PSMA scan

A PSMA scan is a nuclear medicine imaging technique used in the diagnosis and staging of prostate cancer. It is carried out by injection of a radiopharmaceutical with a positron or gamma emitting radionuclide and a prostate-specific membrane antigen (PSMA) targeting ligand. After injection, imaging of positron emitters such as gallium-68 (68Ga), copper-64 (64Cu), and fluorine-18 (18F) is carried out with a positron emission tomography (PET) scanner. For gamma emitters such as technetium-99m (99mTc) and indium-111 (111In) single-photon emission computed tomography (SPECT) imaging is performed with a gamma camera.

As well as the diagnosis and staging of prostate cancer, PSMA imaging can also be used to assess suitability for and plan treatment with external beam radiotherapy and PSMA-targeted radionuclide therapy.

Mechanism
Attempts have been made to target the overexpression of PSMA in prostate cancer cells for several decades, although PSMA is also found in other tissue. PSMA targeting molecules have included antibodies, aptamers, peptides, and small-molecule inhibitors. Initially, development focussed on the antibody capromab. Later research has focussed on small molecule ligands that bind to the extracellular active centre of PSMA, such as PSMA-11. These ligands for PSMA-scanning target the large extracellular region of the PSMA glycoprotein.

PSMA however is also over-expressed in non prostate cancer cells, including kidney, salivary gland, lacrimal gland and duodenal mucosa, where physiological uptake may be seen on imaging.

Clinical use
European Association of Urology (EAU) guidelines recognise that PSMA can provide accurate staging, however there is a lack of outcome data to inform further management. The American Society of Clinical Oncology (ASCO) guidelines for imaging of advanced prostate cancer also recommend PSMA imaging (among other PET radiopharmaceuticals), while acknowledging that these are not FDA approved and therefore limited to a clinical trial or other controlled research setting.

Availability
In part thanks to the wide range of similar PSMA radiopharmaceuticals, approval by regulatory authorities is at varying stages. Even so, use has been widespread in some areas, particularly as part of clinical trials. For example, European Association of Urology (EAU) guidelines have included recommendations to perform PSMA PET scans in certain circumstances since 2018, and there has been widespread agreement of the utility of PSMA scanning for several years.

Australia
A kit for manufacture of a 68Ga-PSMA-11 product, branded Illucix, was approved by Australia's Therapeutic Goods Administration (TGA) in 2021.

Europe
A marketing authorisation application for 68Ga-PSMA-11 (INN Gallium (68Ga) gozetotide), under the brand name Illucix, was made to the Danish Medicines Agency, on behalf of several EU countries and the UK. Approval is expected in 2022.

In 2022 a marketing authorisation application was made by the manufacturer of 18F-DCFPyL (branded Pylclari) to the European Medicines Agency.

Polish manufacturer and distributor of radiopharmaceutical procuts, Polatom, has been granted a US patent for a 99mTc-PSMA-T4 kit. In the UK, Tc-99m labelled PSMA has product authorisation but lacks funding.

Canada
A new drug submission was made to Canada's regulator in 2021, for 68Ga-PSMA-11.

United States
The first approved PSMA imaging agent was indium-111 (111In) capromab pendetide (branded Prostascint). It received Food and Drug Administration (FDA) approval in 1996. However, the agent had poor sensitivity and saw little widespread use.

The first PET PSMA imaging agent, 68Ga-PSMA-11, was approved by the FDA in 2020. Listed indications include suspected metastasis prior to initial treatment, and recurrence of prostate cancer (based on elevated serum prostate-specific antigen (PSA) level). This was followed by two further 68Ga-PSMA-11 agents in 2021 and 2022 (branded Illucix and Locametz). Listed indications for Lucametz additionally includes selection of patients prior to 177Lu-PSMA radionuclide therapy.

An 18F-PSMA agent (18F-DCFPyL) (branded Pylarify) was approved by the FDA in 2021. Indications are as for 68Ga-PSMA-11.

Another 18F-PSMA agent (18F-rhPSMA-7.3) (branded Posluma) was approved by the FDA in 2023.

Brazil
68Ga-PSMA-11 (Illucixwas) was granted initial authorisation in 2021, with full approval expected in 2022.