About nuclear medicine therapy

How Lutathera attacks neuroendocrine tumors

Neuroendocrine tumors, or NETs, are a rare type of tumor that can grow anywhere in the body. But the most common sites they occur are in the pancreas or other areas of the gastrointestinal system, such as the small bowel or rectum. Unfortunately, this type of cancer has limited treatment options after initial therapy fails.

However, a new and unique type of treatment may offer patients new hope. Lutathera, the first FDA-approved peptide receptor radionuclide therapy, or PRRT, allows for precision targeting of NETs cells.

Lutathera consists mainly of two parts — a radionuclide, or radioactive component, that emits beta-particles, and a tumor targeting component that can bind to specific receptors on NETs cells. NETs cells express a certain type of peptide receptor on their surface known as a somatostatin receptor, SSTR. Somatostatin receptors are present in very high numbers on neuroendocrine tumor cells, while normal cells express very few.

Lutathera is designed to specifically target somatostatin receptors, which allows for precise drug delivery. Once bound to the receptor, Lutathera is actively transported into the tumor cell. Here, Lutathera emits highly ionizing beta-particle radiation. Beta-particle emissions induce both single- and double-stranded DNA breaks within tumor cells. This causes cellular damage, ultimately leading to tumor death. In this way, Lutathera reduces tumor progression while increasing overall patient progression-free survival.

Nuclear medicine therapy is an approach to treating cancer that might be used with or after other treatment options, such as chemotherapy and surgery. It won't usually lead to a cure unless combined with other therapies. But for many people it will control symptoms and shrink and stabilize the tumors, sometimes for years. Nuclear medicine therapy is sometimes the best option for people who no longer respond to other treatments.

What makes nuclear medicine therapy effective is the use of radioactive molecules as a drug (molecular radiotherapy). The drug recognizes tumor cells. It's injected intravenously, then circulates in the body, sticks to the tumor cells, delivers radiation directly and causes them to die. Some of the drug never attaches to cancer cells and keeps floating in the blood until the body gets rid of it, mostly in the urine. Over time, the radioactive drug stops giving off radioactivity and stops killing cancer cells. Nuclear medicine therapy is often repeated multiple times to achieve the most benefit.

Nuclear medicine therapy is also called peptide receptor radionuclide therapy (PRRT), targeted radiotherapy, radionuclide therapy, therapeutic nuclear medicine and a theranostic approach to treating cancer.

People with neuroendocrine tumors (NETs), including rare pancreatic NETs, now have wider access to PRRT following the January 2018 U.S. Food and Drug Administration (FDA) approval of lutetium Lu 177 dotatate (Lutathera). This is an important option, as NETs can be widespread throughout the body and hard to remove with surgery.

What you can expect

Once you have a diagnosis and you and your care team have decided that nuclear medicine therapy is the best option for you, you'll be scheduled for treatment. It may take up to a month before you can start therapy while blood and imaging tests are completed, your medications are modified, and therapy is prepared. Usually therapy involves up to four infusion sessions, each usually eight weeks apart.

The treatments are given in an outpatient setting. Plan to be on-site for up to eight hours each time. When you arrive, you'll be cared for by a skilled team of specialists who provide safe and efficient therapy.

Before you start therapy, you're given medications to reduce nausea. Then a small tube (catheter) is inserted into an arm vein through which an amino acid solution drips in. This solution helps protect your kidneys. It flows for about 30 minutes before you start receiving the medication designed to target and kill cancer cells (Lutathera).

Lutathera flows into your vein for 30 to 40 minutes. Then you'll continue receiving the amino acid solution for about 3 hours. Soon after the catheter is removed, you'll be able to leave the hospital.

Care at Mayo Clinic for neuroendocrine tumors

It started suddenly, no sign anything was amiss, just some itching and rashes developing on both of Jay Elston's legs. A trip to his primary care physician in 2012 led to an initial diagnosis of hepatitis, a prescription for antibiotics, and a recommendation to call again if Jay were not feeling better in a few days.

In three days, I couldn't keep anything down. I'd lost 40 pounds in a week. And he said, just go to the ER.

This led to more tests, including a CT scan and the location of a tumor on his pancreas, either adenocarcinoma or neuroendocrine, and a decision of where to go next.

It was too rare what I had. They gave me three choices. The business I was in before, I had dealings with people in Dodge Center, so I knew people up here. And I thought, I'll go to Mayo, because if I get in trouble, I know people up there that can help my wife.

A biopsy at Mayo Clinic in Rochester revealed that Jay had a neuroendocrine tumor in his pancreas.

Neuroendocrine tumors are really a collection of tumors that can arise anywhere, essentially, in the body. But they behave very differently from one person to the next.

The tumor's presentation in patients is so unique that some will experience diarrhea or pain from the tumors, while others will have no symptoms, and the tumors are discovered during an imaging exam for something else. Some tumors are slow growing. Others are aggressive. Neuroendocrine tumors can secrete hormones, which are the source of many of the symptoms patients experience.

They are still a big enigma. And therefore the most common ones, the small bowel neuroendocrine tumors, we really don't have a good understanding why people get them.

Treatment options vary as well, with surgery, chemotherapy, and nuclear medicine therapy among other options. With his diagnosis, Jay had clarity from the beginning.

I was here to fight it from the beginning. And that's what I intend on doing. I want to see my kids graduate. I want to walk my daughter down the aisle. I intend on staying around for a long time.

And it has been a battle. A multidisciplinary team comprising medical oncology, gastroenterology, pulmonary medicine, surgery, radiology, especially nuclear medicine, and pathology has supported Jay through each around.

The care plan never changes, where other places you get a new doctor, they've got a different idea. They decided from the beginning what they were going to do. And that's the same plan that we've carried out through the whole seven years.

Jay's medical oncology team started him on chemotherapy, which shrank the cancer and gave him two years without issues. And then the cancer had spread to his liver. This time, chemotherapy was not effective in bringing his neuroendocrine tumors in check. And another option was needed.

PRRT is a therapy using a radioactive compound that sticks to the neurons and tumor cells. There are three components to it. There is what's called a somatostatin analog, which binds to the receptors of the tumor cells. And then there is a therapeutic radionuclides, or radioactive molecules, which is therapeutic. And then there is almost like a glue that binds these things together. So we inject this into a vein. It circulates around to the body. And it sticks to the tumor cells that express these somatostatin receptors. And then this radiation molecule sits right on the tumor cell and kills the tumor cells with radiation.

The Division of Nuclear Medicine, part of the Department of Radiology uses PET imaging with gallium ga 68 dotatate to locate neuroendocrine tumors and determine whether a patient will respond to lutetium dotatate. Patients receive four doses, each eight weeks apart, with checkups about a month after each infusion. For most patients, improvement in symptom management comes after the second dose. For Jay, the effects of this new treatment were almost immediate.

Doctor Halfdanarson told me before I got the first treatment, don't expect immediate results. It usually takes two rounds before we see anything. Within three or four days, the diarrhea stopped. It had shocked the tumor enough. It quit producing that hormone. And within a week, I was back to normal. It was just amazing.

I think what's absolutely remarkable about his story is the huge improvement in his quality of life. He went from being in and out of the hospital, more days in the hospital than not, because of severe diarrhea and electrolyte abnormalities to being able to do the things that he wanted. So that was really kind of exciting to see somebody have such a big impact following just his first treatment.

It's been a great experience. And when I was in the hospital in Joplin with all this, there was a patient in there. And one of the nurses asked me if I would go talk to him about Mayo. I said, I'll be happy. I'm happy to talk to anybody about Mayo. My family knows that. They probably get tired of hearing about it. Everything runs so much different here than it does at home. And it's just an amazing place.

Tailoring nuclear medicine therapy to you

No two people experience cancer or respond to treatment in the same way. For most people, symptom improvement comes after the second dose. Your care team considers many factors when prescribing your nuclear medicine therapy and adjusts it over time.

After each infusion session, you may be asked to undergo a SPECT scan. This scan measures how much nuclear medicine therapy stuck to the cancer cells and how fast the drug is leaving your body. This information guides your care team members as they choose when and how much therapy to give you to kill the cancer and avoid side effects.

After you have completed your therapy, your doctor will ask that you return regularly for follow-up visits, which may include more blood tests and scans.

Possible side effects

Side effects can occur, and they depend on your specific therapy and medical condition. It used to be common for people to experience nausea when receiving nuclear medicine therapy, but that has become far less of an issue. Many people even enjoy eating during therapy. Some people notice hair loss, but it's usually only a little and the hair grows back.

Rarely, someone who has had nuclear medicine therapy might develop a cancer of the blood months or even years later.

Note also that traveling after Lutathera treatment might result in travel delays. Talk with your doctor about the advantages and risks of this treatment.

Your care team will answer any questions before you begin therapy. Learning about nuclear medicine therapy

Talk with your care team about what to expect before, during and after treatment, which is usually administered in up to four outpatient visits.

Deciding whether nuclear medicine therapy is right for you

Your nuclear medicine care team considers many factors before prescribing this type of therapy for you. You'll likely undergo a positron emission tomography (PET) scan to help determine whether nuclear medicine therapy is right for you and your cancer.

When a PET scan is needed, a version of the drug that will later be used for nuclear medicine therapy is injected into a vein. The drug floats around in the blood. If the drug bumps into cancer cells, it sticks. However, this version of the drug does not kill cells. Instead, it gives off only a very small amount of radioactivity.

The radioactivity is detected by the PET scanner, which turns this information into a 3D image of the entire body that can show where cancer is hiding. The PET scan can show if the drug sticks to the cancer as expected. In this way doctors use a PET scan to test if someone might be a good candidate for nuclear medicine therapy.

Other treatment options

Mayo Clinic doctors will work with you to review all of your treatment options and choose the treatment that suits your needs and goals. Nuclear medicine therapy is usually given by itself, but it can be combined with other therapies delivered by medical oncologists, radiation oncologists or interventional radiologists:

Nuclear medicine therapy is available at three Mayo Clinic locations

Most people are referred to the team of specialists in nuclear medicine therapy by one of their doctors. Talk with your doctor about whether your condition makes this treatment a good choice for you. Eligibility for this therapy depends on many factors related to the tumor and your overall health.

You may be seen at any one of the clinic's main campuses in Phoenix/Scottsdale, Arizona; Jacksonville, Florida; and Rochester, Minnesota. Each campus has the expertise and technology required to guide you through nuclear medicine therapy. Each location has cyclotrons, PET radiochemistry laboratories and nuclear radiopharmacies, all of which are needed to properly handle nuclear medicine therapy and produce the drugs for PET and SPECT imaging. Each campus also has state-of-the-art scanners, including PET/CT, PET/MRI and SPECT/CT.

Cyclotrons are particle accelerators that create radioactive atoms (radionuclides). These atoms then are linked to drugs and checked for quality and safety per FDA regulations. These drugs are made fresh specifically for the people coming to the clinic that day.

April 28, 2022