Skip to main content
SpringerLink
Log in

PET and SPECT Imaging of Neurotoxicity

  • Chapter
  • First Online:
PET and SPECT in Neurology

Abstract

From conception until death, we are exposed to neurotoxins that can potentially induce toxic encephalopathy. Neurotoxins can cause acute adverse effects or show delayed symptoms. They can even induce impaired brain development in the offspring of exposed pregnant females. Both in patients and in animals, it can be difficult to establish the effects of toxins on the (developing) brain. Functional imaging with positron emission tomography (PET) or single photon emission computed tomography (SPECT) could provide useful tools for preclinical testing of (developmental) neurotoxicity of potential toxic substances. These techniques could also aid clinicians in determining the damage that was done to brain functioning by exposure to a neurotoxin, and they may provide insight in the mechanisms that are involved in the intoxication. This book chapter reviews the potential applications of PET and SPECT imaging in (developmental) neurotoxicity testing and evaluation of functional deficits in the brain after exposure to neurotoxins.

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 229.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 299.99
Price excludes VAT (USA)
  • Compact, lightweight 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

Abbreviations

[11C]DOPA:

L-[11C]-3,4-dihydroxyphenylalanine

[18F]FDG:

2′-[18F]fluoro-2′-deoxyglucose

[18F]FDOPA:

L-6-[18F]fluoro-3,4-dihydroxyphenylalanine

BBB:

Blood–brain barrier

LPS:

Lipopolysaccharide

MAM:

methylazoxymethanol

MPTP:

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

MRI:

Magnetic resonance imaging

PET:

Positron emission tomography

SPECT:

Single photon emission computed tomography

References

  • Airas L, Paavilainen T, Marttila RJ, Rinne J (2008) Methanol intoxication-induced nigrostriatal dysfunction detected using 6-[18F]fluoro-L-dopa PET. Neurotoxicology 29:671–674

    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 

  • Bartlett RM, Murali D, Nickles RJ, Barnhart TE, Holden JE, DeJesus OT (2011) Assessment of fetal brain uptake of paraquat in utero using in vivo PET/CT imaging. Toxicol Sci 122:551–556

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Benveniste H, Fowler JS, Rooney WD, Moller DH, Backus WW, Warner DA, Carter P, King P, Scharf B, Alexoff DA, Ma Y, Vaska P, Schlyer D, Volkow ND (2003) Maternal-fetal in vivo imaging: a combined PET and MRI study. J Nucl Med 44:1522–1530

    PubMed  Google Scholar 

  • Benveniste H, Fowler JS, Rooney W, Ding YS, Baumann AL, Moller DH, Du C, Backus W, Logan J, Carter P, Coplan JD, Biegon A, Rosenblum L, Scharf B, Gatley JS, Volkow ND (2005) Maternal and fetal 11C-cocaine uptake and kinetics measured in vivo by combined PET and MRI in pregnant nonhuman primates. J Nucl Med 46:312–320

    CAS  PubMed  Google Scholar 

  • Benveniste H, Fowler JS, Rooney WD, Scharf BA, Backus WW, Izrailtyan I, Knudsen GM, Hasselbalch SG, Volkow ND (2010) Cocaine is pharmacologically active in the nonhuman primate fetal brain. Proc Natl Acad Sci U S A 107:1582–1587

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bondy SC, Campbell A (2005) Developmental neurotoxicology. J Neurosci Res 81:605–612

    Article  CAS  PubMed  Google Scholar 

  • Buckingham-Howes S, Berger SS, Scaletti LA, Black MM (2013) Systematic review of prenatal cocaine exposure and adolescent development. Pediatrics 131:e1917–e1936

    Article  PubMed Central  PubMed  Google Scholar 

  • Bull S (2006) Review of environmental chemicals and toxicity. Focus on neurological diseases. Health Protection Agency publication HPA-ChaPD-001. http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1194947320712

  • Callender TJ, Morrow L, Subramanian K, Duhon D, Ristovv M (1993) Three-dimensional brain metabolic imaging in patients with toxic encephalopathy. Environ Res 60:295–319

    Article  CAS  PubMed  Google Scholar 

  • Chung FS, Eyal S, Muzi M, Link JM, Mankoff DA, Kaddoumi A, O’Sullivan F, Hsiao P, Unadkat JD (2010) Positron emission tomography imaging of tissue P-glycoprotein activity during pregnancy in the non-human primate. Br J Pharmacol 159:394–404

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Coecke S, Eskes C, Gartlon J, Kinsner A, Price A, Van Vliet E, Prieto P, Boveri M, Bremer S, Adler S, Pellizzer C, Wendel A, Hartung T (2006) The value of alternative testing for neurotoxicity in the context of regulatory needs. Environ Toxicol Pharmacol 21:153–167

    Article  CAS  PubMed  Google Scholar 

  • De Esch C, Slieker R, Wolterbeek A, Woutersen R, De Groot DM (2012) Zebrafish as potential model for developmental neurotoxicity testing: a mini review. Neurotoxicol Teratol 34:545–553

    Article  PubMed  Google Scholar 

  • De Groot DM, Bos-Kuijpers MH, Kaufmann WS, Lammers JH, O’Callaghan JP, Pakkenberg B, Pelgrim MT, Waalkens-Berendsen ID, Waanders MM, Gundersen HJ (2005) Regulatory developmental neurotoxicity testing: a model study focussing on conventional neuropathology endpoints and other perspectives. Environ Toxicol Pharmacol 19:745–755

    Article  PubMed  Google Scholar 

  • De Groot DM, Heerschap A, Krul C, Radonjic M, De Vries EF (2011) PET and MRI improve safety testing with far less animals (<50%). ALTEX 28:256

    Google Scholar 

  • De Groot DM, Bogaart M, Nederlof R, Slieker RC, Wolterbeek AP, Dierckx RA, Van Waarde A, De Vries EF (2012a) In vivo [18F]FDG microPET imaging in developmental neurotoxicity: a feasibility study in rat with ethanol. Reprod Toxicol 34:160–161

    Article  Google Scholar 

  • De Groot DM, Kuper CF, Radonjic M, Stierum R, Wolterbeek A, Heerschap A, Veltien A, Dierckx RA, De Vries EF (2012b) Imaging and omics in developing and juvenile rats after exposure to TBTO. Toxicol Lett 211:S155

    Article  Google Scholar 

  • De Groot MWGDM, Westerink RHS, Dingemans MML (2013) Don’t judge a neuron only by its cover: neuronal function in in vitro developmental neurotoxicity testing. Toxicol Sci 132(1):1–7

    Article  PubMed  Google Scholar 

  • De Vries EFJ, Van Waarde A, Willemsen ATM, Dierckx RA, Wolterbeek A, Wesselius A, De Groot DMG (2008) Protection of the unborn child from harmful drugs: a role for PET? Eur J Nucl Med Mol Imaging 35(suppl 2):S141

    Google Scholar 

  • Edling C, Hellman B, Arvidson B, Andersson J, Hartvig P, Lilja A, Valind S, LÃ¥ngström B (1997a) Do organic solvents induce changes in the dopaminergic system? Positron emission tomography studies of occupationally exposed subjects. Int Arch Occup Environ Health 70:180–186

    Article  CAS  PubMed  Google Scholar 

  • Edling C, Hellman B, Arvidson B, Johansson G, Andersson J, Hartvig P, Valind S, LÃ¥ngström B (1997b) Positron emission tomography studies of healthy volunteers—no effects on the dopamine terminals and synthesis after short-term exposure to toluene. Hum Exp Toxicol 16:171–176

    Article  CAS  PubMed  Google Scholar 

  • Ek CJ, Dziegielewska KM, Habgood MD, Saunders NR (2012) Barriers in the developing brain and neurotoxicology. Neurotoxicology 33:586–604

    Article  CAS  PubMed  Google Scholar 

  • Ekino S, Susa M, Ninomiya T, Imamura K, Kitamura T (2007) Minamata disease revisited: an update on the acute and chronic manifestations of methyl mercury poisoning. J Neurol Sci 262:131–144

    Article  CAS  PubMed  Google Scholar 

  • Gómez-Sánchez R, Bravo-San Pedro JM, Niso-Santano M, Soler G, Fuentes JM, González-Polo RA (2010) The neuroprotective effect of talipexole from paraquat-induced cell death in dopaminergic neuronal cells. Neurotoxicology 31:701–708

    Article  PubMed  Google Scholar 

  • Hagstadius S, Orbaek P, Risberg J, Lindgren M (1989) Regional cerebral blood flow at the time of diagnosis of chronic toxic encephalopathy induced by organic-solvent exposure and after the cessation of exposure. Scand J Work Environ Health 15:130–135

    Article  CAS  PubMed  Google Scholar 

  • Hartvig P, Lindberg BS, Lilja A, Lundqvist H, LÃ¥ngström B, Rane A (1989) Positron emission tomography in studies on fetomaternal disposition of opioids. Dev Pharmacol Ther 12:74–80

    CAS  PubMed  Google Scholar 

  • Haut MW, Leach S, Kuwabara H, Whyte S, Callahan T, Ducatman A, Lombardo LJ, Gupta N (2000) Verbal working memory and solvent exposure: a positron emission tomography study. Neuropsychology 14:551–558

    Article  CAS  PubMed  Google Scholar 

  • Huang CC, Weng YH, Lu CS, Chu NS, Yen TC (2003) Dopamine transporter binding in chronic manganese intoxication. J Neurol 250:1335–1339

    Article  CAS  PubMed  Google Scholar 

  • Kim JW, Kim Y, Cheong HK, Ito K (1998) Manganese induced parkinsonism: a case report. J Korean Med Sci 13:437–439

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kim Y, Kim JW, Ito K, Lim HS, Cheong HK, Kim JY, Shin YC, Kim KS, Moon Y (1999) Idiopathic parkinsonism with superimposed manganese exposure: utility of positron emission tomography. Neurotoxicology 20:249–252

    CAS  PubMed  Google Scholar 

  • Kisby GE, Spencer PS (2011) Is neurodegenerative disease a long-latency response to early-life genotoxin exposure? Int J Environ Res Public Health 10:3889–3921

    Article  Google Scholar 

  • Lees-Haley PR, Williams CW (1997) Neurotoxicity of chronic low-dose exposure to organic solvents: a skeptical review. J Clin Psychol 53:699–712

    Article  CAS  PubMed  Google Scholar 

  • Leslie EM, Deeley RG, Cole SP (2005) Multidrug resistance proteins: role of P-glycoprotein, MRP1, MRP2, and BCRP (ABCG2) in tissue defense. Toxicol Appl Pharmacol 204:216–237

    Article  CAS  PubMed  Google Scholar 

  • Liu CH, Lin KJ, Wang HM, Kuo HC, Chuang WL, Weng YH, Shih TS, Huang CC (2013) Brain fluorodeoxyglucose positron emission tomography (18FDG-PET) in patients with acute thallium intoxication. Clin Toxicol 51:167–173

    Article  CAS  Google Scholar 

  • Meyer-Baron M, Kim EA, Nuwayhid I, Ichihara G, Kang SK (2012) Occupational exposure to neurotoxic substances in Asian countries - challenges and approaches. Neurotoxicology 33:853–861

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Morrow LA, Callender T, Lottenberg S, Buchsbaum MS, Hodgson MJ, Robin N (1990) PET and neurobehavioral evidence of tetrabromoethane encephalopathy. J Neuropsychiatry Clin Neurosci 2:431–435

    CAS  PubMed  Google Scholar 

  • Olanow CW, Good PF, Shinotoh H, Hewitt KA, Vingerhoets F, Snow BJ, Beal MF, Calne DB, Perl DP (1996) Manganese intoxication in the rhesus monkey: a clinical, imaging, pathologic, and biochemical study. Neurology 46:492–498

    Article  CAS  PubMed  Google Scholar 

  • Organisation for Economic Co-operation and Development (OECD) (2007) OECD guidelines for the testing of chemicals, section 4: health effects test no.426: developmental neurotoxicity study. doi:10.1787/9789264067394

  • Prüss-Ustün A, Vickers C, Haefliger P, Bertollini R (2011) Knowns and unknowns on burden of disease due to chemicals: a systematic review. Environ Health 10:9

    Article  PubMed Central  PubMed  Google Scholar 

  • Radonjic M, Cappaert NL, De Vries EF, De Esch CE, Kuper FC, Van Waarde A, Dierckx RA, Wadman WJ, Wolterbeek AP, Stierum RH, De Groot DM (2013) Delay and impairment in brain development and function in rat offspring after maternal exposure to methylmercury. Toxicol Sci 133:112–124

    Article  CAS  PubMed  Google Scholar 

  • Rosenberg NL, Myers JA, Martin WR (1989) Cyanide-induced parkinsonism: clinical, MRI, and 6-fluorodopa PET studies. Neurology 39:142–144

    Article  CAS  PubMed  Google Scholar 

  • Sarkar S, Schmued L (2010) Neurotoxicity of ecstasy (MDMA): an overview. Curr Pharm Biotechnol 11:460–469

    Article  CAS  PubMed  Google Scholar 

  • Schiffer WK, Lee DE, Alexoff DL, Ferrieri R, Brodie JD, Dewey SL (2006) Metabolic correlates of toluene abuse: decline and recovery of function in adolescent animals. Psychopharmacology (Berl) 186:159–167

    Article  CAS  Google Scholar 

  • Schiffer WK, Mirrione MM, Dewey SL (2007) Optimizing experimental protocols for quantitative behavioral imaging with 18F-FDG in rodents. J Nucl Med 48:277–287

    CAS  PubMed  Google Scholar 

  • Shinotoh H, Snow BJ, Hewitt KA, Pate BD, Doudet D, Nugent R, Perl DP, Olanow W, Calne DB (1995) MRI and PET studies of manganese-intoxicated monkeys. Neurology 45:1199–1204

    Article  CAS  PubMed  Google Scholar 

  • Shinotoh H, Snow BJ, Chu NS, Huang CC, Lu CS, Lee C, Takahashi H, Calne DB (1997) Presynaptic and postsynaptic striatal dopaminergic function in patients with manganese intoxication: a positron emission tomography study. Neurology 48:1053–1056

    Article  CAS  PubMed  Google Scholar 

  • Szólics M, Chaudhry M, Ljubisavljevic M, Corr P, Samir HA, Van Gorkom KN (2012) Neuroimaging findings in a case of fluoxetine overdose. J Neuroradiol 39:254–257

    Article  PubMed  Google Scholar 

  • Tennekes HA, Sánchez-Bayo F (2013) The molecular basis of simple relationships between exposure concentration and toxic effects with time. Toxicology 309:39–51

    Article  CAS  PubMed  Google Scholar 

  • US Environmental Protection Agency (US EPA) (1998) Health effect test guidelines OPPTS 870.6300 Developmental neurotoxicity study. Docket ID:EPA 712-C-98-239

    Google Scholar 

  • Uitti RJ, Rajput AH, Ashenhurst EM, Rozdilsky B (1985) Cyanide-induced parkinsonism: a clinicopathologic report. Neurology 35:921–925

    Article  CAS  PubMed  Google Scholar 

  • Varney NR, Morrow LA, Pinkston JB, Wu JC (1998) PET scan findings in a patient with a remote history of exposure to organic solvents. Appl Neuropsychol 5:100–106

    Article  CAS  PubMed  Google Scholar 

  • Visser I, Lavini C, Booij J, Reneman L, Majoie C, De Boer AG, Wekking EM, De Joode EA, Van der Laan G, Van Dijk FJ, Schene AH, Den Heeten GJ (2008) Cerebral impairment in chronic solvent-induced encephalopathy. Ann Neurol 63:572–580

    Article  CAS  PubMed  Google Scholar 

  • Wang AG, Liu RS, Liu JH, Teng MM, Yen MY (1999) Positron emission tomography scan in cortical visual loss in patients with organophosphate intoxication. Ophthalmology 106:1287–1291

    Article  CAS  PubMed  Google Scholar 

  • Wang JH, Scollard DA, Teng S, Reilly RM, Piquette-Miller M (2005) Detection of P-glycoprotein activity in endotoxemic rats by 99mTc-sestamibi imaging. J Nucl Med 46:1537–1545

    CAS  PubMed  Google Scholar 

  • Wolters EC, Huang CC, Clark C, Peppard RF, Okada J, Chu NS, Adam MJ, Ruth TJ, Li D, Calne DB (1989) Positron emission tomography in manganese intoxication. Ann Neurol 26:647–651

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, EB50, 30.001, Groningen, 9713 GZ, The Netherlands

    Erik F. J. de Vries

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

    Rudi A. J. O. Dierckx

  3. Department of Radiology and Nuclear Medicine, Ghent University, De Pintelaan 185 K12, Ghent, 9000, Belgium

    Rudi A. J. O. Dierckx

  4. Netherlands Organization for Applied Scientific Research (TNO), Utrechtseweg, 3700 AJ Zeist, The Netherlands

    Didima M. G. de Groot

Authors
  1. Erik F. J. de Vries
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rudi A. J. O. Dierckx
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Didima M. G. de Groot
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Erik F. J. de Vries .

Editor information

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

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

de Vries, E.F.J., Dierckx, R.A.J.O., de Groot, D.M.G. (2014). PET and SPECT Imaging of Neurotoxicity. 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_36

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-54307-4_36

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-54306-7

  • Online ISBN: 978-3-642-54307-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation