What is Lu PSMA (Lutetium-Prostate Specific Membrane Antigen) Therapy?

Lu177 PSMA Therapy is a treatment for patients with prostate cancer, especially those who have become refractory to conventional therapy. Lutetium PSMA therapy helps to slow down the growth of the cancer cells, reduce the size of the tumours and most importantly improve the quality of life of the patients by reducing the pain caused by the cancer.

Many prostate cancers, in particular those that have spread or become resistant to hormonal therapies, express a unique receptor on their cell surface called Prostate Specific Membrane Antigen (PSMA). When Prostate Cancer metastasizes i.e. spreads to other parts of the body, the PSMA receptor is expressed over the sites of metastases as well.

How does Lu PSMA Therapy Work?

Lutetium-177 is a radioactive substance that emits beta radiation, a destructive kind of radiation. Lutetium-177 is bound to a small peptide which attaches to the PSMA receptor expressed on the cancer cell surface. The Lutetium 177 – PSMA complex, thus attached to the prostate cancer cell, then emits killing radiation causing cell death of the cancer cell. Since the penetration of the emitted beta particle is very small, the surrounding normal cells are spared.

How is the Therapy Done?

Lu177 PSMA is administered intravenously. The patient is admitted to the hospital for 24 hours. A kidney function scan called a MAG3/EC scan is done prior to the administration of the Lu177 PSMA.

What are the Side Effects of Lu PSMA Therapy?

Lu177 PSMA is well tolerated. The most common side effects are a slightly dry mouth, fatigue and nausea. There may also be a slight fall in the white blood cells and platelets about 2 – 3 weeks after the Lu177 PSMA administration.

What is the Response Rate With Lu PSMA Therapy?

The response rates of Lu177 PSMA depend on the tumour biology of prostate cancer, the initial Gleason Score, the extent of disease and the responses to prior therapies. Typically, more than 70% of patients demonstrate a reduction in S. PSA and a shrinkage of tumours following Lu177 PSMA therapy.

When would the doctor consider using this Therapy?

Lu PSMA Therapy is a very specific therapy and is used for managing metastatic Prostate Cancer or when Prostate Cancer is no longer responsive to other types of treatment.

What are the Treatment Schedules with Lu PSMA Therapy?

Most patients undergo three-four treatment cycles at intervals of 8-12 weeks. The number of cycles and the interim duration may vary between individuals depending on the response and interim assessments.

Why should I choose the nuclear medicine therapy center at Fortis Memorial & Research Institute (FMRI), Gurugram (Haryana, India)?

The Nuclear Medicine Therapy Centre at FMRI was one of the first institutes to offer Radio-ligand Therapy with Lu PSMA, and today, the center receives patients from the country and from across the world.

Is PRRT Right for You

Summary (10 sec read)

Peptide Receptor Radionuclide Therapy (PRRT) is a molecular therapy used for treating Neuroendocrine Tumors (NETs) by delivering targeted radiation via radiopeptides (Yttrium-90 or Lutetium-177) that bind to tumor cells. Doctors determine PRRT suitability based on several parameters:

Tumor Origin: PRRT is recommended for NETs originating from the thymus, lungs, stomach, small intestine (jejunum or ileum), rectum, or pancreas. Tumors from lungs and pancreas tend to be more aggressive than those from the intestine or rectum.
Tumor Aggressiveness: The Ki-67 or Mib Index from histopathology reports indicates tumor proliferation. PRRT is typically advised for Grade II tumors (Ki-67 between 2-20%).
Tumor Progression: Doctors assess if the tumor is stable or progressing. PRRT is preferred for progressive tumors spreading to other sites. Stable tumors may be managed with a watchful waiting approach.
Receptor Expression: Doctors use Gallium 68 Dotanoc or Octreotide PET CT scans to check if tumors express receptors that PRRT targets. Additionally, an FDG PET CT scan helps assess tumor aggressiveness and prognosis. Positive FDG PET CT results indicate a less likely benefit from PRRT.

PRRT is especially used for advanced, metastatic, or progressive NETs, improving symptoms, quality of life, and survival rates, despite being primarily palliative.

How do doctors determine that PRRT should be the treatment of choice for a neuroendocrine tumour?

PRRT or Peptide Receptor Radionuclide Therapy is a molecular therapy that is one of the accepted modes of treatment for Neuroendocrine Tumours (NETs).

Before we go on to discuss the above topic at hand, let me explain PRRT. In PRRT, a radiopeptide is created by combining a small amount of radioactive material or radionuclide (Yttrium-90 or Y-90 and Lutetium-177 or Lu-77) with a cell-targeting protein. This radiopeptide, when injected into a neuroendocrine tumour patient’s bloodstream, travels and binds itself to the neuroendocrine tumour cells to deliver a high dose of radiation that targets only the cancer cells.

Also Read: How Does a Typical PRRT Day look like?

Doctors recommend PRRT for patients diagnosed with Advanced Metastatic or Progressive Neuroendocrine Tumours (NETs); also for NET patients who are ineligible for surgery; and also for those NET patients who are unresponsive to other modes of treatment. While, PRRT is a palliative treatment, it does help in alleviating the symptoms, slow or in some cases even stop the tumour progression thereby improving not only the quality of life, but also the survival rate.

Now, the questions that most NET patients ask the doctors is –

“How do you determine whether PRRT is the recommended mode of treatment for my condition?”

The doctor’s decision to treat an NET patient with PRRT depends on the following parameters:

The origin of the tumour
The aggressiveness and proliferation of the tumour
The progression or stability of the tumour – how aggressive it is growing?
And, the most important point of consideration for the doctors is whether the tumour is expressing the receptors that is used to target PRRT.

Let’s address these parameters one-by-one.

1. What is the Origin of the Neuroendocrine Tumour?

A neuroendocrine tumour or NET has its origin in the specialised cells that have the traits of both hormone-producing endocrine cells and nerve cells, of the body’s neuroendocrine system. These cells can be found throughout the body and are responsible for controlling many of the body’s functions. While the neuroendocrine tumour can grow from anywhere, doctors recommend PRRT for neuroendocrine tumour patients who have the origin of the tumour from either the thymus – a specialized primary lymphoid of organ of the immune system; or from the lungs; or stomach; or the upper part of the intestines (i.e. small intestines – the jejunum or ileum); or from the lower part of the intestines (the rectum); or the pancreas.

Also Read: Is PRRT Safe for you?

The neuroendocrine tumours originating from the lungs and the pancreas are often the more aggressive ones as compared to the neuroendocrine tumours originating from the small intestine and the rectum. The tumour originating from the intestine and the rectum has a tendency to spread to the liver much more than the tumour originating from the lungs. The neuroendocrine tumour originating from the lungs has a more indolent (lazy) progression.

2. How aggressive is the tumour? What is the proliferation of the tumour?

To understand this aspect of the neuroendocrine tumours, doctors look at the patient’s Histopathology Report. In the report, there is something called the Ki-67 or a Mib Index. This index tells the doctors how aggressive is the growth of the tumour.

Ki-67 or Mib Index in the Histopathology Report:

If Ki-67 is less than 2%, the neuroendocrine tumour is classified as a Grade I tumour;
If Ki-67 is between 2-20%, then it is classified as a Grade II tumour; and
If Ki-67 is above 20%, then it is classified as a Grade III tumour.

Doctors typically recommend PRRT if the neuroendocrine tumour is classified as a Grade II tumour.

3. How aggressive is the growth of the tumour?

This is where the doctors understand the progression or the stability of the tumour. This is an important parameter that doctors need to understand. If the tumour is stable and the patient is fairly asymptomatic, doctors recommend to wait and watch. And if the tumour is progressing and is spreading to other sites, doctors recommend PRRT as the recommended mode of treatment.

To determine whether the tumour cells are showing a good receptor expressions that can be used for targeting PRRT, doctors ask for a Gallium 68 Dotanoc Scan or an Octreotide PET CT. A Gallium 68 Dotanoc whole body scan is a type of PET CT that is specifically done for neuroendocrine tumours. Apart from this scan, doctors might also look at a Technetium Hynic-TOC Scan that also looks at the receptors.

Further, doctors also ask for a regular FDG PET CT so as to determine the aggressiveness of the tumour. This FDG PET CT also helps doctors on the prognosis of the condition – if the neuroendocrine tumour shows positive on the FDG PET CT scan, then doctors know that the condition of the patient is less likely to benefit from PRRT.