MSACL 

Quantifying Clinical Markers of Disease and Therapy with 14C-AMS
Wed 11:00 AM - Track 1: Accelerator MS
John S. Vogel
Vitalea Science
Stephen R. Dueker, Le Vuong, Bradly Keck, Peter Lohstroh, Jason Giacomo, and John S. Vogel

Vitalea Science, 2121 Second Street Suite 101B, Davis CA 95618
A laboratory-scale, continuous operating AMS is described that has the throughput, accuracy, and precision for quantifying clinical biomarkers derived from 14C-labeled compounds. Absorption of cobalamin is AMS quantified by a single small dose of the labeled vitamin followed by a blood-stick sampling 7 hours later. Distribution of an antiretroviral into circulating lymphocytes is AMS quantified 12 hours after dosing with the 14C-parent. Metabolism of another antiretroviral shows a distinct compound pair in plasma 4 hours post dose that maintains relative AMS quantitation integrated in urine over 12 hours. Elimination terminal time constants quantify drug reservoir sizes and lifetimes without biopsy at concentrations heretofore unquantified. Steady-state AMS quantitation of introduced endogenous substrates and products provides new clinical biomarker candidates and is feasible with isotopic labeling that adds no more radiation risk than a few extra days of living. No clinical population need be excluded, as shown by AMS nano-tracer probing of cholestasis in pre-term neonates within their first week of life. New AMS technology brings the high sensitivity and specificity of 14C labeling to new clinical markers of both disease and therapy.
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