NEW IMAGING TECHNOLOGY

In 2003, Apple CEO Steve Jobs was getting a routine CT scan when his doctors discovered a tumor in his pancreas. Everyone feared the worst. Swift and deadly, pancreatic cancer snatches lives like a thief in the night. When a biopsy later revealed it was actually a neuroendocrine tumor, his physicians were actually relieved, Jobs later said.

Neuroendocrine tumors (NETs) are rare. Only about 12,000 people in the U.S. are diagnosed with this cancer each year. In medicine, you sometimes hear the expression, "When you hear hoof beats think horses not zebras," meaning rare disease are rare and it's the common diseases that doctors should expect to encounter. But what if this one time it is a zebra? NETs arise from hormone-producing cells in various organs. Some are slow-growing and often curable. But others can quietly enlarge and spread (metastasize) without immediately causing symptoms. So its essential to diagnose these "zebra diseases" as early as possible. Unfortunately, that was not the case with Steve Jobs.

If Jobs had been diagnosed in 2017 instead of 2003 its possible his story could have unfolded differently. Last year, a scan debuted that's significantly better at pinpointing, measuring and monitoring neuroendocrine tumors than any previous technique. It's caked Netspot.

Neuroendocrine Tumors

"Because (NetSpot) has a higher sensitivity for neuroendocrine tumors, you have a much better chance of finding an isolated tumor. This is a game changer for the patient," says Nishant Verma, M.D., a nuclear medicine specialty radiologist with Southwest Medical Imaging, one of the first practices in the Southwest to offer Netspot."

Until now, radiologists have had two scans in their arsenal for detecting neuroendocrine tumors, in addition to the CT scan. One is MIBG (metaiodobenzylguanidine), which yields low quality images. The other is the Octreoscan, which uses an agent called octreotide that binds to specific tumors and will "light up" the tumor when scanned. Both Octreoscan and MIBG can successfully identify different types of neuroendocrine tumors but do not always provide the detail required to make important disease management decisions, and both deliver a relatively high dose of radiation to the patient.

Netspot's masterstroke is to utilize a molecule called dotatate. This is a look alike for a hormone (somatostatin) that binds to receptors on NET call surfaces. Netspot piggybacks dotatate molecules with gallium-68, a safe radioactive tracer that can be detected and clearly visualized using PET (positron emission tomography) scans.

Typically, with a PET scan, the patient is injected with a small, safe amount of radioactive glucose as a tracer. PET imaging can then "see" where the tracer is going. All cells use glucose as an energy source and many cancer cells become glucose gobblers as they grow faster than normal healthy cells. The PET scan can then identify areas of the body that are consuming glucose at an abnormally high consuming glucose at an abnormally high rate and pinpoint the tumor. PET scans are very good at shining a searchlight on glucose-hungry tumors but the challenge with neuroendocrine tumors is they often don't consume much glucose. They do, however, have receptors for somatostatin. By replacing the glucose preparation with gallium-68 dotatate, Netspot allows radiologists to search for neuroendocrine tumors, and produce crisp, focused PET images. Radiologists can zoom down to the millimeter rather than to the centimeter which means Netspot can detect 30 percent more lesions than Octreoscan.

"You now have an agent that binds to the receptor in greater concentration, and you have an imaging technique that allows you to see smaller targets with a higher resolution," Verma says. "Combined, your chance of detecting disease goes up big time."

The imaging advancement is particularly striking if you compare Netspot to the MIBG scan, Verma says. "(MIBG Images) can look quite like a basic drawing, whereas images from this new scan look more like Michelangelo. MIBG was infamously known to be the ugliest, grainiest and poorest quality imaging we did in nuclear medicine. With this scan, they're crisp. Imagine image drawn with fine-tipped colored pencils rather than splotches of paint."

Unlike previous imaging techniques for neuroendocrine tumors, Netspot also importantly allows physicians to quantify how active the tumor is. Using the PET scan, radiologists can calculate the standard uptake value (SUV), to compare the amount of an agent injected into the patient and the amount taken up by the tumor. If doctors compute a baseline SUV and then discover that after treatment, the SUV has halved, they know the tumor's activity has lessened. That's an indication to treatment.

What's more, Netspot significantly improves the imaging experience for patients. The Octreoscan takes two days since patients have to be injected, then scanned four hours later and 24 hours later. Netspot takes 90 minutes total, and patients are on the scanner for only 30 minutes during that time. With Netspot, patients with suspected abdominal NETs don't have to endure a bowel cleansing beforehand. Plus, gallium-68 dotatate ernits a low dose of radiation, resulting in a safer procedure. "For the patient this is a much better study," Verma says. "It gives them less radiation and better answers."

Netspot is also a game changed when it comes to treatment strategy. Depending on the type of neuroendocrine tumor, some patients will exhibit, such as blood pressure problems, flushed skin, sweating and abdominal pain. But that essentially only indicates there is a needle somewhere in the haystack; it doesn't give doctors many clues as to where. And as "needles" go, NETS can be extremely difficult to find.

"With the old scans, if you couldn't find the disease, the only option the treating clinician has was to give the patient systematic therapy reaching cells all over the body (such as chemotherapy)," Verma explains. "But if you can identify the single site of a tumor, you may be able to operate or directly target that tumor with radiation."

Thanks to its ability to zero in on tumors, Netspot changed the way physicians treated and managed neuroendocrine cancer in 71 percent of patients, according to one study. Some patients considered inoperable went on to have surgery. Some avoided unnecessary operations or the grueling side effects of chemotherapy. Some were cured with simple, targeted treatments.

"Netspot gives you a significantly higher level of confidence that you've done whatever you can do to localize the tumors and given your patients the best chance of success," Verma says.