
One of the most talked applications of molecular imaging is in the drug discovery and development field, as it can improve research practices and reduce overall research & development spending. According to the Pharmaceutical Research and Manufacturers of America, it takes between 10 to 15 years to bring a drug from concept to market, which reflects the greater complexity of target diseases, the longer and larger clinical trials required by the FDA, and the medical system’s growing demand for more complex data about new drugs. The cost of developing a new, novel drug is about US$802 million per drug – almost 6 times greater than what it was in 1975. The number of new drugs produced by the pharmaceutical industry has risen only modestly despite a six-fold increase in research spending to more than US$38 billion annually. The FDA has publicly stated, among its concerns, the need to speed and improve development and approval of new genetic and traditional drugs and medical devices. The regulating body recently issued guidelines permitting the use of innovative molecular imaging technologies to track drug "microdoses" in preclinical studies in order to allow pharmaceutical companies to enter into phase I faster.
By tagging a target molecule, antibody, gene or protein with fluorescent agents, scientists use optical imaging, an emerging modality of molecular imaging, to view a physiological process in a laboratory animal in vivo. For example, they can see how a potential new drug is absorbed, distributed, metabolized and excreted at the functional and molecular levels. Ultimately, optical molecular imaging could yield critical information previously unavailable to researchers, helping to expedite development of therapies and interventions. Standard practice is to sacrifice animals for tissue analysis or to take blood or urine at regular time points. This requires time-consuming analysis and extrapolation of in vitro data to make the data applicable to the in vivo situation. Since optical imaging is innocuous, molecular events can be detected and characterized in real-time, and perhaps more importantly, over time, in the same animal. Following a single animal over time allows researchers to accurately monitor the effects of interventions on disease progression and outcome. This ultimately results in a faster and less costly drug development cycle.
For the last few years, optical imaging techniques have been an essential instrument for molecular-based drug research and development. Optical imaging has become an indispensable aid in making new discoveries in molecular biology laboratories. In the 13 years since it was founded, Canada-based ART Advanced Research Technologies Inc. (ART) has become a worldwide supplier of optical molecular imaging products for the healthcare and pharmaceutical industries, developing an array of products in medical imaging, medical diagnostics, disease research, and drug discovery.
Although the company is also well known for its development of a breast imaging technology that aids in detecting and diagnosing breast cancer (SoftScan®), the in vivo animal imaging technology is what academia, pharmaceutical, biotech, and other companies involved in preclinical research, are keenly interested in. The pre-clinical optical molecular imager, called eXplore Optix™, allows the user to map biodistribution and pharmacokinetics parameters using fluorescent intensity, absorption and fluorescent lifetime.
In late 2003, ART introduced the first generation of eXplore Optix, a single-wavelength system. At the end of 2004, the next generation system, a multi-wavelength small animal imaging device was introduced, allowing researchers to select up to 4 lasers, at the wavelengths that specifically fit their needs. The wavelengths give the user the ability to perform different types of experiments, with different fluorescence probes commercially available, that emit at different wavelengths.
The eXplore Optix can be configured with picosecond-pulsed lasers, emitting in either the blue part of the spectrum or the near-infrared range, to excite fluorescence compounds within living animals. Fluorescence photons are collected by a photomultiplier tube coupled to a time-correlated photon-counting system.
Other optical molecular imaging systems, based on the continuous wave (CW) technique, measure all of the photons that propagate through tissue without any temporal discrimination. eXplore Optix unique time-domain optical technology offers the user the unique capability to determine the relative concentration and depth of the emission, and to establish where it is coming from within the animal. Only ART’s technology is capable of measuring the fluorescence lifetime of the injected fluorescence probes, which is an indication of the biochemical environment of that injected agent. For example, an injected agent will display a different fluorescence lifetime in a diseased area in comparison to a healthy area.
In regards to the future, ART is developing several hardware and software enhancements to the system, including basic and advanced software and a brand range of targeted applications, taking advantage of the unique features associated with the eXplore Optix time-domain optical imaging technology. In addition, the company intends to play an instrumental role in facilitating the use of microCT as an increasingly important component of both basic research and commercial drug development through the commercialization of Fenestra™ VC and LC as superior contrast molecular imaging agents in numerous vascular and hepatobiliary applications.