Skip to main content
SpringerLink
Log in

Nuclear Medicine Imaging Tracers for Neurology

  • Chapter
  • First Online:
PET and SPECT in Neurology

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 the human brain in vivo, both in health and disease. Initially, most attention was given to tracers for translocator protein (TSPO), deposition of beta-amyloid, and the dopaminergic system. Many clinical studies have been published with application of a variety of tracers for these targets. During the past few years, more tracers have reached the stage of human studies such as imaging agents for tau protein, P2X7 receptor, SV2A receptor, and the cholinergic system. Other targets of interest that have been studied in man to a lesser extent are N-methyl-d-aspartic acid (NMDA), serotonergic, adenosine, gamma-aminobutyric acid (GABA), sigma, opioid, and metabotropic glutamate subtype 5 (mGlu5) receptors. In addition, several transporter systems have received a great deal of attention. Many tracers for new molecular targets are under development and may open new horizons in the future. Most PET tracers for the brain were initially labeled with 11C but were later replaced by 18F-labeled analogs, since this radionuclide enables longer scanning protocols, dissemination to other hospitals, and commercialization. This initial chapter will highlight PET tracers that have already reached the state of human application.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aghourian M, Legault-Denis C, Soucy JP et al (2017) Quantification of brain cholinergic denervation in Alzheimer's disease using PET imaging with [18F]FEOBV. Mol Psychiatry 22:1531–1538

    Article  CAS  PubMed  Google Scholar 

  • Ahmad R, Postnov A, Bormans G et al (2016) Decreased in vivo availability of the cannabinoid type 2 receptor in Alzheimer's disease. Eur J Nucl Med Mol Imaging 43:2219–2227

    Article  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

    Article  PubMed  CAS  Google Scholar 

  • Bauckneht M, Capitanio S, Raffa S (2019) Molecular imaging of multiple sclerosis: from the clinical demand to novel radiotracers. EJNMMI Radiopharm Chem 4:6

    Article  PubMed  PubMed Central  Google Scholar 

  • Bauer M, Karch R, Neumann F et al (2009) Age dependency of cerebral P-gp function measured with (R)-[11C]verapamil and PET. Eur J Clin Pharmacol 65:941–946

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Best L, Ghadery C, Pavese N et al (2019) New and old TSPO PET Radioligands for imaging brain microglial activation in neurodegenerative disease. Curr Neurol Neurosci Rep 19:24

    Article  PubMed  Google Scholar 

  • Bretin F, Bahri MA, Bernard C et al (2015) Biodistribution and radiation dosimetry for the novel SV2A radiotracer [18F]UCB-H: first-in-human study. Mol Imaging Biol 17:557–564

    Article  CAS  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 

  • Boscutti G, Rabiner EA, Plisson C (2019) PET Radioligands for imaging of the PDE10A in human: current status. Neurosci Lett 691:11–17

    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  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  Google Scholar 

  • Chen MK, Mecca AP, Naganawa M et al (2018) Assessing synaptic density in Alzheimer disease with synaptic vesicle glycoprotein 2A positron emission tomographic imaging. JAMA Neurol 75:1215–1224

    Article  PubMed  PubMed Central  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 

  • Coughlin JM, Slania S, Du Y et al (2018) [18F]XTRA PET for enhanced imaging of the Extrathalamic α4β2 nicotinic acetylcholine receptor. J Nucl Med 59:1603–1608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • da Cunha-Bang S, Ettrup A, Mc Mahon B et al (2019) Measuring endogenous changes in serotonergic neurotransmission with [11C]Cimbi-36 positron emission tomography in humans. Transl. Psychiatry 9:134

    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  PubMed Central  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  PubMed Central  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  Google Scholar 

  • Eidelberg D, Moeller JR, Dhawan V 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 

  • Elmenhorst D, Meyer PT, Matusch A et al (2012) Caffeine occupancy of human cerebral A1 adenosine receptors: in vivo quantification with [18F]CPFPX and PET. J Nucl Med 53:1723–1729

    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 92:278–284

    Article  CAS  PubMed  Google Scholar 

  • de Paula Faria D, Copray S, Sijbesma JW et al (2014) PET imaging of focal demyelination and remyelination in a rat model of multiple sclerosis: comparison of [11C]MeDAS, [11C]CIC and [11C]PIB. Eur J Nucl Med Mol Imaging 41:995–1003

    Article  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 

  • Fujita M, Richards EM, Niciu MJ et al (2017) cAMP signaling in brain is decreased in unmedicated depressed patients and increased by treatment with a selective serotonin reuptake inhibitor. Mol Psychiatry 22:754–759

    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 

  • 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 

  • Hodolic M, Topakian R, Pichler R (2016) [18F]fluorodeoxyglucose and [18F]flumazenil positron emission tomography in patients with refractory epilepsy. Radiol Oncol 50:247–253

    Article  CAS  PubMed  PubMed Central  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 

  • Hong CM, Ryu HS, Ahn BC (2018) Early perfusion and dopamine transporter imaging using [18F]FP-CIT PET/CT in patients with parkinsonism. Am J Nucl Med Mol Imaging 8:360–372

    CAS  PubMed  PubMed Central  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  PubMed Central  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 

  • Ishibashi K, Miura Y, Wagatsuma K et al (2018) Occupancy of adenosine A2A receptors by istradefylline in patients with Parkinson's disease using [11C]preladenant PET. Neuropharmacology 143:106–112

    Article  CAS  PubMed  Google Scholar 

  • Ishikawa M, Sakata M, Toyohara J et al (2011) Occupancy of α7 nicotinic acetylcholine receptors in the brain by Tropisetron: a positron emission tomography study using [11C]CHIBA-1001 in healthy human subjects. Clin Psychopharmacol Neurosci 9:111–116

    Article  CAS  PubMed  PubMed Central  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 

  • Jakobson Mo S, Axelsson J, Jonasson L et al (2018) Dopamine transporter imaging with [18F]FE-PE2I PET and [123I]FP-CIT SPECT-a clinical comparison. EJNMMI Res 8:100

    Article  PubMed  PubMed Central  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  PubMed Central  Google Scholar 

  • Jung KH, Oh SJ, Kang KJ et al (2019) Effects of P-gp and Bcrp as brain efflux transporters on the uptake of [18F]FPEB in the murine brain. Synapse 73(11):e22123

    Article  PubMed  CAS  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 

  • Khanapur S, van Waarde A, Dierckx RA et al (2017) Preclinical evaluation and quantification of [18F]Fluoroethyl and [18F]Fluoropropyl analogs of SCH442416 as Radioligands for PET imaging of the adenosine A2A receptor in rat brain. J Nucl Med 58:466–472

    Article  CAS  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

    PubMed  Google Scholar 

  • Kogan RV, de Jong BA, Renken RJ, JPND-PETMETPAT Working Group et al (2019) Factors affecting the harmonization of disease-related metabolic brain pattern expression quantification in [18F]FDG-PET (PETMETPAT). Alzheimers Dement (Amst) 11:472–482

    Article  Google Scholar 

  • Koole M, Schmidt ME, Hijzen A et al (2019) [18F]JNJ-64413739, a novel PET ligand for the P2X7 Ion Channel: radiation dosimetry, kinetic modeling, test-retest variability, and occupancy of the P2X7 antagonist JNJ-54175446. J Nucl Med 60:683–690

    Article  CAS  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 [123I] 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 [99mTc] TRODAT-1. Eur J Nucl Med 23:1527–1530

    Article  CAS  PubMed  Google Scholar 

  • Lee J, Kim BH, Kim E et al (2018) Higher serotonin transporter availability in early-onset obsessive-compulsive disorder patients undergoing escitalopram treatment: a [11C]DASB PET study. Hum Psychopharmacol 33(1)

    Google Scholar 

  • Leurquin-Sterk G, Ceccarini J, Crunelle CL et al (2018) Cerebral dopaminergic and glutamatergic transmission relate to different subjective responses of acute alcohol intake: an in vivo multimodal imaging study. Addict Biol 23:931–944

    Article  CAS  PubMed  Google Scholar 

  • Li S, Cai Z, Zheng MQ, Holden D et al (2018) Novel 18F-labeled κ-opioid receptor antagonist as PET radiotracer: synthesis and in vivo evaluation of [18F]LY2459989 in nonhuman primates. J Nucl Med 59:140–146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ludwig FA, Fischer S, Houska R et al (2019) In vitro and in vivo human metabolism of (S)-[18F]Fluspidine - a Radioligand for imaging σ1 receptors with positron emission tomography (PET). Front Pharmacol 10:534

    Article  CAS  PubMed  PubMed Central  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 

  • McGinnity CJ, Hammers A, Riaño Barros DA et al (2014) Initial evaluation of [18F]GE-179, a putative PET tracer for activated N-methyl D-aspartate receptors. J Nucl Med 55:423–430

    Article  CAS  PubMed  Google Scholar 

  • McGinnity CJ, Koepp MJ, Hammers A et al (2015) NMDA receptor binding in focal epilepsies. J Neurol Neurosurg Psychiatry 86:1150–1157

    Article  CAS  PubMed  Google Scholar 

  • Mercier J, Provins L, Valade A (2017) Discovery and development of SV2A PET tracers: potential for imaging synaptic density and clinical applications. Drug Discov Today Technol 25:45–52

    Article  PubMed  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, Ohyama M, Ishii K et al (2008) Low density of sigma1 receptors in early Alzheimer's disease. Ann Nucl Med 22:151–156

    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  PubMed Central  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 

  • Mukherjee J, Lao PJ, Betthauser TJ et al (2018) Human brain imaging of nicotinic acetylcholine α4β2 receptors using [18F]Nifene: selectivity, functional activity, toxicity, aging effects, gender effects, and extrathalamic pathways. J Comp Neurol 526:80–95

    Article  CAS  PubMed  Google Scholar 

  • Nabbi-Schroeter D, Elmenhorst D, Oskamp A et al (2018) Effects of long-term caffeine consumption on the adenosine A1 receptor in the rat brain: an in vivo PET study with [18F]CPFPX. Mol Imaging Biol 20:284–291

    Article  CAS  PubMed  Google Scholar 

  • Nag S, Fazio P, Lehmann L et al (2016) In vivo and in vitro characterization of a novel MAO-B inhibitor Radioligand, 18F-labeled deuterated Fluorodeprenyl. J Nucl Med 57:315–320

    Article  CAS  PubMed  Google Scholar 

  • Naganawa M, Dickinson GL, Zheng MQ et al (2016) Receptor occupancy of the κ-opioid antagonist LY2456302 measured with positron emission tomography and the novel radiotracer [11C]LY2795050. J Pharmacol Exp Ther 356:260–266

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Naganawa M, Lim K, Nabulsi NB et al (2018) Evaluation of pancreatic VMAT2 binding with active and inactive enantiomers of [18F]FP-DTBZ in healthy subjects and patients with type 1 diabetes. Mol Imaging Biol 20:835–845

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Narayanaswami V, Dahl K, Bernard-Gauthier V et al (2018) Emerging PET radiotracers and targets for imaging of neuroinflammation in neurodegenerative diseases: outlook beyond TSPO. Mol Imaging 17:1–25

    Article  CAS  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  PubMed Central  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  PubMed Central  Google Scholar 

  • Niccolini F, Wilson H, Pagano G et al (2017) Loss of phosphodiesterase-4 in Parkinson disease: relevance to cognitive deficits. Neurology 89:586–593

    Article  CAS  PubMed  Google Scholar 

  • Nobili F, Festari C, Altomare D et al (2018) Automated assessment of FDG-PET for differential diagnosis in patients with neurodegenerative disorders. EANM-EAN task force for the prescription of FDG-PET for dementing neurodegenerative disorders. Eur J Nucl Med Mol Imaging 45:1557–1566

    Article  CAS  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 

  • Nummenmaa L, Saanijoki T, Tuominen L et al (2018) μ-Opioid receptor system mediates reward processing in humans. Nat Commun 9:1500

    Article  PubMed  PubMed Central  CAS  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 

  • Paghera B, Altomare D, Peli A et al (2019) Comparison of visual criteria for amyloid-PET reading: could their merging reduce the inter-raters variability? Q J Nucl Med Mol Imaging. [Epub ahead of print]

    Google Scholar 

  • Palermo G, Tommasini L, Aghakhanyan G et al (2019) Clinical correlates of cerebral amyloid deposition in Parkinson's disease dementia: evidence from a PET study. J Alzheimers Dis 70:595–607

    Article  CAS  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 

  • Petrou M, Frey KA, Kilbourn MR et al (2014) In vivo imaging of human cholinergic nerve terminals with (−)-5-[18F]fluoroethoxybenzovesamicol: biodistribution, dosimetry, and tracer kinetic analyses. J Nucl Med 55:396–404

    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 

  • Plavén-Sigray P, Matheson GJ, Gustavsson P et al (2018) Is dopamine D1 receptor availability related to social behavior? A positron emission tomography replication study. PLoS One 13(3):e0193770

    Article  PubMed  PubMed Central  CAS  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  PubMed Central  CAS  Google Scholar 

  • Raaphorst RM, Luurtsema G, Schokker CJ et al (2018) Improving metabolic stability of fluorine-18 labeled verapamil analogs. Nucl Med Biol 64-65:47–56

    Article  CAS  PubMed  Google Scholar 

  • Sabri O, Becker GA, Meyer PM et al (2015) First-in-human PET quantification study of cerebral α4β2 nicotinic acetylcholine receptors using the novel specific radioligand (−)-[18F]Flubatine. NeuroImage 118:199–208

    Article  CAS  PubMed  Google Scholar 

  • Sabri O, Meyer PM, Gräf S et al (2018) Cognitive correlates of α4β2 nicotinic acetylcholine receptors in mild Alzheimer's dementia. Brain 141:1840–1854

    Article  PubMed  PubMed Central  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  Google Scholar 

  • Saint-Aubert L, Lemoine L, Chiotis K et al (2017) Tau PET imaging: present and future directions. Mol Neurodegener 12:19

    Article  PubMed  PubMed Central  CAS  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 

  • Sala-Llonch R, Falgàs N, Bosch B et al (2019) Regional patterns of [18F]florbetaben uptake in presenilin 1 mutation carriers. Neurobiol Aging 81:1–8

    Article  CAS  PubMed  Google Scholar 

  • Savolainen H, Windhorst AD, Elsinga PH et al (2017) Evaluation of [18F]MC225 as a PET radiotracer for measuring P-glycoprotein function at the blood-brain barrier in rats: kinetics, metabolism, and selectivity. J Cereb Blood Flow Metab 37:1286–1298

    Article  CAS  PubMed  Google Scholar 

  • Sehlin D, Syvänen S (2019) Engineered antibodies: new possibilities for brain PET? Eur J Nucl Med Mol Imaging 46(13):2848–2858

    Article  CAS  PubMed  PubMed Central  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

    Article  PubMed  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  Google Scholar 

  • Shin JW, Chu K, Shin SA et al (2016) Clinical applications of simultaneous PET/MR imaging using (R)-[11C]verapamil with cyclosporine a: preliminary results on a surrogate marker of drug-resistant epilepsy. Am J Neuroradiol 37:600–606

    Article  PubMed  PubMed Central  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 

  • Stenkrona P, Matheson GJ, Halldin C et al (2019) D1-dopamine receptor availability in first-episode neuroleptic naive psychosis patients. Int J Neuropsychopharmacol 22:415–425

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stephenson NA, Holland JP, Kassenbrock A et al (2015) Iodonium ylide-mediated radiofluorination of [18F]FPEB and validation for human use. J Nucl Med 56:489–492

    Article  CAS  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  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 

  • Tiepolt S, Patt M, Aghakhanyan G (2019) Current status/need for tracers to diagnose neurodegenerative diseases. EJNMMI Radiopharm Chem 4:17

    Article  PubMed  PubMed Central  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 

  • Tournier N, Bauer M, Pichler V et al (2019) Impact of P-glycoprotein function on the brain kinetics of the weak substrate [11C]metoclopramide assessed with PET imaging in humans. J Nucl Med 60:985–991

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tredwell M, Preshlock SM, Taylor NJ et al (2014) A general copper-mediated nucleophilic 18F-fluorination of arenes. Angew Chem Int Ed Engl 53:7751–7755

    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  Google Scholar 

  • Villemagne VL, Okamura N, Pejoska S et al (2012) Differential diagnosis in Alzheimer's disease and dementia with Lewy bodies via VMAT2 and amyloid imaging. Neurodegener Dis 10:161–165

    Article  CAS  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  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Wang YT, Edison P (2019) Tau imaging in neurodegenerative diseases using positron emission tomography. Curr Neurol Neurosci Rep 19:45

    Article  PubMed  PubMed Central  Google Scholar 

  • Warnock G, Sommerauer M, Mu L et al (2018) A first-in-man PET study of [18F]PSS232, a fluorinated ABP688 derivative for imaging metabotropic glutamate receptor subtype 5. Eur J Nucl Med Mol Imaging 45:1041–1051

    Article  CAS  PubMed  Google Scholar 

  • Van Weehaeghe D, Koole M, Schmidt ME et al (2019) [11C]JNJ54173717, a novel P2X7 receptor radioligand as marker for neuroinflammation: human biodistribution, dosimetry, brain kinetic modelling and quantification of brain P2X7 receptors in patients with Parkinson's disease and healthy volunteers. Eur J Nucl Med Mol Imaging 46(10):2051–2064

    Article  PubMed  CAS  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 

  • Wong DF, Kuwabara H, Horti AG et al (2018) Brain PET imaging of α7-nAChR with [18F]ASEM: reproducibility, occupancy, receptor density, and changes in schizophrenia. Int J Neuropsychopharmacol 21:656–667

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yasuno F, Ota M, Ito H et al (2008) Increased binding of peripheral benzodiazepine receptor in Alzheimer‘s disease measured by positron emission tomography with [11C]DAA1106. Biol Psychiatry 64:835–841

    Article  CAS  PubMed  Google Scholar 

  • Yeh YW, Ho PS, Chen CY et al (2015) Suicidal ideation modulates the reduction in serotonin transporter availability in male military conscripts with major depression: a 4-[18F]-ADAM PET study. World J Biol Psychiatry 16:502–512

    Article  PubMed  Google Scholar 

  • Yoo HS, Chung SJ, Kim SJ et al (2018) The role of [18F]FP-CIT PET in differentiation of progressive supranuclear palsy and frontotemporal dementia in the early stage. Eur J Nucl Med Mol Imaging 45:1585–1595

    Article  PubMed  Google Scholar 

  • Yue X, Xin Y, Chugani HT et al (2019) Automated production of a N-methyl-D-aspartate receptor radioligand [18F]GE179 for clinical use. Appl Radiat Isot 148:246–252

    Article  CAS  PubMed  Google Scholar 

  • Zanotti-Fregonara P, Pascual B, Rizzo G et al (2018) Head-to-head comparison of [11C]PBR28 and [18F]GE180 for quantification of the translocator protein in the human brain. J Nucl Med 59:1260–1266

    Article  CAS  PubMed  Google Scholar 

  • Zarrad F, Zlatopolskiy BD, Krapf P et al (2017) A practical method for the preparation of 18F-labeled aromatic amino acids from nucleophilic [18F]fluoride and Stannyl precursors for electrophilic Radiohalogenation. Molecules 15:22

    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 

  • Zhang X, Basuli F, Swenson RE (2019) An azeotropic drying-free approach for copper-mediated radiofluorination without addition of base. J Labelled Comp Radiopharm 62:139–145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou X, Khanapur S, Huizing AP et al (2014) Synthesis and preclinical evaluation of 2-(2-furanyl)-7-[2-[4-[4-(2-[11C]methoxyethoxy)phenyl]-1-piperazinyl]ethyl]7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine-5-amine ([11C]Preladenant) as a PET tracer for the imaging of cerebral adenosine A2A receptors. J Med Chem 57:9204–9210

    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  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

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

    Philip H. Elsinga

Authors
  1. Philip H. Elsinga
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Philip H. Elsinga .

Editor information

Editors and Affiliations

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

    Rudi A. J. O. Dierckx

  2. Faculty of Electrical Engineering, Medical Engineering and Computer Science, Offenburg University, 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

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Elsinga, P.H. (2021). Nuclear Medicine Imaging Tracers for Neurology. In: Dierckx, R.A.J.O., Otte, A., de Vries, E.F.J., van Waarde, A., Leenders, K.L. (eds) PET and SPECT in Neurology. Springer, Cham. https://doi.org/10.1007/978-3-030-53168-3_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-53168-3_1

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-53167-6

  • Online ISBN: 978-3-030-53168-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation