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.

Advancements in PRRT for treating Neuroendocrine tumours and other cancers. A look at Targeted Alpha

Summary (10 sec read)

Advancements in Peptide Receptor Radionuclide Therapy (PRRT) and Targeted Alpha Therapy (TAT) have revolutionized the treatment of Neuroendocrine Tumors (NETs) and other cancers. PRRT, initially using 111In-DTPA-octreotide, transitioned to Y90, which, despite its effectiveness, posed renal toxicity risks. Lutetium 177 (Lu-177) emerged as a superior alternative, offering extended progression-free survival with minimal renal side effects.

Key improvements in PRRT include intra-arterial treatments for liver metastases, precise dosimetry for radiopeptide uptake, combining Lu-177 and Y90 for varied tumor sizes, chemotherapy as a radiosensitizer, and somatostatin receptor antagonist PRRT. TAT, gaining traction, employs alpha particles with higher energy and shorter therapeutic range than beta particles, enabling precise tumor targeting and severe, irreparable DNA damage due to high Linear Energy Transfer (LET).

TAT is effective not only for NETs but also for prostate, breast, colon, myeloma, and ovarian cancers. Prostate cancer, particularly, benefits from PSMA-targeted therapies like 177Lu-PSMA. Recent studies from Germany and South Africa emphasize TAT's efficacy, highlighting its potential as a potent cancer treatment alongside established therapies. TAT's ability to deliver focused, high-energy radiation makes it a promising option for advanced cancer treatment.

This Article is a sum of a discussion with Dr. Ishita B Sen (Director and Head of the Department of Nuclear Medicine & Molecular Imaging at Fortis Memorial Research Institute (FMRI), Gurgaon).

Neuroendocrine tumours (NETs) are heterogeneous with varying behaviour. Treatment decisions are taken basis Histological studies plus imaging data and clinical studies. Surgery is a curative option for NET patients with localized well-differentiated tumours, for non-localized metastatic tumours, Surgery is not an option.

PRRT (Peptide Receptor Radionuclide Therapy) is a curative option for non-localised, heterogeneous, metastatic neuroendocrine tumours. PRRT has proven to be the most promising treatment modality amongst various systemic treatments such as Somatostatin Analogues, Chemotherapy, Molecular Targeted Treatments, Alpha Interferon etc. PRRT causes DNA damage to the tumour cells.

In the 1990s PRRT was administered using the radiopeptide 111In-DTPA-octreotide (Octreoscan®), the responses were reasonable but the effects were not long-lived and there were long term adverse sequelae.

Next PRRT agent to be developed was the more effective beta-emitting radionuclide Y90, sustained symptomatic and objective responses with 90Y-PRRT were frequently observed, but it also led to significant renal damage. The renal toxicity is related to reabsorption of the radiopeptide in the proximal tubules, with the long path length of the 90Y beta particle imparting a significant absorbed dose to the radiosensitive glomeruli.

Lutetium 177 was the next PRRT radiopharmaceutical to be developed, it is one of the most widely used PRRT agents even today. Lu 177 therapy led to prolonged progression-free survival for the patients and a low degree of renal toxicity compared to 90Y PRRT.

There have been significant advancements in optimising the effectiveness of PRRT, some of these include the introduction of intra-arterial treatments (especially effective in treating Liver Metastases), usage of dosimetry to assess the uptake of the radio peptide, combining of Lu 177 DOTATATE and 90Y PRRT to target large and small tumours, using chemotherapy as a PRRT radiosensitiser, a somatostatin receptor (SSR) antagonist PRRT and targeted alpha-particle therapy (TAT).

Targeted Alpha Therapy has been gaining popularity and acceptance over the last few years, there are some advantages of Targeted Alpha Therapy versus Beta Particle Therapy, these are enlisted below:

Alpha particles have higher energy than Beta particles and have a short therapeutic range. This helps impart higher energy to the nuclei of the tumour cells and ultimately damaging them, since the energy is higher than Beta Particles, Alpha therapy also called the Magic Bullet Therapy. The range of alpha particles is equivalent to the thickness of 1-3 cell widths, due to this short therapeutic range alpha particles better target and damage the tumour cells.
Alpha particles have a very high Linear Energy Transfer (LET) value, which enables them higher molecular damage per unit length of the tumour cells. Beta Particles, on the other hand, have a lower range of LET which requires a much higher accumulation compared to Alpha Particles for similar molecular damage to tumour cells.
High LET radiation results in more severe and less reparable cell damage than low-LET radiation, alpha particles create a high ionisation density, which causes a high number of double-strand breaks as compared with beta particles which have a lower ionisation density - this caused irreparable DNA damage to the tumour cells.

In addition to Neuroendocrine tumours, there have been various studies which have examined the effects of TATs on other cancers including prostate, NET, breast, colon, myeloma, and ovarian cancer. Of these, prostate cancer is attracting the most interest. PSMA is the target overexpressed in prostate cancers. 177Lu-PSMA therapies have become an established treatment for patients with progressive metastatic prostate cancer. However, more recently there have been publications by German and South African groups describing the benefit of TAT.

Also Read: Which Patients can benefit with PRRT?

Also Read: Is PRRT Safe for you?

For more information on Targeted Alpha Therapy please write Dr. Ishita B Sen Email: dr.ishitasen@nuclearmedicinetherapy.in

This article has been written using the below-published paper as a reference.

Targeted Alpha Particle Therapy for Neuroendocrine Tumours: The Next Generation of Peptide Receptor Radionuclide Therapy

Shaunak Navalkissoor and Ashley Grossman
Department of Nuclear Medicine, ENETS Centre of Excellence, Royal Free Hospital, London, UK; b NET Unit, ENETS Centre of Excellence, Royal Free Hospital, London, UK