Sanofi imaging cancer drug 'sensors'
assess how its cancer drugs affect organisms at the molecular
The experiments are carried out at the pharma heavyweight's dedicated oncology imaging centre near Paris. Sanofi says the fact that a whole building is designed for imaging within one therapeutic category is unique, and enabled its oncologists to have a say in the design. Imaging is a particularly powerful tool within drug discovery because, often, the same tools are used all the way from discovery to development (in clinical trials) to point of care. However, the techniques are commonly used to assess anatomical changes, such as the size of a tumour, which compared to molecular changes, is a very slow process. In a visit to Sanofi's R&D site in Vitry, Chantal Carrez, head of the company's molecular imaging team, explained to DrugResearcher.com that if imaging is used to track protein 'sensors', the effect of a drug can be seen within few minutes as opposed to days or weeks for physical changes. Researchers at the site are using different imaging techniques all across the electromagnetic spectrum: from ultrasound to positron emission tomography (PET), through optical (using properties such as bioluminescence), X-ray computed tomography (CT) and single photon emission CT. Only magnetic resonance imaging (MRI) is missing. All of those techniques are used in drug discovery in animal models and drug development in humans, except for optical imaging which is only used in the former. Previously the size of a tumour might be measured using callipers, although this has an obvious drawback if the tumour is not accessible and also it clearly cannot track metastasis. Carrez explained that, using imaging, the disease can be tracked prior to the occurrence of anatomical changes. Also, the same animals can be used at each stage of the disease and so less are used per trial. Taking imaging one step further is the concept of targeted imaging. Here, a tracking molecule is 'tagged' in order to measure how a given drug causes protein expression levels to change. For example, if a ligand to a membrane receptor is tagged, the levels of that protein can be monitored. What tag is used depends on which imaging technique the scientist wishes to use, for example, using luminescent tags for optical imagery or a positron emitter for PET scans. Using vascular disrupting agents as an example, Carrez explained that this class of drug changed the structure of epithelial cells such that blood vessels become leaky. Proteins can then leak out of the blood vessel and it is thought the increased pressure surrounding the vessel causes it to collapse. When delivered to a tumour, these molecular events can be observed within about five minutes Carrez said, whereas anatomical effects would take much longer to observe. However, when asked if the system could also be used to study the safety of the drug, Carrez admitted that currently Sanofi were only studying efficacy and mechanism. She did say it was theoretically possible though and might become more commonplace in several years.