Biodistribution

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 positrons (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.

=Biodistribution imaging after dissection=

For example, a new compound would be injected (I.V.)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 humanely killed, 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 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 therapy, 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 have became 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 (Räty et al, 2006).

=References=


 * 1) Raty JK et al, Magnetic resonance imaging of viral particle biodistribution in vivo, Gene Ther. 2006 Oct;13(20):1440-6