Preclinical imaging is rapidly becoming a standard technology for drug discovery and development. This adoption has been driven by the increasing pressure on pharmaceutical companies to identify ways to reduce costs, increase safety and efficacy, and minimize side effects.
Preclinical imaging technologies, when used appropriately in the right stage of the drug discovery process, can contribute significantly to efficiency gains by identifying failures early, providing safety and efficacy data based upon in vivo results, gathering insight into long-term effects using small animals with much shorter life spans, and minimizing the number of animals used by virtue of being able to perform longitudinal studies.
Although a number of imaging modalities are commonly used, technologies that utilize radioactive tracers such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) have found widespread acceptance due to high sensitivity, excellent spatial resolution, and the ability to perform dynamic studies. Hybrid technologies that incorporate computed tomography (CT) have also become a standard component of preclinical imaging studies.
The Inveon® family of imaging systems from Siemens encompasses PET, SPECT, and CT technologies (Figure 1). The Inveon preclinical imaging systems also include Inveon Acquisition Workplace (IAW) and Inveon Research Workplace (IRW) software solutions.
Preclinical Imaging Workflow
Recent imaging advances have helped to speed up both basic preclinical research and drug discovery research. As for any transformational technology, however, it is important to incorporate this technology into the existing workflow with minimal disruption. An understanding of the preclinical imaging application workflow is critical to this process. This workflow can be broken down into two stages (Figure 2). Stage 1 can be further divided into three distinct steps, primarily focusing on image acquisition and reconstruction of acquired data.
• Plan—The details of the image acquisition and reconstruction protocols are set up depending on the technology that is used, which, in turn, dictates the experimental workflow.
• Acquire—The experimental subject is placed on the scanner bed and image data is acquired. In a PET or SPECT study, the gamma photons emanating from the radiotracer injected into the subject are detected along with positional information. In the case of a CT study, the x-ray source emits a beam that transverses the subject. The attenuated photons are detected by the detector and the intensity and positional information are stored.
• Reconstruct—The stored data is then reconstructed to form a 3-D image volume, with several different choices of reconstruction algorithms. Reconstruction methods vary depending on the specifics of the data that were acquired.
Stage 2 can also be divided into three distinct steps, primarily dealing with visualization of images and quantitative analysis of regions of interest.
• Visualize—Reconstructed images from a single subject acquired over several days or multiple experimental subjects may be viewed simultaneously to identify any changes and regions that require further quantitative analysis. Data that was processed into dynamic and gated or gated-dynamic image volumes can also be viewed.
•Analyze—Regions of interest that are identified from the previous step can be subjected to quantitative statistical analysis including calculating the mean activity value, volume, and surface area for a region. Additionally, time-activity curves can be generated to track the pharmacodynamics of radiotracers and to perform pharmacokinetic modeling as required.
• Distribute—Finally, the data can be exported to several formats for archiving and future analysis. It is also possible to create movie files from dynamic and gated image data, generate graphs, and capture specific images for distribution or storage.
A typical preclinical imaging experiment in drug discovery applications involves multiple studies in parallel utilizing several experimental subjects. The compounded effect of the time invested could easily impact the overall efficiency gains and cost advantages despite the overarching benefits of this technology.