Importance of quantitative local imaging in drug discovery for diversified therapeutic modalities

<p>Global research and development of “new drug modalities” (e.g., antibodies, nucleic acids, genes) is growing rapidly. Additionally, drug-delivery systems (DDS), such as mRNA vaccines for COVID-19, have been employed to enhance drug stability and targeted delivery, leading to safer and more potent drugs.</p><p>In pharmacokinetics, systemic drug concentration is commonly used to assess PKPD (pharmacokinetics-pharmacodynamics) or TKTD (toxicokinetics-toxicodynamics). However, the unique characteristics of new drug modalities, like large molecular size and hydrophilicity, often make systemic concentration an inaccurate reflection of the concentration at the site of action, since these drugs are typically distributed heterogeneously and present in trace amounts within tissues. Additionally, the DDS type applied can affect the tissue distribution. Thus, the concentration information obtained by homogenizing tissue extraction does not always reflect the true PKPD/TKTD. It is thus crucial to develop quantitative methodologies for evaluating drug localization in microenvironments.</p><p>Immunohistochemistry (IHC) is widely used to visualize biomarker/drug localization within the body. However, challenges of sensitivity and quantification remain when evaluating the dynamics of new drug modalities that often exhibit biased and trace amounts of tissue localization. In my presentation, I will highlight the importance of quantitative local imaging for new drug modalities, and introduce case studies on Quanticell^®, an ultra-sensitive and quantitative IHC technique.</p>