Sharper imaging sheds light on hidden tumors

March 13th, 2017
Jeanne and John Lambert with dogs Mollie and Ollie outside Colorado Youth Outdoors’ Swift Ponds recreation center in Fort Collins.

Jeanne Lambert was given at most five years to live in 2004. In 2017, a new imaging approach at UCHealth promises to help keep her neuroendocrine cancer in check into the future.

That approach involves mainstay hardware – a positron emission tomography/computed tomography (PET/CT) scanner – and a radiopharmaceutical called Gallium-68 dotatate. Ga 68 dotatate lets nuclear medicine physicians see more, smaller neuroendocrine tumors than has been possible with previous imaging agents. Ga 68 dotatate, trade name Netspot, won U.S. Food and Drug Administration approval in June 2016; UCHealth University of Colorado Hospital (UCH) scanned the first of about a dozen patients so far starting in January.

Lambert, now 73, was a perianesthesia care unit nurse at what’s now UCHealth General Surgery in Fort Collins when a combination of symptoms including fatigue, breathing problems, hot flashes, confusion, randomly fluctuating blood pressure and, finally, an acute rectal bleed sent her to UCHealth Poudre Valley Hospital.  Such a hodgepodge of symptoms, which combine into something called carcinoid syndrome, is common with neuroendocrine cancers. The tumors, called carcinoids, pour serotonin and other hormones into the body, disrupting the delicate biochemical equilibrium our bodies work so hard to sustain for our blithe enjoyment.

She had surgery to remove a two-centimeter tumor from the small intestine; some of the intestine and neighboring colon went with it. A second surgery excised three large tumors from her liver and zapped four smaller ones with a radiofrequency ablation.  She started taking monthly injections of Sandostatin LAR hormone analog to help alleviate her carcinoid syndrome as well to tackle hundreds of tiny tumors found on the surface of her liver. It worked. By the next year, Lambert and her husband John were spearheading the Fort Collins Run For Hope to raise awareness of carcinoids and funds for cancer research. Through a lecture series associated with the event, she met Tom Purcell, MD, MBA, executive director of Cancer Services for University of Colorado Hospital and the CU School of Medicine medical oncologist.

Relapse

In September 2016, Lambert started wheezing and coughing. She didn’t run a fever, she said, but “it felt like I should be a TB patient in a sanatorium.”

Tom Purcell, MD, MBA, during a neuroendocrine multidisciplinary clinic.

For three months she took the steroids and antibiotics her doctor prescribed, and then remembered back to 2004: “All those years ago, I had been diagnosed mistakenly with adult-onset asthma,” Lambert said.

She reached out to Purcell, who quickly scheduled her in the University of Colorado Cancer Center’s neuroendocrine multidisciplinary clinic.

“There is no other multidisciplinary program in the region that brings specialists and experts in neuroendocrine tumors to the table,” said Purcell.

An MRI showed no carcinoids. The next step was a PET/CT scan, and the timing was good:  use of Ga-68 dotatate radioactivity  had required additional state approvals by the Colorado Department of Public Health and Environment. But by January, it was ready to go.

Jennifer Kwak, MD, a University of Colorado Cancer Center nuclear medicine specialist, did Lambert’s PET/CT scan early that month. She explained how Ga-68 dotatate works.

Cancer experts have known that carcinoid tumor cells have a lot of receptors for somatostatin, a hormone that regulates the endocrine system. The mainstay approach has been to do an indium-111 octreotide scan. In-111 octreotide binds to somatostatin receptors and emits radiation detected by PET/CT. Ga 68 dotatate does the same thing, but the new compound binds with much greater affinity to somatostatin receptors, which greatly increases the detection sensitivity for neuroendocrine tumors that overexpress somatostatin receptors, Kwak said.

A big fringe benefit for patients is that In-111 octreotide must be injected a day before imaging; Ga 68 dotatate is injected just an hour beforehand.

Jennifer Kwak, MD, has been using Ga 68 for UCHealth neuroendocrine cancer patients since it became available in January.

“So it’s more like a two-hour process rather than two days,” Kwak said.

Lambert’s Ga 68 dotatate PET/CT scan showed two “tiny” possible carcinoids in the liver, Lambert said. They’re small enough that Purcell suggested they watch and wait. “I’m not a good sitting-around-and-waiting type, but it’s a little hard to do a biopsy intraoperatively if it’s just a tiny amount showing up,” she said. So they’ll do another Ga 68 scan six months after the first.

Tackling tumors

Soon, Kwak said, Lambert and other patients will have access to a Ga 68 dotatate treatment counterpart that binds to the tumor and kills the tumor with radiation. The idea is to inject an agent similar to Ga 68 dotatate – one that binds to somatostatin receptors – but which also emits cell-pounding beta radiation. Such a compound exists and is already approved in Europe: Lutetium-177 dotatate. Patients undergo a Ga 68 dotatate scan first to confirm the presence of carcinoids with somatostatin binding sites, then receive Lu-177 dotatate to attack the tumors. Also known as peptide receptor radionuclide therapy (PRRT), it’s a great example of both the concept of “theranostics” (therapeutics + diagnostics) and, more generally, of the precision medicine that’s become a driving force in cancer care.

Kwak said she expects the FDA to approve Lu-177 dotatate sometime this year, and in the meantime, Purcell is working to bring it to UCHealth sooner through the agency’s compassionate use program.

Lambert may or may not need it. Either way, this new Ga 68 dotatate scan has given the grandmother of eight peace of mind and a path forward.

“It’s finally here, and it’s our hope,” she said, adding that, until Ga 68 and its ability to image tumors previously unseen, hope was all she and others with neuroendocrine tumors had. “I’m so thrilled it’s there for all of us.”