Unusual Compound Seeks and Destroys Cancerous Tumors
MADISON — Imagine a compound that can both detect and treat nearly 50 different kinds of cancerous tumors, irradiating them from the inside out.
Researchers at the University of Wisconsin-Madison need not imagine. Following highly promising studies in animals, UW scientists will begin a clinical trial of this extremely unusual "seek and destroy" compound this summer.
"We call this compound a 'diapeutic,'" says Jamey Weichert, a professor of radiology at the UW School of Medicine and Public Health. "It is one of only a handful of such dual-purpose compounds known to exist."
Imaging studies in animals have shown that the unusual compound, now called CLR1404, works on at least 45 different kinds of solid tumors, including those that have spread, or metastasized, to other parts of the body.
The research shows that only cancerous tumors take up and retain CLR1404 following IV injection. And when scientists attached a therapeutic radioisotope to the compound, they saw anti-tumor activity in breast, prostate, ovarian, pancreatic, kidney, colon and certain types of brain and skin cancers.
"CLR1404 selectively localizes in malignant tumor cells and then radiates them from the inside until the tumor cells die," says Weichert. "But noncancerous cells and tissues clear the compound, if they take it up at all."
Weichert doesn't know yet exactly how or why this happens, but he suspects it has something to do with the way normal cells change into malignant cells.
"Our hypothesis is that this compound becomes trapped in tumor cell membranes because the tumor cells can't metabolize and eliminate it," says Weichert, a member of the UW Carbone Cancer Center (UWCCC).
Weichert and his collaborators have begun sophisticated experiments to understand the unique targeting and retention mechanisms.
Weichert brought the compound from laboratories at the University of Michigan when he came to UW in 1998. Once on the Madison campus, he quickly began working with UWCCC investigators, including several at the McArdle Laboratory for Cancer Research. The collaborations showed that the compound could locate and eradicate tumors in rodents, restoring cancer-ridden animals to good health.
The animal imaging studies wouldn't have been possible without a special small-scale, super-high-resolution scanner that combines two technologies: CT (computed tomography) and PET (positron emission tomography). Manufactured by Siemens with much input from UW medical physicists, the scanners are now in use at about 100 research institutions. But UW retains the first.
"The images from this hybrid micro-CT/micro-PET scanner are phenomenal," says Weichert, who also has an appointment in the medical physics department. "When we inject a live cancer-inflicted mouse with CLR1404, we can vividly see how the compound moves through the body and comes to rest in the tumor."
This tumor-seeking movement was also demonstrated by UWCCC oncologists in a physician-sponsored trial involving patients with non-small-cell lung cancer. The drug was safely administered to the volunteers, and images confirmed CLR1404's unique tumor uptake and retention capabilities. Additional PET/CT imaging studies involving lung, pancreatic and prostate cancer patients are now being planned by the university.
In 2002, Weichert formed a local company, Cellectar, to carry out additional work on the compound, including more clinical trials in humans. Cellectar, which owns the licensing rights to CLR1404, will take the drug through the Food and Drug Administration regulatory approval process. Cellectar's own trials in humans are set to begin in the second quarter of the year.
Weichert is extremely hopeful about CLR1404's clinical potential. In addition to its ability to seek and destroy hard-to-treat metastasized tumors, the compound should also be useful for determining how far the initial cancer has progressed and how well the tumor responds to treatment.
Date Published: 03/04/2009