IR Determines the Effectiveness of Drugs

As the worldwide pharmaceutical market continues to grow, it requires more effective and quicker drug-testing methods in order to thrive. Thermal imaging may be the answer.

Thermogenic Imaging (Billerica, MA), a spinoff of FLIR Systems Inc. (Portland, OR) and GlaxoSmithKline PLC (GSK; Greenford, UK), has developed thermal-imaging technology designed to help streamline drug-discovery applications. An in-vivo version provides noninvasive, high-throughput screening of drug compounds in rodents. Another system, a fully automated 96-well microtiter plate reader, measures thermogenesis in cell culture. The company will eventually offer a portable system for investigatory human diagnostics.

“These systems could be quite useful,” says Brent Stockwell, principal investigator of molecular biology at the Whitehead Institute (Cambridge, MA). “One can do more experiments with the lab animals and drug compounds in less time than with traditional invasive technology.”

Temperature is directly related to disease, says Jay Tiech, CEO of Thermogenic Imaging. In the case of a tumor, for example, very tiny blood cells grow uncontrollably and feed the growth, which makes the tumor very hot. Temperature also is associated with the effectiveness of a drug. Cells produce heat as a byproduct of their metabolic activity. Cellular metabolism often changes as a result of receptor activation by a drug compound.

In the drug discovery process, researchers start with a protein that is found in a disease, says Stockwell. Then they try to find a small molecular drug that would inhibit the function of the protein in the test tube. “Usually you test hundreds of thousands of such molecules until you find the one that sufficiently inhibits the protein,” says Stockwell. At that point, the researcher must determine whether the candidate drug works in a cell or an animal, typically by developing a cell-based assay or injecting the compound into a mouse.

Thermogenic’s Mercury Wellplate reader measures thermal activity to determine how long and to what extent the cell may be affected by a drug. An automated compound delivery system deposits the experimental drug onto proprietary, note-sized wellplates containing cells. A robotic feeder moves the plates through the process. As the drug reacts with the cells, a gallium-arsenide quantum-well focal-plane-array detector reads the infrared (IR) radiation emitted by cells through an IR-transparent window on the bottom of each well. The refrigerator-sized instrument can measure thermal variations as small as 5 mK (0.005°C).

With a similar technique, the bench-sized animal reader images one to 10 animals in vivo. A heating pad under the holding pen warms the mice while a high-sensitivity IR camera takes an image. Simultaneous animal core temperature reading can be used as a correction factor.

“One can immediately see the rise in temperature as the drug reacts with the [sample/subject], then measure how long before it cools down as the drug wears off,” says Tiech.

The thermal-based process can speed up individual tests and allow a researcher to move more drug candidates through the process, says Stockwell. Considering how many candidates fail, it is important to process as many potential drugs as possible in the hopes that one will be the solution.

“There is the potential for hundreds of millions of dollars in this [IR testing] market,” says Skip Irving, managing director of Health Advances Inc. (Wellesley, MA). “We visit a company with one idea of how they might use the technology, and then they come up with six or seven others.”

( By Laurie Ann Toupin, OEMagazine, 2001, Jule)

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