How Are Isotopes Used in Biological Research?

Isotopes

Isotopes for a given atomic element are a variety of atoms with the same number of protons, but a different number of neutrons.

Isotopes occurring naturally in an organism or injected can be used for imaging internal structure and function. This includes, but is not exclusive to, highly radioactive, short-lived radioisotopes.

Longer-lived radioisotopes are useful for placing organisms in the geological record, aiding determination of evolutionary rates.

Nuclear Magnetic Resonance Imaging (NMRI)

NMRI is a visualization technique used to image the internal bodily structures and functions. Isotopes naturally occurring in the body that have a magnetic moment will precess around an axis along the direction of a strong external magnetic field. Hydrogen isotopes in water molecules throughout the body are commonly used.

Protons with a magnetic moment enter a state of excitation when the magnets of the NMRI scanner are on. When the magnetic fields are turned off, the protons release their excitation energy at resonance radio frequencies that are detected by the NMRI scanner. Difference in tissues is measurable because the protons in different tissues return to their equilibrium state at different rates. Position of physiological structures can be determined by varying the magnetic fields, and because resonance frequencies differ by the strength of the magnetic field, and therefore by the distance to the magnets.

Because difference in tissue can be imaged, so can blood flow, which has been useful in, for example, mapping brain function.

Radioactive Isotopes

Radioisotopic labeling is the injection of radioactive isotopes into a system and mapping the course of the injected substance with a scanner.

A well-known example is the positron emission tomography (PET) scan. If the injected tracer is fludeoxyglucose (FDG), then the imaging will show tissue metabolic activity, because the FDG is similar to glucose and would be spiked with the positron-emitting radioactive isotope fluorine-18.

Because different molecules are absorbed by different tissues, a wide arsenal of radionuclei has been accumulated. For example, phosphorus-32 and -33 are used to label nucleotides, the basic units of DNA. Sodium-22 and chloride-36 are used to study ion transport. Tritium and sulfur-35 are used to label amino acids and proteins.

In vivo examinations substitute with fluorescent dyes where possible, to avoid an unnecessary exposure to radioactivity in the patient.

Stable Isotopic Labeling

Stable isotopic labeling is isotopic labeling but without the use of radioactive isotopes.

An example is stable isotope labeling with amino acids in cell culture (SILAC), in which two cell populations are fed amino acids using different isotopes. Instead of detecting radioactivity in a single sample (for example, a patient), the two (nonradioactive) isotopes used in separate cultures are differentiable by weight. Specifically, the weight difference is detected by mass spectrometry.

Because SILAC can trace amino acid metabolism and protein synthesis, it is useful in studying signaling between cells, protein-protein interactions and the regulation of gene expression.

Radiometric Dating

Radiometric dating is the use of the known decay rate of an isotope to date the introduction of the isotope. Radiocarbon dating, used to determine the age of carbonaceous materials, is the most widely known example of radiometric dating.

For example, the unstable isotope carbon-14 is renewed in the upper atmosphere by cosmic rays. If one knows from tree ring or glacial ice core samples the atmospheric ratio of carbon-12 to carbon-14 ingested by living organisms at a certain date, then one can accurately estimate the age of animal remains as far back as 26,000 years ago.

For older samples, such as fossils, other radiometric dating methods are available, which enable the deduction of rates of evolutionary change.

References

• Stable isotope labeling with amino acids in cell culture
• Molecular Biology of the Cell; Bruce Alberts et al.; 2007
• Radionuclide Scanning; The Merck Manual; 2008

Resources

• Essential Molecular Biology; Terence A. Brown; 2002