Prof. Howard Lee shared his past experiences and future perspectives on the 14C-based microtracing and macrodosing studies in humans in South Korea as an invited speaker to the 9th East Asia Accelerator Mass Spectrometry Symposium (EAAMS-9), held at KIST, Seoul, South Korea, on November 22-24, 2023. 

Prof. Lee has introduced the concept and utilizes of the 14C-based microtracing and macrodosing study for new drug development since 2024. As of today, Prof. Lee has completed a total of six microtracing/microdosing studies with one being the IND-opening study for the US FDA. In his talk, Prof. Lee shared his experiences in starting a 14C-labelled human study using the microdosing technology in Korea. Additionally, Prof. Lee gave hist perspective as to how this technology can be further utilized to increase the efficiency of clinical drug development.

The best model for humans is human. Drug development has long been suffering from the lack of translatability and predictability of the preclinical animal experiments to humans. Dr. Richard Klausner, former Director of the US National Cancer Institute, commented in 1998, “the history of cancer research has been a history of curing cancer in the mouse. … and it simply didn’t work in humans.” Twenty years fast forward, drug development scientists are still struggling with the same issue.

Microtracing/microdosing is an innovative technology that can revolutionize the current paradigm of clinical drug development. Typically, a very small amount of the drug, i.e., ‘microdose’, which is less than 100 micrograms (or 30 nmoles for proteins), is administered to humans. Since this is much smaller than 1/100 of the pharmacologically active dose, microtracing/microdosing technology can be employed at a very early stage of clinical drug development even when there is limited animal toxicology data. Furthermore, in order to trace minute doses, an accelerator mass spectrometer (AMS) is required and the compound should be labeled, typically with ¹⁴C. The microtracing/microdosing study allows clinical drug development scientists for generating the intravenous pharmacokinetics, mass balance, metabolite profiling, and absolute bioavailability data much easier, faster, and at a lower cost.  

Dr. Howard Lee has spearheaded the employment of microtracing/microdosing technology for drug development in Korea since 2012, supported by three government grants. Dr. Lee has successfully d a new research ecosystem for the microtracing/microdosing study, which helped him perform the first microtracing/microdosing study under a full investigational new drug (IND) application in 2014. The result of this study was published at the most reputable journal in the field. Dr. Lee has conducted two additional microtracing/microdosing studies, and has recently won a two-year grant of $1 mil, in which microtracing/microdosing technology will be applied to a new drug development study with biologics.