A non-invasive way to detect the exact location of very small life-threatening tumors in the pancreas (insulinomas) has been discovered by a team of researchers in Switzerland. This new technique will help surgeons to successfully remove the tumors that can be less than 1 centimeter in diameter.

Professor Emanuel Christ, a clinical researcher in the Department of Endocrinology at the University Hospital of Bern, Switzerland, presented the study findings at the joint International Congress of Endocrinology/European Congress of Endocrinology on May 7, 2012.

According to Prof. Christ, current conventional imaging procedures make it difficult to identify insulinomas, therefore making it hard for surgeons to remove them. However, the researchers discovered that the insulinomas could be targeted with a radioactively labelled drug, as they had high densities of a particular type of receptor on their cell surfaces.

The researchers were able to locate the precise location of the tumors, even when they were around 1 centimeter in diameter, by scanning patients with a 2-D/3-D imaging technique called Single Photon Emission Computed Tomography (SPECT) combined with conventional computerized tomography (CT) scan. By using these two scanning techniques, the team was able to identify where the drug had attached to insulinoma cells.

Prof. Christ explained:

“These data suggest that it’s possible to detect very small, life-threatening insulinomas within the pancreas, based on the characteristic receptors on the surface of these tumors.

This technique avoids the more invasive test to localize the insulinomas and facilitates the surgical approach. Surgery is still the only method of curing this particular disease.”

Insulinomas occur in about 2 to 4 people per 1 million individuals each year. Insulinomas are pancreatic tumors derived from beta cells. They are known as secreting neuroendocrine tumors (NET) as they secrete insulin. However, they secrete insulin in an unregulated way, causing blood sugar levels to drop lower than normal.

Prof. Christ said:

“In the majority of cases these tumors are benign, but they are life-threatening because they can lead to severe hypoglycemia – low blood glucose.

In contrast to other NETs, insulinomas do not exhibit receptors for a hormone called somatostatin in sufficient number and density to enable them to be detected by the well-established Octreoscan – a method of scanning that targets somatostatin receptors in NETs.

However, they do have high numbers and density of another receptor for a hormone called glucagon-like peptide-1 (GLP-1). In collaboration with researchers in basic science and radiochemistry, we have developed a compound that successfully targets the GLP-1 receptors in humans – a radioactively labelled drug called 111In-exendin-4, and which can be detected using SPECT/CT.”

The researchers enrolled 30 patients to participate in the study. Each participant was injected with the drug and then scanned after 30 minutes, 4 hours, 23 hours, 96 hours and up to 168 hours after the injections.

According to the researchers, 4 and 23 hours after the injection were the most vital time points. Convention imaging detected the tumors in 17 participants where as SPECT imaging with 111In-exendin-4 correctly detected 23 benign insulinomas, two islets hyperplasia (groups of proliferating cells), two uncharacterized lesions, and one malignant insulinoma. There were no false negative results.

Furthermore, the team found that the techniques also identified another malignant insulinoma as well as an islets hyperplasia – which were important clinically, as they also suggested over-production of insulin.

According to the researchers, the test correctly identified 85% of positive results and and correctly identified 100% of patients without the disease.

After the tumors were surgically removed, pathologists examined the tissues and confirmed the diagnosis.

Prof. Christ explains:

“This suggests that when clinical and biochemical tests have proved that unregulated over-production of insulin is occurring, but there is a lack of evidence for insulinomas using MRI, CT or endosonography, then GLP-1 receptor imaging could replace the more invasive approach in this situation.”

In order to detect small insulinomas, doctors currently need to perform an invasive procedure called arterial stimulation with venous sampling (ASVS). ASVS involves inserting catheters into the patient’s arteries and veins that are located around the pancreas, after which the doctor injects calcium gluconate into the arteries that supply the pancreas, before taking samples from veins to test for insulin.

The team now plans to determine whether positron emission tomography (PET), another 2-D/3-D nuclear medical imagine technique, could further enhance the quality of tumor localization.

Written By Grace Rattue