Radioligand
Encyclopedia
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.
In PET the isotopes fluorine-18
and carbon-11 are often used in molecular neuroimaging.
.
Examples of radioligands include:
Ligand (biochemistry)
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. In a narrower sense, it is a signal triggering molecule, binding to a site on a target protein.The binding occurs by intermolecular forces, such as ionic bonds, hydrogen...
) that is used for diagnosis or for research-oriented study of the receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
systems of the body.
In a neuroimaging
Neuroimaging
Neuroimaging includes the use of various techniques to either directly or indirectly image the structure, function/pharmacology of the brain...
application the radioligand is injected into the pertinent tissue, or infused into the bloodstream.
It binds to its receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
.
When the radioactive isotope in the ligand decays it can be measured by positron emission tomography
Positron emission tomography
Positron emission tomography is nuclear medicine imaging technique that produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide , which is introduced into the body on a...
(PET) or single photon emission computed tomography
Single photon emission computed tomography
Single-photon emission computed tomography is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera. However, it is able to provide true 3D information...
(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
Scintillography
Scintillography is an imaging method of nuclear events provoked by collisions or charged current interactions among nuclear particles or ionizing radiation and atoms which result in a brief, localised pulse of electromagnetic radiation, usually in the visible light range...
. 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. With this capacity radioligand techniques enabled researchers to identify receptor devices within cells.Radioactive isotopes commonly used
- TritiumTritiumTritium is a radioactive isotope of hydrogen. The nucleus of tritium contains one proton and two neutrons, whereas the nucleus of protium contains one proton and no neutrons...
, 3H - Carbon-14Carbon-14Carbon-14, 14C, or radiocarbon, is a radioactive isotope of carbon with a nucleus containing 6 protons and 8 neutrons. Its presence in organic materials is the basis of the radiocarbon dating method pioneered by Willard Libby and colleagues , to date archaeological, geological, and hydrogeological...
, 14C - Sulfur-35SulfurSulfur or sulphur is the chemical element with atomic number 16. In the periodic table it is represented by the symbol S. It is an abundant, multivalent non-metal. Under normal conditions, sulfur atoms form cyclic octatomic molecules with chemical formula S8. Elemental sulfur is a bright yellow...
, 35S - Iodine-131IodineIodine is a chemical element with the symbol I and atomic number 53. The name is pronounced , , or . The name is from the , meaning violet or purple, due to the color of elemental iodine vapor....
, 131I - Fluorine-18FluorineFluorine is the chemical element with atomic number 9, represented by the symbol F. It is the lightest element of the halogen column of the periodic table and has a single stable isotope, fluorine-19. At standard pressure and temperature, fluorine is a pale yellow gas composed of diatomic...
, 18F - Technetium-99mTechnetium-99mTechnetium-99m is a metastable nuclear isomer of technetium-99, symbolized as 99mTc. The "m" indicates that this is a metastable nuclear isomer, i.e., that its half-life of 6 hours is considerably longer than most nuclear isomers that undergo gamma decay...
, 99mTc
In PET the isotopes fluorine-18
Fluorine-18
Fluorine-18 is a fluorine radioisotope which is an important source of positrons. It has a mass of 18.0009380 u and its half-life is 109.771 minutes....
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 transporterNeurotransmitter transporter
Neurotransmitter transporters are a class of membrane transport proteins that span the cellular membranes of neurons. Their primary function is to carry neurotransmitters across these membranes and to direct their further transport to specific intracellular locations...
.
Examples of radioligands include:
- 11C-WAY-100635WAY-100635WAY-100,635 is a piperazine drug and research chemical widely used in scientific studies. It was originally believed to act as a selective 5-HT1A receptor antagonist, but subsequent research showed that it also acts as potent full agonist at the D4 receptor. It is sometimes referred to as a silent...
for the 5-HT1A receptor5-HT1A receptorThe 5-HT1A receptor is a subtype of 5-HT receptor that binds the endogenous neurotransmitter serotonin . It is a G protein-coupled receptor that is coupled to Gi/Go and mediates inhibitory neurotransmission... - N(1)-([11C]-methyl)-2-Br-LSD ([11C]-MBL) for 5-HT2 receptor5-HT2 receptorThe 5-HT2 receptors are a subfamily of 5-HT receptors that bind the endogenous neurotransmitter serotonin . The 5-HT2 subfamily consists of three G protein-coupled receptors which are coupled to Gq/G11 and mediate excitatory neurotransmission, including 5-HT2A, 5-HT2B, and 5-HT2C...
s - 18F-altanserinAltanserinAltanserin is a compound that binds to the 5-HT2A receptor .It is a yellowish solid.Labeled with the isotope fluorine-18 it is used as a radioligand in positron emission tomography studies of the brain, i.e., studies of the serotonin-2A neuroreceptors.Besides human neuroimaging studies altanserin...
and 18F-setoperoneSetoperoneSetoperone is a compound that is a ligand to the 5-HT2A receptor.It can be radiolabeled with the radioisotope fluorine-18 and used as a radioligand with positron emission tomography ....
for the 5-HT2A receptor5-HT2A receptorThe mammalian 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor . This is the main excitatory receptor subtype among the GPCRs for serotonin , although 5-HT2A may also have an inhibitory effect on certain areas such... - 11C-ketanserinKetanserinKetanserin is a drug with affinity for multiple G protein-coupled receptors . Initially it was believed to be a highly selective antagonist for serotonin 5-HT2A receptors, however this is not true. Ketanserin only has moderate selectivity for 5-HT2A receptors over 5-HT2C receptors...
and tritiated ketanserin - 11C-DASBDASBDASB is a compound that binds to the serotonin transporter.Labeled with carbon-11 — a radioactive isotope — it has been used as a radioligand in neuroimaging with positron emission tomography since around year 2000....
for the serotonin transporterSerotonin transporterThe serotonin transporter is a monoamine transporter protein.This protein is an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. This transport of serotonin by the SERT protein terminates the action of serotonin and recycles it... - 3H-WIN55,212-2 for cannabinoid receptors
- [11C]flumazenilFlumazenilFlumazenil is a benzodiazepine antagonist available for injection only, and the only benzodiazepine receptor antagonist on the market today.It was first introduced in 1987 by Hoffmann-La Roche under the trade name Anexate, but only approved by...
for GABAA receptors. - (+)PHNO for D2 dopamine receptorsDopamine receptor D2Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the DRD2 gene.- Function :This gene encodes the D2 subtype of the dopamine receptor. This G protein-coupled receptor inhibits adenylyl cyclase activity...
. - [11C]racloprideRacloprideRaclopride is a synthetic compound that acts as an antagonist on D2 dopamine receptors.It can be radiolabelled with the carbon-11 radioisotope and used in positron emission tomography scanning to assess the degree of dopamine binding to the D2 Dopamine receptor.For example, one study found...
for D2 dopamine receptorsDopamine receptor D2Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the DRD2 gene.- Function :This gene encodes the D2 subtype of the dopamine receptor. This G protein-coupled receptor inhibits adenylyl cyclase activity...
.