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St. Vincent’s Hospital, Sydney study explained

Unless you have had prostate cancer, or graduated in medicine, or hold a PhD in physics, chances are you have never heard of the terms radiotherapy brachytherapy and 177-lutetium-PSMA peptide complex. So here goes with an explanation…an easy one first and then a more in-depth explanation if you are up to it. Simple explanation: a […]

Unless you have had prostate cancer, or graduated in medicine, or hold a PhD in physics, chances are you have never heard of the terms radiotherapy brachytherapy and 177-lutetium-PSMA peptide complex.

So here goes with an explanation…an easy one first and then a more in-depth explanation if you are up to it.

Simple explanation:

  • a new experimental treatment is being trialled by 2 Australian hospitals (St Vincent’s Hospital, Sydney, and Peter MacCallum Hospital, Melbourne) and is being heralded as a potentially ground-breaking technology in the treatment of prostate cancer
  • late-stage prostate cancer typically is associated with a multitude of secondary tumours scattered throughout the body, particularly in the skeleton. Irradiating all these tumours with standard forms of radiotherapy is impractical. This new treatment offers the ability to deliver radiation to the full complement of prostate cancer cells throughout the body
  • it is an adaption of an existing diagnostic tool that identifies the extent of the spread of prostate cancer in the body. The adaption converts a safe diagnostic tool into a radioactive therapeutic drug
  • the new treatment involves an intravenous injection of an antibody that seeks out the prostate cancer cells. The antibody is carrying a radioactive cargo that then damages the cancer cell while doing little or no harm to surrounding healthy tissue
  • the new treatment has proven very successful in some patients with long-term remission, but most patients show a relatively short-lived partial response
  • the proposal is that giving NOX66 at the same time will sensitise the cancer cells to radiation, converting an incomplete response into a full and durable response
  • NOX66 technology is perfectly suited to partner this new technology
  • the Company is honoured to have been invited to join in this ground-breaking clinical study
  • this new form of radiotherapy is being used initially in the treatment of prostate cancer, but is expected to be used in the future for a wide range of other cancer types, in particular those involving the kidney and small intestine.

The more in-depth explanation:

Brachytherapy radiotherapy

There are two basic ways of administering radiotherapy – either externally or internally. External radiotherapy involves exposing the body to a machine that emits high-energy radiation. The rays are aimed at the cancer, but inevitably means hitting some healthy tissue, including skin as the rays pass through the body. That’s the way most cancer patients receive radiotherapy.

The alternative is to place a low-energy radiation source inside the body so that it is in direct contact with the cancer. That is known as brachytherapy. Its purpose is to try and get the radiation precisely to where it is needed, thereby increasing the likelihood of killing the cancer cells as well as limiting the amount of radiation hitting healthy tissues.

Brachytherapy generally involves placing a radioactive element known as an isotope (or radionuclide) directly into the target tissue. The radiation coming from the isotope usually only travels a matter of a few millimetres, thereby limiting radiation side-effects; the isotope also usually goes on delivering radiation for days, weeks or months depending on the isotope, providing long-term anti-cancer activity.

Brachytherapy and prostate cancer

Brachytherapy is well-suited to prostate cancer because it is one of those cancers that readily spreads from its point of origin. That spread starts with the tumour breaking out of the prostate gland (around the neck of the bladder) and spreading to the surrounding tissues in the pelvis, particularly to the pelvic lymph nodes. The tumour cells also track along the nerves supplying the prostate gland back up towards the spinal cord, eventually settling in the vertebral bones. From there, the tumour cells spread around the body, mainly to other bones (eg. ribs, arm and leg bones) and various lymph nodes around the body. Sometimes it invades organs such as the liver and lungs.

Prostate cancer responds very poorly to chemotherapy, so once it has spread, radiotherapy remains really the only practical way of trying to contain the rate of growth of the cancer. Externally-delivered radiotherapy can be helpful when the spread of the cancer is limited to a specific region such as the pelvic cavity, but once it becomes more widespread, it becomes impractical to use external radiotherapy over large parts of the body and so is used on a more limited palliative basis to provide symptomatic relief such as shrinking larger tumours for pain relief.

The advantage of this new form of brachytherapy is that it offers the chance to get radiation to all prostate cancer cells no matter how many different tumours there are and no matter where they are scattered throughout the body.

177Lutetium-PSMA peptide complex (LuPSMA)

  •  PSMA

This is a story that we need to build. It starts with PSMA, a protein found on the surface of a wide range of cells including prostate, salivary gland, kidney and small intestine cells. When prostate cells become cancerous, they express more than usual amounts of PSMA and when they progress to become highly aggressive, they express even more. So while PSMA is not exclusively found on prostate cancer cells, prostate cancer cells will express more of the protein than other cells.

  •  PSMA peptide

About 20 years ago, an antibody was created against PSMA. The antibody locked onto the PSMA expressed on the surface of the prostate cancer cell.

The tiny part of the antibody that actually binds to the PSMA was identified. This is known as a peptide, and is used instead of the whole antibody.

  •   68Gallium-PSMA peptide complex

The initial use of the PSMA peptide has been as a diagnostic tool to determine the extent of spread of prostate cancer. In that role, it has become a widely-used means of determining the extent of the disease when first diagnosed.

The idea was to use the peptide to deliver a marker that would identify prostate cancer cells, with the marker then being detected by PET scan.

This involved attaching the harmless isotope, 68gallium, to the PSMA peptide to create a 68gallium-PSMA peptide complex . 68gallium emits gamma rays, so it does no harm. When the complex is injected intravenously, it homes in on clusters of prostate cancer cells anywhere in the body, allowing them to be identified by a PET scan.

The following figure demonstrates the sensitivity of this technique. The figure on the left (a) show a traditional CT or MRI scan picking up 3 tumours cancer. The 68gallium-PSMA peptide complex/PET scan on the right (b) shows just how extensive the cancer actually is with dozens of small tumours scattered throughout the body.

  • 177Lutetium-PSMA peptide complex (LuPSMA)

The final step has been to replace the gallium isotope with an isotope of the element, lutetium. Where 68gallium emits harmless gamma rays, 177lutetium emits beta rays which physically damage any cells in their path. Thus the complex is transformed from a diagnostic tool to a therapeutic tool.

While LuPSMA will bind preferentially to the prostate cancer cells, it also will bind to some extent to cells in the salivary glands, lacrimal glands (eyes), kidneys and small intestine, resulting in some side-effects such as dry mouth, dry eyes and tiredness.

  • 177Lutetium-PSMA peptide complex (LuPSMA) + NOX66

The fact that LuPSMA binds to non-cancer cells means that the dose of radiation that can be injected into the body has to be limited. In turn, this limits the effectiveness of the treatment. The rationale behind adding NOX66 to the treatment is to weaken the cancer cells to the point where a sub-lethal amount of radiation damage becomes lethal.