Biodistribution
Encyclopedia
Biodistribution is a method of tracking where compounds of interest travel in an experimental animal or human subject. For example, in the development of new compounds for PET (positron emission tomography
) scanning, a radioactive isotope is chemically joined with a peptide
(subunit of a protein
). This particular class of isotopes emits positron
s (which are antimatter
particles, equal in mass to the electron, but with a positive charge). When ejected from the nucleus, positrons encounter an electron, and undergo annihilation
which produces two gamma rays travelling in opposite directions. These gamma rays can be measured, and when compared to a standard, quantified.
A useful compound is one that is used either for the medical imaging
of certain body parts or tumors (at low doses of radioactivity) or treating tumors (at high doses of radioactivity).
, gene delivery vectors, such as viruses, can be imaged according either to their particle biodistribution or their transduction
pattern. The former means labeling the viruses with a contrast agent, being visible in some imaging modality, such as MRI or SPECT/PET
and latter means visualising the marker gene
of gene delivery vector to be visible by the means of immunohistochemical methods, optical imaging
or even by PCR. Non-invasive imaging has gained popularity as the imaging equipment has become available for research use from clinics.
For example, avidin
-displaying baculoviruses could be imaged in rat brain by coating them with biotinylated iron particles, rendering them visible in MR imaging. The biodistribution of the iron-virus particles was seen to concentrate on the choroid plexus
cells of lateral ventricles.
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...
) scanning, a radioactive isotope is chemically joined with a peptide
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
(subunit of a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
). This particular class of isotopes emits positron
Positron
The positron or antielectron is the antiparticle or the antimatter counterpart of the electron. The positron has an electric charge of +1e, a spin of ½, and has the same mass as an electron...
s (which are antimatter
Antimatter
In particle physics, antimatter is the extension of the concept of the antiparticle to matter, where antimatter is composed of antiparticles in the same way that normal matter is composed of particles...
particles, equal in mass to the electron, but with a positive charge). When ejected from the nucleus, positrons encounter an electron, and undergo annihilation
Annihilation
Annihilation is defined as "total destruction" or "complete obliteration" of an object; having its root in the Latin nihil . A literal translation is "to make into nothing"....
which produces two gamma rays travelling in opposite directions. These gamma rays can be measured, and when compared to a standard, quantified.
Biodistribution imaging after dissection
For example, a new compound would be injected intravenously into a group of 16-20 rodents (typically mice or rats). At intervals of 1, 2, 4, and 24 hours, smaller groups (4-5) of the animals are euthanized, then dissected. The organs of interest (usually: blood, liver, spleen, kidney, muscle, fat, adrenals, pancreas, brain, bone, stomach, small intestine, and upper and lower large intestine) are placed in pre-weighed containers, then into a device that measures gamma radiation. The results give a dynamic view of how the compound moves through the animal.A useful compound is one that is used either for the medical imaging
Medical imaging
Medical imaging is the technique and process used to create images of the human body for clinical purposes or medical science...
of certain body parts or tumors (at low doses of radioactivity) or treating tumors (at high doses of radioactivity).
Non-invasive biodistribution imaging in gene therapy
In gene therapyGene therapy
Gene therapy is the insertion, alteration, or removal of genes within an individual's cells and biological tissues to treat disease. It is a technique for correcting defective genes that are responsible for disease development...
, gene delivery vectors, such as viruses, can be imaged according either to their particle biodistribution or their transduction
Transduction (genetics)
Transduction is the process by which DNA is transferred from one bacterium to another by a virus. It also refers to the process whereby foreign DNA is introduced into another cell via a viral vector. Transduction does not require cell-to-cell contact , and it is DNAase resistant...
pattern. The former means labeling the viruses with a contrast agent, being visible in some imaging modality, such as MRI or SPECT/PET
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...
and latter means visualising the marker gene
Marker gene
A marker gene is a gene used in molecular biology to determine if a nucleic acid sequence has been successfully inserted into an organism's DNA. There are two types of marker genes: a selectable marker and a marker for screening.-Selectable marker:...
of gene delivery vector to be visible by the means of immunohistochemical methods, optical imaging
Optical imaging
Optical imaging is an imaging technique.Optics usually describes the behavior of visible, ultraviolet, and infrared light used in imaging.Because light is an electromagnetic wave, similar phenomena occur in X-rays, microwaves, radio waves. Chemical imaging or molecular imaging involves inference...
or even by PCR. Non-invasive imaging has gained popularity as the imaging equipment has become available for research use from clinics.
For example, 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...
-displaying baculoviruses could be imaged in rat brain by coating them with biotinylated iron particles, rendering them visible in MR imaging. The biodistribution of the iron-virus particles was seen to concentrate on the choroid plexus
Choroid plexus
The choroid plexus is a structure in the ventricles of the brain where cerebrospinal fluid is produced...
cells of lateral ventricles.