When developing an innovative medicine, you need to be able to assure regulators, investors and commercial partners that it goes where you say it does, and does only what it is supposed to do.  

Biodistribution, cell penetration, localisation and target efficacy are essential information for the development of novel, unprecedented medicines. Advanced molecular imaging technologies enable in-depth analysis and a mechanistic understanding of each of these steps in the molecule's journey to the clinic. 

Using translatable imaging techniques, progressing from cells into tissues and whole-body settings, can provide consistent, interpretable information for predicting dosage, efficacy and safety in patients. Robust, decision-making information is critical for clinical development and investment decisions.

For seeing where a new molecule goes within a relevant animal model, nuclear imaging techniques are key. These rely on detection of radioactive nuclides that emit either positrons (in PET) or gamma ray photons (in SPECT). Small-animal PET and SPECT offer high depth of penetration through tissues, and sensitivity that make them highly suited to studies of  pharmacokinetics, whole-body biodistribution, and target-site accumulation.

A limitation of nuclear imaging techniques is that their spatial resolution is limited to micron-mm, limiting for detailed interpretation of biological action. For this, complementary imaging techniques can be applied to acquire information at higher spatial, and temporal scale of resolution. Intravital microscopy -  imaging of live animals at microscopic resolution - is a powerful way to reveal the dynamic interactions between drug molecules and cells. Also, mass spectrometry imaging enables multiplexed analysis of the distribution of drugs, nanomedicines, and endogenous lipids and proteins, in ex vivo tissue sections.

To really study detailed molecular interactions, high resolution fluorescence imaging of 2D and 3D cell cultures remains a key approach. STORM super-resolution imaging, for example, has been used to elucidate the entry routes of complex molecules into cells and sites where they bind intracellularly. 

At present, not all of these imaging methods are widely implemented in drug discovery pipelines. But, they are moving fast, and ongoing technical improvements in these technologies will likely make them more accessible, faster, cheaper, and simpler to implement. This should enable a greater understanding of the dynamic interactions of novel medicines with cells tissues and organs, supporting confident translation of great new ideas into marketed medicines. 

Acknowledging the debt due to insights from my former colleagues in MDC, who contributed so much to https://doi.org/10.1016/j.drudis.2022.03.001