Originally published 2/14/2022
The blog below discusses PET/CT scans that are molecularly labeled with radioactive isotopes that bind with PSMA (prostate specific membrane antigen) on prostate cancer cells to make them “light up” on CT scans. This enables the detection of microscopic locations of prostate cancer (PCa) in soft tissue and bones in the pelvic area and throughout the body. More recently, PSMA-radiolabeled molecules are now being incorporated in multiparametric MRI (mpMRI). This enlarges the detection and diagnostic properties of PSMA-PET imaging beyond what CT scanning is capable of.
As Evangelista, et al. write, PSMA-PET/MRI makes it possible to “… explore the practical potential of multimodal, combined metabolic-receptor, anatomical, and functional imaging.”[i] In other words, the ability of mpMRI to characterize tissue composition (cancer vs. normal tissue) and reveal the location and extent of cancerous lesions is “married” to PSMA-PET detection. In turn, such a detailed and specific portrait of PCa allows treatment planning to be tailored to the individual’s needs. Earlier published studies were based on PSMA-PET/CT, but now a growing number of clinical protocols recognize MRI as the preferred imaging choice for PSMA staging and restaging of PCa patients. In fact, when PSMA-labeled isotopes are used with MRI, “In primary tumors, the pooled sensitivity for the patient-based analysis was 94.9%. At restaging, the pooled detection rate was 80.9% and was higher for radiolabeled PSMA than for choline (81.8% and 77.3%, respectively).”[ii] These numbers attest to the ever growing global utility of mpMRI in cancer, and specifically in the world of PCa.
Movies about international spy rings gain popularity as thrillers because they keep audiences in suspense over the identity of the true good guys and bad guys. No one would waste their time and money to see a film in which the villains wore large neon badges saying “I am a SPY!” Within the first 15 minutes, their evil activities would be promptly ended as they are identified, rounded up, and annihilated—The End.
In the field of prostate cancer (PCa) diagnosis and treatment, staging the cancer is a key element in therapeutic decisions that have the greatest likelihood of success as well as lifestyle preservation. The majority of today’s cases are diagnosed when they are low to favorable-risk intermediate PCa, and at a stage where they are still confined to the gland.
However, there are two situations in which detection and diagnosis are more elusive:
- Staging PCa to detect advanced or metastatic disease before primary (first) treatment, and
- Detection/localizing recurrence if PSA is rising following primary treatment.
In either of these staging scenarios, it is essential to pinpoint the site(s) and extent of PCa activity that has escaped the prostate. Is it local in the prostate bed? Is it regional in the pelvic lymph nodes, organs, or nearby bones? Has it metastasized (spread) to a more remote organ or part of the skeleton?
Until very, very recently, searching for PCa activity when it is still microscopic was a challenge. In fact, the PCa cells ARE wearing telltale ID badges, but they are hardly large or neon. Now, however, we have what amounts to a new “superpower” to spotlight those badges and make them glow in the dark. It’s called prostate specific membrane antigen (PSMA) PET/CT scanning.
What is PSMA?
You already know about prostate specific antigen (PSA), a type of protein that is expressed on the surface of prostate cells and sheds into the bloodstream, where it can be measured. Many conditions can cause such shedding, such as infection, inflammation, BPH, certain physical/sexual activities, and PCa. Thus, a rising PSA needs more clarification
However, there’s another surface protein with increased expression on PCa cells, and as the cells become more aggressive, the expression grows to 100 – 1000 times more than on normal prostate cells. However, instead of doing a blood count as with PSA, the unique characteristic of PSMA is the way it shows up when a special radiotracer (detection agent) is administered by IV during a PET/CT scan. As I wrote in a previous blog about PSMA, “Radiotracers are molecules composed of radioactive isotopes (atoms that emit excess energy in the form of short-lived alpha, beta and gamma rays) bonded with a substance that PSMA will ‘take up’ or adhere to.” The small amounts of radiation emitted are not long-lasting nor do they travel far, but it’s enough to light up on the scan.
Nearly all PCa cells (estimates up to 95%) express PSMA. Early studies comparing the detection rates of a radiotracer called Gallium 68 is significantly more accurate and precise than conventional PCa imaging. Results were compelling enough that in early December 2020, the FDA granted approval to two California academic medical centers, UCLA and UCSF, for its use in the two scenarios described above.[iii]
The ability to identify microscopic advanced/metastatic PCa by targeting PSMA is very appealing to urologists, since the earlier they can detect and identify the spread of the disease, the more options are open for managing the disease through increasingly targeted treatments. In fact, in some international locations, a cell-by-cell tumor destruction that takes advantage of PSMA is now being offered to certain patients with metastatic disease. Using the same principle as radiotracers, a more destructive radioactive element called lutetium that damages cancer cells can be “bound” to surface PSMA molecules, essentially delivering a form of assassination to each villain. Though not yet FDA approved in the U.S., clinical trials are ongoing.
Meanwhile, several additional radiotracers besides Gallium 68 are in development. The race is on to generate easy-to-produce, cost-effective tracers that deliver the same or better detection results.
In many ways, expanding the possibilities with PSMA is almost like a spy thriller movie. However, the stakes in real life are high, since the lives of men with metastatic PCa depend on more targeted diagnosis and therapeutics.
Although it’s still a way off in the future, this is one clinical adventure that is sure to have a happy ending, not just for patients and urologists, but for all specialists (oncologists, radiologists, etc.) who strive to provide lifesaving detection and treatment for all men with PCa.
NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.
[i] Evangelista L, Zattoni F, Cassarino G, Artioli P, Cecchin D, Dal Moro F, Zucchetta P. PET/MRI in prostate cancer: a systematic review and meta-analysis. Eur J Nucl Med Mol Imaging. 2021 Mar;48(3):859-873. doi: 10.1007/s00259- 020-05025-0. Epub 2020 Sep 8.
[iii] Hilton, Lisette. “Urologists target PSMA in prostate cancer.” Urology Times, Mar. 18, 2021. https://www.urologytimes.com/view/urologists-target-psma-in-prostate-cancer