Nuklearmedizin 2004; 43(01): 33-42
DOI: 10.1055/s-0038-1623912
Original Article
Schattauer GmbH

PET in neuroscience

Dopaminergic, GABA/benzodiazepine, and opiate systemPET in den Neurowissenschaftendopaminerges, GABA/Benzodiazepin- und Opiatsystem
P. Bartenstein
1   Klinik und Poliklinik für Nuklearmedizin, Johannes-Gutenberg-Universität Mainz
› Author Affiliations
Further Information

Publication History

Eingegangen: 24 September 2003

24 September 2003

Publication Date:
11 January 2018 (online)

Summary

This article gives an overview on radiotracer imaging with positron emission tomography (PET) in measuring various aspects of neurotransmission. The review focusses on the dopaminergic system, the GABA/benzodiazepine system, and the opiate system. Besides dealing with the current clinical applications for brain PET studies with specific radiopharmaceuticals this article outlines an idea on potential future developments for the use of these methods in basic neuroscience.

Zusammenfassung

Diese Arbeit präsentiert eine Übersicht zur aktuellen Forschung und klinischen Anwendung von PET-Untersuchungen mit Radiopharmaka, die verschiedene Komponenten der Neurotransmission erfassen. Außerdem werden Perspektiven und Trends der Methodik gezeigt. Im Mittelpunkt stehen das dopaminerge System, das GABA/Benzodiazepinsystem, und das Opiatsystem. Ausführlich dargestellt werden aktuelle klinische und kliniknahe Möglichkeiten sowie methodische Aspekte der grundlagenorientierten Forschung, die für eine zukunftsorientierte Anwendung von PET-Studien mit Rezeptorliganden u. a. Radiopharmaka zur Bildgebung komplexer biochemischer Prozesse von Bedeutung sind.

 
  • Literatur

  • 1 Abi-Dargham A, Krystal JH, Anjilvel S. et al. Alterations of benzodiazepine receptors in type II alcoholic subjects measured with SPECT and I-123 iomazenil. Am J Psychiatry 1998; 155: 1550-5.
  • 2 Albertson TE, Joy RM, Stark LG. Modification of kindled amygdaloid seizures by opiate agonists and antagonists. J Pharmakol Exp Ther 1984; 228: 620-7.
  • 3 Albin RL, Reiner A, Anderson KD. et al. Preferential loss of striato-external pallidal projection neurons in presymptomatic Hunting-ton’s disease. Ann Neurol 1992; 31: 425-30.
  • 4 Antonini A, Leenders KL, Vontobel P. et al. Complementary PET studies of striatal neuronal function in the differential diagnosis between multiple system atrophy and Parkinson’s disease. Brain 1997; 120: 2187-95.
  • 5 Arnold S, Berthele A, Drzezga A. et al. Reduction of benzodiazepine receptor binding is related to the seizure onset zone in extratemporal focal cortical dysplasia. Epilepsia 2000; 41: 818-24.
  • 6 Atack JR, Smith AJ, Emms F. et al. Regional differences in the inhibition of mouse in vivo (3H)Ro 15-1788 binding reflect selectivity for alpha 1 versus alpha 2 and alpha 3 subunit-containing GABAA receptors. Neuropsycho-pharmacology 1999; 20: 255-62.
  • 7 Banati RB, Newcombe J, Gunn RN. et al. The peripheral benzodiazepine binding site in the brain in multiple sclerosis: quantitative in vivo imaging of microglia as a measure of disease activity. Brain 2000; 123: 2321-37.
  • 8 Barker RA, Dunnett SB. Functional integration of neural grafts in Parkinson’s disease. Nat Neurosci 1999; 2: 1047-8.
  • 9 Bartenstein P, Ludolph A, Schober O. et al. Benzodiazepine receptors and cerebral blood flow in partial epilepsy. Eur J Nucl Med 1991; 18: 111-8.
  • 10 Bartenstein PA, Duncan JS, Prevett MC. et al. Investigation of the opioid system in absence seizures with positron emission tomography. J Neurol Neurosurg Psychiatry 1993; 56: 1295-302.
  • 11 Bartenstein PA, Prevett MC, Duncan JS. et al. Quantification of opiate receptors in two patients with mesiobasal temporal lobe epilepsy, before and after selective amygdalohippocampectomy, using positron emission tomography. Epilepsy Res 1994; 18: 119-25.
  • 12 Bartenstein P, Grünwald F, Kuwert T. et al. Klinische Anwendungen der Single-Photon-Emissionstomographie in der Neuromedizin. 1: Neuroonkologie, Epilepsien, Basalganglienerkrankungen, zerebrovaskuläre Erkrankungen. Nuklearmedizin 2000; 39: 180-95.
  • 13 Bauer A, Holschbach MH, Meyer PT. et al. In vivo imaging of adenosine A1 receptors in the human brain with (18F)CPFPX and PET. Neuroimage 2003; 19: 1760-9.
  • 14 Beer HF, Bläuenstein PA, Hasler PH. et al. In vitro and in vivo evaluation of Iodine-123-Ro 16-0154: A new imaging agent for SPECT investigations of benzodiazepine receptors. J Nucl Med 1990; 31: 1007-14.
  • 15 Bencherif B, Fuchs PN, Sheth R. et al. Pain activation of human supraspinal opioid pathways as demonstrated by (11C)-carfentanil and positron emission tomography (PET). Pain 2002; 99: 589-98.
  • 16 Bigliani V, Pilowsky LS. In vivo neuropharmacology of schizophrenia. Br J Psychiatry (Suppl) 1999; 38: 23-33.
  • 17 Breier A, Su TP, Saunders R. et al. Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: evidence from a novel positron emission tomography method. Proc Natl Acad Sci U S A 1997; 94: 2569-74.
  • 18 Brooks DJ, Ibanez V, Sawle GV. et al. Differing patterns of striatal 18F-dopa uptake in Parkinson’s disease, multiple system atrophy, and progressive supranuclear palsy. Ann Neurol 1990; 28: 547-55.
  • 19 Brooks DJ. Morphological and functional imaging studies on the diagnosis and progression of Parkinson’s disease. J Neurol 2000; 247 (Suppl. 02) II11-8.
  • 20 Cagnin A, Brooks DJ, Kennedy AM. et al. Invivo measurement of activated microglia in dementia. Lancet 2001; 358 9280 461-7.
  • 21 Calautti C, Baron JC. Functional neuroimaging studies of motor recovery after stroke in adults: a review. Stroke 2003; 34: 1553-66.
  • 22 Carson RE, Lang L, Watabe H. et al. PET evaluation of 18F-FCWAY, an analog of the 5-HT(1A) receptor antagonist, WAY-100635. Nucl Med Biol 2000; 27: 493-7.
  • 23 Carter BD, Medzihradsky F. Receptor mechanisms of opioid tolerance in SH-SY5Y human neural cells. Mol Pharmacol 1993; 43: 465-73.
  • 24 Chavkin C, Shoemaker WJ, McGinty JF. et al. Characterization of the prodynorphin and proenkephalin neuropeptide systems in rat hippocampus. J Neurosci 1985; 5: 808-16.
  • 25 Coenen HH, Laufer P, Stöcklin G. et al. 3-N(2-(18F)-fluoroethyl)-piperone: a novel ligand for cerebral dopamine receptor studies with PET. Life Sci 1987; 40: 81-8.
  • 26 Cohen RM, Andreason PJ, Doudet DJ. et al. Opiate receptor avidity and cerebral blood flow in Alzheimer’s disease. J Neurol Sci 1997; 148: 171-80.
  • 27 Comar D, Maziere M, Godot JM. et al. Visualization of 11C-flunitrazepam displacement in the brain of the life baboon. Nature 1979; 280: 329-31.
  • 28 Cunningham V, Jones T. Spectral analysis of dynamic PET data. J Cereb Blood Flow Metab 1993; 13: 15-23.
  • 29 Dannals RF, Ravert HT, Frost JJ. et al. Radio-synthesis of an opiate receptor binding radio-tracer: (11C)Carfentanil. Int J Appl Radiat Isot 1985; 36: 303-6.
  • 30 DeLorey TM, Olsen RW. γ-Aminobutyric acid-A receptor structure and function. J Biol Chem 1992; 267: 16747-50.
  • 31 Fahey FH. Positron emission tomography instrumentation. Radiol Clin North Am 2001; 39: 919-29.
  • 32 Forutan F, Estalji S, Beu M. et al. Distribution of 5HT2A receptors in the human brain: comparison of data in vivo and post mortem. Nuklearmedizin 2002; 197-201.
  • 33 Foster NL, Minoshima S, Johanns J. et al. PET measures of benzodiazepine receptors in progressive supranuclear palsy. Neurology 2000; 54: 1768-73.
  • 34 Fowler JS, Volkow ND, Wang GJ. et al. Inhibition of monoamine oxidase B in the brains of smokers. Nature 1996; 379: 733-6.
  • 35 Frenk H. Pro- and anticonvulsant actions of morphine and the endogenous opioids: involvement and interactions of multiple opiate and non-opiate systems. Brain Res Rev 1983; 6: 197-210.
  • 36 Frost JJ, Wagner Jr HN, Dannals RF. et al. Imaging benzodiazepine receptors in man with 11C-suriclone by positron emission tomography. Eur J Pharmacol 1986; 122: 381-3.
  • 37 Frost JJ, Mayberg HS, Fisher RS. et al. Mü-opiate receptors measured by positron emission tomography are increased in temporal lobe epilepsy. Ann Neurol 1988; 23: 231-7.
  • 38 Frost JJ, Douglass KH, Mayberg HS. et al. Multicompartmental analysis of (11C)-carfentanil binding to opiate receptors in humans measured by positron emission tomography. J Cereb Blood Flow Metab 1989; 9: 398-409.
  • 39 Garnett ES, Firnau G, Chan PK. et al. (18F)Fluoro-dopa, an analogue of dopa, and its use in direct external measurements of storage, degradation, and turnover of intracerebral dopa-mine. Proc Natl Acad Sci USA 1978; 75: 464-7.
  • 40 Gerhard A, Neumaier B, Elitok E. et al. In vivo imaging of activated microglia using (11C)PK11195 and positron emission tomography in patients after ischemic stroke. Neuroreport 2000; 11: 2957-60.
  • 41 Gründer G, Siessmeier T, Lange-Asschenfeldt C. et al. PET imaging of benzodiazepine receptors in the human brain with F-18 fluoroethylflumazenil. Eur J Nucl Med 2001; 28: 1463-70.
  • 42 Gründer G, Siessmeier T, Piel M. et al. Quantification of D2-like dopamine receptors in the human brain with 18F-desmethoxyfallypride. J Nucl Med 2003; 44: 109-16.
  • 43 Halldin C, Gulyas B, Langer O. et al. Brain radioligands – state of the art and new trends. Q J Nucl Med 2001; 45: 139-52.
  • 44 Hammers A, Koepp MJ, Richardson MP. et al. Central benzodiazepine receptors in malformations of cortical development: A quantitative study. Brain 2001; 124: 1555-65.
  • 45 Hammers A, Koepp MJ, Labbe C. et al. Neo-cortical abnormalities of (11C)-flumazenil PET in mesial temporal lobe epilepsy. Neurology 2001; 56: 897-906.
  • 46 Heinz A, Reimold M, Hermann D. et al. Craving and relapse are associated with μ-opioid availability in alcoholics a C-11 carfentanil study. J Nucl Med 2001; 42 Suppl 107.
  • 47 Heiss WD, Würker M. Möglichkeiten und Grenzen funktioneller bildgebender Verfahren beim Parkinson-Syndrom. Nervenarzt 1999; 70 (Suppl. 01) S2-10.
  • 48 Heiss WD, Kracht L, Grond M. et al. Early C-11 flumazenil/H2O positron emission tomography predicts irreversible ischemic cortical damage in stroke patients receiving acute thrombolytic therapy. Stroke 2000; 31: 366-9.
  • 49 Henry TR, Frey KA, Sackellares JC. et al. In vivo cerebral metabolism and central benzodiazepine-receptor binding in temporal lobe epilepsy. Neurology 1993; 43: 1998-2006.
  • 50 Jacobs AH, Li H, Winkeler A. et al. PET-based molecular imaging in neuroscience. Eur J Nucl Med Mol Imaging 2003; 30: 1051-65.
  • 51 Jalan R, Turjanski N, Taylor Robinson SD. et al. Increased availability of central benzodiazepine receptors in patients with chronic hepatic encephalopathy and alcohol related cirrhosis. Gut 2000; 46: 546-52.
  • 52 Johnström P, Duelfer T, Stone-Elander S. et al. Synthesis of the benzodiazepine-1 antagonist 18F-2-oxoquazepam. J Label Compound Radiopharm 1988; 26: 334-5.
  • 53 Jones AK, Luthra SK, Maziere B. et al. Regional cerebral opioid receptor studies with (11C)diprenorphine in normal volunteers. J Neurosci Methods 1988; 23: 121-9.
  • 54 Jones AK, Liyi Q, Cunningham VV. et al. Endogenous opiate response to pain in rheumatoid arthritis and cortical and subcortical response to pain in normal volunteers using positron emission tomography. Int J Clin Pharmacol Res 1991; 11: 261-6.
  • 55 Jones AK, Kitchen ND, Watabe H. et al. Measurement of changes in opioid receptor binding in vivo during trigeminal neuralgic pain using (11C) diprenorphine and positron emission tomography. J Cereb Blood Flow Metab 1999; 19: 803-8.
  • 56 Juhasz C, Chugani DC, Muzik O. et al. Relationship of flumazenil and glucose PET abnormalities to neocortical epilepsy surgery outcome. Neurology 2001; 56: 1650-8.
  • 57 Kelsley JE, Belluzi JD. Endorphin mediation of post-ictal effects of kindled seizures in rats. Brain Res 1982; 253: 337-40.
  • 58 Kling MA, Carson RE, Borg L. et al. Opioid receptor imaging with positron emission tomography and 18F cyclofoxy in long-term, methadone-treated former heroin addicts. J Pharmacol Exp Ther 2000; 295: 1070-6.
  • 59 Koepp MJ, Gunn RN, Lawrence AD. et al. Evidence for striatal dopamine release during a video game. Nature 1998; 393: 266-8.
  • 60 Koepp MJ, Richardson MP, Brooks DJ. et al. Focal cortical release of endogenous opioids during reading-induced seizures. Lancet 1998; 352: 952-5.
  • 61 Koepp MJ, Hammers A, Labbe C. et al. 11Cflumazenil PET in patients with refractory temporal lobe epilepsy and normal MRI. Neurology 2000; 54: 332-9.
  • 62 Koepp MJ, Duncan JS. PET: Opiate receptor mapping. In: Henry TR, Duncan JS, Berkovic SF. (eds). Functional imaging in the epilepsies. Philadelphia: Lippincott Williams & Wilkins; 2000: 145-56.
  • 63 Koeppe RA, Holthoff VA, Frey KA. et al. Compartmental analysis of (11C) flumazenil kinetics for the estimation of ligand transport rate and receptor distribution using positron emission tomography. J Cereb Blood Flow Metab 991 11: 735-44.
  • 64 Koutroumanidis M, Binnie CD, Elwes RD. et al. Interictal regional slow activity in temporal lobe epilepsy correlates with lateral temporal hypometabolism as imaged with 18FDG PET: neurophysiological and metabolic implications. J Neurol Neurosurg Psychiatry 1998; 65: 170-6.
  • 65 Kuwert T, Bartenstein P, Grünwald F. et al. Klinische Wertigkeit der Positronenemissionstomographie in der Neuromedizin: Positionspa-pier zu den Ergebnissen einer interdisziplinären Konsensuskonferenz. Nervenarzt 1998; 69: 1045-60.
  • 66 Lammertsma AA, Hume SP. Simplified reference tissue model for PET receptor studies. Neuroimage 1996; 4: 153-8.
  • 67 Laruelle M. Imaging synaptic neurotransmission with in vivo binding competition techniques: a critical review. J Cereb Blood Flow Metab 2000; 20: 423-51.
  • 68 Lassen NA, Bartenstein PA, Lammertsma AA. et al. Benzodiazepine receptor quantification in vivo in humans using (11C-flumazenil and PET: application of the steady-state principle. J Cereb Blood Flow Metab 1995; 15: 152-65.
  • 69 Lever JR, Ilgin N, Musachio JL. et al. Autoradiographic and SPECT imaging of cerebral opioid receptors with an iodine-123 labeled analogue of diprenorphine. Synapse 1998; 29: 172-82.
  • 70 Lloyd CM, Richardson MP, Brooks DJ. et al. Extramotor involvement in ALS: PET studies with the GABA(A) ligand 11C flumazenil. Brain 2000; 123: 2289-96.
  • 71 Lochmann M, Buchholz HG, Siesmeier T. et al. Comparison of different quantification methods for calculating binding potential (BP) of the new unselective opiate-receptor ligand F-18 fluoroethyldiprenorphine. J Cereb Blood Flow Metab 2003; 23 (Suppl. 01) 669.
  • 72 Logan J, Fowler JS, Volkow ND. et al. Graphical analysis of reversible radioligand binding from time-activity measurements applied to (N-11C-methyl)-(-)-cocaine PET studies in human subjects. J Cereb Blood Flow Metab 1990; 10: 740-7.
  • 73 Macdonald GA, Frey KA, Agranoff BW. et al. Cerebral benzodiazepine receptor binding in vivo in patients with recurrent hepathic encephalopathy. Hepatology 1997; 26: 277-82.
  • 74 Madar I, Lesser RP, Krauss G. et al. Imaging of delta- and mu-opioid receptors in temporal lobe epilepsy by positron emission tomography. Ann Neurol 1997; 41: 358-67.
  • 75 Malizia AL, Cunningham VJ, Bell CJ. et al. Decreased brain GABA(A)-benzodiazepine receptor binding in panic disorder: preliminary results from a quantitative PET-study. Arch Gen Psychiatry 1998; 55: 715-20.
  • 76 Mayberg HS, Sadzot B, Meltzer CC. et al. Quantification of mu and non-mu opiate receptors in temporal lobe epilepsy using positron emission tomography. Ann Neurol 1991; 30: 3-11.
  • 77 Maziere M, Hantraye P, Prenant C. et al. Synthesis of ethyl-8-fluoro-5,6-dihydroxy-5-(11C) methyl-6-oxo-4H-imidazo(1,5-a)(1,4)benzodiazepine-3-carboxylate (RO 15.1788-11C): a specific radioligand for the in vivo study of central benzodiazepine receptors by positron emission tomography. Int J Appl Radiat Isot 1984; 35: 973-6.
  • 78 Melega WP, Luxen A, Perlmutter MM. et al. Comparative in vivo metabolism of 6-(18F)fluoro-L-dopa and (3H)L-dopa in rats. Biochem Pharmacol 1990 15 39: 1853-60.
  • 79 Moerlein SM, Perlmutter JS. Binding of 5-(2’-[18F]fluoroethyl)flumazenil to central benzodiazepine receptors measured in living baboon by positron emission tomography. Eur J Pharmacol 1992; 218: 109-15.
  • 80 Mukherjee J, Yang YZ, Brown T. et al. Preliminary assessment of extrastriatal dopamine D-2 receptor binding in the rodent and nonhuman primate brains using the high affinity radioligand, 18F-fallypride. Nucl Med Biol 1999; 26: 519-27.
  • 81 Munz F, Ludwig T, Ziegler S. et al. Performance assessment of parallel spectral analysis: Towards a practical performance model for parallel medical applications. Proceedings of the 7th International Conference on High Performance Computing and Networking, Europe. Lecture notes in computer science 1539. Berlin: Springer; 1999: 430-9.
  • 82 Odano I, Miyashita K, Minoshima S. et al. A potential use of a 123I-labelled benzodiazepine receptor antagonist as a predictor of neuronal cell viability: comparisons with 14C-labelled 2-deoxyglucose autoradiography and histopathological examination. Nucl Med Commun 1995; 16: 443-6.
  • 83 Olsen RW, Tobin AJ. Molecular biology of GABAA-receptors. FASEB J 1990; 4: 1469-80.
  • 84 Pasternak GW, Wood PJ. Multiple Mu opiate receptors. Life Sci 1986; 38: 1889-98.
  • 85 Perlmutter JS, Kilbourn MR, Raichle ME. et al. MPTP-induced up-regulation of in vivo dopaminergic radioligand-receptor binding in humans. Neurology 1987; 37: 1575-9.
  • 86 Pfeiffer A, Pasi A, Mehraein P. et al. Opiate receptor binding sites in human brain. Brain Res 1982; 248: 87-96.
  • 87 Piccini P, Weeks RA, Brooks DJ. Alterations in opioid receptor binding in Parkinson’s disease patients with levodopa-induced dyskinesias. Ann Neurol 1997; 42: 720-6.
  • 88 Piccini P, Burn DJ, Ceravolo R. et al. The role of inheritance in sporadic Parkinson’s disease: evidence from a longitudinal study of dopaminergic function in twins. Ann Neurol 1999; 45: 577-82.
  • 89 Sadzot B, Debets RM, Delfiore G. et al. 11CFlumazenil positron emission tomography:An in vivo marker of neuronal loss in temporal lobe epilepsy. Epilepsia 1994; 35 (Suppl. 07) S28.
  • 90 Savage DD, Mills SA, Jobe PC. et al. Elevation of naloxone-sensitive 3H-dihydromorphine binding in hippocampal formation of genetically epilepsy-prone rats. Life Sci 1988; 43: 239-46.
  • 91 Savic I, Thorell JO, Roland P. (11C)flumazenil positron emission tomography visualizes frontal epileptogenic regions. Epilepsia 1995; 36: 1225-32.
  • 92 Schäfers KP. Imaging small animals with positron emission tomography. Nuklearmedizin 2003; 42: 86-9.
  • 93 Siessmeier T, Heinz A, Wrase J. et al. Craving is associated with D2-receptor binding in ventral striatum/nucleus accumbens. J Nucl Med 2002; 5 suppl 109p.
  • 94 Smith YR, Zubieta JK, del Carmen MG. et al. Brain opioid receptor measurements by positron emission tomography in normal cycling women: relationship to luteinizing hormone pulsatility and gonadal steroid hormones. J Clin Endocrinol Metab 1998; 83: 4498-505.
  • 95 Smith JS, Zubieta JK, Price JC. et al. Quantification of delta-opioid receptors in human brain with N1’-(11C methyl) naltrindole and positron emission tomography. J Cereb Blood Flow Metab 1999; 19: 956-66.
  • 96 Sprenger T, Valet M, Boecker H. et al. Heat pain triggers F-18 diprenophine displacement in the limbic system. J Cereb Blood Flow 2003; 23 (Suppl. 01) 719.
  • 97 Stöcklin GL. Is there a future for clinical fluorine-18 radiopharmaceuticals (excluding FDG)?. Eur J Nucl Med 1998; 25: 1612-6.
  • 98 Tatsch K. Imaging of the dopaminergic system in parkinsonism with SPECT. Nucl Med Commun 2001; 22: 819-27.
  • 99 Theodore WH, Carson RE, Andreasen P. et al. PET imaging of opiate receptor binding in human epilepsy using (18F)cyclofoxy. Epilepsy Res 1992; 13: 129-39.
  • 100 Treede RD, Kenshalo DR, Gracely RH. et al. The cortical representation of pain. Pain 1999; 79: 105-11.
  • 101 Turjanski N, Weeks R, Dolan R. et al. Striatal D1 and D2 receptor binding in patients with Huntington’s disease and other choreas. A PET study. Brain 1995; 118: 689-99.
  • 102 Uhl GR, Sora I, Wang Z. The mu opiate receptor as a candidate gene for pain: polymorphisms, variations in expression, nociception, and opiate responses. Proc Natl Acad Sci USA 1999; 96: 7752-5.
  • 103 Urca G, Frenk H. Liebesking et al. Morphine and enkephalin. analgesic and epileptic properties. Science 1977; 197: 83-6.
  • 104 Verhoeff NP. Radiotracer imaging of dopaminergic transmission in neuropsychiatric disorders. Psychopharmacology 1999; 147: 217-49.
  • 105 Volkow ND, Wang GJ, Fowler JS. et al. Imaging endogenous dopamine competition with (11C)raclopride in the human brain. Synapse 1994; 16: 255-62.
  • 106 Wagner KJ, Willoch F, Kochs EF. et al. Dose-dependent regional cerebral blood flow changes during remifentanil infusion in humans: a positron emission tomography study. Anesthesiology 2001; 94: 732-9.
  • 107 Weckesser M, Schmidt D, Matheja P. et al. The role of L-3-I-123-iodine-alpha-methyltyrosine SPECT in cerebral gliomas. Nuklearmedizin 2000; 39: 233-40.
  • 108 Weeks RA, Cunningham VJ, Piccini P. et al. 11C-diprenorphine binding in Huntington’s disease: a comparison of region of interest analysis with statistical parametric mapping. J Cereb Blood Flow Metab 1997; 17: 943-9.
  • 109 Weinmann HJ, Ebert W, Misselwitz B. et al. Tissue-specific MR contrast agents. Eur J Radiol 2003; 46: 33-44.
  • 110 Weiller C, May A, Limmroth V. et al. Brain stem activation in spontaneous human migraine attacks. Nat Med 1995; 1: 658-60.
  • 111 Wester HJ, Willoch F, Tölle TR. et al. 6-O-(2-18F fluoroethyl)-6-O-desmethyldiprenorphine (18F-DPN): synthesis, biologic evaluation, and comparison with (11C)DPN in humans. J Nucl Med 2000; 41: 1279-86.
  • 112 Willoch F, Schütz C, Wester HJ. et al. Opioid receptor binding changes in alcohol dependent males during detoxification and in comparison to control. J Nucl Med 1999; 40: 111p.
  • 113 Willoch F, Tölle TR, Wester HJ. et al. Central pain following pontine infarction is associated with changes in opioid receptor binding: a PET study with C-11 diprenorphine. Am J Neuroradiol 1999; 20: 145-9.
  • 114 Winkler PA, Herzog C, Henkel A. et al. Nicht invasives Protokoll für die epilepsiechirurgische Behandlung fokaler Epilepsien. Nervenarzt 1999; 70: 1088-93.
  • 115 Zartler ER, Yan J, Mo H. et al. ID NMR Methods in ligand-receptor interactions. Curr Top Med Chem 2003; 3: 25-37.
  • 116 Zeki S, Watson JD, Lueck CJ. et al. A direct demonstration of functional specialization in human visual cortex. J Neurosci 1991; 11: 641-9.
  • 117 Zieglgänsberger W, French ED, Siggins GR. et al. Opioid peptides may excite hippocampal pyramidal neurons by inhibiting adjacent inhibitory interneurons. Science 1979; 205: 415-7.
  • 118 Zubieta JK, Gorelick DA, Stauffer R. et al. Increased mu opioid receptor binding detected by PET in cocaine-dependent man is associated with cocaine craving. Nature Med 1996; 2: 1225-9.
  • 119 Zubieta JK, Dannals RF, Frost JJ. Gender and age influences on human brain mu-opioid receptor binding measured by PET. Am J Psychiatry 1999; 156: 842-8.
  • 120 Zubieta JK, Smith YR, Bueller JA. et al. Regional mu opioid receptor regulation of sensory and affective dimensions of pain. Science 2001; 293: 311-5.
  • 121 Zubieta JK, Koeppe RA, Frey KA. et al. Assessment of muscarinic receptor concentrations in aging and Alzheimer disease with (11C) NMPB and PET. Synapse 2001; 39: 275-87.