Lizard saliva may help detect a rare pancreatic tumor

A molecule in lizard saliva may make it easier to find some tumors in the pancreas.

Insulinomas – benign tumors that can cause low blood sugar and sudden fainting spells – are notoriously difficult to detect using current scanning methods. But using a modified variant of a protein found in the saliva of the Gila monster as a radioactive tracer, a new type of PET scan found tumors in 95 percent of confirmed cases, researchers reported in October. Journal of Nuclear Medicine. PET scans now used to detect such tumors had only a 65 percent success rate, the team found.

One of the main functions of the pancreas is to produce insulin, a hormone that keeps blood sugar levels under control (SN: 22.10.24). The task of producing this insulin belongs to specialized cells called beta cells. But sometimes these cells malfunction and form insulinomas. These tumors are rare, affecting only 1 to 4 people in a million a year globally, but debilitating for those who have them.

“Many of [these tumors] they are benign, very small and very efficient insulin factories. They can cause you to have low blood sugar, which can make you pass out or have a seizure,” says Peter Choyke, a radiologist at the National Cancer Institute in Bethesda, Md. “Even when they are very small, it is very urgent to get the diagnosis quickly and accurately so that a surgeon can go in knowing exactly where the tumor is and remove exactly that.”

If doctors manage to find the tumors, surgically removing them cures patients and lets them live a normal life. But finding insulinomas is difficult. Current methods of finding them include CT and MRI scans as well as PET scans that are used to find malignant tumors of the pancreas, but they cannot always detect the much smaller insulinomas. In a PET scan, doctors inject radioactive molecules into patients. The molecules build up in specific places in the body, such as in cancers, so analyzing their radiation can give doctors a three-dimensional picture of cancer cells.SN: 18.4.22).

“If [they] he didn’t know where [the tumor] so surgeons cut the pancreas until they found it,” says Martin Gotthardt, a nuclear medicine researcher at the Radboud University Medical Center in Nijmegen, the Netherlands. “In the event that an insulinoma cannot be detected nowadays, [the patients] are not operated, because [doctors] I don’t want to remove the whole pancreas.”

Enter the Gila Monster (Suspicious heloderma), a lizard found in the deserts of the US Southwest. A protein found in her saliva, called exendin-4, is produced in the laboratory and used to treat diabetes.SN: 8/12/03). It can bind to and activate pancreatic receptors called GLP1Rs, prompting them to produce more insulin. Shortly after its success with the treatment of diabetes, Gotthardt and other scientists realized in the mid-2000s that insulinomas, usually a cluster of many beta cells, also contain a high amount of GLP1Rs, making exendin-4 an attractive candidate. to help localize these pesky tumors. .

Early studies showed that exendin-4 with a radioactive molecule attached could be used in PET scans to detect insulinomas in humans, but injecting high amounts caused some side effects, such as nausea, headaches and even decreased blood sugar. In the current study, Gotthardt and his team added another molecule to help further stabilize the radioactive exendin-4. This ensured that even low amounts of modified exendin-4 showed high radioactivity; doctors could inject less of it into patients, thus leading to fewer adverse effects.

To test their new tracker, the researchers recruited 69 people who had been biochemically diagnosed as having low blood sugar due to excess insulin. Each underwent all the standard imaging tests, as well as the new exendin-4 PET scan, which led to 53 individuals undergoing surgery to remove suspected tumors. Of those 53 confirmed cases, the tumor showed up in 50 of the exendin-4 PET scans, compared to just 35 of the standard PET scans. In seven cases, exendin-4 scans revealed insulinomas while standard PET, CT, and MRI imaging revealed nothing.

Exendin-4 was also very good at capturing insulinomas alone on the scan, with less background noise compared to currently used PET scans and had fewer side effects in patients compared to previous versions of the exendin-4 radiotracer.

“I think [this] The work is very valuable in showing how exendin-4 can be used in the diagnosis of insulinoma and possibly replace many of the imaging techniques currently used that are not as good,” says Choyke.

Gotthardt and his team are now focused on helping other labs and hospitals deploy this technique. “We just want to spread the technology,” he says. “Everyone should be able to use it because it really helps patients.”