Effective Use of Microdosing and Positron Emission Tomography (PET) Studies on New Drug Discovery and Development

The biodistribution and pharmacokinetics of drugs are vital to the mechanistic understanding of their efficacy. Measuring antimicrobial drug efficacy has been challenging as plasma drug concentration is used as a surrogate for tissue drug concentration, yet typically does not reflect that at the intended site(s) of action. Utilizing an image-guided approach, it is feasible to accurately quantify the biodistribution and pharmacokinetics within the desired site(s) of action. We outline imaging modalities used in visualizing drug distribution with examples ranging from in vitro cellular drug uptake to clinical treatment of microbial infections. The imaging modalities of interest are: radio-labeling, magnetic resonance, mass spectrometry imaging, computed tomography, fluorescence, and Raman spectroscopy. We outline the progress, limitations, and future outlook for each methodology. Further advances in these optical approaches would benefit patients and researchers alike, as non-invasive imaging could yield more profound insights with a lower clinical burden than invasive measurement approaches used today.