What Is PSMA-PET? Why Is It the Best Imaging Method for Prostate Cancer Spread?

The most useful imaging method currently used to diagnose cancer, detect its spread and determine treatment response is PET-CT. A new form is called PSMA-PET , using a "special imaging agent" to detect prostate cancer cells much more accurately and sensitively than all other known methods.

PSMA-PET FDA Approval

On 1 December 2020, the FDA (United States Food and Drug Administration) approved the radioactive tracer Gallium (Ga) 68 PSMA-11 for PET imaging in men with prostate cancer. Under the approval, it can be used when cancer is suspected of spreading elsewhere. Ga 68 PSMA-PET can also be used in successfully treated men whose elevated PSA suggests recurrence.

The weakness of existing imaging in prostate cancer makes predicting spread, and therefore successful treatment, difficult. Standard methods such as computed tomography, magnetic resonance imaging and bone scintigraphy are insufficient for showing prostate cancer metastases.

Even standard PET-CT, considered the best cancer imaging method today, is unsuccessful in assessing prostate cancer. Standard PET-CT uses glucose, or sugar, while prostate cancer cells use little sugar; conventional PET-CT is therefore not preferred. However, the newly developed molecular imaging method PSMA-PET has been highly successful in showing prostate cancer.

How Does PSMA-PET Work?

PSMA-PET uses a protein on prostate cancer cells called "Prostate-Specific Membrane Antigen" (PSMA), capturing and imaging that protein.

For this new method, a molecule combining a PSMA-binding antibody with a radioactive substance called Gallium-68 has been developed. The antibody binds PSMA, while its attached Gallium-68 allows metastatic prostate cancer cells to be imaged with PET. Cells spread throughout the body can thus be detected much better.

A PSMA-PET Example

The image source is Nuclear Medicine Specialist Prof. Dr. Akın Yıldız and his explanation: PSMA PET-CT has %80 sensitivity and %97 specificity for detecting lymph node metastases. Correctly identifying out-of-field nodes before major treatments such as surgery and radiotherapy is essential, because distant nodes cannot be included in standard surgical and radiotherapy fields. Most lie in para-aortic, pararectal, paravesical, preacetabular, presacral and inguinal areas. Metastatic nodes are most frequently internal iliac %25, para-aortic %14 and presacral %16. Standard salvage pelvic radiotherapy planning without PSMA PET-CT therefore appears insufficient, particularly in high-risk patients. Nodal metastases missed by 68Ga-PSMA PET-CT average 4 mm, demonstrating its substantial superiority over size-based methods (threshold 8 mm). It also outperforms diffusion MRI in detecting metastatic nodes.

Radionuclide Therapies with PSMA-PET in Advanced Prostate Cancer

Today, in stage 4 (metastatic) prostate cancer, Gallium 68 PSMA PET can be used for both imaging and treatment . There are Lutetium and Actinium treatments, 2 methods for this purpose.

The mechanism of Actinium treatment is shown below:

Figure explanation: Prostate cancer cells often have large amounts of prostate-specific membrane antigen (PSMA) on their surfaces. Small carriers called gallium-68 bind to PSMA and also have a cancer-killing radioactive substance attached. Cancer cells are therefore both located and imaged and killed with radiation. Above, attachment to a PSMA-positive prostate cancer cell of the radioactive substance emitting short-range alpha waves, Actinium-225 , is illustrated. This application is called 225Ac-PSMA .