Neuropsychopharmacol. 18, 249-254
11. Dell'Osso, L., Da Pozzo, E., Carmassi, C., Trincavelli, M. L., Ciapparelli, A., and Martini, C. (2010) Lifetime manic-hypomanic symptoms in post-traumatic stress disorder: relationship with the 18 kDa mitochondrial translocator protein density Psychiatry Res. 177, 139-143
12. Kreisl, W. C., Lyoo, C. H., McGwier, M., Snow, J., Jenko, K. J., Kimura, N., Corona, W., Morse, C. L., Zoghbi, S. S., Pike, V. W., McMahon, F. J., Turner, R. S., Innis, R. B., and Biomarkers Consortium PET Radioligand Project Team. (2013) In vivo radioligand binding to translocator protein correlates with severity of Alzheimer's disease Brain 136, 2228-2238
13. Benavides, J., Fage, D., Carter, C., and Scatton, B. (1987) Peripheral type benzodiazepine binding sites are a sensitive indirect index of neuronal damage Brain Res. 421, 167-172
14. Chen, M.-K. and Guilarte, T. R. (2008) Translocator protein 18 kDa (TSPO): molecular sensor of brain injury and repair Pharmacol. Ther. 118, 1-17
15. Chaveau, F., Boutin, H., Van Camp, N., Dollè, F., and Tavitian, B. (2008) Nuclear imaging of neuroinflammation: a comprehensive review of [11C]PK11195 challengers Eur. J. Nucl. Med. Mol. Imaging 35, 2304-2319
16. Dollè, F., Luus, C., Reynolds, A., and Kassiou, M. (2009) Radiolabelled molecules for imaging the translocator protein (18 kDa) using positron emission tomography Curr. Med. Chem. 16, 2899-2923
17. Schweitzer, P. J., Fallon, B. A., Mann, J. J., and Kumar, J. S. D. (2010) PET tracers for the peripheral benzodiazepine receptor and uses thereof Drug Discovery Today 15, 933-942
18. Venneti, S., Lopresti, B. J., and Wiley, C. A. (2006) The peripheral benzodiazepine receptor (translocator protein 18 kDa) in microglia: from pathology to imaging Prog. Neurobiol. 80, 308-322
19. Camsonne, R., Moulin, M. A., Crouzel, C., Syrota, A., Maziere, M., and Comar, D. (1986) 11C-Labeling of PK 11195 and visualization of peripheral receptors of benzodiazepines by positron emission tomography J. Pharmacologie 17, 383
20. Petit-Taboué, M. C., Baron, J. C., Barré, L., Travere, J. M., Speckel, D., Camsonne, R., and MacKenzie, E. T. (1991) Brain kinetics and specific binding of [11C]PK11195 to ω3 sites in baboon Eur. J. Pharmacol. 200, 347-351
21. Shah, F., Hume, S. P., Pike, V. W., Ashworth, S., and McDermott, J. (1994) 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, 573-581
22. Banati, R. B., Goerres, G. W., Myers, R., Gunn, R. N., Turkheimer, F. E., Kreutzberg, G. W., Brooks, D. J., Jones, T., and Duncan, J. S. (1999) [11C](R)-PK11195 positron emission tomography imaging of activated microglia in vivo in Rasmussen's encephalitis Neurology 53, 2199-2203
23. Kreisl, W. C., Fujita, M., Fujimura, Y., Kimura, N., Jenko, K. J., Kannan, P., Hong, J., Morse, C. L., Zoghbi, S. S., Gladding, R. L., Jacobson, S., Oh, U., Pike, V. W., and Innis, R. B. (2010) 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 NeuroImage 49, 2924-2932
24. Briard, E., Zoghbi, S. S., Imaizumi, M., Gourley, J. P., Shetty, H. U., Hong, J., Cropley, V., Fujita, M., Innis, R. B., and Pike, V. W. (2008) Synthesis and evaluation in monkey of two sensitive 11C-labeled aryloxyanilide ligands for imaging brain peripheral benzodiazepine receptors in vivo J. Med. Chem. 51, 17-30
25. Imaizumi, M., Briard, E., Zoghbi, S. S., Gourley, J. P., Hong, J., Fujimura, Y., Pike, V. W., Innis, R. B., and Fujita, M. (2008) Brain and whole-body imaging in nonhuman primates of [11C]PBR28, a promising PET radioligand for peripheral benzodiazepine receptors NeuroImage 39, 1289-1298
26. Fujita, M., Imaizumi, M., Zoghbi, S. S., Fujimura, Y., Farris, A. G., Suhara, T., Hong, J., Pike, V. W., and Innis, R. B. (2008) Kinetic analysis in healthy humans of a novel positron emission tomography radioligand to image the peripheral benzodiazepine receptor, a potential biomarker for inflammation NeuroImage 40, 43-52
27. Briard, E., Zoghbi, S. S., Siméon, F., Imaizumi, M., Gourley, J. P., Shetty, H. U., Lu, S.-Y., Fujita, M., Innis, R. B., and Pike, V. W. (2009) Single-step high-yield radiosynthesis and evaluation of a selective 18F-labeled ligand for imaging brain peripheral benzodiazepine receptors with PET J. Med. Chem. 52, 688-699
28. Endres, C. J., Pomper, M. G., James, M., Uzuner, O., Hammoud, D. A., Watkins, C. C., Reynolds, A., Hilton, J., Dannals, R. F., and Kassiou, M. (2009) Initial evaluation of [11C]DPA-713, a novel TSPO PET ligand, in humans J. Nucl. Med. 50, 1276-1282
29. Guo, Q., Colasanti, A., Owen, D. R., Onega, M., Kamalakaran, A., Bennacef, I., Matthews, P. M., Rabiner, E. A., Turkheimer, F. E., and Gunn, R. N. (2013) Quantification of the specific translocator protein signal of 18F-PBR111 in healthy humans: a genetic polymorphism effect on in vivo binding J. Nucl. Med. 54, 1915-1923
30. Mizrahi, R., Rusjan, P. M., Kennedy, J., Pollock, B., Mulsant, B., Suridjan, I., De Luca, V., Wilson, A. A., and Houle, S. (2012) Translocator protein (18 kDa) polymorphism (rs6971) explains in-vivo brain binding affinity of the PET radioligand [18F]-FEPPA J. Cereb. Blood Flow Metab. 32, 968-972
31. Owen, D. R., Howell, O. W., Tang, S.-P., Wells, L. A., Bennacef, I., Bergstrom, M., Gunn, R. N., Rabiner, E. A., Wilkins, M. R., Reynolds, R., Matthews, P. M., and Parker, C. A. (2010) Two binding sites for [3H]PBR28 in human brain: implications for TSPO PET imaging of neuroinflammation J. Cerebr. Blood Flow Metab. 30, 1608-1618
32. Kreisl, W. C., Jenko, K. J., Hines, C. S., Lyoo, C. H., Corona, W., Morse, C. L., Zoghbi, S. S., Hyde, T., Kleinman, J. E., Pike, V. W., McMahon, F. J., and Innis, R. B. (2013) A genetic polymorphism for translocator protein 18 kDa affects both in vitro and in vivo radioligand binding in human brain to this putative biomarker of neuroinflammation J. Cerebr. Blood Flow Metab. 33, 53-58
33. Owen, D. R. J., Gunn, R. N., Rabiner, E. A., Bennacef, I., Fujita, M., Kreisl, W. C., Innis, R. B., Pike, V. W., Reynolds, R., Matthews, P. M., and Parker, C. A. (2011) Mixed-affinity binding in humans with 18-kDa translocator protein ligands J. Nucl. Med. 52, 24-32
34. Owen, D. R., Yeo, A. J., Gunn, R. N., Song, K., Wadsworth, G., Lewis, A., Rhodes, C., Pulford, D. J., Bennacef, I., Parker, C. A., StJean, P. L., Cardon, L. R., Mooser, V. E., Matthews, P. M., Rabiner, E. A., and Rubio, J. P. (2012) An 18-kDa translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28 J. Cereb. Blood Flow Metab. 32, 1-5
35. Castellano, S., Taliani, S., Milite, C., Pugliesi, I., Da Pozzo, E., Rizzetto, E., Bendinelli, S., Costa, B., Cosconati, S., Greco, G., Novellino, E., Sbardella, G., Stefancich, G., Martini, C., and Da Settimo, F. (2012) 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, 4506-4510
36. Castellano, S., Taliani, S., Viviano, M., Milite, C., Da Pozzo, E., Costa, B., Barresi, E., Bruno, A., Cosconati, S., Marinelli, L., Greco, G., Novellino, E., Sbardella, G., Da Settimo, F., and Martini, C. (2014) Structure-activity relationship refinement and further assessment of 4-phenylquinazoline-2-carboxamide translocator protein ligands as antiproliferative agents in human glioblastoma tumors J. Med. Chem. 57, 2413-2428
37. Pike, V. W. (1993) Positron-emitting radioligands for studies in vivo - probes for human psychopharmacology J. Psychopharmacol. 7, 139-158
38. Laruelle, M., Slifstein, M., and Huang, Y. (2003) Relationships between radiotracer properties and image quality in molecular imaging of the brain with positron emission tomography Mol. Imaging Biol. 5, 363-375
39. Waterhouse, R. N. (2003) Determination of lipophilicity and its use as a predictor of blood-brain barrier penetration of molecular imaging agents Mol. Imaging Biol. 5, 376-389
40. Pike, V. W. (2009) PET Radiotracers: crossing the blood-brain barrier and surviving metabolism Trends Pharmacol. Sci. 30, 431-440
41. Logan, J., Fowler, J. S., Volkow, N. D., Wolf, A. P., Dewey, S. L., Schlyer, D. J., MacGregor, R. R., Hitzemann, R., Bendriem, B., Gatley, S. J., and Christman, D. R. (1990) Graphical analysis of reversible radioligand binding from time-activity measurements applied to [ N -11C-methyl]-(-)-cocaine PET studies in human subjects J. Cerebr. Blood Flow Metab. 10, 740-747
42. Innis, R. B., Cunningham, V. J., Delforge, J., Fujita, M., Gjedde, A., Gunn, R. N., Holden, J., Houle, S., Huang, S.-C., Ichise, M., Iida, H., Ito, H., Kimura, Y., Koeppe, R. A., Knudsen, G.-M., Knuuti, J., Lammertsma, A. A., Laruelle, M., Logan, J., Maguire, R. P., Mintun, M. A., Morris, E. D., Parsey, R., Price, J. C., Slifstein, M., Sossi, V., Suhara, T., Votaw, J. R., Wong, D. F., and Carson, R. E. (2007) Consensus nomenclature for in vivo imaging of reversibly binding radioligands J. Cereb. Blood Flow Metab. 27, 1533-1539
43. Zoghbi, S. S., Anderson, K. B., Jenko, K. J., Luckenbaugh, D. A., Innis, R. B., and Pike, V. W. (2012) On quantitative relationships between drug-like compound lipophilicity and plasma free fraction in monkey and human J. Pharm. Sci. 101, 1028-1039
44. Shultz, M. D. (2013) Setting expectations in molecular optimizations: strengths and limitations of commonly used composite parameters Bioorg. Med. Chem. Lett. 23, 5980-5991
45. Cheng, Y. and Prusoff, W. H. (1973) Relationship between constant (Ki) and the concentration of inhibitor which causes 50% inhibition (IC50) of an enzymatic reaction Biochem. Pharmacol. 22, 3099-3108
46. Christman, D. R., Finn, R. D., Karlström, K., and Wolf, A. P. (1975) The production of ultra high specific activity 11C-labeled hydrogen cyanide, carbon dioxide, carbon monoxide and methane via the 14N(p,α)11C reaction Int. J. Appl. Radiat. Isot. 26, 435-442
47. Smith, D. (2008) Synthia gets extreme makeover courtesy of National Instruments, pp 24-25, ftp://ftp.ni.com/pub/branches/.../NIDaysBooklet.pdf.
48. Bjurling, P., Reineck, R., Westerburg, G., Gee, A. D., Sutcliffe, J., and Långström, B. (1995) Synthia, a compact radiochemistry system for automated production of radiopharmaceuticals, in Proceedings - Sixth Workshop on Targetry and Target Chemistry (Link, J. M. and Ruth, T. J., Eds.), pp 282-284, TRIUMF, Vancouver.
49. Larsen, P., Ulin, J., Dahlström, K., and Jensen, M. (1997) Synthesis of [11C]iodomethane by iodination of [11C]methane Appl. Radiat. Isot. 48, 153-157
50. Clark, J. D., Baldwin, R. L., Bayne, K. A., Brown, M. J., Gebhart, G. F., Gonder, J. C., Gwathmey, J. K., Keeling, M. E., Kohn, D. F., Robb, J. W., Smith, O. A., Steggerda, J.-A. D., and VandeBer, J. L. (1996) Guide for the Care and Use of Laboratory Animals, National Academy Press, Washington, DC.
51. Gandelman, M. S., Baldwin, R. M., Zoghbi, S. S., Zea-Ponce, Y., and Innis, R. B. (1994) Evaluation of ultrafiltration for the free-fraction determination of single photon emission computed tomography (SPECT) radiotracers: β-CIT, IBF, and iomazenil J. Pharm. Sci. 83, 1014-1019