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THESE FOUR LETTERS: PRRT (PART I)

An Overview of PRRT
Peptide Receptor Radionuclide Therapy
Original post April 2, 2019; Updated 12/17/2022

By now, you’ve probably heard of PRRT. Maybe your doctor recommended it. Or maybe you’ve heard another patient mention it on a discussion board. You may have heard it’s a type of radiation. Or you may have read that it’s a promising new treatment available to NET patients. Right now, these four letters – P-R-R-T– are very powerful letters. They are packed with information and meaning. PRRT is perhaps one of the hottest topics in the NET community, sparking much interest and discussion. This article is intended to give a general overview by answering some frequently asked questions about PRRT.


Note: NET patients in the United States may see these terms used interchangeably: PRRT, Lutetium 177 Dotatate, often abbreviated as Lu-177 and Lutathera®, the brand name for the FDA approved drug.


 

What is Theranostics?


Theranostics = therapeutics + diagnostics


Theranostics is a combination of the words therapeutics and diagnostics. PRRT is a type of theranostics that uses the same targeting molecule for diagnostic imaging followed by treatment. With NET, the diagnostic phase in the U.S. is the Ga-68 DOTATATE scan (NETSPOT®) or Cu-64 DOTATATE scan (DETECTNET®), and the therapeutic phase is the Lu-177 (Lutathera®). Because they are paired in this way, Ga-68 or Cu-64 DOTATATE and Lu-177 are sometimes referred to as “theranostic twins.” Since you can’t have one without the other, a discussion about PRRT must also include the Ga-68 DOTATATE or Cu-64 DOTATATE scan.


Note: Radioisotopes such as Ga-68 and Lu-177 are used not only for NET but also other types of cancer. In this article, we address their use for NET.

What is the Gallium-68 or Copper-64 DOTATATE scan (SSTR-imaging or SSTR-PET)?

The Gallium-68 (Ga68) DOTATATE scan and the Copper-64 (Cu64) DOTATATE scan (or simply known as DOTATATE scan) in a class of special PET scans that are paired with a radionuclide-labeled somatostatin analogue to detect somatostatin receptors on NET cells. With a DOTATATE scan, DOTATATE binds to the tumor cells and Gallium-68 (Ga-68) or Copper-64 (Cu-64) is taken into the cell. The scan “lights up” showing that somatostatin receptors are present. This is why you may also see it referred to as SSTR-imaging or SSTR-PET. The DOTATATE PET is done simultaneously with either a CT or MRI scan. The PET scan highlights the tumor and the CT or MRI scan shows a detailed view of the body. The two scans are fused together, resulting in clear, high-resolution images.

The Ga-68 DOTATATE scan, also known as Netspot® was FDA approved in 2016 and the Cu-64 DOTATATE scan, also known as (DETECTNET®) was approved in 2020. DOTATATE scans are now considered the gold standard molecular imaging study, replacing the octreotide scan, to show the presence of somatostatin receptors. It does not measure tumor size.


It is important to remember that the DOTATATE scan does not replace “conventional imaging” scans, MRI or CT. The DOTATATE scan is a functional imaging study that shows if tumors have somatostatin receptors. An MRI or CT scan is a structural imaging study that measures the size of tumors. One is not superior to the other; the scans show different types of information.


DOTATATE scans are not used routinely to see whether tumors are progressing. CT or MRI are used for “surveillance,” to detect the presence of tumor(s) and measure their growth. Practically speaking, this means that you will have fewer scans than MRI and CT scans.


Because the DOTATATE scan detects the presence of somatostatin receptors, it can reveal tumors that are not yet large enough to be seen on a CT or MRI scan. In other words, you might see tumors on your DOTATATE scan that you did not see on your CT or MRI scan. This does not necessarily mean that there has been a progression since your last CT or MRI scan. Remember, these are two different types of scans.


You must compare one DOTATATE scan to another DOTATATE scan (or one MRI scan to another MRI scan) to determine disease progression. Tumor progression on DOTATATE scans would appear as more spots lighting up or more areas that have spots. Tumor progression on conventional imaging, MRI or CT, would appear as increased tumor size, which the radiologist measures using “RECIST” criteria. Both scans give you important information in different ways.


Not all areas that “light up” (areas of uptake) on the DOTATATE scan are tumors. There are also “false positives” and areas of physiological uptake. Physiological uptake means it is normal for these areas to light up; these areas are not cancer cells. Areas of inflammation which are not cancerous may also show uptake which is not cancerous. It is important that these scans are read by nuclear medicine doctors who know how to read them properly. If there is any doubt, it is reasonable to request a copy of the scans on CD to be sent to an expert on your medical team for another opinion. If you have this scan done at a facility other than where your NET expert is, he/she will likely want to review the scans.


The DOTATATE scan (or octreotide scan) must show uptake, indicating the presence of receptors on the tumors, in order for a patient to be a candidate for PRRT treatment.


For more information on Ga-68 DOTATATE scans:


What is PRRT?

PRRT (peptide receptor radionuclide therapy) is a type of treatment that uses targeted radiation to kill specific cancer cells. PRRT is a form of nuclear medicine. This means that it must be given by doctors who specialize in nuclear medicine. They are specially trained to use radioactive materials to diagnose and/or treat medical conditions. These nuclear medicine doctors are the ones who read and interpret DOTATATE scans, as well as other nuclear medicine scans such as PET-FDG scans, bone scans, and MIBG scans. They are typically the doctors who determine if you are a candidate for PRRT, and they oversee the actual treatment.


PRRT is a method of delivering a radiolabeled somatostatin analog that targets specific receptors called somatostatin receptors (SSTR). You may notice it referred to as SSTR-therapy in medical literature.

  • Somatostatin receptors are expressed by many NET tumors.

  • Somatostatin receptors are the same receptors that somatostatin analogues (SSA), lanreotide or octreotide, bind to. An analogue drug is one that has a structure similar to something else. With NETs, the analogue drug (lanreotide, octreotide, Ga-68, Cu-64, or Lu-177) mimics the naturally occurring hormone, somatostatin. Think of it like a copy of a key (i.e. SSA, Ga-68, Cu-64, and Lu-177) that fits in a lock (somatostatin receptor).

  • These are also the same receptors that light up on the DOTATATE scan. The DOTATATE scan must show uptake, indicating the presence of receptors on the tumors, in order for the patient to be a candidate for PRRT treatment.

  • Your pathology report from biopsy and/or surgery may also mention if your tumors have somatostatin receptors. They are often abbreviated “SSTR” on the report. You may see SSTR subtypes on your pathology report on your report listed such as SSTR-1, SSTR-2, SSTR-3, SSTR-4, and SSTR-5.

  • If you have somatostatin receptors, PRRT can reach these receptors regardless of the tumor location or grade. Remember that with NET, the grade (based on Ki67) of the tumor is often more important than its stage.

PRRT works by using a targeting molecule called a peptide (a group of amino acids) that binds to somatostatin receptors on the surface of the tumor cells. Using a chelator, the peptide is joined to a radionucleotide, specifically Lutetium-177, otherwise known as Lu-177. This combination of peptide plus radionucleotide is called a radiopeptide. Currently, PRRT using Lu-177 is the first FDA-approved PRRT in the United States. PRRT using other types of radionucleotides are being developed and may be available through clinical trials and in Europe.


PRRT is likened to a “Trojan horse” packed with cancer-killing radiation that is snuck into enemy territory and causes destruction by killing the tumor cells from the inside. It is given intravenously into the bloodstream and travels to the cells that have somatostatin receptors. It binds to these cells and delivers the radiation into the tumor cells.


What should I expect?

Key Facts about PRRT
Click the above image for the complete infographic by Carcinoid Cancer Foundation which describes how PRRT works, who might benefit from it, how it is administered, etc.

PRRT is not a magic bullet. It is not intended to be curative. The goal of PRRT treatment is to increase survival, relieve symptoms, and improve quality of life. The NETTER-1 study measured progression-free survival (PFS) as its endpoint. This means the goal is to stop tumor growth. In other words, stable disease is good news!

  • Remember that each individual is unique. Each person responds differently to PRRT.

  • PRRT is one of many available treatments. It is typically not used as first-line therapy. The first line therapy is somatostatin analogues. Surgery should also be considered. PRRT may be used if tumors are considered inoperable and if there continues to be progression on somatostatin analogues.

  • For more on who and when PRRT should be used, refer to the 2020 NANETS/SNMMI Consensus Statement on Patient Selection and Appropriate Use of 177Lu-DOTATATE Peptide Receptor Radionuclide Therapy.

  • The FDA approval of PRRT with Lutathera® is not the end but the beginning. We hope to see many more advances in PRRT such as other types of PRRT and combination treatments.


 

Read part two of this two-part blog post series, “PRRT (Part Two).”

 
Resources:

 

Written by Lisa Yen, NP, NBC-HWC

Director of Programs & Outreach, LACNETS

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