Shining a Light on Efficacy and Safety
Safety Assessment
Aurore Varela

Shining a Light on Efficacy and Safety

Molecular imaging has long been a major player in clinical medicine. What about its utility in earlier phases of preclinical drug development?

Yesterday during one of the CE Courses at the SOT Annual Meeting that I co-chaired, the presentations by our speakers, Roger Lecomte, Scientific Head of the Molecular Imaging Center of Sherbrooke and Paul McCracken, Head of Medical Imaging at ICON, generated a lively discussion around the increasingly integral role advanced in vivo imaging is playing in the drug development process, specifically within the efficacy and safety phases. In vivo imaging techniques such as magnetic resonance, nuclear and tomographic have long played a major role in several areas of clinical medicine. Their role in the earlier phases of drug development is not as substantiated, but quite interesting given the potential for these techniques to considerably reduce program timelines and cost as well as contribute to 3Rs compliance. 

These non-invasive techniques provide data on the mechanisms of drug action or its toxicity. A large range of these modalities can be incorporated into discovery, efficacy and safety study designs including: optical (bioluminescence and fluorescence); ultrasound; X-ray technologies—radiography, computed tomography systems (e.g. CT, pQCT, micro-CT), and dual-energy X-ray absorptiometry (DEXA); magnetic resonance (MRI); positron emission tomography (PET); single photon emission computed tomography (SPECT). Coupled with pharmacokinetic modeling, molecular imaging allows quantitative in vivo monitoring of various physiological parameters (e.g. blood flow and blood oxygenation), various metabolisms (e.g. glucose, oxygen, lipid) and the quantification of specific disease or pathology biomarkers. Development of target-specific radioligands for PET allows for the quantification of target occupancy, biodistribution, toxicological and pharmacodynamics response. 

Imaging stands out as one of the most significant translational techniques to improve decision-making in the early phase of development to kill compounds that are destined to fail later on. It is still finding its footing in safety assessment, however several applications currently exist for cardiovascular, neurology, teratology, musculoskeletal and reproductive toxicity. These applications allow for the quantification of the same physiological parameters for both pharmacology and toxicology applications confirming the role of in vivo imaging as a translational biomarker for both efficacy and safety assessment.

At the conclusion of the CE course presentations, Roger and Paul fielded questions from the audience around how to incorporate these techniques into study designs and why consider them in the first place so it seems to me that our industry lacks awareness as to the benefits of incorporating imaging modalities into programs and more educational tools are needed. The future trends will certainly be in multimodality imaging, combining high sensitivity and molecular techniques with high spatial resolution and morphological techniques.

I am excited to see what happens in the next several years! Stay tuned!