90Y-DOTA-biotin
Encyclopedia
90Y-DOTA-biotin consists of a radioactive substance (yttrium-90
) complexed by a chelating agent (DOTA), which in turn is attached to the vitamin biotin
via a chemical linker. It is used experimentally in pretargeted radioimmunotherapy
. Animal studies have been conducted as well as clinical studies in humans.
In pretargeted radioimmunotherapy, two or three medications are applied in succession. At first, an antibody-drug conjugate
is administered, which consists of a monoclonal antibody designed to target the tumour, and a chemical marker which in the case of DOTA-biotin therapy is one of the proteins avidin
and streptavidin
. After a time of typically one or two days to let the antibody accumulate in the tumour, a clearing agent may be given to eliminate residues of antibody that are still circulating in the bloodstream; this is especially done in humans. After a further waiting time, the radiotherapy (90Y-DOTA-biotin) is administered. Due to the high affinity of biotin to avidin and streptavidin, the radiotherapy accumulates where the antibody is, namely in the tumour, where it delivers its radioactivity.
Yttrium-90
Yttrium-90 is a medically significant isotope of yttrium.It emits beta rays of 2.3 MeV.Yttrium-90 is a decay product of Strontium-90 which makes up about 5% of the Nuclear daughter isotopes when Uranium is fissioned....
) complexed by a chelating agent (DOTA), which in turn is attached to the vitamin biotin
Biotin
Biotin, also known as Vitamin H or Coenzyme R, is a water-soluble B-complex vitamin discovered by Bateman in 1916. It is composed of a ureido ring fused with a tetrahydrothiophene ring. A valeric acid substituent is attached to one of the carbon atoms of the tetrahydrothiophene ring...
via a chemical linker. It is used experimentally in pretargeted radioimmunotherapy
Radioimmunotherapy
Radioimmunotherapy uses an antibody labeled with a radionuclide to deliver cytotoxic radiation to a target cell. In cancer therapy, an antibody with specificity for a tumor-associated antigen is used to deliver a lethal dose of radiation to the tumor cells...
. Animal studies have been conducted as well as clinical studies in humans.
In pretargeted radioimmunotherapy, two or three medications are applied in succession. At first, an antibody-drug conjugate
Antibody-drug conjugate
Antibody-drug conjugates are a new type of targeted therapy, used for example for cancer. They consist of an antibody linked to a payload drug . Hence, they are a type of immunoconjugate and often an immunotoxin.The antibody causes the ADC to bind to the target cancer cells...
is administered, which consists of a monoclonal antibody designed to target the tumour, and a chemical marker which in the case of DOTA-biotin therapy is one of the proteins avidin
Avidin
Avidin is a tetrameric biotin-binding protein produced in the oviducts of birds, reptiles and amphibians deposited in the whites of their eggs. In chicken egg white, avidin makes up approximately 0.05% of total protein...
and streptavidin
Streptavidin
Streptavidin is a 60000 dalton protein purified from the bacterium Streptomyces avidinii. Streptavidin homo-tetramers have an extraordinarily high affinity for biotin . With a dissociation constant on the order of ≈10-14 mol/L, the binding of biotin to streptavidin is one of the strongest...
. After a time of typically one or two days to let the antibody accumulate in the tumour, a clearing agent may be given to eliminate residues of antibody that are still circulating in the bloodstream; this is especially done in humans. After a further waiting time, the radiotherapy (90Y-DOTA-biotin) is administered. Due to the high affinity of biotin to avidin and streptavidin, the radiotherapy accumulates where the antibody is, namely in the tumour, where it delivers its radioactivity.