Abstract

This review summarizes recent developments in radiocarbon tracer technology and applications. Technologies covered include accelerator mass spectrometry (AMS), including conversion of samples to graphite, and rapid combustion to carbon dioxide to enable direct liquid sample analysis, coupling to HPLC for real-time AMS analysis, and combined molecular mass spectrometry and AMS for analyte identification and quantitation. Laser-based alternatives, such as cavity ring down spectrometry, are emerging to enable lower cost, higher throughput measurements of biological samples. Applications covered include radiocarbon dating, use of environmental atomic bomb pulse radiocarbon content for cell and protein age determination and turnover studies, and carbon source identification. Low dose toxicology applications reviewed include studies of naphthalene-DNA adduct formation, benzo[a]pyrene pharmacokinetics in humans, and triclocarban exposure and risk assessment. Cancer-related studies covered include the use of radiocarbon-labeled cells for better defining mechanisms of metastasis and the use of drug-DNA adducts as predictive biomarkers of response to chemotherapy.

Highlights

  • Radioisotopes play an important role in advancing our knowledge in the biomedical sciences.The applications are broad, ranging from positron-emission-tomography to the use of scintillation radiometry for determining protein turnover rates [1,2,3,4]

  • The most important considerations in preparing samples for radiocarbon analysis are the amount of radioisotope in each sample, preventing contamination, and knowing the sources and amounts of any carbon introduced during processing

  • Analysis systems that are compatible with the direct input of biochemical separation instrumentation, such as liquid chromatography, would allow real-time analysis, leading to increased resolution, minimal handling, and the ability to do molecule-specific tracing of small samples

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Summary

Introduction

Radioisotopes play an important role in advancing our knowledge in the biomedical sciences. AMS does not rely on the nuclear decay, but rather on the direct quantification of the isotopic nuclei through mass spectrometry (reviewed in [7]). This provides much greater sensitivity for isotope detection (103 to 109 times greater than decay counting), leading to the use of lower chemical and radioisotope doses and the analysis of smaller samples, which enables studies to be performed safely in humans, using exposures that are environmentally or therapeutically relevant while generating little radioactive waste. Technologies that are reviewed include the conversion of samples to graphite or carbon dioxide, followed by direct AMS analysis, combined AMS/ion trap mass spectrometry, and laser-based quantitation, along with examples of applications of these technologies to molecular toxicology, cell turnover, metastasis, and chemotherapy drug resistance

Graphite
Gas Ionization
Parallel
Radiocarbon Dating
Bomb Pulse Dating
Carbon Source Determination
Structural and Pathological Protein Dating
Cell Lifetime and Turnover
Workflow and validationofof 14C-labeling
Low Dose Toxicity
Naphthalene
Triclocarban
Diagnostic Microdosing
Predicting Response to Platinum-Based Therapy with Microdosing
Correlation of microdose-induced adduct levels to therapy response
Overview of the ex vivo microdosing”
Findings
Conclusions
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