Cedars-Sinai Medical Center

medical staff pulse newsletter

Text size: A A A
A BI-WEEKLY PUBLICATION FROM THE CEDARS-SINAI CHIEF OF STAFF March 28, 2014 | Archived Issues

Meetings and Events


Grand Rounds

Click here to view upcoming grand rounds.


Upcoming CME Conferences

Click below to view a complete list of all scheduled Continuing Medical Education conferences.

CME Newsletter - March 2014 (PDF)


Milestones

Do you know of a significant event in the life of a medical staff member? Please let us know, and we'll post these milestones in Medical Staff Pulse. Also, feel free to submit comments on milestones, and we'll post the comments in the next issue. Click here to email us your milestones and comments.

» Read more

Share Your News

Won any awards or had an article accepted for publication? Share your news about professional achievements and other items of interest.

Click here to share your news

Scorpion Venom, Laser Help Illuminate Tumors

Tumor tissue in the brain of a laboratory mouse glows bluish-green after an injection of Tumor Paint BLZ-100 and illumination by a camera designed and developed at Cedars-Sinai. At left is a composite of visible light and near-infrared fluorescence. At right is the fluorescence alone. The camera is pictured below.

Researchers at the Cedars-Sinai Maxine Dunitz Neurosurgical Institute and Department of Neurosurgery have developed a unique, compact, relatively inexpensive imaging device to "light up" malignant brain tumors and other cancers.

The experimental system consists of a special camera designed and developed at Cedars-Sinai and a new, targeted imaging agent based on a synthetic version of a small protein — a peptide — found in the venom of the deathstalker scorpion. The imaging agent, Tumor Paint BLZ-100, a product of Blaze Bioscience Inc., homes in on brain tumor cells. When stimulated by a laser in the near-infrared part of the spectrum, it emits a glow that is invisible to the eye but can be captured by the camera.

Results of animal studies, published as the feature article in the February issue of Neurosurgical Focus, provide the basis for the launch of human clinical trials. The system would be used during surgery to determine if it enables neurosurgeons to remove more tumor and spare more healthy tissue.

Malignant brain tumors called gliomas are among the most lethal tumors, with patients typically surviving about 15 months after diagnosis. "We know that survival statistics increase if we can remove all of a tumor, but it is impossible to visualize with the naked eye where tumor stops and brain tissue starts, and current imaging systems don't provide a definitive view," said Keith Black, MD, chair and professor of the Department of Neurosurgery, the article's senior author.

"Gliomas have tentacles that invade normal tissue and present big challenges for neurosurgeons: Taking out too much normal brain tissue can have catastrophic consequences, but stopping short of total removal gives remaining cancer cells a head start on growing back. That's why we have worked to develop imaging systems that will provide a clear distinction — during surgery — between diseased tissue and normal brain," said Black, director of the Maxine Dunitz Neurosurgical Institute, director of the Johnnie L. Cochran Jr. Brain Tumor Center and the Ruth and Lawrence Harvey Chair in Neuroscience.

In studies in laboratory mice with implanted human brain tumors, the new device clearly delineated tumor tissue from normal brain tissue. Also, with near-infrared light's ability to penetrate deep into the tissue, the system identified tumors that had migrated away from the main tumor and otherwise would have evaded detection.

Pramod Butte, MBBS, PhD, research scientist and assistant professor in the Department of Neurosurgery, the article's first author, said the tumor-imaging process consists of two parts: deploying a fluorescent "dye" that sticks only to cancer cells, and using a laser and a special camera to make an invisible image visible.

To get the dye to the tumor, it is linked to a peptide called chlorotoxin, which despite its name is not toxic. It ignores normal tissue but seeks out and binds to a variety of malignant tumor cells. It first was derived from the venom of the yellow Israeli scorpion, also called the deathstalker. Article co-author Adam Mamelak, MD, professor of neurosurgery and director of functional neurosurgery, has studied the synthetic version of chlorotoxin and its tumor-targeting properties for more than a decade.

In this study, chlorotoxin was bonded to a molecule, indocyanine green, a near-infrared dye, a version of which is approved by the Food and Drug Administration. The chlorotoxin-indocyanine green combination — Tumor Paint BLZ-100 — emits a glow when stimulated by near-infrared light.

"Injected intravenously, the chlorotoxin seeks out the brain tumor, carrying with it indocyanine green, which has been used in a variety of medical imaging applications. When we shine a near-infrared laser on the tissue, the tumor glows. But the glow emitted by the tumor is invisible to the human eye," said Butte, whose MBBS is India's equivalent of an MD. The camera device, designed in Butte's lab, solves this problem by capturing two images and combining them on a high-definition monitor.

Authors of the article besides Butte, Mamelak and Black are Julia Parrish-Novak, PhD, Doniel Drazin, MD, Faris Shweikeh, BS, Pallavi R. Gangalum, PhD, Alexandra Chesnokova, MD, and Julia Y. Ljubimova, MD, PhD.

Stacy Hansen and Disha Sahetya from Blaze Bioscience Inc., Seattle, provided the BLZ-100 samples.

The study was internally funded by the Cedars-Sinai Department of Neurosurgery. Mamelak has ownership in Teal Light Surgical. Parrish-Novak is an employee of Blaze Bioscience Inc.

An editorial accompanying the article can be found here.