As yesterday’s lead molecule enters today’s clinical trial, the standard operating script seems to call for product developers and clinicians to push away the originating basic scientists, lest their lofty impractical ideals disrupt a delicate balance of strategic compromise. Indeed many scientists may not understand the competing push and pull of efficacy versus toxicity and quality versus production costs.
Imaging has long been indispensable in clinical practice, and researchers have for many years used the same toolbox of imaging modalities as a component of their preclinical and drug development work.
The recent high-profile translational failures in mouse models have highlighted the need for more relevant animal models. Advances in gene editing tools, including the CRISPR/Cas9 system, have enabled the modification of highly translational organisms such as rats and rabbits, and have also greatly reduced model development timelines.
It is now readily accepted that we are in a post genomic era. With the steady flow of genomic information available to researchers worldwide, the focus turns to ways to analyse this information effectively and then utilise it in a practical manner.
In vivo imaging of small animals (mainly mice) is increasingly being deployed across the drug development process, particularly in the oncology/cancer therapeutic area. One of the main applications is monitoring the treatment response for early indications of efficacy. The most used imaging modalities are currently optical (bioluminescence and fluorescence), magnetic resonance imaging (MRI) and positron emission tomography (PET). Single modality imaging predominates, with multi-modality currently accessed mainly through coregistration with other imaging modes. The most used imaging combination today is PET+CT (x-ray computed tomography). In vivo imaging is expected to have greatest impact in drug development through monitoring disease progression and therapeutic response in longitudinal studies. Bioluminescent markers/reporters (eg luciferins, proluciferins) and PET Tracers (eg Fluorine-18 based) were the most used reagents in imaging studies. Maximising the depth of tissue penetration is perceived as the main limitation associated with optical imaging. From vendor updates it is possible to make some general observations: more compact benchtop imaging systems are being developed to promote accessibility; multi-modality imaging combinations are increasingly being offered: higher spatial resolution imaging is expected to be realised on new imagers: a broader range of imaging and contrasting reagents is under development; imaging systems are heavily reliant on advanced software systems and algorithms for reconstruction of the 3D image and co-registration of multiple imaging modalities; and finally the industry as a whole appears to be focusing on translational research applications. In summary, in vivo preclinical imaging is poised to rapidly advance, such that the specification and capabilities of small animal imagers will soon exceed their clinical counterparts.
During the 20th century, medical research has observed enormous advances in basic science discovery, highlighted by the sequencing of the human genome. However, we have not witnessed a corresponding success in the widespread application of these advances into medical practice;