A radioligand is a radioactive biochemical substance (in particular, a ligand that is radiolabeled) 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 radioligand. The higher the affinity of the molecule the more radioligand 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
- Tritium, 3H
- Carbon-14, 14C
- Sulfur-35, 35S
- Iodine-131, 131I
- Fluorine-18, 18F
- Technetium-99m, 99mTc
- Copper-64, 64Cu
In PET the isotopes fluorine-18, carbon-11, and copper-64 are often used in molecular imaging.
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-HT1A receptor
- N(1)-([11C]-methyl)-2-Br-LSD ([11C]-MBL) for 5-HT2 receptors[2]
- 18F-altanserin and 18F-setoperone for the 5-HT2A 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 GABAA receptors.[7]
- (+)PHNO for D2 dopamine receptors.[8]
- [11C]raclopride for D2 dopamine receptors.[9]
See also
- Binding potential
- Distribution volume
- PET radiotracer
- Radioactivity in biology
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.; Links, Jonathan M. (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. S2CID 29487429.
- ^ 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-HT2A 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. S2CID 24403109.
- ^ 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]". Revue neurologique (in French). 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. S2CID 33872765.
- ^ 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. S2CID 24111743.
- ^ 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. S2CID 28591014.
Further reading
- John Charles Matthews (1993). Fundamentals of Receptor, Enzyme, and Transport Kinetics. CRC Press. ISBN 0-8493-4426-3.