Nuclear medicine combines radioactive drugs and special features of neuroendocrine tumors (NETs) into a powerful way of spotting disease. As therapy, it can also provide tumor control and long periods of symptom relief. These treatments include metaiodobenzylguanidine (MIBG) therapy and peptide receptor radionuclide therapy (PRRT).
At Penn Medicine, we’re leaders in this evolving field. We led national trials for both forms of approved nuclear medicine therapy. We’re also thoughtful about who receives this type of therapy and when. We consider not just what you need in the moment, but what you could need in the coming months and years.
What Is Nuclear Medicine for Neuroendocrine Tumors?
Nuclear medicine is important for NET care, as both a detailed imaging technology and a form of treatment. It can:
- Provide a level of detail other imaging can’t, gauge the extent of disease, identify more aggressive tumors and watch for the return of cancer
- Deliver radiation treatment across the body, aimed solely at cancerous cells to minimize side effects
- Relieve symptoms and slow or stop tumor growth
Our nuclear medicine imaging and therapy come in a range of forms. Each kind involves a radiopharmaceutical which is a special drug combining two main parts:
- Molecule we expect tumors to take into their cells, providing a way to target them
- Isotope, or radionuclide, the form of an element giving off radiation
For imaging, we detect signals from the radiation with special scanners, pinpointing the location of cancer cells. For treatment, the radiation starts destroying cancerous cells. Imaging involves lower doses of radiation than treatment.
We use a range of radiopharmaceuticals with different targeting molecules and isotopes, depending on the circumstances. We typically give the drugs to your whole body, usually through injection but sometimes by pill.
Peptide Receptor Radionuclide Therapy (PRRT)
PRRT is a newer, promising way to treat certain cancerous NETs that have spread. We often wait to recommend it until other treatments such as surgery for NETs or liver-directed therapy have been tried or ruled out. But we may consider it sooner in some cases.
We led clinical trials gaining PRRT approval for gastrointestinal (GI) NETs and pancreatic NETs. We can also safely use PRRT for some lung NETs. Pheochromocytomas and paragangliomas (pheo-paras) currently have separate nuclear medicine therapy but are sometimes treated with PRRT.
Other key aspects of PRRT include:
- How it works: PRRT relies on receptors in many NET tumors that attach to the hormone somatostatin. By creating molecules called peptides based on somatostatin, drug makers provide a path into tumor cells. They add a radionuclide for treatment. Current PRRT combines DOTATATE — a peptide and binding agent — with the radionuclide lutetium-177 (Lu-177). The brand name is Lutathera. Future PRRT could try other components.
- Who it’s for: PPRT works best for tumors whose cells still look fairly normal, or well-differentiated. Before pursuing PRRT, we perform a nuclear medicine scan involving DOTATATE and isotopes with less radiation. This imaging determines if the tumors have enough somatostatin receptors.
- Where it fits into treatment: PRRT can affect the ability of bone marrow (spongy tissue inside bones) to make blood cells. Other NET therapies given to the whole body can as well, such as chemotherapy. It’s important to consider when to use PRRT and how it may relate to other treatments you may need in the future.
- How we give it: We give PRRT over four treatments, each eight weeks apart. Before treatment, we adjust any use of somatostatin analogs, a type of drug therapy for NETs. Each PRRT visit last about five hours. Besides the injection, we flush residual radiation to protect the kidneys and control nausea with medication. You typically leave the hospital that day, with basic steps at home for a few days to keep others safe from radiation.
- How tumors respond: It can take several months to see the full effect of PPRT. If you have a NET that could respond to PRRT but acts more aggressively, we may recommend other therapy first.
- Possible side effects: Many people tolerate PRRT well. But it can cause moderate side effects during therapy. You may experience fatigue, as well as nausea and vomiting from medications protecting the kidneys. Longer term, people may see blood counts fall, sometimes severely. PRRT may also damage the liver or pose a risk for other cancers down the line. We watch for these possibilities and always consider future health.
Repeating PPRT Treatment
With successful PRRT, people may not need treatment again for several years, particularly for GI NETs. Sometimes, the disease progresses again in isolated spots, which we can treat with surgery, radiation therapy or ablation (heating or freezing).
Eventually, we can pursue PRRT again if it worked well the first time, though follow-up treatments may not be as long-lasting as it was the first time. We can also consider other treatment, such as a different nuclear medicine therapy, other systemic therapy or a NET clinical trial. We evaluate how long your response lasted and how aggressive the disease is. We also think about any side effects experienced and longer-term risk to the liver, kidneys and blood cells.
Future of PRRT
Researchers continue to look for ways to make PRRT work for a greater number of tumors, achieve longer responses and cause fewer side effects. In addition to different molecules, we might pair PRRT with other therapies or give it after treatment aimed at making it more effective. We could also personalize doses.
MIBG Therapy for Neuroendocrine Tumors
We can use metaiodobenzylguanidine, or MIBG, to image and treat certain NETs that release the hormone norepinephrine (noradrenaline).
Many of these tumors quickly reabsorb some of the released hormones, providing an opening to the use of nuclear medicine. Most pheochromocytomas and paragangliomas contain this pathway. A number of GI NETS also do, as well as a smaller percentage of pancreatic and lung NETs.
MIBG was created in the lab to mimic noradrenaline and get drawn into tumors. For treatment, we attach the isotope iodine 131, or I-131. We led the clinical trials that secured approval for I-131 therapy for pheo-paras, under the brand name Azedra.
For imaging, we pair MIBG with a different iodine isotope, I-123. MIBG scans can show how far the disease has spread. They’re also needed before treatment, to see if tumors will take up MIBG.
Other notable aspects of MIBG therapy include:
- How it works: Unlike with PRRT, we need to individualize MIBG doses for safety. During planning, we give you a small dose, then watch with imaging over several days. We see where radiation goes and how quickly it clears out, making sure any organs don’t receive too much radiation. We adjust the dose based on the results.
- How we give it: We give MIBG therapy via intravenous (IV) injection, most commonly with two doses spread at least 90 days apart. We use medication to block the thyroid gland from taking in the radioactive iodine and do follow-up scans. For each treatment, you typically spend several days in a special hospital room because of the radioactivity, though in some cases it’s possible to receive injections in an outpatient setting. You then take basic precautions at home for several more days.
- How tumors respond: Like PRRT, it takes several months to see the full effect of treatment.
- Possible side effects: Most people tolerate MIBG therapy fairly well. But it can cause dry mouth, as well as nausea and vomiting at higher doses. People may also experience salivary gland inflammation soon after treatment and a drop in blood cell levels in the weeks to come. Rarely, people who have MIBG therapy develop future thyroid problems. They may also face a risk of eventually developing another cancer.
Y-90 to Treat Liver Metastases
Another form of nuclear medicine delivers radiation directly into NET metastases in the liver. This treatment, radioembolization with yttrium-90 (Y-90), can shrink tumors.
Learn more about liver-directed therapy for neuroendocrine tumors.
Nuclear Medicine Imaging for NETs
Properly imaging NETs relies on a range of tools. Standard MRI and CT over the course of your care lets us see changes in tumor size. But nuclear medicine scans can provide greater detail, helping to identify as much disease as possible at diagnosis, including small NETs. The scans can also check for cancer spread over time.
The two types of imaging complement each other; CT or MRI is often added to nuclear imaging to show surrounding anatomy. At Penn, we have the experience to know what imaging to choose for each need. We also have the expertise to interpret the nuances between different forms. You receive a personalized plan for evaluation and monitoring.
Our nuclear imaging includes:
- FDG PET: This scan is the main type of positron emission tomography (PET) given for a range of cancers. It looks for injected fludeoxyglucose (FDG), a radioactive molecule that acts like the sugar, glucose. Many common cancers pull in glucose for energy, so they readily absorb FDG. NETs tend not to behave this way, since they usually grow slowly and don’t need much glucose. Occasionally, though, NETs take a more aggressive form and do take up FDG. We use this metabolism scan to look for more aggressive tumors or rule them out.
- DOTATATE PET: This form of PET is the gold standard for NET imaging. It uses the same peptide as PRRT, so can find a wider range of NETs than FDG PET. It highlights receptors for the hormone somatostatin by working with isotopes of the metals copper (Cu-64) or gallium (Ga-68). DOTATATE PET provides greater detail and less radiation than a previous test, OctreoScan (pentetreotide plus indium 111). It also takes less than 30 minutes of scan time; the scan starts about an hour after injection. Given the differences between FDG PET and its high contrast, DOTATATE PET requires specialized interpretation expertise.
- MIBG: We may use this imaging for paraganglioma and pheochromocytoma and, less commonly, for other NETs. It works similarly to treatment planning for MIBG therapy. Findings on MIBG imaging can be subtle and require excellent equipment and expert interpretations, both of which we provide.
Why Choose the Abramson Cancer Center’s Nuclear Medicine for NETs?
Not only are neuroendocrine tumors uncommon, they’re also complex. Nuclear medicine provides an effective option for imaging and treating these challenging tumors, but it’s a very technical field, and one that’s constantly evolving.
Our team provides leading nuclear medicine care for NETs. When you come to our program, you’ll find:
- Expertise and experience: PRRT and MIBG provide powerful treatment tools, but timing is key — you don’t want to turn to the therapies too soon, or too late. Our team understands how NETs behave and how these treatments can help. We led or participated in the clinical trials that gained approvals for each therapy. We also have one of the highest treatment volumes in the country. Learn more about our neuroendocrine tumor team.
- Innovation: In addition to working towards the approvals for PRRT and MIBG, we’re participating in clinical trials gathering evidence for further radioactive drug use in NETs. These trials evaluate new drugs, as well as innovative ways to use current drugs. Learn more about our clinical trials for neuroendocrine tumors.
- Personal involvement: Often with nuclear medicine, providers make decisions behind the scenes. Or recommendations come from team members who don’t specialize in the field. At our NET program, nuclear medicine specialists meet with you directly. They also take part in weekly tumor boards to discuss cases with a range of other experts — another unique way to practice nuclear medicine.
- Reliability: Having the right equipment doesn’t guarantee a result you can depend on. We have the technology as well as the team members required, all with extensive experience — from technologists and physicists to nurses and board-certified doctors. We also use the latest equipment and keep it meticulously maintained, ensuring accurate results for interpretation.
- Support: A nurse navigator or nurse coordinator helps arrange all of your care. We also provide a range of further support for neuroendocrine tumors.
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