New Imaging Technology Shows Promise for Diagnosing and Treating Brain Tumors

The Bottom Line

• Scientists have designed a nanoprobe that targets cells of the most common type of human brain tumor, glioma.
• In laboratory and mouse studies, the nanoprobe was preferentially taken up by glioma cells, and it did not appear to cause any acute tissue toxicity or physical, neurologic, or behavioral adverse effects in mice.
• Using the nanoprobe, scientists were able to obtain enhanced magnetic resonance imaging (MRI) of glioma tumors growing in mice.

The Whole Story

Malignant glioma is the most common type of primary tumor of the brain and other central nervous system (CNS) tissue in humans. Approximately 16,000 new cases of malignant glioma are diagnosed each year in the United States, and patients with the most aggressive form of this tumor, glioblastoma multiforme, typically survive less than one year following diagnosis.

Surgery is a standard approach for treating malignant glioma, but complete removal of the tumor is often hindered by an inability to accurately locate tumor cells and distinguish them from normal brain cells. An improved ability to distinguish tumor tissue from normal tissue during surgery is likely to lead to improved patient outcomes.

Scientists are exploring the use of nanotechnology for imaging tumors. However, the usefulness of this technology in imaging has been limited by the fact that nanoparticle accumulation in tumor tissue has not been specific enough to optimally distinguish malignant tissue from normal tissue. To overcome this limitation, researchers created a nanoparticle, or nanoprobe, that specifically targets glioma cells and accumulates within them. The nanoprobe is composed of an iron oxide nanoparticle surrounded by a coat of the chemical polyethylene glycol (PEG) that is attached to a small protein-like toxin, chlorotoxin (CTX), originally obtained from scorpions. CTX specifically binds to glioma and a few other types of cancer cells.

Study findings included the following:

• The CTX-containing nanoprobe was readily taken up by rat glioma cells in vitro, whereas a nanoparticle coated with PEG but lacking CTX was not.
• The CTX-containing nanoprobe accumulated specifically and to a much greater extent in glioma tumors growing in mice than nanoparticles coated with PEG but lacking CTX; this specific accumulation allowed enhanced MRI images of the growing tumors to be obtained, with the border between tumor tissue and normal tissue clearly defined.
• The CTX-containing nanoprobe did not appear to cause any acute tissue toxicity or physical, neurologic, or behavioral adverse effects in mice.

Nanoprobes similar to the one used in this study may significantly improve the ability to distinguish brain and other types of tumor tissue from normal tissue and aid in earlier cancer detection, tumor staging, and surgical planning. They may also be used as platforms to specifically guide drugs, toxic biological agents, or radioactive substances to tumor cells, killing them while sparing normal cells. One of the major challenges ahead in using such nanoprobes to image or treat human brain tumors is that their access to some regions of brain tumors may be hindered by the blood-brain barrier, which protects the brain from potentially harmful substances.

Publication: Sun C, Veiseh O, Gunn J, et al. In vivo MRI detection of gliomas by chlorotoxin-conjugated superparamagnetic nanoprobes. Small 2008;4(3):372-379.