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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/12/17 02:52:42」(JST)

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A radioligand is a radioactive biochemical substance (in particular, a ligand) that is used for diagnosis or for research-oriented study of the receptor systems of the body.

In a neuroimaging application the radioligand is injected into the pertinent tissue, or infused into the bloodstream. It binds to its receptor. When the radioactive isotope in the ligand decays it can be measured by positron emission tomography (PET) or single photon emission computed tomography (SPECT). In in vivo systems it is often used to quantify the binding of a test molecule to the binding site of radio ligand. The higher the affinity of the molecule the more radio ligand is displaced from the binding site and the increasing radioactive decay can be measured by scintillography. This assay is commonly used to calculate binding constant of molecules to receptors.

The transport of the radioligand is described by receptor kinetics.

History

Radioligands are credited with making possible the study of biomolecular behaviour, a previously mysterious area of research that had evaded researchers.^[1] With this capacity radioligand techniques enabled researchers to identify receptor devices within cells.

Radioactive isotopes commonly used

Main article: Radioactivity in biology

Tritium, ³H
Carbon-14, ¹⁴C
Sulfur-35, ³⁵S
Iodine-131, ¹³¹I
Fluorine-18, ¹⁸F
Technetium-99m, ^99mTc

In PET the isotopes fluorine-18 and carbon-11 are often used in molecular neuroimaging.

List of radioligands

Radioligands may be constructed to bind selectively to a particular neuroreceptor or a particular neurotransmitter transporter. Examples of radioligands include:

¹¹C-WAY-100635 for the 5-HT_1A receptor
N(1)-([¹¹C]-methyl)-2-Br-LSD ([¹¹C]-MBL) for 5-HT2 receptors^[2]
¹⁸F-altanserin and ¹⁸F-setoperone for the 5-HT_2A receptor^[3]
¹¹C-ketanserin^[4] and tritiated ketanserin
¹¹C-DASB for the serotonin transporter^[5]
³H-WIN55,212-2 for cannabinoid receptors^[6]
[¹¹C]flumazenil for GABA_A receptors.^[7]
(+)PHNO for D₂ dopamine receptors.^[8]
[¹¹C]raclopride for D₂ dopamine receptors.^[9]

References

^ Niehoff, Debra (2005). The Language of Life: How cells communicate in life & disease. Joseph Henry Press. ISBN 0-309-08989-1.
^ Wong, Dean F.; Lever, John R.; Hartig, Paul R.; Dannals, Robert F.; Villemagne, Victor; Hoffman, Beth J.; Wilson, Alan A.; Ravert, Hayden T. et al. (1987). "Localization of serotonin 5-HT2 receptors in living human brain by positron emission tomography using N1-([11C]-methyl)-2-bromo-LSD". Synapse 1 (5): 393–398.. doi:10.1002/syn.890010502. PMID 2905532.
^ Karen H. Adams, Lars H. Pinborg, Claus Svarer, S. G. Hasselbalch, Søren Holm, Steven Haugbøl, K. Madsen, Vibe G. Frøkjær, L. Martiny Olaf B. Paulson, Gitte Moos Knudsen (March 2004). "A database of [¹⁸F]-altanserin binding to 5-HT_2A receptors in normal volunteers: normative data and relationship to physiological and demographic variables". NeuroImage 21 (3): 1105–1113. doi:10.1016/j.neuroimage.2003.10.046. ISSN 1053-8119. PMID 15006678.
^ J. C. Baron, Y. Samson, D. Comar, C. Crouzel, P. Deniker, Y. Agid (1985). "Etude in vivo des recepteurs serotoninergiques centraux chez l'homme par tomographie a positions. [In vivo study of central serotoninergic receptors in man using positron tomography]" (in French). Revue neurologique 141 (8–9): 537–545. PMID 2935920.
^ Reimold M, Smolka MN, Zimmer A et al. (2007). "Reduced availability of serotonin transporters in obsessive-compulsive disorder correlates with symptom severity - a [11C]DASB PET study". J Neural Transm 114 (12): 1603–9. doi:10.1007/s00702-007-0785-6. PMID 17713719.
^ Pertwee RG (1999). "Pharmacology of cannabinoid receptor ligands". Curr. Med. Chem. 6 (8): 635–64. PMID 10469884.
^ Alexander Hammers, Matthias J. Koepp, Mark P. Richardson, Rene Hurlemann, David J. Brooks & John S. Duncan (June 2003). "Grey and white matter flumazenil binding in neocortical epilepsy with normal MRI. A PET study of 44 patients". Brain 126 (Pt 6): 1300–1308. doi:10.1093/brain/awg138. PMID 12764053. http://brain.oxfordjournals.org/cgi/content/abstract/126/6/1300.
^ Seeman P, Ulpian C, Larsen RD, Anderson PS (August 1993). "Dopamine receptors labelled by PHNO". Synapse 14 (4): 254–262. doi:10.1002/syn.890140403. PMID 7902615. http://www3.interscience.wiley.com/journal/109702957/abstract.
^ Volkow ND, Wang GJ, Fowler JS, Logan J, Franceschi D, Maynard L, Ding YS, Gatley SJ, Gifford A, Zhu W, Swanson JM. (March 2002). "Relationship between blockade of dopamine transporters by oral methylphenidate and the increases in extracellular dopamine: therapeutic implications". Synapse 43 (3): 181–187. doi:10.1002/syn.10038. PMID 11793423.

UpToDate Contents

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English Journal

Speech-induced striatal dopamine release is left lateralized and coupled to functional striatal circuits in healthy humans: A combined PET, fMRI and DTI study.

Simonyan K, Herscovitch P, Horwitz B.SourceDepartment of Neurology, Mount Sinai School of Medicine, New York, NY, USA; Department of Otolaryngology, Mount Sinai School of Medicine, New York, NY, USA; Laryngeal and Speech Section, National Institutes of Neurological Disorders and Stroke, National Institutes of Health, USA. Electronic address: kristina.simonyan@mssm.edu.
NeuroImage.Neuroimage.2013 Apr 15;70:21-32. doi: 10.1016/j.neuroimage.2012.12.042. Epub 2012 Dec 28.
Considerable progress has been recently made in understanding the brain mechanisms underlying speech and language control. However, the neurochemical underpinnings of normal speech production remain largely unknown. We investigated the extent of striatal endogenous dopamine release and its influence
PMID 23277111

Low background and high contrast PET imaging of amyloid-β with [(11)C]AZD2995 and [ (11)C]AZD2184 in Alzheimer's disease patients.

Forsberg A, Juréus A, Cselényi Z, Eriksdotter M, Freund-Levi Y, Jeppsson F, Swahn BM, Sandell J, Julin P, Schou M, Andersson J, Johnström P, Varnäs K, Halldin C, Farde L, Svensson S.SourceCentre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden, anton.forsberg@ki.se.
European journal of nuclear medicine and molecular imaging.Eur J Nucl Med Mol Imaging.2013 Apr;40(4):580-93. doi: 10.1007/s00259-012-2322-6. Epub 2013 Jan 17.
PURPOSE: The aim of this study was to evaluate AZD2995 side by side with AZD2184 as novel PET radioligands for imaging of amyloid-β in Alzheimer's disease (AD).METHODS: In vitro binding of tritium-labelled AZD2995 and AZD2184 was studied and compared with that of the established amyloid-β PET radi
PMID 23324871

Allopregnanolone and Pregnanolone Analogues Modified in the C Ring: Synthesis and Activity.

Slavíková B, Bujons J, Matyáš L, Vidal M, Babot Z, Krištofíková Z, Suñol C, Kasal A.SourceInstitute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic , 166 10 Prague 6, Czech Republic.
Journal of medicinal chemistry.J Med Chem.2013 Mar 7. [Epub ahead of print]
(25R)-3β-Hydroxy-5α-spirostan-12-one (hecogenin) and 11α-hydroxypregn-4-ene-3,20-dione (11α-hydroxyprogesterone) were used as starting materials for the synthesis of a series of 11- and 12-substituted derivatives of 5ξ-pregnanolone (3α-hydroxy-5α-pregnan-20-one and 3α-hydroxy-5β-pregnan-20-
PMID 23421641

Japanese Journal

Novel enzyme-linked immunosorbent assay for bivalent ZnT8 autoantibodies

Kawasaki Eiji,Tanaka Megumi,Miwa Masaki,Abiru Norio,Kawakami Atsushi
Acta Diabetologica 51(3), 429-434, 2014-06
… However, the widely used current ZnT8A radioligand binding assay (RBA) has proved to be difficult for many laboratories to implement. …
NAID 120005477040

18F-AV45（Florbetapir）を用いた脳アミロイドイメージング

工藤雅子,米澤久司,柴田俊秀,小原智子,高橋純子,佐々木敏秋,寺崎一典,世良耕一郎,寺山靖夫
脳循環代謝（日本脳循環代謝学会機関誌） 25(2), 91-96, 2014
Alzheimer 病（AD）において脳内に蓄積したアミロイドの描出を18F-AV45（Florbetapir）を用いたPET で評価し，軽度認知機能障害（MCI），前頭側頭葉変性症（FTLD）および正常対照（HC）と比較検討を行った．前頭葉，側頭葉，頭頂葉，後頭葉および被殻，視床，橋に関心領域を設定し小脳を対照としたstandardized uptake value ratio（SUVR）を測定 …
NAID 130004708209

Endothelin-1 Receptors in Rat Tissues: Characterization by Bosentan, Ambrisentan and CI-1020

, , [他], , , , ,
Biological and Pharmaceutical Bulletin 37(3), 461-465, 2014
… The present study aimed to characterize comparatively endothelin-1 (ET-1) receptors in rat tissues by radioligand binding assay using [125I]ET-1 and to examine receptor binding after oral administration of bosentan. …
NAID 130003390952