Pharmacokinetics Using Carbon-14 and Cavity Ring-Down Spectroscopy

A. D. McCartt, T. Ognibene, G. Bench, K. Turteltaub Lawrence Livermore National Laboratory Purpose The prevalence of carbon in living organisms makes carbon-14 an ideal isotopic tracer for biological studies. In the past decades, carbon-14 has been used in studies of pharmacology, nutrition, carcinogenesis, toxicology, and fundamental biology. For micro-tracer studies, where small, physiologically relevant, xenobiotic doses are administered, accelerator mass spectroscopy (AMS) has been used for carbon-14 quantification. However, AMS systems are large, complex, and costly which has limited the proliferation of carbon-14 micro-tracer techniques. For this reason several efforts have been made to develop more robust and cost effective methods of carbon14 detection. Methods Here we present our prototype carbon-14 cavity ring-down spectrometer (CRDS). This spectrometer was developed using simple robust hardware for the explicit purpose of measuring carbon-14 concentrations in biological samples. This capability is demonstrated by comparing CRDS and accelerator mass spectrometry (AMS) results. Samples from a pharmacokinetic case study using guinea pigs as the model organism were measured with CRDS and compared to measurements made with AMS on duplicate samples. Guinea pigs were dosed intravenously with an oxime aceteyltransferase reactivator with tissue and plasma samples taken in a geometric time series. Results The Figure below plots the carbon-14 labeled oxime concentrations measured by both AMS and CRDS in guinea pig liver and plasma samples. The measurements of carbon-14 in the guinea-pig samples by CRDS accurately reproduced the AMS results (R=.99739 ). Pharmacokinetic parameters have been calculated for both AMS and CRDS concentration curves and presented for comparison.