AAD  Vol.2 No.1 , March 2013
Biomarkers for the early diagnosis of Alzheimer’s disease: The challenge of XXI century
ABSTRACT

AD is the most common form of dementia among the aging population. The neuropathological alterations of AD are represented by the neurofibrillary tangles and extracellular amyloid plaques formation. These two hallmarks are routinely used as biomarkers for AD diagnosis and can allow the identification of the pathology in a late phase. The urgent need to develop probes for PET analysis that can be used in an early diagnosis of this disorder opened a new scenario in which new biomarkers involved in the first step of AD can be easily detected. Recently, an increasing number of studies indicated as new biomarkers P-gp, TLR4, MIR and free serum copper that are involved in the onset of AD. It has been extensively reported that a P-gp dysfunction in brain can be considered one of the causes of the ADaccumulation in brain parenchyma and that the up-regulation of inflammatory gene expression and inflammatory signaling due to MIR and TLR4 modulated the development and the progression of AD.


Cite this paper
Contino, M., Cantore, M., Leopoldo, M. and Colabufo, N. (2013) Biomarkers for the early diagnosis of Alzheimer’s disease: The challenge of XXI century. Advances in Alzheimer's Disease, 2, 13-30. doi: 10.4236/aad.2013.21003.
References
[1]   Kung, H.F. (2012) The β-amyloid hypothesis in Alzheimer’s disease: Seeing is believing. ACS Medicinal Chemistry Letters, 3, 265-267. doi:10.1021/ml300058m

[2]   Jack Jr., C. R. (2012) Alzheimer disease: New concepts on its neurobiology and the clinical role imaging will play. Radiology, 263, 344-361. doi:10.1148/radiol.12110433

[3]   Hampel, H., Prvulovic, D., Teipel, S., Jessen, F., Luckhaus, C., Frolich, L., Riepe, M.W., Dodel, R., Leyhe, T., Bertram, L., Hoffmann, W. and Faltraco, F. (2011) The future of Alzheimer’s disease: The next 10 years. Progress in Neurobiology, 95, 718-728. doi:10.1016/j.pneurobio.2011.11.008

[4]   Blennow, K., Hampel, H., Weiner, M. and Zetterberg, H. (2010) Cere-brospinal fluid and plasma biomarkers in Alzheimer disease. Nature Reviews: Neurology, 6, 131-144. doi:10.1038/nrneurol.2010.4

[5]   Mattsson, N., Zetter-berg, H., Hansson, O., Andreasen, N., Parnetti, L., Jonsson, M., Herukka, S.K., Van der Flier, W. M., Blanken-stein, M.A., Ewers, M., Rich, K., Kaiser, E., Verbeek, M., Tsolaki, M., Mulugeta, E., Rosén, E., Aarsland, D., Visser, P.J., Schröder, J., Marcusson, J., De Leon, M., Hampel, H., Scheltens, P., Pirttilä, T., Wallin, A., Jönhagen, M.E., Minthon, L., Winblad, B. and Blennow, K. (2009) CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. The Journal of the American Medical Association (JAMA), 302, 385-393. doi:10.1001/jama.2009.1064?

[6]   Bekris, L.M., Gallo-way, N.M., Montine, T.J., Schellenberg, G.D. and Yu, C.E. (2010) APOE mRNA and protein expression in postmortem brain are modulated by an extended haplo-type structure. American Journal of Medical Genetics B: Neuropsychiatric Genetic, 153B, 409-417.

[7]   Prvu-lovic, D., Bokde, A.L., Faltraco, F. and Hampel, H. (2011) Functional magnetic resonance imaging as a dynamic candidate biomarker for Alzheimer’s disease. Progress in Neurobiology, 95, 557-569.
doi:10.1016/j.pneurobio.2011.05.008

[8]   Winslow, B.T., Onysko, M.K., Stob, C.M. and Hazlewood, K.A. (2011) Treatment of Alzheimer disease. American Family Physician, 83, 1403-1412.

[9]   Morris, J.C., Roe, C.M., Xiong, C., Fagan, A.M., Goate, A.M., Holtzman, D.M. and Mintun, M.A. (2010) APOE predicts amyloid-beta but not tau Alzheimer pathology in cognitively normal aging. Annals of Neurology, 67, 122-131. doi:10.1002/ana.21843

[10]   Vemuri, P., Wiste, H.J., Weigand, S.D., Knopman, D.S., Shaw, L.M., Trojanowski, J.Q., Aisen, P.S., Weiner, M., Petersen, R.C. and Jack Jr., C.R. (2010) Effect of apolipoprotein E on biomarkers of amyloid load and neuronal pathology in Alzheimer disease. Annals of Neurology, 67, 308-316.

[11]   Jack Jr., C.R., Knopman, D.S., Jagust, W.J., Shaw, L.M., Aisen, P.S., Weiner, M.W., Petersen, R.C. and Trojanowski, J. Q. (2010) Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. The Lancet Neurology, 9, 119-128. doi:10.1016/S1474-4422(09)70299-6

[12]   Masoodi, T.A., Al Shammari, S.A., Al-Muammar, M.N. and Alhamdan, A.A. (2012) Screening and evaluation of deleterious SNPs in APOE gene of Alzheimer’s disease. Neurology Research International, 2012, Article ID: 480609.

[13]   Schellenberg, G.D. and Montine, T.J. (2012) The genetics and neuropathology of Alzheimer’s disease. Acta Neuropathologica, 124, 305-323. doi:10.1007/s00401-012-0996-2

[14]   Ferencz, B., Karlsson, S. and Kalpouzos, G. (2012) Promising genetic biomarkers of preclinical Alzheimer’s disease: The influence of APOE and TOMM40 on brain integrity. Int. J. Alzheimers Dis., 15 pages.

[15]   Baloyannis, S.J., et al. (2011) Mitochondria are related to synaptic pathology in Alzheimer’s disease. International Journal of Alzheimer’s Disease, 2011, Article ID: 421452.

[16]   Hong, M.G., Alexeyenko, A., Lambert, J.C., Amouyel, P. and Prince, J.A. (2010) Genome-wide pathway analysis implicates intracellular transmembrane protein transport in Alzheimer disease. Journal of Human Genetics, 55, 707-709. doi:10.1038/jhg.2010.92

[17]   Johnson, S.C., La Rue, A., Hermann, B.P., Xu, G., Koscik, R.L., Jonaitis, E.M., Bendlin, B.B., Hogan, K.J., Roses, A. D., Saunders, A.M., Lutz, M.W., Asthana, S., Green, R.C. and Sager, M.A. (2011) The effect of TOMM40 poly-T length on gray matter volume and cognition in middle-aged persons with APOE epsilon3/epsilon3 genotype. Alzheimer’s & Dementia, 7, 456-465. doi:10.1016/j.jalz.2010.11.012

[18]   Roses, A.D. (2010) An inherited variable poly-T repeat genotype in TOMM40 in Alzheimer disease. Archives of Neurology, 67, 536-541. doi:10.1001/archneurol.2010.88

[19]   Kim, S., Swaminathan, S., Shen, L., Risacher, S. L., Nho, K., Foroud, T., Shaw, L.M., Trojanowski, J.Q., Potkin, S. G., Huentelman, M.J., Craig, D.W., DeChairo, B.M., Aisen, P.S., Petersen, R.C., Weiner, M.W. and Saykin, A.J. (2011) Genome-wide association study of CSF biomarkers A β1-42, t-τ, and p-τ181p in the ADNI cohort. Neurology, 76, 69-79. doi:10.1212/WNL.0b013e318204a397

[20]   Rosenmann, H. (2012) CSF biomarkers for amyloid and tau pathology in Alzheimer’s disease. Journal of Molecular Neurosci-ence, 47, 1-14. doi:10.1007/s12031-011-9665-5

[21]   Ono, M., Wilson, A., Nobrega, J., Westaway, D., Verhoeff, P., Zhuang, Z.P., Kung, M.P. and Kung, H.F. (2003) 11C-Labeled stilbene derivatives as Aβ-aggregate-specific PET imaging agents for Alzheimer’s disease. Nuclear Medicine and Biology, 30, 565-571. doi:10.1016/S0969-8051(03)00049-0

[22]   Mathis, C.A., Wang, Y., Holt, D.P., Huang, G.F., Debnath, M.L. and Klunk, W.E. (2003) Synthesis and evaluation of 11C-Labeled 6-Substituted 2-Arylbenzothiazoles as amyloid imaging agents. Journal of Medical Chemistry, 46, 2740-2755. doi:10.1021/jm030026b

[23]   Kudo, Y., Okamura, N., Furumoto, S., Tashiro, M., Furukawa, K., Maruyama, M., Itoh, M., Iwata, R., Yanai, K. and Arai, H. (2007) 2-(2-[2-Dimethylaminothiazol-5-yl] ethenyl)-6-(2-[fluoro]ethoxy)benzoxazole: A novel PET agent for in vivo detection of dense amyloid plaques in Alzheimer’s disease patients. Journal of Nuclear Medicine, 48, 553-561. doi:10.2967/jnumed.106.037556

[24]   Kung, M.P., Hou, C., Zhuang, Z.-P., Zhang, B., Skovronsky, D.M., Troja-nowski, J.Q., Lee, V.M.-Y. and Kung, F. (2002) HIMPY: An improved thioflavin-T derivative for in vivo labeling of beta-amyloid plaques. Brain Research, 956, 202-210. doi:10.1016/S0006-8993(02)03436-4

[25]   Chopra, A. (2012) 2-{3-[18F]Fluoro-4-(methylamino) phenyl}-1,3-benzothiazol-6-ol. Molecular Imaging and Contrast Agent Database (MICAD). http://www.ncbi.nlm.nih.gov/books/NBK115136/

[26]   Saint-Aubert, L., Planton, M., Hannequin, D., Albucher, J., Delisle, M., Payoux, P., Hitzel, A., Viallard, G., Péran, P., Campion, D., Laquerriere, A., Barbeau, E., Puel, M., Raposo, N., Chollet, F. and Parient, J. (2012) Amy-loid imaging with AV45 ((18)F-florbetapir) in a cognitively normal AβPP duplication carrier. Journal of Alzheimer’s Disease, 28, 877-883.

[27]   Poisnel, G., Dhilly, M., Moustié, O., Delamare, J., Abbas, A., Guilloteau, D. and Barredoi, L. (2011) PET imaging with [18F]AV-45 in an APP/PS1-21 murine model of amyloid plaque deposition. Neurobiology of Aging, 3, 2561-2571.

[28]   Manook, A., Yousefi, B.H., Willuweit, A., Platzer, S., Reder, S., Voss, A., Huisman, M., Settles, M., Neff, F., Velden, J., Schoor, M., Von der Kammer, H., Wester, H., Schwaiger, M., Henriksen, G. and Drzezga, A. (2012) Small-animal PET imaging of amyloid-beta plaques with [11C]PiB and its multi-modal validation in an APP/PS1 mouse model of Alzheimer’s disease. PLoS One, 7, e31310. doi:10.1371/journal.pone.0031310

[29]   Kadir, A., Almkvist, O., Forsberg, A., Wall, A., Engler, H., Långström, B. and Nordberg, A. (2012) Dynamic changes in PET amyloid and FDG imaging at different stages of Alzheimer’s disease. Neurobiology of Aging, 33, 198.e1- 198.e14. doi:10.1016/j.neurobiolaging.2010.06.015?

[30]   Villemagne, V.L., Pike, K.E., Chételat, G., Ellis, K.A., Mulligan, R.S., Bourgeat, P., Ackermann, U., Jones, G., Szoeke, C., Salvado, O., Martins, R., O’Keefe, G., Mathis, C.A., Klunk, W.E., Ames, D., Masters, C.L. and Rowe, C.C. (2011) Longitudinal assessment of Aβ and cognition in aging and Alzheimer disease. Annals of Neurology, 69, 181-192. doi:10.1002/ana.22248

[31]   Vandenberghe, R., Laere, K., Ivanoiu, A., Salmon, E., Bastin, C., Triau, E., Hasselbalch, S., Law, I., Andersen, A., Korner, A., Minthon, L., Garraux, G., Nelissen, N., Bormans, G., Buckley, C., Owenius, R., Thurfjell, L., Farrar, G. and Brooks, D. (2010) 18F-flutemetamol amyloid imaging in Alzheimer disease and mild cognitive impairment: A phase 2 trial. Annals of Neurology, 68, 319-329. doi:10.1002/ana.22068

[32]   Villemagne, V.L., Ong, K., Mulligan, R.S., Holl, G., Pejoska, S., Jones, G., O’Keefe, G., Ackerman, U., Tochon-Danguy, H., Chan, J.G., Reininger, C.B., Fels, L., Putz, B., Rohde, B., Masters, C.L. and Rowe, C.C. (2011) Amyloid imaging with 18F-florbetaben in Alzheimer disease and other dementias. Journal of Nuclear Medicine, 52, 1210-1217. doi:10.2967/jnumed.111.089730

[33]   Fodero-Tavoletti, M.T., Mulligan, R.S., Okamura, N., Furumoto, S., Rowe, C.C., Kudo, Y., Masters, C.L., Cappai, R., Yanai, K. and Villemagne, V.L. (2009) In vitro characterisation of BF227 binding to alpha-synuclein/ Lewy bodies. European Journal of Pharmacology, 617, 54-58. doi:10.1016/j.ejphar.2009.06.042

[34]   Chang, K.W., Chen, C.C., Lee, S.Y., Shen, L.H. and Wang, H.E. (2009) The synthesis and characterization of [124I] IMPY, a thioflavinS derivative, in transgenic mouse models of Alzheimer’s disease. Applied Radiation and Isotopes, 67, 1397-1400. doi:10.1016/j.apradiso.2009.02.039

[35]   Neumaier, B., Deisenhofer, S., Sommer, C., Solbach, C., Reske, S.N. and Mottaghy, F. (2010) Synthesis and evaluation of 18F-fluoroethylated benzothiazole derivatives for in vivo imaging of amyloid plaques in Alzheimer’s disease. Applied Radiation and Isotopes, 68, 1066-1072. doi:10.1016/j.apradiso.2009.12.044

[36]   Alagille, D., DaCosta, H., Baldwin, R.M., Tamagnan, G. D. (2011) 2-Arylimidazo[2,1-b]benzothiazoles: A new family of amyloid binding agents with potential for PET and SPECT imaging of Alzheimer’s brain. Bioorganic & Medicinal Chemistry Letters, 21, 2966-2968.
doi:10.1016/j.bmcl.2011.03.052

[37]   Ono, M., Watanabe, R., Kawashima, H., Kawai, T., Watanabe, H., Haratake, M., Saji, H. and Nakayama, M. (2009) 18F-labeled flavones for in vivo imaging of beta-amyloid plaques in Alzheimer’s brains. Bioorganic & Medicinal Chemistry, 17, 2069-2072. doi:10.1016/j.bmc.2009.01.025

[38]   Watanabe, H., Ono, M., Kimura, H., Kagawa, S., Nishii, R., Fuchigami, T., Haratake, M., Nakayama, M., Saji and H. (2011) A dual fluorinated and iodinated radiotracer for PET and SPECT imaging of β-amyloid plaques in the brain. Bioorganic & Medicinal Chemistry Letters, 21, 6519-6522. doi:10.1016/j.bmcl.2011.08.063

[39]   Cui, M., Ono, M., Kimura, H., Liu, B.L. and Saji, H. (2011) Synthesis and biological evaluation of indole-chalcone derivatives as β-amyloid imaging probe. Bioorganic & Medicinal Chemistry Letters, 21, 980-982. doi:10.1016/j.bmcl.2010.12.045

[40]   Nordberg, A. (2011) Molecular imaging in Alzheimer’s disease: New perspec-tives on biomarkers for early diagnosis and drug development. Alzheimer’s Research & Therapy, 3, 34-43. doi:10.1186/alzrt96

[41]   Bohnen, N. I., Djang, D.S.W., Herholz, K., Anzai, Y. and Minoshima, S. (2012) Effectiveness and safety of 18F-FDG PET in the evaluation of dementia: A review of the recent literature. Journal of Nuclear Medicine, 53, 59-71. doi:10.2967/jnumed.111.096578

[42]   Kadir, A. and Nordberg, A. (2010) Target-specific PET probes for neurodegenerative disorders related to dementia. Journal of Nuclear Medicine, 51, 1418-1430. doi:10.2967/jnumed.110.077164

[43]   Parri, R.H. and Dineley, T.K. (2010) Nicotinic acetylcholine receptors interact with beta amyloid: Molecular, cellular and physiological consequences. Current Alzheimer Research, 7, 27-39.
doi:10.2174/156720510790274464

[44]   Shin, J., Kepe, V., Barrio, J.R. and Small, G.W. (2011) The merits of FDDNP-PET imaging in Alzheimer’s disease. Journal of Alzheimer’s Disease, 26, 135-145.

[45]   Zhang, W., Arteaga, J., Cashion, D.K., Chen, G., Gangadharmath, U., Gomez, L.F., Kasi, D., Lam, C., Liang, Q., Liu, C., Mocharla, V.P., Mu Sinha, A., Szardenings, A. K., Wang, E., Walsh, J.C., Xia, C., Yu, C., Zhao, T. and Kolb, H.C.A. (2012) Highly selective and specific PET tracer for imaging of tau pathologies. Journal of Alzheimer’s Disease, 31, 601-612.

[46]   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. doi:10.1016/S0140-6736(01)05625-2

[47]   Yasuno, F., Ota, M., Kosaka, J., Ito, H., Higuchi, M., Doronbekov, T.K., Nozaki, S., Fujimura, Y., Koeda, M., Asada, T. and Suhara, T. (2008) Increased binding of peripheral ben-zodiazepine receptor in Alzheimer’s disease measured by positron emission tomography with [11C] DAA1106. Biological Psychiatry, 64, 835-841. doi:10.1016/j.biopsych.2008.04.021

[48]   Carter, S.F., Schöll, M., Almkvist, O., Wall, A., Engler, H., Långström, B. and Nordberg, A. (2012) Evidence for astrocytosis in prodromal Alzheimer’s disease provided by 11C-deuterium-L-deprenyl: A multi-tracer PET paradigm combining 11C-PIB and 18F-FDG. Journal of Nuclear Medicine, 53, 37-46. doi:10.2967/jnumed.110.087031

[49]   Colabufo, N.A., Berardi, F., Cantore, M., Contino, M., Inglese, C., Niso, M. and Perrone, R. (2010) Perspectives of Pglycoprotein modulating agents in oncology and neurodegenerative diseases: Pharmaceutical, biological and diagnostic potentials. Journal of Medicinal Chemistry, 53, 1883-1897.
doi:10.1021/jm900743c

[50]   Lam, F.C., Liu, R., Lu, P., Shapiro, A.B., Renoir, J.M., Sharom, F.J. and Reiner, P.B. (2001) Beta-amyloid efflux mediated by p-glycoprotein. Journal of Neurochemistry, 76, 1121-1128.
doi:10.1046/j.1471-4159.2001.00113.x

[51]   De Smaele, E., Ferretti, E. and Gulino, A. (2010) Micro-RNAs as biomarkers for CNS cancer and other disorders. Brain Research, 1338, 100-111. doi:10.1016/j.brainres.2010.03.103

[52]   Wang, L.L., Huang, Y., Wang, G. and Chen, S.D. (2012) The potential role of microRNA-146 in Alzheimer’s disease: Bio-marker or therapeutic target? Medical Hypotheses, 78, 398-401.
doi:10.1016/j.mehy.2011.11.019

[53]   Capo, C.R., Arciello, M., Squitti, R., Cassetta, E., Rossini, P.M., Calabrese, L. and Rossi, L. (2008) Features of ceruloplasmin in the cerebrospinal fluid of Alzheimer’s dis-ease patients. BioMetals, 21, 367-372. doi:10.1007/s10534-007-9125-4

[54]   Squitti, R., Ven-triglia, M., Barbati, G., Cassetta, E., Ferreri, F., Dal Forno, G., Ramires, S., Zappasodi, F. and Rossini, P.M. (2007) “Free” copper in serum of Alzheimer’s disease patients correlates with markers of liver function. Journal of Neural Transmission, 114, 1589-1594. doi:10.1007/s00702-007-0777-6

[55]   Squitti, R., Barbati, G., Rossi, L., Ventriglia, M., Dal Forno, G., Cesaretti, S., Cesaretti, S., Moffa, F., Caridi, I., Cassetta, E., Pasqualetti, P., Calabrese, L., Lupoi, D. and Rossini, P.M. (2006) Excess of nonceruloplasmin serum copper in AD correlates with MMSE, CSF beta-amyloid, and htau. Neurology, 67, 76-82. doi:10.1212/01.wnl.0000223343.82809.cf

[56]   Squitti, R. (2012) Copper dysfunction in Alzheimer’s disease: From meta-analysis of biochemical studies to new insight into genetics. Journal of Trace Elements in Medicine and Biology, 26, 93-96. doi:10.1016/j.jtemb.2012.04.012

[57]   Ventriglia, M., Bucossi, S., Panetta, V. and Squitti, R. (2012) Copper in Alzheimer’s disease: A meta-analysis of serum, plasma, and cerebrospinal fluid studies. Journal of Alzheimer’s Disease, 30, 981-984.

[58]   Capiralla, H., Vingtdeux, V., Zhao, H., Sankowski, R., Al-Abed, Y., Davies, P. and Marambaud, P. (2012) Resveratrol mitigates lipopoly-saccharide- and Aβ-mediated microglial inflammation by inhibiting the TLR4/NF-κB/ STAT signaling cascade. Journal of Neurochemistry, 120, 461-472. doi:10.1111/j.1471-4159.2011.07594.x

[59]   Song, M., Jin, J., Lim, J.E., Kou, J., Pattanayak, A., Rehman, J.A., Kim, H.D., Tahara, K., Lalonde, R. and Fukuchi, K. (2011) TLR4 mutation reduces microglial activation, increases Aβ deposits and exacerbates cognitive deficits in a mouse model of Alzheimer’s disease. Journal of Neuroinflammation, 8, 92. doi:10.1186/1742-2094-8-92

[60]   Martin, C., Berridge, G., Mistry, P., Higgins, C., Charlton, P. and Callaghan, R. (2000) Drug binding sites on Pglycoprotein are altered by ATP binding prior to nucleotide hydrolysis. Bio-chemistry, 39, 11901-11906. doi:10.1021/b i000559b

[61]   Colabufo, N.A. and Van Waarde, A. (2010) Imaging of ABC transporter function and expression. Current Topics in Medicinal Chemistry, 10, 1701-1702.

[62]   Luurtsema, G., Molthoff, C.FM., Windhorst, A.D., Smit, J. W., Keizer, H., Boellaard, R., Lammertsma, A.A. and Franssen, E.J. (2003) (R)-and (S)-[11C]verapamil as PET- tracers for measuring P-glycoprotein function: In vitro and in vivo evaluation. Nuclear Medicine and Biology, 30, 747-751. doi:10.1016/S0969-8051(03)00078-7

[63]   Lazarova, N., Zoghbi, S.S., Hong, J., Seneca, N., Tuan, E., Gladding, R.L., Liow, J.S., Taku, A., Innis, R.B. and Pike, V.W. (2008) Synthesis and evaluation of [N-methyl-11C] N-desmethyl-loperamide as a new and improved PET radiotracer for imaging P-gp function. Journal of Medicinal Chemistry, 51, 6034-6043. doi:10.1021/jm800510m

[64]   Luurtsema, G., Schuit, R.C., Klok, R.P., Verbeek, J., Leysen, J.E., Lammertsma, A.A. and Windhorst A.D. (2009) Evaluation of [11C]laniquidar as a tracer of Pglycoprotein: Radiosynthesis and biodistribution in rats. Nuclear Medicine and Biology, 36, 643-649. doi:10.1016/j.nucmedbio.2009.03.004

[65]   Dörner, B., Kuntner, C., Bankstahl, J.P., Stanek, J., Wanek, T., Stundner, G., Mairinger, S., Löscher, W., Müller, M., Langer, O. and Erker, T. (2009) Synthesis and small-animal positron emission tomography evaluation of [11C]- elacridar as a radiotracer to assess the distribution of Pglycoprotein at the blood-brain barrier. Journal of Medicinal Chemistry, 52, 6073-6082. doi:10.1021/jm900940f

[66]   Bauer, F., Kuntner, C., Bankstahl, J.P., Stanek, J., Mairinger, S., Dörner, B., Löscher, W., Müller, M., Erker, T. and Langer, O. (2010) Synthesis and in vivo evaluation of [11C]tariquidar, a positron emission tomography radio-tracer based on a third-generation Pglycoprotein inhibitor. Bioorganic & Medicinal Chemistry, 18, 5489-5497. doi:10.1016/j.bmc.2010.06.057

[67]   Van Waarde, A., Ramakrishnan, N.K., Rybczynska, A., Elsinga, P.H., Berardi, F., De Jong, J.R., Kwizera, C., Perrone, R., Cantore, M., Sijbesma, J.W., Dierckx, R.A. and Colabufo, N.A. (2009) Synthesis and preclinical evaluation of novel PET probes for P-glycoprotein function and expression. Journal of Medicinal Chemistry, 52, 4524-4532. doi:10.1021/jm900485a

[68]   Colabufo, N.A. and Van Waarde, A. (2010) Preclinical evaluation of [11C]MC18, a radiotracer for PET imaging of P-gp expression. Current Topics in Medicinal Chemistry, 10, 1.

[69]   Leung, K. (2010) 6,7-Dimethoxy-2-{3-[4-[11C]methoxy- 3,4-dihydro-2H-naphthalen-(1E)-ylidene]-propyl}-1,2,3,4-tetrahydro-isoquinoline. Molecular Imaging and Contrast Agent Database (MICAD). http://www.ncbi.nlm.nih.gov/books/NBK45979/

[70]   Kawamura, K., Yamasaki, T., Konno, F., Yui, J., Hatori, A., Yanamoto, K., Wakizaka, H., Ogawa, M., Yo-shida, Y., Nengaki, N., Fukumura, T. and Zhang, M.R. (2011) Synthesis and in vivo evaluation of 18F-fluoroethyl GF120918 and XR9576 as positron emission tomography probes for assessing the function of drug efflux transporters. Bioorganic & Medicinal Chemistry, 19, 861-870. doi:10.1016/j.bmc.2010.12.004

[71]   Kawamura, K., Yamasaki, T., Konno, F., Yui, J., Hatori, A., Yanamoto, K., Wakizaka, H., Takei, M., Kimura, Y., Fukumura, T. and Zhang, M.R. (2011) Evaluation of limiting brain pene-tration related to Pglycoprotein and breast cancer resis-tance protein using [(11)C]GF120918 by PET in mice. Molecular Imaging and Biology (MIB), 13, 152-160.

[72]   Kannan, P., Telu, S., Shukla, S., Ambudkar, S.V., Pike, V. W., Halldin, C., Gottesman, M.M Innis, R.B. and Hall, M.D. (2011) The “Specific” Pglycoprotein inhibitor Tariquidar is also a substrate and an inhibitor for Breast Cancer Resistance Protein (BCRP/ABCG2). ACS Chemical Neuroscience, 2, 82-89. doi:10.1021/cn100078a

[73]   Colabufo, N.A., Perrone, R., Leopoldo, M., Cantore, M., Contino, M. and Niso, M. (2011) Novel tetrahydroiso- quinoline compounds for use in the diagnosis and treatment of neurodegenerative diseases. WO2012159666. http://worldwide.espacenet.com/publicationDetails/originalDocument?CC=WO&NR=2012159666A1&KC=A1&FT= D&ND=3&date=20121129&DB=EPODOC&locale=en_EP

[74]   Paradiso, A., Azzariti, A., Berardi, F., Colabufo, N.A. and Perrone, R. (2006) Verapamil analogues with inhibition activity on ABC (ATP Binding cassette) cell extrution pumps. WO2008017588. http://worldwide.espacenet.com/publicationDetails/originalDocument?CC=WO&NR=2008017588A1&KC=A1&FT= D&ND=3&date=20080214&DB=EPODOC&locale=en_EP

 
 
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