Radioligand

Radioligand je radioaktivna biohemijska supstanca koja se koristi za dijagnozu ili naučno istraživanje receptorskih sistema u telu.

U neurovizalizacijskim primenama radioligand se unosi putem injekcije u tkivo, ili krvotok. On se zatim vezuje za njegov receptor. Kad dođe do raspada radioaktivnog izotopa, to se meri pomoću pozitronske emisione tomografije (PET) ili jednofotonska emisiona kompjuterska tomografija (SPECT). U in vivo sistemima on se često koristi za kvantifikovanje vezivanja testiranog molekula za mesto vezivanja radioliganda. Što je veći afinitet molekula to je više radioliganda zamenjeno njime na mestu vezivanja i povećani radioaktivni raspad se može meriti scintilografski. Ovaj tip testa se često koristi za izračunavanje konstante vezivanja molekula na receptorima.

Istorija

Radioligandi se prave da bi se omogućilo studiranje biomolekulskog ponašanja.^[1] Radioligandne tehnike omogućavaju istraživačima da identifikuju receptore unutar ćelija.

Radioaktivni izotopi u širokoj upotrebi

Tricijum, ³H
Ugljenik-14, ¹⁴C
Sumpor-35, ³⁵S
Jod-131, ¹³¹I
Fluor-18, ¹⁸F
Tehnecijum-99m, ^99mTc

Pri primeni PET tehnike za molekulsku vizuelizaciju često se koriste izotopi fluor-18 i ugljenik-11.

Lista radioliganda

Radioligandi se mogu selektivno da se vežu za specifični neuroreceptor ili transporter neurotransmiter.

Primer radioliganda su:

¹¹C-WAY-100635 za 5-HT_1A receptor
N(1)-([¹¹C]-metil)-2-Br-LSD ([¹¹C]-MBL) za 5-HT2 receptore^[2]
¹⁸F-altanserin i ¹⁸F-setoperon za 5-HT_2A receptor^[3]
¹¹C-ketanserin^[4] i tricijumski ketanserin
¹¹C-DASB za serotoninski transporter^[5]
³H-WIN55,212-2 za kanabinoidne receptore^[6]
[¹¹C]flumazenil za GABA_A receptore.^[7]
(+)PHNO za D₂ dopaminske receptore.^[8]
[¹¹C]rakloprid za D₂ dopaminske receptore.^[9]

Povezano

Reference

↑ Niehoff, Debra (2005). The Language of Life: How cells communicate in life & disease. Joseph Henry Press. ISBN 978-0-309-08989-0.
↑ Wong, Dean F.; Lever, John R.; Hartig, Paul R.; Dannals, Robert F.; Villemagne, Victor; Hoffman, Beth J.; Wilson, Alan A.; Ravert, Hayden T. i dr.. (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]” (French). Revue neurologique 141 (8-9): 537-545. PMID 2935920.
↑ Reimold M, Smolka MN, Zimmer A i dr.. (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.
↑ 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. ^{[mrtav link]}
↑ 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.

Literatura

John Charles Matthews (1993). Fundamentals of Receptor, Enzyme, and Transport Kinetics. CRC Press. ISBN 978-0-8493-4426-8.

[1] Niehoff, Debra (2005). The Language of Life: How cells communicate in life & disease. Joseph Henry Press. ISBN 978-0-309-08989-0.

[2] Wong, Dean F.; Lever, John R.; Hartig, Paul R.; Dannals, Robert F.; Villemagne, Victor; Hoffman, Beth J.; Wilson, Alan A.; Ravert, Hayden T. i dr.. (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.

[3] 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.

[4] 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]” (French). Revue neurologique 141 (8-9): 537-545. PMID 2935920.

[pmid17713719-5] Reimold M, Smolka MN, Zimmer A i dr.. (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.

[pmid10469884-6] Pertwee RG (1999). „Pharmacology of cannabinoid receptor ligands”. Curr. Med. Chem. 6 (8): 635-64. PMID 10469884.

[7] 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.

[8] 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. ^{[mrtav link]}

[9] 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.

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