What is Peptide Receptor Radionuclide Therapy (PRRT)?

What is PRRT?

Peptide Receptor Radionuclide Therapy (PRRT) using Lutetium 177  (Lu-177) dotatate treats neuroendocrine tumors (NETs) by converting a cancer cell’s unique characteristics into a welcome mat for a “Trojan Horse” packed with cancer-killing radiation. This novel approach was approved for use in the United States on January 26, 2018.

How does PRRT work?

Some NET cells, unlike healthy cells, have proteins on their cell surface called receptors, that can bind to hormones, such as somatostatin. PRRT with Lu-177  targets these receptors with radiopeptides.

  • A peptide (a group of amino acids) is created that can bind to the receptors on a tumor cell’s surface.
  • The peptide is then paired with a radionucleotide (a radioactive atom) using a chelator (bonding agent).
  • The combination creates a radiopeptide.
  • The radiopeptide is injected into a patient’s bloodstream.
  • The radiopeptide finds and binds to the NET cancer cell’s somastatin receptor.

The radiopeptide emits radiation that kills the NET cancer cell.

Benefits of PRRT

Patients undergo multiple sessions of PRRT with Lu 177 a few months apart. Studies have shown PRRT can:

  • Increase survival
  • Improve the quality of life
  • Relieve symptoms
  • Decrease tumor size

PRRT Side Effects

PRRT with Lu 177  is generally well tolerated. Common side-effects of Lu-177 therapy are nausea, vomiting, and abdominal pain. Other less common side-effects are bone, liver and kidney toxicity, and mild hair loss.

Research on PRRT

Two radiopeptides are commonly used in PRRT: yttrium 90 (90Y) and lutetium 177 (Lu 177). Results of the NETTER-1 study, a large phase III randomized clinical trial published earlier this year, showed lutetium Lu 177 dotatate improved progression-free survival a median of 33 months when compared to high-dose OctreotideLAR in patients with advanced midgut NETs.

The Neuroendocrine Tumor Research Foundation (NETRF) uses charitable donations to fund promising treatments for NETs, like PRRT. Recently, NETRF, in collaboration with the Educational Research Fund for Nuclear Medicine and Molecular Imaging, funded an early phase clinical research of PRRT. Tom Hope, M.D, University of California, San Francisco is conducting a pilot study to evaluate the safety of Yttrium-90 DOTA-TOC Intra-arterial (IA) Peptide Receptor Radionuclide Therapy (PRRT) for Neuroendocrine Tumor. Dr. Hope’s study delivers PRRT through the arteries (intra-arterial) as opposed to the veins (intravenous or IV) to concentrate dosages in tumors and limit toxicity.

Watch Dr. Hope present an overview of PRRT at a regional NETRF patient education conference

PRRT in Europe

Physicians in the Netherlands, Germany, and other countries have used PRRT for years. On September 29, 2017, the European Commission approved the marketing of lutetium (177Lu) oxodotreotide for midgut NETs in all 28 European Union member states, as well as Iceland, Norway, and Liechtenstein.

PRRT in the United States

US Food and Drug Administration (FDA) approved lutetium Lu 177 dotatate for the treatment of somatostatin receptor positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults.

Lutathera is manufactured by Advanced Accelerator Applications (AAA), a Novartis company.