Abstract

The use of radioisotopes has a long history in biomedical science, and the technique of accelerator mass spectrometry (AMS), an extremely sensitive nuclear physics technique for detection of very low-abundant, stable and long-lived isotopes, has now revolutionized high-sensitivity isotope detection in biomedical research, because it allows the direct determination of the amount of isotope in a sample rather than measuring its decay, and thus the quantitative analysis of the fate of the radiolabeled probes under the given conditions. Since AMS was first used in the early 90's for the analysis of biological samples containing enriched 14C for toxicology and cancer research, the biomedical applications of AMS to date range from in vitro to in vivo studies, including the studies of 1) toxicant and drug metabolism, 2) neuroscience, 3) pharmacokinetics, and 4) nutrition and metabolism of endogenous molecules such as vitamins. In addition, a new drug development concept that relies on the ultrasensitivity of AMS, known as human microdosing, is being used to obtain early human metabolism information of candidate drugs. These various aspects of AMS are reviewed and a perspective on future applications of AMS to biomedical research is provided.

Highlights

  • Accelerator mass spectrometry (AMS; see Figure 1 for AMS schematic diagram) is an extremely sensitive nuclear physics technique for detection of very low-abundant, stable and long-lived isotopes, initially developed in the mid-70's as a method of determining isotope ratios for geochronology and archaeological research [1,2]

  • Conclusions and future prospects While the initial themes of biomedical research with AMS involved primarily the kinetics and binding of carcinogenic toxins and focused on toxicokinetics and toxin metabolism with new initiatives in nutrition and immunoassays, scientists have expanded the study of kinetics and dynamics directly in humans for disease [91,92], nutritional [75], and pharmaceutical [16] research, since AMS is a proven sensitive and robust method for quantifying rare isotopes in biological systems

  • A decrease in a metabolic biomarker might be due to increased catabolism or decreased anabolism

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Summary

Introduction

Accelerator mass spectrometry (AMS; see Figure 1 for AMS schematic diagram) is an extremely sensitive nuclear physics technique for detection of very low-abundant, stable and long-lived isotopes, initially developed in the mid-70's as a method of determining isotope ratios for geochronology and archaeological research [1,2]. AMS, an innovation technology for this purpose, has made it possible to administer such low amounts of 14Clabeled candidate drugs to humans and still retain sufficient levels of analytical sensitivity to determine its metabolism and pharmacokinetics, even though the amount of radioactivity that can be administered to humans is limited owing to the radiation exposure, not surprisingly This technique is, very much in its infancy and it is not known, for the majority of drugs, whether the pharmacokinetics will be sufficiently linear so that the pharmacokinetics observed at the microdose will be predictive of those at the therapeutic dose. The combustion gases can come from sealed combustion tubes that are the most efficient process for large numbers of mg-sized samples

Conclusions and future prospects
Vogel JS
14. Lill J
22. Committee for Proprietary Medicinal Products
48. Holland MG
52. Jellinger KA
Findings
54. Zucker RS
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