Lutetium-177 PSMA therapy kills prostate cancer cells

Lutetium-177 PSMA therapy kills prostate cancer cells

Prostate cancer cells express PSMA (Prostate-specific Membrane Antigen) which can be targeted by a specific binding agent carrying Lutetium-177, or 177 Lu, a radioactive isotope that kills prostate cancer cells wherever they are in the body.

Lutetium PSMA therapy, or 177 Lu-PSMA therapy, is a treatment for advanced prostate cancer which has metastasized to other parts of the body. It is currently in clinical trials.

Prostate-specific membrane antigen

With the concerns over the inaccuracy of the PSA test and an attitude from oncologists that ‘it’s better than nothing’, attention has been drawn to the Prostate-specific Membrane Antigen or PSMA as an alternative and useful biomarker. It’s a glycoprotein that can be made to show up in a PET scan. It is known to be up-regulated in metastatic prostate cancer – it is present in low levels in normal prostates but increases with increases in prostate cancer cells. However, it is not actually specific to the prostate and is expressed by the salivary glands, duodenum, and is found in the inside lining of blood vessels that supply other cancers such as colon cancer, bladder cancer and renal carcinoma.

PSMA in prostate cancer cell growth

Jan Grimm and a team at Sloan Kettering have shown that PSMA causes the release of glutamate which binds to the surface of prostate cancer cells. This then triggers levels of P13K, which causes growth. Glutamate and P13K are, in effect, feeding and growing the prostate cancer. Glutamine is an amino acid found in animal protein, and glutamate is derived from it. It is widely available in human tissues, for example, in muscles and in the brain.

Lutetium-177 and advanced prostate cancer

Lutetium-177 is a radioactive isotope which decays quite rapidly over just a few years. It is useful in cancer treatments such as brachytherapy because the particles emitted only travel short distances. It is also used with neuroendocrine tumours and can be targeted to attack many over-expressed receptors on cancer cells.

PSMA is an enzyme which hydrolyses n-acetylaspartylglutamate, or NAAG. 177 Lu-NAAG, which is also termed 177 Lu-PSMA, is the agent used in metastatic prostate cancers. Injections into the body result in 177 Lu-NAAG binding to PMSA molecules and killing prostate cancer cells.

Clinical trials with Lutetium-177 PSMA Therapy are taking place in several countries; In the UK the VISION trial is taking place at the Royal Marsden.

In the UK, a PSMA PET scan can cost £3700 at the Royal Marsden and £2588 at the London Clinic. The injections at the Royal Marsden cost £8685 per session including overnight stay or £7805 without, and you probably need 4-6 sessions.

2019 Research
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