Researchers in the Cancer Center of Albert Einstein College of Medicine of Yeshiva University have received a five-year, $10-million grant renewal from the National Cancer Institute (NCI) to study how cancer cells spread, or metastasize. Understanding this process is crucial, since most of the 553,000 U.S. cancer deaths each year are caused by complications from the spread of cancer to distant tissues and organs, rather than from the primary tumor itself.

John S. Condeelis, Ph.D.In previous research funded by NCI (part of the National Institutes of Health), Einstein researchers demonstrated that immune system scavenger cells called macrophages play an important role in how cancer is spread. The research team determined that these macrophages enhance the ability of tumor cells to move and to invade tissues.

Here's how the process works: macrophages cluster along blood vessels that feed a tumor. These clusters emit chemical signals that make it easier for tumor cells to enter the blood vessels, a process called intravasation. Once in the bloodstream, tumor cells are able to travel to sites throughout the body.

"The contribution of intravasation to metastasis has not been clear, and this has led many researchers to look elsewhere for potential therapeutic interventions," says the principal investigator, Dr. John Condeelis, co-chair and professor of anatomy and structural biology. "Our findings have completely turned this around"

The discoveries were made possible by an imaging technology called intravital multiphoton microscopy. Developed by Dr. Condeelis and colleagues, this technology allows researchers to capture high-resolution, three-dimensional moving images revealing the behavior of individual cells deep within living tissues.

In the study's current phase, Einstein cancer researchers aim to identify the subtypes of macrophages involved in metastasis and to clarify how each of these cell types affect the development of blood vessels (angiogenesis), the movement of cancer cells into the bloodstream (intravasation), and the movement of cancer cells from blood vessels into organs (extravasation).

The researchers also hope to define various factors and biochemical pathways that regulate the spread of cancer cells at the molecular level. In addition, they will evaluate biomarkers — identified in earlier studies — for their ability to predict outcomes in human breast cancer.

The research has important implications for therapy. According to Dr. Condeelis, treatments that prolong life and improve quality of life of cancer patients will probably depend on a combination of therapies — those that minimize the growth of existing tumors and others that limit their spread to new sites. To develop the latter, researchers will need a detailed understanding of the basic steps of metastasis — the ultimate goal of this research. From Blurry To Razor-Sharp: 25 Years Of Advances In Nuclear Medicine Celebrated This Week In the early 1980s when a doctor suspected a patient had heart disease or cancer, the ability to provide an accurate diagnosis through nuclear imaging was limited. It was still a relatively young and undeveloped specialty. Today, high-tech nuclear medicine equipment including next-generation PET/CT scans is allowing physicians to see the tiniest metabolic details to evaluate tumor images, monitor blood flow and evaluate metabolic functions associated with dozens of diseases. A PET/CT scan is an imaging test that combines positron emission tomography (PET) and computed tomography (CT) techniques.

Cardiac imaging 2007Strides in the field of nuclear medicine, both in the United States and globally, have corresponded to and benefited from the growth of the Department of Nuclear Medicine at Albert Einstein College of Medicine and Montefiore Medical Center. It is the only department-level program among medical schools and their academic medical center partners in New York City and today is celebrating its 25th year. To commemorate the anniversary, the department is holding a four-day symposium to highlight its achievements.

"Nuclear medicine has played an increasingly important role in collaborating with other specialties, such as radiation oncology, to diagnose and treat cancer and other diseases and engage in studies that lead to a better understanding of these diseases," said Steven M. Safyer, M.D., President and CEO, Montefiore Medical Center, where endocrinologist Dr. Sam Seidlin first used radioactive iodine to treat thyroid cancer in the 1940s. "It is the synergy of technology and expertise between departments, and between Montefiore and Einstein, that is producing so many advances in patient care now."

"We have a lot to celebrate," said M. Donald Blaufox, M.D., Ph.D., chairman of the department at Einstein and Montefiore since its inception in 1982. "Advances in technology over the past two and half decades have vastly improved our ability to diagnose and treat brain and heart diseases, cancer and an array of other serious illnesses," he said. "Recent findings by our researchers have produced innovative approaches to treating melanoma and potentially identifying Alzheimer's disease at an earlier stage."

Nuclear Medicine's Role in Identifying Alzheimer's and Treating Melanoma
Nuclear medicine faculty in 1997While diagnostic scanning, including the use of gamma cameras and SPECT (single photon emission computed tomography) technology has become routine, one of the newest areas of nuclear medicine utilized at Einstein involves an advanced form of PET/CT, called "time of flight," considered far more accurate than traditional PET/CT scans.

At Einstein beta testing of time of flight technology is ongoing to distinguish Alzheimer's disease from healthy brain aging. Working with Bayer HealthCare, Einstein researchers are testing a molecular imaging agent, known as BAY 94-9172, that targets amyloid plaques in the brain. "Amyloid plaques are hallmarks of Alzheimer's which, until now, could only be detected under a microscope after one had passed away. This research could lead to earlier and more accurate diagnosis of the disease," said Joshua R. Steinerman, M.D., assistant professor of neurology and associate director of the Einstein-Montefiore Brain Aging Center.

In collaboration with Arturo Casadevall, M.D., Ph.D., chair and Forchheimer Professor of Microbiology & Immunology, Ekaterina Dadachova, Ph.D., associate professor of nuclear medicine and microbiology & immunology, identified a potential new treatment for melanoma.

"In animal models, Einstein researchers developed a way to deliver lethal radiation to melanoma cancer cells. The antibody molecule armed with radioactive isotope 188-Rhenium binds to free melanin in the cells and destroys cancer cells by bombarding them with radiation emitted by 188-Rhenium," said Dr. Dadachova. This novel approach has cured melanoma in mice and proved safe in human phase 1 clinical trials. Phase 2 clinical trials are in preparation.

From Humble Beginnings to Powerhouse

Einstein and Montefiore's Department of Nuclear Medicine began as a division of the Department of Radiology in 1966, when it had a faculty of two who Nuclear medicine faculty in 2008primarily performed brain, liver and spleen scans using rectilinear scanners. Today, the department is one of the largest, busiest and most successful patient-focused nuclear medicine programs in the tri-state region, with 12 full-time faculty. The Department of Nuclear Medicine is affiliated with a network of diagnostic centers through Montefiore Medical Center and the Albert Einstein College of Medicine. Every year, the center at Montefiore performs about 24,000 nuclear medicine tests — including over 6,000 cardiac scans, 4,000 bone scans, 3,000 lung scans and 3,000 PET scans.

The department includes a radiochemist and a physicist who are interested in the practice of academic medicine. "This diversity and depth of expertise is unique in the metro region and fosters a high degree of excellence," said Dr. Blaufox. "The 12 faculty members discuss cases on a daily basis, attend tumor boards and conferences in other departments and help to coordinate the results as a team." The department's faculty has also helped to set the standard of medical care in nuclear medicine. For the past 40 years, Dr. Blaufox, along with Dr. Leonard M. Freeman, M.D., vice chair, nuclear medicine at Einstein and Montefiore, has edited Seminars in Nuclear Medicine, the most respected international review journal in the field.

How Nuclear Medicine Has Changed
Dr. Blaufox recalls that in 1982, when the department was formed, there were no clinical PET scans. "PET technology has been the biggest breakthrough in the past decade because it allows us to view metabolic functions in the body's tissues," said Dr. Blaufox. "In traditional staging for lymphoma, using CT alone, we could see that various lymph nodes were enlarged, but that enlargement could be for many reasons — an inflammation not caused by cancer cells, for example. Today, we inject a patient with radioactive glucose and, using a PET scan, we can see if there is an increase in glucose uptake in the node, Brain PET/CT 2007which indicates it is cancerous. And after chemotherapy and radiotherapy, we can see if the treatment was a success by observing if the glucose uptake has slowed."

Dr. Blaufox continues to marvel at how much technology in nuclear medicine has changed. "In 1982, newly invented renography allowed us to measure the function of each kidney. It was revolutionary. In 2008, we can actually look at the metabolism of the kidney, see how it works and determine what is wrong when it is diseased," he said. What does the future hold? "In the next 25 years, we will see a host of new diagnostic agents emerge for routine use. No organ of the body will be invisible to us. We will be able to observe the function of virtually every organ within the body and detect disease when it is so early that cure will be possible."