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1970s discovery makes bones ‘light up like a Christmas tree’

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John McAfee MD, chairman of radiology and radiological sciences, 1965-1989, and Robert Richardson PhD, associate professor of radiology,  in the nuclear medicine lab at Upstate University Hospital, circa 1970.

John McAfee MD, chairman of radiology and radiological sciences, 1965-1989, and Robert Richardson PhD, associate professor of radiology, 1970-2014, in the nuclear medicine lab at Upstate University Hospital, circa 1970.

If you’ve read or seen the teen romance, “The Fault in Our Stars,” you remember the moment that Gus tells his girlfriend about his cancer recurrence by explaining that he had had a bone scan that “lit up like a Christmas tree.”

Gus, who had osteosarcoma, was likely referring to a scan of his skeleton performed using technetium-99m-methylene diphosphonate (Tc99m-MDP), an imaging agent that was developed at Upstate Medical University in the 1970s and is still the agent of choice for many radiologists.

Gopal (Mani) Subramanian PhD (1937-2000),  assistant professor of radiology, 1970-2000

Gopal Subramanian PhD, assistant professor of radiology, 1970-2000

Two Upstate faculty members — John McAfee MD (1926-2008) and Gopal Subramanian PhD (1937-2000) — led the research that developed Tc99m-MDP, a short-lived radioactive material that is injected into a vein and absorbed by the bones. The bone metabolizes the agent and shows high- and low-concentrations of it, indicating tumors or lesions in the bone.

Tc99m-MDP proved better than other imaging agents because it moves quickly from blood  to bones, stays long enough for the nuclear medicine staff to get good images, and leaves the body quickly through the urinary tract, reducing the patient’s exposure to radiation.

Robert Richardson PhD and Marsha Roskopf, today

Robert Richardson PhD and Marsha Roskopf, today

Several Upstate employees and retirees — Robert Richardson PhD, Marsha Roskopf and Ted Duxbury – worked with Drs. McAfee and Subramanian in the 1970s.

Richardson and Roskopf explain the importance of this discovery: “At the time, it could find bone tumors six to 12 months before they could be seen on an x-ray.”

(A bone x-ray shows the anatomy of the bone, a nuclear medicine bone scan demonstrates function.)

Duxbury, retired chief technologist, describes nuclear medicine in the 1960s. “Bone imaging was in its infancy. Rectilinear scanners were slow and the images were inferior,” he explains. “Once the gamma camera came out, patients could be scanned using lower doses of radioactive material with better images. That’s when McAfee and Subramanian started researching technetium compounds.”

Roskopf, a 1973 graduate of Upstate’s College of Health Professions, was a research technologist in the lab of Drs. McAfee and Subramanian.

“The imaging agent (Tc99m-MDP) is injected and absorbed by the bones in two to three hours. MDP is the chemical that concentrates in the bone, Tc99m is the radioactive component,” explains Roskopf. “The patient is scanned with a gamma camera. Gamma rays from the skeleton are absorbed by a crystal in the camera, causing it to flash. Then,  through complicated electronics, a picture of the patient’s skeleton is created.”

David Feiglin MD, chairman of radiology and director of nuclear medicine, and Ted Duxbury, retired nuclear medicine chief technologist

David Feiglin MD, chairman of radiology and director of nuclear medicine, and Ted Duxbury, retired nuclear medicine chief technologist

How does the use of Tc99m-MDP and the gamma camera compare with other diagnostic tools available today?

Today, CTs and MRIs give the same information, reports David Feiglin MD, chairman of radiology and director of nuclear medicine. But, bone scans done with Tc99m-MDP show the entire skeleton and are easier, quicker, and less expensive to use. CTs provide images of particular areas of the body, and MRIs are time-consuming and costly.

However,  CT and MRI show information outside the skeleton that the Tc99m-MDP bone scan cannot.

“A Tc99m-MDP bone scan is one alternative,” says Feiglin, “and the best one in many instances.”

Top-tier equipment and dedicated staff remain the standard for radiology and nuclear medicine at Upstate.

“We have the best imaging equipment in the region, the best PET CT scanner,” notes Feiglin. “Patients would have to travel to New York City for the same quality.”

Feiglin leads a radiology staff of nearly 300, including 34 radiologists, three PhD medical physicists, 24 medical residents and scores of nurses and technicians.

Imaging services are available at five locations: the hospital’s community and downtown campuses, the Harrison Specialty Services Center, the Upstate Health Care Center and the new Upstate Cancer Center.

Feiglin is proud of his department and indebted to McAfee and Subramanian for their influence on the fields of nuclear medicine and radiology. “They were internationally renowned,” says Feiglin. “People came from all around the world to do fellowships with them at Upstate.”

Thank you,  Marsha Roskopf,  for sharing this history with the hospital’s 50th anniversary committee.

An update from Scott Macfarlane, director, Technology Transfer: Discovered in 1937, technetium-99m began to be used in medical imaging in the 1960s. Used in over 20 million diagnostic nuclear medical procedures each year, it is currently the most widely used radiotracer. McAfee and Subramanian’s innovation was to chemically attach technetium-99m to methylene-diphosphonate (MDP), a ligand known to be preferentially taken up by bone. Attached to MDP, the radiotracer is transported to bones where it concentrates in areas with increased physiological function, such as the site of a fracture or cancerous lesion, creating a radioactive “hot spot” which can easily be detected. Two patent applications were filed on behalf of SUNY and McAfee and Subramanian in 1971 and 1972, resulting in the issue of three patents covering: the technetium-99m-tin-methylene diphosphonate complex and how to make it (US 3,989,730); an aqueous solution containing the complex suitable for intravenous administration (US 4,032,625); and a method of using the solution for skeletal imaging (US 4,115,541).

A current bone scan done using Tc99m-MDP, an imaging agent developed at Upstate in the 1970s. Courtesy Department of Radiology, Division of Nuclear Medicine

A current bone scan done using Tc99m-MDP, an imaging agent developed at Upstate in the 1970s. Courtesy of the Department of Radiology, Division of Nuclear Medicine.

 

 

 



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