In addition to the usefulness of AMS in conventional preclinical and clinical trials, the extreme sensitivity of AMS also allows for the administration of microdoses of 14C labeled investigational drugs in phase 0 studies, as well as microdosing of approved drugs to distinguish low and high responding cancer patients prior to initiation of therapeutic dosing.
Regulatory authorities have provided guidance on the design and conduct of microdosing studies. The purpose of these studies is to allow for initial assessment of a drug’s pharmacokinetic properties in humans at a dose far below the level at which it would be expected to have pharmacologic or toxic effects. The sensitivity of AMS provides the means to collect PK data at extremely low doses.
Accium BioSciences has a strong interest in developing personalized medicine tools in oncology with academic and industry partners which can lead to predicting patient response to chemotherapeutic or targeted drugs. Accium BioSciences has worked with researchers from the University of Washington, the Ivy Brain Institute, and the California Pacific Medical Center, quantifying the incorporation of 14C into malignant cell DNA using radiolabeled chemotherapeutic drugs.
Due to the underlying heterogeneity (genetic and environmental) that drives response, patients may exhibit a wide range of response to the same treatment. To uncover the pharmacologic basis of response (or lack of response), patients are administered a microdose of 14C labeled drug to permit detection by AMS. The extreme sensitivity of AMS allows the both the drug and radioactive dose to be reduced <100 µg and <200 µCi respectively to eliminate pharmacologic effect yet provide sufficient 14C for assessment of tracer kinetics and tumor cell uptake. This technique allows for a phenotypic quantification of the drug at the cellular or molecular target, which could lead to a predictive companion diagnostic test that could be co-developed with an investigational drug in order to reduce heterogeneity and the proportion of poor-responding patients within the study population.