Molecular Therapies

Lutetium-177 Dotatate (Lutathera)

Lu-177 dotatate is a molecular therapy. It is a type of peptide receptor radionuclide therapy (PRRT) used mainly for neuroendocrine tumors (NETs).

PRRT combines a compound called a peptide with a radioactive element, called a radionuclide. The peptide finds and binds to cancer cells. It delivers the radionuclide. Then the radionuclide emits energy (radioactivity) that damages the cancer cells.

PRRT may:

  • Help relieve cancer symptoms and improve the quality of life
  • Stop or slow growth of tumors or shrink tumors

What is Lu-177 Dotate?

In Lu-177 dotatate, the dotatate is the peptide, or delivery system. Lu-177 is the radioactive element that can damage cancer cells. 

After this combination is put into your bloodstream, it travels through your body. When it comes to cells with receptors for the hormone somatostatin, the dotatate binds there and goes into the cells. Then it releases the radiation.

Dotatate is good at binding to cells that have many tightly packed somatostatin receptors, avoiding other cells. When drugs are good at binding to certain cells, we say that they target or are “highly selective” for these cells.

Who Needs Lu-177 Dotrate?

This treatment is only for people whose cancer cells overexpress somatostatin receptors. In most cases, this means people with NETs that started in the stomach, intestine or pancreas. (These are called gastroenteropancreatic NETs, or GEP-NETs.) It can also include people with paragangliomas or pheochromocytomas (types of NETs), some lung carcinoids or prostate cancer.

Your Fred Hutch team can check the level of somatostatin receptors on your cancer cells. We do this with a PET (positron-emission tomography) scan. For the scan, you get the radiotracer gallium-68 dotatate or copper-64 dotatate. If the scan shows that your tumors easily take up either radiotracer, this is a sign they have many somatostatin receptors. It means they will take up Lu-177 dotatate, too.

Usually, physicians use Lu-177 dotatate for patients who:

  • Have advanced or worsening tumors
  • Are not eligible for surgery
  • Do not get enough relief for their symptoms using other methods

Treatment Process?

This treatment is only for people whose cancer cells overexpress somatostatin receptors. In most cases, this means people with NETs that started in the stomach, intestine or pancreas. (These are called gastroenteropancreatic NETs, or GEP-NETs.) It can also include people with paragangliomas or pheochromocytomas (types of NETs), some lung carcinoids or prostate cancer.

Your Fred Hutch team can check the level of somatostatin receptors on your cancer cells. We do this with a PET (positron-emission tomography) scan. For the scan, you get the radiotracer gallium-68 dotatate or copper-64 dotatate. If the scan shows that your tumors easily take up either radiotracer, this is a sign they have many somatostatin receptors. It means they will take up Lu-177 dotatate, too.

Usually, physicians use Lu-177 dotatate for patients who:

  • Have advanced or worsening tumors
  • Are not eligible for surgery
  • Do not get enough relief for their symptoms using other methods

Research

The U.S. Food and Drug Administration approved Lu-177 dotatate for GEP-NETs in 2018. Today, researchers at Fred Hutch and elsewhere continue to study its effects. We want to learn more about the best ways to help people who have neuroendocrine tumors or other cancers that respond to this treatment. For example, researchers are checking whether NET patients who benefited from Lu-177 dotatate will benefit from getting it again later in life if their NETs worsen.

Lutetium-177 Vipivotide Tetraxetan (Pluvicto)

Lu-177 vipivotide tetraxetan is a molecular therapy that was approved in 2022 for prostate cancer. It combines a compound called a ligand with a radionuclide. The ligand delivers the radionuclide to cancer cells by finding and binding to these cells. Then the radionuclide emits energy (radioactivity) that damages the cancer cells.

Pluvicto may:

  • Help you live longer
  • Delay cancer getting worse or spreading farther

What is Lu-177 Vipivotide Tetraxetan?

In Lu-177 vipivotide tetraxetan, the vipivotide tetraxetan is the ligand, or delivery system. Lu-177 is the radioactive element that can damage cancer cells.

After this combination is put into your bloodstream, it travels through your body. When it comes to cells with prostate-specific membrane antigen on their surface, the vipivotide tetraxetan binds there and goes into the cells. Then it releases the radiation.

Who Needs Lu-177 Vipivotide Tetraxetan?

This treatment is only for people with prostate cancer whose cancer cells are positive for prostate-specific membrane antigen (PSMA+). About 80 percent of men with prostate cancer have this biomarker.

Your Fred Hutch team can check the level of PSMA on your cancer cells. We do this with a PET (positron-emission tomography) scan. For the scan, you get the radiotracer gallium-68 gozetotide. If the scan shows that your tumors easily take up the radiotracer, this is a sign they will take up Lu-177 vipivotide tetraxetan, too.

Physicians use Lu-177 vipivotide tetraxetan for prostate cancer which:

  • Is PSMA+
  • Has spread to other parts of the body (metastatic)
  • Does not respond to treatment to lower testosterone (which may be called castration-resistant disease)

Treatment Process

Patients get Lu-177 vipivotide tetraxetan through an infusion (injection) at the South Lake Union Clinic. The entire visit takes about two to three hours. The radioactive drug infusion lasts for about 20 minutes. Infusions are done every six weeks for up to six cycles. This is an outpatient treatment; patients go home later the same day.

Your care team will include a nuclear medicine specialist, a molecular therapy technologist and nurses who help with your care and any side effects.

Before you begin treatment, your care team will talk with you in detail about topics such as: 

  • Your diagnosis and how Lu-177 vipivotide tetraxetan may fit into your treatment plan.
  • What to expect during and after treatment.
  • How to prepare for your infusions, such as if and when to stop taking other medicines.
  • How to relieve any side effects you might have.
  • How to reach us if you have questions or concerns after you leave the clinic.
  • Ways to limit the risk of radiation to other people. (The risk is very low but important.)

During your infusions, you will receive only one medicine: Lu-177 vipivotide tetraxetan. Side effects are very uncommon, but if you do have any side effects, your care team will help treat or manage them, such as giving you medicine to help with nausea.

In the days and weeks after each treatment, you will have lab tests and imaging scans. Your molecular imaging and therapy specialist uses these to see where the Lu-177 vipivotide tetraxetan went in your body and how it is affecting you.

Research

The U.S. Food and Drug Administration approved Lu-177 vipivotide tetraxetan for metastatic castration-resistant prostate cancer in 2022. At Fred Hutch, we continue to study this medicine to learn more about the best ways to help people with prostate cancers that either do or do not respond to this treatment. Our research includes:

  • Using blood and tissue samples (with patients’ permission) to collect molecular information on how the therapy works 
  • Studying how to use imaging, such as PSMA PET (prostate-specific membrane antigen positron-emission tomography), to predict which cancers will respond to the therapy
  • Designing clinical trials to test if Lu-177 vipivotide tetraxetan will work better if combined with other therapies