Jefferson-Based Technology Promises to Help Find Hard-to-Diagnose Appendicitis Cases

About half of the 700,000 annual cases of suspected appendicitis in the United States lack the usual symptoms – pain in the lower right abdomen, fever and a rising white blood cell count – making the decision to operate somewhat problematic. Now, thanks to a new imaging agent based on technology developed by nuclear medicine researchers at Thomas Jefferson University in Philadelphia, doctors may finally have a way to rapidly and accurately detect those hard-to-diagnose cases.

The U.S. Food and Drug Administration has approved NeutroSpec, a monoclonal antibody that binds to a type of infection-fighting white blood cell, for use in patients five years and older who have inconclusive symptoms of appendicitis.

NeutroSpec is “radiolabeled,” meaning it carries technetium, a radioactive substance. When injected into the blood, NeutroSpec finds and binds to a certain receptor on neutrophils, white blood cells that the body uses to fight infection. Doctors can then locate the antibody and the infection site by using a device called a gamma camera. In case of hard to diagnose cases, the gamma camera pictures allow doctors to accurately see if the appendix is infected or not and permits them to treat the cause appropriately.

“NeutroSpec is easy, quick and reliable – and has no known risk,” says Mathew Thakur, Ph.D., professor of radiology and radiation oncology and director of radiopharmaceutical research at Jefferson Medical College of Thomas Jefferson University, who holds a patent on the antibody and who invented and patented the antibody radiolabeling process.

In 1976, Dr. Thakur, then at the Medical Research Council at Hammersmith Hospital in London, and his colleagues invented a procedure that allowed nuclear medicine physicians and scientists to label such infection fighting blood cells for the first time outside the patient’s body. The procedure continues to be used routinely around the world to find unknown infections in the body, he says.

But labeling cells outside the body is “lengthy, cumbersome and requires technical skills,” says Dr.Thakur. It poses potential risk in handling blood as well as accidentally injecting a blood product into another patient with infection, and requires 24 hours to get accurate results after the labeled cells are injected back into the patient.

Neutrospec, which labels the cells inside the patient’s body, also provides results in less than one hour. During clinical trials, NeutroSpec accurately detected appendicitis 60 percent of the time in less than 5 minutes after injection and nearly 100 percent of appendicitis cases were diagnosed within an hour. “This is a tremendous advantage to the management of patients’ condition,” says Dr.Thakur, who began his research on NeutroSpec in 1984 and did the first clinical feasibility study in 1991.

Dr. Thakur says the new technique will have broad applications. Approximately 15 percent to 30 percent of all appendectomies are unnecessary because the appendix is actually normal. Neutrospec, in helping physicians rapidly and accurately diagnose appendicitis in cases without straightforward symptoms can reduce the number of unneeded surgeries.

“The radiolabeled antibody will enable physicians to pinpoint infections in a number of tissue types,” he says. “It could also be used for patients who have fevers of unknown origin, bone infections (osteomyelitis) and diabetic foot infections.”

NeutroSpec will be marketed by Mallinckrodt Imaging, a business unit of Tyco Healthcare, a global medical products company. Jefferson previously licensed its patents to Palatin Technologies, Inc., of Cranbury, N.J., which subsequently entered into a marketing and distribution agreement with Mallinckrodt. The original antibody was obtained from the Wistar Institute in Philadelphia.