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Nuclear Medicine Imaging Tracers for Neurology

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PET and SPECT in Neurology

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Abstract

Tracers to investigate neurological disorders with positron emission tomography (PET) or single photon emission computed tomography (SPECT) have found many applications. Several molecular targets can be studied in vivo in man in combination with pathophysiological conditions. Most attention has been given to tracers for the investigation of the role of translocator protein (TSPO), deposition of beta-amyloid, and the dopaminergic system. For these targets, many clinical studies have been published with application of a variety of tracers. Other targets of interest that have been studied in man to lesser extent are receptors for N-methyl-d-aspartate acid (NMDA), the serotonergic system, receptors for adenosine, gamma-aminobutyric acid (GABA), opioids, metabotropic glutamate receptor subtype 5 (mGlu5), and tracers for the cholinergic system. In addition, several transporter systems have received a great deal of attention. Many other tracers are under development for new molecular targets opening new horizons in the future. This chapter will highlight PET tracers that have already reached the state of human application.

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References

  • Abi-Dargham A, Mawlawi O, Lombardo I et al (2002) Prefrontal dopamine D1 receptors and working memory in schizophrenia. J Neurosci 22:3708–3719

    CAS  PubMed  Google Scholar 

  • Aznavour N, Zimmer L (2007) [18F]MPPF as a tool for the in vivo imaging of 5-HT1A receptors in animal and human brain. Neuropharmacology 52:695–707

    Article  CAS  PubMed  Google Scholar 

  • Bartels AL (2011) Blood-brain barrier P-glycoprotein function in neurodegenerative disease. Curr Pharm Des 17:2771–2777

    Article  CAS  PubMed  Google Scholar 

  • Bartels AL, de Klerk OL, Kortekaas R et al (2010) [11C]verapamil to assess P-gp function in human brain during aging, depression and neurodegenerative disease. Curr Top Med Chem 10:1775–1784

    Article  CAS  PubMed  Google Scholar 

  • Barthel H, Sabri O (2011) Florbetaben to trace amyloid-β in the Alzheimer brain by means of PET. J Alzheimers Dis 26(Suppl 3):117–121

    PubMed  Google Scholar 

  • Brooks DJ (2010) Imaging dopamine transporters in Parkinson’s disease. Biomark Med 4:651–660

    Article  CAS  PubMed  Google Scholar 

  • Brooks DJ, Frey KA, Marek KL (2003) Assessment of neuroimaging techniques as biomarkers of the progression of Parkinson’s disease. Exp Neurol 184(Suppl 1):S68–S79

    Article  CAS  PubMed  Google Scholar 

  • Carter SF, Scholl M, Almkvist O et al (2012) Evidence for astrocytosis in prodromal Alzheimer disease provided by 11C-deuterium-L-deprenyl: a multitracer PET paradigm combining [11C]-Pittsburgh compound B and [18F]FDG. J Nucl Med 53:37–46

    Article  CAS  PubMed  Google Scholar 

  • Catafau AM, Suarez M, Bullich S, Barcelona Clinical Imaging in Psychiatry Group (2009) Within-subject comparison of striatal D2 receptor occupancy measurements using [123I]IBZM SPECT and [11C]Raclopride PET. Neuroimage 46:447–458

    Article  PubMed  Google Scholar 

  • Catafau AM, Searle GE, Bullich S et al (2010) Imaging cortical dopamine D1 receptors using [11C]NNC112 and ketanserin blockade of the 5-HT2A receptors. J Cereb Blood Flow Metab 30:985–993

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chauveau F, Boutin H, Van Camp N et al (2008) Nuclear imaging of neuroinflammation: a comprehensive review of [11C]PK11195 challengers. Eur J Nucl Med Mol Imaging 35:2304–2319

    Article  PubMed  Google Scholar 

  • Chen KC, Yang YK, Howes O et al (2013) Striatal dopamine transporter availability in drug-naive patients with schizophrenia: a case-control SPECT study with [99mTc]-TRODAT-1 and a meta-analysis. Schizophr Bull 39:378–386

    Article  PubMed Central  PubMed  Google Scholar 

  • Colabufo NA, Berardi F, Perrone MG et al (2010) Substrates, inhibitors and activators of P-glycoprotein: candidates for radiolabeling and imaging perspectives. Curr Top Med Chem 10:1703–1714

    Article  CAS  PubMed  Google Scholar 

  • de Vries EF, Dierckx RA, Klein HC (2006) Nuclear imaging of inflammation in neurologic and psychiatric disorders. Curr Clin Pharmacol 1:229–242

    Article  PubMed  Google Scholar 

  • DeLorenzo C, Kumar JS, Mann JJ (2011) In vivo variation in metabotropic glutamate receptor subtype 5 binding using positron emission tomography and [11C]ABP688. J Cereb Blood Flow Metab 31:2169–2180

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Demetriades AK (2002) Functional neuroimaging in Alzheimer’s type dementia. J Neurol Sci 15:247–251

    Article  Google Scholar 

  • Ding YS, Singhal T, Planeta-Wilson B et al (2010) PET imaging of the effects of age and cocaine on the norepinephrine transporter in the human brain using (S, S)-[11C]-O-methylreboxetine and HRRT. Synapse 64:30–38

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Dollé F, Luus C, Reynolds A et al (2009) Radiolabelled molecules for imaging the translocator protein (18 kDa) using positron emission tomography. Curr Med Chem 16:2899–2923

    Article  PubMed  Google Scholar 

  • Doraiswamy PM, Sperling RA, Coleman RE et al (2012) Amyloid-β assessed by [18F]florbetapir-PET and 18-month cognitive decline: a multicenter study. Neurology 79:1636–1644

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Eidelberg D, Moeller JR, Dhawan et al (1990) The metabolic anatomy of Parkinson’s disease: complementary [18F]FDG and [18F]FDOPA positron emission tomography studies. Mov Disord 5:203–213

    Article  CAS  PubMed  Google Scholar 

  • Elsinga PH (2002) Radiopharmaceutical chemistry for positron emission tomography. Methods 27:208–217

    Article  CAS  PubMed  Google Scholar 

  • Elsinga PH, Hendrikse NH, Bart J et al (2005) Positron emission tomography studies on binding of central nervous system drugs and P-glycoprotein function in the rodent brain. Mol Imaging Biol 7:37–44

    Article  PubMed  Google Scholar 

  • Elsinga PH, Hatano K, Ishiwata K (2006) PET tracers for imaging of the dopaminergic system. Curr Med Chem 13:2139–2153

    Article  CAS  PubMed  Google Scholar 

  • Farde L, Halldin C, Stone-Elander S et al (1987) PET analysis of human dopamine receptor subtypes using [11C]SCH23390 and [11C]raclopride. Psychopharmacology (Berl) 92:278–284

    Article  CAS  Google Scholar 

  • Fowler JS, MacGregor RR, Wolf AP et al (1987) Mapping human brain monoamine oxidase A and B with 11C-labelled suicide inactivators and PET. Science 235:481–485

    Article  CAS  PubMed  Google Scholar 

  • Fukumitsu N, Ishii K, Kimura Y et al (2008) Adenosine A1 receptors using 8-dicyclopropylmethyl-1-[11C]methyl-3-propylxanthine PET in Alzheimer’s disease. Ann Nucl Med 22:841–847

    Article  PubMed  Google Scholar 

  • Furukawa K, Okamura N, Tashiro M et al (2010) Amyloid PET in mild cognitive impairment and Alzheimer’s disease with BF-227 comparison to FDG-PET. J Neurol 257:721–727

    Article  CAS  PubMed  Google Scholar 

  • Graff-Guerrero A, Willeit M, Ginovart N et al (2008) Brain region binding of the D2/3 agonist [11C]-(+)-PHNO and the D2/3 antagonist [11C]raclopride in healthy humans. Hum Brain Mapp 29:400–410

    Article  PubMed  Google Scholar 

  • Gunn RN, Murthy V, Catafau AM et al (2011) Translational characterization of [11C]GSK931145, a PET ligand for the glycine transporter type 1. Synapse 65:1319–1332

    Article  CAS  PubMed  Google Scholar 

  • Halldin C, Stone-Elander S, Thorell JO et al (1988) 11C-labelling of Ro 15-1788 in two different positions and also 11C-labelling of its main metabolite R0 15-3890 for PET-studies of benzodiazepine receptors. Int J Rad Appl Instrum A 39:993–997

    Article  CAS  PubMed  Google Scholar 

  • Hammers A (2004) Flumazenil positron emission tomography and other ligands for functional imaging. Neuroimaging Clin N Am 14:537–551

    Article  PubMed  Google Scholar 

  • Hashimoto K, Inoue O, Suzuki K et al (1989) Synthesis and evaluation of [11C]PK 11195 for in vivo study of peripheral-type benzodiazepine receptors using positron emission tomography. Ann Nucl Med 3:63–71

    Article  CAS  PubMed  Google Scholar 

  • Homayoun H, Moghaddam B (2010) Group 5 metabotropic glutamate receptors: role in modulating cortical activity and relevance to cognition. Eur J Pharmacol 639:33–39

    Article  CAS  PubMed  Google Scholar 

  • Houle S, Ginovart N, Hussey D et al (2000) Imaging the serotonin transporter with positron emission tomography: initial human studies with [11C]DAPP and [11C]DASB. Eur J Nucl Med 27:1719–1722

    Article  CAS  PubMed  Google Scholar 

  • Huang Y, Mucke L (2012) Alzheimer mechanisms and therapeutic strategies. Cell 148:1204–1222

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Innis R, Baldwin R, Sybirska E et al (1991) Single photon emission computed tomography imaging of monoamine reuptake sites in primate brain with [123I]CIT. Eur J Pharmacol 200:369–370

    Article  CAS  PubMed  Google Scholar 

  • Irie T, Fukushi K, Namba H et al (1996) Brain acetylcholinesterase activity: validation of a PET-tracer in a rat model of Alzheimer’s disease. J Nucl Med 37:649–655

    CAS  PubMed  Google Scholar 

  • Ishiwata K, Kimura Y, de Vries EFJ et al (2007) PET tracers for mapping adenosine receptors as probes for diagnosis of CNS disorders. Cent Nerv Syst Agents Med Chem 7:57–77

    Article  CAS  Google Scholar 

  • Jayanthi LD, Ramamoorthy S (2005) Regulation of monoamine transporters: influence of psychostimulants and therapeutic antidepressants. AAPS J 7:E728–E738

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Karlsson P, Farde L, Halldin C et al (2002) PET study of D1 dopamine receptor binding in neuroleptic-naive patients with schizophrenia. Am J Psychiatry 159:761–767

    Article  PubMed  Google Scholar 

  • Klunk WE, Engler H, Norgberg A et al (2004) Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann Neurol 55:306–319

    Article  CAS  PubMed  Google Scholar 

  • Koepp MJ, Duncan JS (2000) PET: opiate neuroreceptor mapping. Adv Neurol 83:145–156

    CAS  PubMed  Google Scholar 

  • Koeppe RA, Frey KA, Vander Borght TM et al (1996) Kinetic evaluation of [11C]dihydrotetrabenazine by dynamic PET measurement of vesicular monoamine transporter. J Cereb Blood Flow Metab 16:1288–1299

    Article  CAS  PubMed  Google Scholar 

  • Koeppe RA, Gilman S, Junck L et al (2008) Differentiating Alzheimer’s disease from dementia with Lewy bodies and Parkinson’s disease with (+)-[11C]dihydrotetrabenazine positron emission tomography. Alzheimers Dement 4(1 Suppl 1):S67–S76

    Article  PubMed  Google Scholar 

  • Kosaka J, Takahashi H, Ito H (2010) Decreased binding of [11C]NNC112 and [11C]SCH23390 in patients with chronic schizophrenia. Life Sci 86:814–818

    Article  CAS  PubMed  Google Scholar 

  • Kung HF, Alavi A, Chang W et al (1990) In vivo SPECT imaging of CNS D2 dopamine receptors: initial studies with iodine-123 IBZM in humans. J Nucl Med 31:573–579

    CAS  PubMed  Google Scholar 

  • Kung HF, Kim HJ, Kung MP et al (1996) Imaging of dopamine transporters in human with technetium-99 m TRODAT-1. Eur J Nucl Med 23:1527–1530

    Article  CAS  PubMed  Google Scholar 

  • Lundkvist C, Halldin C, Ginovart N et al (1996) [11C]MDL 100907, a radioligand for selective imaging of 5-HT2A receptors with positron emission tomography. Life Sci 58:187–192

    Article  Google Scholar 

  • Mielke R, Heis WD (1998) Positron emission tomography for diagnosis of Alzheimer’s disease and vascular dementia. J Neural Transm Suppl 53:237–250

    Article  CAS  PubMed  Google Scholar 

  • Millet P, Moulin-Sallanon M, Tournier BB (2012) Quantification of dopamine D2/3 receptors in rat brain using factor analysis corrected [18F]Fallypride images. Neuroimage 62:1455–1468

    Article  CAS  PubMed  Google Scholar 

  • Mishina M, Ishiwata K, Naganawa M et al (2011) Adenosine A2A receptors measured with [11C]TMSX PET in the striata of Parkinson’s disease patients. PLoS One 6:e17338

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Mozley LH, Gur RC, Mozley PD, Gur RE (2001) Striatal dopamine transporters and cognitive functioning in healthy men and women. Am J Psychiatry 158:1492–1499

    Article  CAS  PubMed  Google Scholar 

  • Narendran R, Mason NS, May MA (2011a) Positron emission tomography imaging of dopamine D2/3 receptors in the human cortex with [11C]FLB 457: reproducibility studies. Synapse 65:35–40

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Narendran R, Martinez D, Mason NS et al (2011b) Imaging of dopamine D2/3 agonist binding in cocaine dependence: a [11C]NPA positron emission tomography study. Synapse 65:1344–1349

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Nocker M, Seppi K, Donnemiller E (2012) Progression of dopamine transporter decline in patients with the Parkinson variant of multiple system atrophy: a voxel-based analysis of [123I]β-CIT SPECT. Eur J Nucl Med Mol Imaging 39:1012–1020

    Article  CAS  PubMed  Google Scholar 

  • Ossenkoppele R, Tolboom N, Foster-Dingley JC (2012) Longitudinal imaging of Alzheimer pathology using [11C]PIB, [18F]FDDNP and [18F]FDG PET. Eur J Nucl Med Mol Imaging 39:990–1000

    Article  CAS  PubMed  Google Scholar 

  • Palma E, Conti L, Roseti C et al (2012) Novel approaches to study the involvement of α7-nAChR in human diseases. Curr Drug Targets 13:579–586

    Article  CAS  PubMed  Google Scholar 

  • Passchier J, van Waarde A (2001) Visualisation of serotonin-1A (5-HT1A) receptors in the central nervous system. Eur J Nucl Med 28:113–129

    Article  CAS  PubMed  Google Scholar 

  • Pike VW, McCarron JA, Lammertsma AA et al (1995) First delineation of 5-HT1A receptors in human brain with PET and [11C]WAY-100635. Eur J Pharmacol 283:R1–R3

    Article  CAS  PubMed  Google Scholar 

  • Podruchny TA, Connolly C, Bokde A (2003) In vivo muscarinic-2 receptor imaging in cognitively normal young and older volunteers. Synapse 48:39–44

    Article  CAS  PubMed  Google Scholar 

  • Politis M, Su P, Piccini P (2012) Imaging of microglia in patients with neurodegenerative disorders. Front Pharmacol 3:96

    Article  PubMed Central  PubMed  Google Scholar 

  • Sacher J, Rabiner EA, Clark M et al (2012) Dynamic, adaptive changes in MAO-A binding after alterations in substrate availability: an in vivo [11C]-harmine positron emission tomography study. J Cereb Blood Flow Metab 32:443–446

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sakata M, Wu J, Toyohara J (2011) Biodistribution and radiation dosimetry of the α7 nicotinic acetylcholine receptor ligand [11C]CHIBA-1001 in humans. Nucl Med Biol 38:443–448

    Article  CAS  PubMed  Google Scholar 

  • Seki C, Ito H, Ichimiya T et al (2010) Quantitative analysis of dopamine transporters in human brain using [11C]PE2I and positron emission tomography: evaluation of reference tissue models. Ann Nucl Med 24:249–260

    Google Scholar 

  • Seneca N, Zoghbi SS, Liow JS (2009) Human brain imaging and radiation dosimetry of [11C]-N-desmethyl-loperamide, a PET radiotracer to measure the function of P-glycoprotein. J Nucl Med 50:807–813

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Shinotoh H, Fukushi K, Nagatsuka S et al (2004) Acetylcholinesterase imaging: its use in therapy evaluation and drug design. Curr Pharm Des 10:1505–1517

    Article  CAS  PubMed  Google Scholar 

  • Shiue CY, Shiue GG, Mozley PD et al (1997) p-[18F]MPPF: a potential radioligand for PET-studies of 5-HT1A receptors in humans. Synapse 25:147–154

    Article  CAS  PubMed  Google Scholar 

  • Sihver W, Drewes B, Schulze A (2007) Evaluation of novel tropane analogues in comparison with the binding characteristics of [18F]FP-CIT and [131I]beta-CIT. Nucl Med Biol 34:211–219

    Article  CAS  PubMed  Google Scholar 

  • Sioka C, Fotopoulos A, Kyritsis AP (2010) Recent advances in PET imaging for evaluation of Parkinson’s disease. Eur J Nucl Med Mol Imaging 37:1594–1603

    Article  PubMed  Google Scholar 

  • Takano H, Ito H, Takahashi H et al (2011) Serotonergic neurotransmission in the living human brain: a positron emission tomography study using [11C]DASB and [11C]WAY100635 in young healthy men. Synapse 65:624–633

    Article  CAS  PubMed  Google Scholar 

  • Talbot PS, Slifstein M, Hwang DR et al (2012) Extended characterisation of the serotonin 2A (5-HT2A) receptor-selective PET radiotracer [11C]MDL100907 in humans: quantitative analysis, test-retest reproducibility, and vulnerability to endogenous 5-HT tone. Neuroimage 59:271–285

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Thurfjell L, Lötjönen J, Lundqvist R et al (2012) Combination of biomarkers: PET [18F]flutemetamol imaging and structural MRI in dementia and mild cognitive impairment. Neurodegener Dis 10:246–249

    Article  CAS  PubMed  Google Scholar 

  • Tissingh G, Booij J, Winogrodzka A et al (1997) IBZM- and CIT-SPECT of the dopaminergic system in parkinsonism. J Neural Transm Suppl 50:31–37

    Article  CAS  PubMed  Google Scholar 

  • Turkheimer FE, Selvaraj S, Hinz R et al (2012) Quantification of ligand PET studies using a reference region with a displaceable fraction: application to occupancy studies with [11C]-DASB as an example. J Cereb Blood Flow Metab 32:70–80

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • van Waarde A, Ramakrishnan NK, Rybczynska AA (2011) The cholinergic system, sigma-1 receptors and cognition. Behav Brain Res 221:543–554

    Article  PubMed  Google Scholar 

  • Waldhoer M, Bartlett SE, Whistler JL (2004) Opioid receptors. Annu Rev Biochem 73:953–990

    Article  CAS  PubMed  Google Scholar 

  • Willeit M, Ginovart N, Kapur S et al (2006) High-affinity states of human brain dopamine D2/3 receptors imaged by the agonist [11C]-(+)-PHNO. Biol Psychiatry 59:389–394

    Article  CAS  PubMed  Google Scholar 

  • Zhang S, Han D, Tan X (2012) Diagnostic accuracy of [18F]FDG and [11C]PIB-PET for prediction of short-term conversion to Alzheimer’s disease in subjects with mild cognitive impairment. Int J Clin Pract 66:185–198

    Article  CAS  PubMed  Google Scholar 

  • Ziebell M (2011) Evaluation of the superselective radioligand [123I]PE2I for imaging of the dopamine transporter in SPECT. Dan Med Bull 58:B4279

    PubMed  Google Scholar 

  • Zorumski CF, Izumi Y (2012) NMDA receptors and metaplasticity: mechanisms and possible roles in neuropsychiatric disorders. Neurosci Biobehav Rev 36:989–1000

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Hanzeplein 1, Groningen, 9713GZ, The Netherlands

    Philip H. Elsinga

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  1. Philip H. Elsinga
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Correspondence to Philip H. Elsinga .

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Editors and Affiliations

  1. Dept. of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

    Rudi A.J.O. Dierckx

  2. Faculty of Electrical Engineering and Information Technology, University of Applied Sciences Offenburg, Offenburg, Germany

    Andreas Otte

  3. Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands

    Erik F.J. de Vries

  4. Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands

    Aren van Waarde

  5. Neurology, University Medical Center Groningen, Groningen, The Netherlands

    Klaus L. Leenders

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Elsinga, P.H. (2014). Nuclear Medicine Imaging Tracers for Neurology. In: Dierckx, R., Otte, A., de Vries, E., van Waarde, A., Leenders, K. (eds) PET and SPECT in Neurology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-54307-4_1

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