Radio-tracing 'without' radioactivity: accelerator mass spectrometry in biomedicine

Accelerator mass spectrometry (AMS) is a form of isotope-ratio mass spectrometry that quantifies concentrations of certain long-lived radioisotopes independently of their radioactive decay. AMS is primarily used in the geosciences for determining the age of a material that contains naturally occurring radioisotopes. AMS uses the same high specificity for enriched levels of these radioisotopes in tracing low chemical doses for long periods in biological systems, including humans. AMS provides the safety of low radiative exposure to experimental subjects and investigators, while obtaining attomole sensitivities that are not possible with stable isotope tracers because of their natural isotopic abundances. AMS isotope tracing was first applied to quantifying the genotoxicity of low level environmental chemicals in animals and later in humans. Physiologic concentrations of 14C-labeled trace nutrients (folate, carotene, and tocopherol) are now measured directly in humans without concern about radiation. The radiative exposure is less than the commonly accepted risks of natural background radiation or the radiation fields found in high altitude air flights. AMS measures very small biological samples (such as 20 microliters of blood) that are easily obtained from human volunteers or model animals at frequent intervals for detailed analysis of kinetic profiles. This high data density enables the construction of compartmental models that elucidate nutrient behavior in tissues that cannot be directly sampled. The pharmaceutical industry is enthusiastic about AMS as a detector for 'micro-dosing' in which the human kinetics of an assuredly non-toxic dose of a candidate drug is tested early in a development project. Molecular tracing uses 3H or 14C as common isotopic labels, but AMS contributes to elemental tracing with certain radioisotopes having very long lives, such as 26AL or 41Ca. Calcium-41 is a particularly useful isotope in biomedical research because it is used to study changes in bone remodeling due to illness, diet, or age. The decay of 41Ca is especially benign because the internal electron capture transfers most of the decay energy to the non-interacting neutrino. The pattern of calcium absorption and equilibration in individuals are remarkably similar among healthy people but are distinctive in some illness. Finally, AMS reduces the radioactive waste generated by an experimental program. The spectrometers are also becoming much smaller and more affordable. At least one major drug company now owns two spectrometers. AMS is becoming a necessary tool in biochemical tracing for environmental, nutritional, and therapeutic research.