Preface for the special issue on analysis of drug or drug targets by molecular imaging

To increase the chance of a successful outcome in clinic and in the development of innovative drugs, researchers aim to provide more comprehensive information about the disease and drugs to adapt treatment decisions according to an individual disease’s molecular characteristics. It is thus increasingly desirable to illuminate fundamental molecular pathways of the drug and its targets inside organisms in a non-invasive manner. Technologies developed in molecular imaging assist in visualizing, characterizing, and quantifying targets of interest at the molecular level within intact living organisms. This special issue of Journal of Pharmaceutical Analysis is therefore dedicated to highlighting current progresses made in molecular imaging towards various drugs, important or promising drug targets, and their interactions, as well as to providing a forum for sharing new methods reported recently for the efficient pharmaceutical analysis.

Macroscopic imaging systems such as computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound that pro- vide anatomical and physiological information are now in wide- spread clinical and preclinical applications. By contrast, systems that obtain molecular information have just emerged in the last two decades, including positron emission tomography (PET), single-photon-emission CT (SPECT), fluorescence imaging, and bioluminescence imaging. Enormous strides have also been made in the complementary approaches to releasing the target- responsive signals during detection. Based on these systems, this issue mainly focuses on the detection of the following objectives:

(1) drug or drug candidates like small-molecule drugs, natural products, or macromolecular drugs (e.g., peptides and antibodies), (2) drug targets such as enzymes, receptors, transporters, biological factors, or disease-related bioactive small molecules (e.g., gas and ions), and (3) drug-target interactions.

In this special issue, we are pleased to have five representative review articles to describe recent advances in the imaging of small-molecule and macro-molecule drugs as well as drug targets. Yao and Ge discuss practical strategies applied in the preparation of fluorophore-drug conjugates, including non-cleavable and cleavable ones. Such conjugation is capable of visualizing small- molecule drug delivery and distribution to providing new insights into the process of drug effects at cellular and molecular levels. In view of the rapid growth of monoclonal antibodies, as one of the central components in the therapy of cancer, autoimmune disorders and chronic inflammatory diseases, the  characterization  of the antibody’s interaction with the target antigen as well as its cellular and intercellular behavior is crucial to guaranteeing the safety and efficacy during the drug development, manufacturing and clinical applications. To this end, Qian et al. introduce tech- niques applicable for the detection of antibodies with an emphasis on methods suitable for illuminating the molecular dynamics to obtain more imperative information regarding their biological functions.

Meanwhile, the therapeutic outcome is also highly dependent on the status of drug targets. Fluorescence imaging can provide valuable information on the expression, distribution, and activity of drug targets. Hamachi et al. introduce two classic strategies for the visualization of drug target proteins: (1) enzymatically activatable probes with specific enzymatic transformations to produce a fluorogenic response upon reacting with target enzymes and (2) specific imaging conferred with a ligand that drives the probes to target proteins for specific fluorescence labeling. More detailed examples of fluorescent probes in the detection of tyrosinase, which is associated with several diseases including melanoma, are given by Li, Wu, and Du. This review may shed light on the design of more efficient and sensitive probes and inhibitors towards tyrosinase, a promising drug target of melanoma. Other than enzymes, the long-term fight between humans and exogenous biomolecules such as pathogenic bacteria has promoted extensive research on antibiotics. However, the mechanisms of bacterial infection, anti- biotic mode of action, and bacterial antimicrobial resistance remain to be answered. Xu and Li summarize the recent development of fluorescent antibiotics and their applications in tracking pathogenic bacteria to better understand their physiological processes.

In addition to the overview of molecular imaging in pharmaceutical analysis, there are five research articles/communications describing the latest methods developed for the detection of drug targets and their interactions with selected drugs. Receptors are key drug targets and disease biomarkers. Scott et al. synthesized novel small-molecule radiotracers for PET imaging of the receptor for advanced glycation endproducts (RAGE) for investigating the role of RAGE as a therapeutic target and an inflammatory biomarker. Not only the resulting radiotracers are useful for the detection of RAGE, but also the process of how to design and evaluate the probe is instructive to the future development of new PET radiotracers. Another rapidly expanding area in molecular imaging is the nanomaterial-based imaging system. Zhao and Liang re- ported a novel sensor to detect trypsin quantitatively using a purpose-designed fluorescein-labelled peptide with negatively charged carbon nanoparticles modified by acid oxidation, giving an example of the new detection tool facilitated with the “smart” materials.

Other than proteins, bioactive small molecules also play pivotal roles in homeostasis. Among them, hydrogen peroxide (H2O2), one of the major reactive oxygen species (ROS), plays a crucial role in cell growth, proliferation, apoptosis and signaling pathways. Sun and co-workers prepared a new pyrene-based fluorescent probe with improved photophysical properties to visualize exogenous and endogenous H2O2 in living cells for unmasking the biological roles of mitochondrial H2O2. Another small molecule, nitric oxide (NO), is a second messenger playing crucial roles in the signaling of a variety of cellular functions. To directly observe the pharmacological effects of various NO modulators in cells, a selective and sensitive fluorescence probe developed by Li et al. was applied in cell models directly. Their study highlights the value of chemical probes as valuable tools to reveal microenvironment-dependent pharmacological effects. Increasing attention has also been paid to the interaction between the drug and drug target to better understand the pharmaceutical effects as well as to guide medication decisions. Towards this, Ozkan et al. constructed an electrochemical DNA biosensor to investigate the interaction of indinavir with calf thymus double-stranded DNA in a straightforward manner for the first time. The results obtained can offer insights into the inhibitory activity of indinavir, which could help to broaden its potential applications to inhibit other viral diseases.

As described above, this special issue is a collection of the latest research focusing on molecular imaging for the study of drug, drug targets and their interaction. We thank all authors for their contributions, and hope wider applications of these strategies will be applied in pharmaceutical analysis together with more elegant work to be done in this area.