[摘要]：The phase O microdosing concept was introduced recently by the FDA in order to shorten the timeline for drug development and to reduce the overall cost of the process. The aim of this approach is to provide drug pharmacokinetic and pharmacodynamic data using subpharmacological doses of prospective drug candidates in a small number of human volunteers at the earliest stages of drug development. A microdose is defined as 1/100th of the pharmacological dose or a maximum of 100 mu g, which requires ultrasensitive analytical methods for measuring such a small amount of drug. Molecular imaging plays a fundamental role in this process. Radionuclide-based imaging modalities such as single-photon emission computed tomography (SPECT) and positron emission tomography (PET) allow the noninvasive visualization and quantitative assessment of physiological and biochemical processes occurring at cellular and subcellular levels within the human body Due to the high sensitivity of such techniques it is possible to evaluate in vivo the biodistribution and pharmacokinetics of drug candidates in the nano- to picomolar concentration range. This information obtained in the earlier phases of drug development might have a tremendous impact on the success rate of agents entering clinical trials and on the overall efficiency of the process. In this article we provide an overview of the basic principles of molecular imaging with SPECT and PET and explain how these techniques can be implemented in exploratory IND studies and used to accelerate new drug approvals.
