Abstract
Positron emission tomography （PET） visualizes radiolabeled compounds in the living body with a high sensitivity, quantitative performance, and considerably high spatial and temporal resolution. This technique is useful for pharmacokinetic analysis and drug efficacy evaluation in preclinical and clinical studies. PET enables the investigation of drug concentrations in human tissues, which was impossible by conventional evaluation technologies. In addition, we can use PET probes to visualize the expression and function of disease-related molecules as surrogate endpoints in clinical trials. In this review, we will exemplify our collaborative preclinical and clinical studies on pharmacokinetics, DDS, and theranostics with a variety of academic and industrial collaboraters. First, we developed a series of PET probes to study transporters （organic anion transporting polypeptides, multidrug resistance-associated protein 2, etc.） such as ［11C］Dehydropravastatin. Because substantial species differences in expression and function of transporters have been reported, these probes are especially useful to examine drug-drug interactions in human beings. Secondly, we established a PET-based system to visualize translocation of intranasally administered drugs and analyze pharmacokinetics on nasal drug absorption using 2-deoxy-2-［18F］fluoroglucose in rats. As far as we know, this is the first study that demonstrated the visualization of nasal absorption process and detailed pharmacokinetic analysis. Thirdly, HER2-positive breast cancer and its metastasis were successfully delineated in a 64Cu-trastuzumab clinical PET study, which indicates immuno-PET probes are potential companion diagnostics for molecular target medicines and will become alternatives to biopsy. PET imaging strongly connects drug efficacy with pharmacokinetics, which could accelerate drug development during overall process.
