Laser ultrasound, radiopharmaceuticals show promising results

Columbia, Mo. - In recent years, the trend in nuclear medicine has been toward the development of tailor-made or receptor-specific carrier molecules that target specific organs or disease states.

At the University of Missouri - Columbia (MU), Yubin Miao, Ph.D., a research assistant professor of internal medicine, has been collaborating with Thomas P. Quinn, Ph.D., professor of biochemistry at MU in evaluating the use of radiopharmaceuticals to visualize and treat melanoma.

Research focus Their research has focused particularly on technetium-99m (Tc-99m) a widely used radionuclide that forms when another radionuclide, molybdenum-99 (99Mo), emits radioactivity. As 99Mo gradually disintegrates, Tc-99m is formed and has been found to bind easily to various carrier molecules, which target specific disease states and carry Tc-99m or other radionuclides to areas where imaging is desired.

"For imaging, we would anticipate a single IV injection of around 4 mCi of Tc-99m," Dr. Miao explains. "Our targeting peptide is based on a natural peptide hormone which shouldn't be too foreign to the body. Other groups have injected MSH peptide hormone analogs at high doses into humans with negligible or very minor side-effects."

Dr. Miao notes that this particular radiopharmaceutical targets only the MC1 receptor that is over-expressed in melanoma cells. Thus, it would only be useful for targeting cancers with MC1 over-expression.

"We have not looked to see if the MC1 receptor is over-expressed in other skin cancers, but it might be possible to use it with other types of deeper tumors if they express the MC1 receptor," he says.

Rhenium-188 Dr. Miao and his colleagues have also been exploring the potential use of another radiopharmaceutical, rhenium-188, (Re-188) for cancer treatment through the delivery of a toxic dose of radiation to cancer cells selectively and at close range. Re-188 is a desirable agent. It emits beta radiation that only penetrates locally.

"Re-188 has a maximum particle range of about 10 millimeters," Dr. Miao explains. "If we target Re-188 to a tumor via our peptide, it should produce a localized fairly homogenous radiation field at the tumor site resulting in tumor cell destruction with minimal normal organ damage."

Standard external beam radiotherapy is not applicable for the treatment of metastatic melanoma, but Re-188 is designed to target metastatic melanoma disseminated throughout the body. Dr. Miao says they are hopeful that use of Re-188, or radiopharmaceutical and chemotherapy combinations, will provide an effective treatment for metastatic melanoma.

Laser-induced ultrasound Ultrasound has been used for many years to visualize a variety of internal organs in the body. Other researchers at the University of Missouri - Columbia have been looking at laser-induced ultrasound to better evaluate skin lesions.

The premise behind it is that a fast laser pulse is directed at tissue, such as skin. The laser light is absorbed by melanin or hemoglobin, creating a rapid thermal expansion and a subsequent acoustic wave. These waves are then detected by a sensitive microphone and transformed into electric impulses that can be displayed as an image on a computer screen.

"At this point, the laser-induced technique won't specifically discriminate between malignant and normal cells," says John Viator, Ph.D., assistant professor of biological engineering at MU. "What it can do is give a more detailed subsurface image of the lesion itself."

Having this kind of image might sometimes remove the need for a biopsy. Dr. Viator notes that biopsy enables histological evaluation of the cells themselves, but "if one is otherwise convinced that the lesion is a melanoma, it is possible to look at the subsurface extent of it non-invasively and not have to do a biopsy."

While most of his work on the use of laser-induced ultrasound for melanoma is still at the laboratory stage, Dr. Viator says he has used it to look at vascular lesions in human subjects.