More than a quarter of all cancers diagnosed in American men are of the prostate. Caught early enough, prostate cancer patients have good odds of beating the disease, but recurrence and metastasis are always lurking. Helping to improve those odds is Johns Hopkins radiologist Martin Pomper, who recently culminated a 25-year quest to develop better prostate cancer imaging with PET/CT.
In May 2021, the U.S. Food and Drug Administration approved the use of PyL (PYLARIFY®) — also known as 18F-DCFPyL — a positron-emitting imaging agent that Pomper and team developed.
PET/CT with PyL greatly enhances the specificity and resolution of prostate cancer imaging to a degree that was unimagineable just a short time ago. The ability to detect small lesions with PyL PET/CT, some only a few millimeters in width, is on a par with tumor detection in blood through circulating tumor DNA. That suggests that the blood test can be used as a screening tool in high-risk populations as a prelude to PyL PET/ CT imaging, which can provide spatial information and guide therapy, Pomper notes.
That ability to see smaller tumors translates directly into earlier detection. PyL can also be used for detecting the recurrence of cancer in patients who have had their prostates removed, or for detecting when a cancer once confined to the prostate has metastasized to other organs or the bones. This is key as, with the prostate removed, levels of prostate-specific antigen (PSA), the traditional biomarker for prostate cancer, can remain low when the disease has returned or has spread. PyL can spot minimal disease even when PSA values are very low.
In PyL, Pomper and colleagues have created a chemical that harnesses the precision targeting capabilities of a specific enzyme-inhibitor pair. The target cellular protein is known as prostate-specific membrane antigen (PSMA), which is present in great numbers in the membranes of prostate cancer cells, and much less so in the prostate itself. “PyL attaches itself only to PSMA. And PSMA is nearly always present when prostate cancer is present. You marry that with the high sensitivity of detection of radioactivity and you have the makings of a powerful diagnostic tool,” Pomper says.
One promising area being explored by researchers at various institutions is whether PyL or similar chemistries can be used to detect other forms of cancer. Despite its prostate-specific name, PSMA is not actually specific only to prostate cancer, but is found in the newly emerging bloods vessels of all solid tumors, Pomper notes. Renal carcinomas and glioblastomas both have particularly high levels of PSMA, he says.
Pomper is happy that PET/CT with PyL stands a good chance of supplanting traditional bone and CT scans that are the normal course of action when prostate cancer is suspected. Neither of those tests are nearly as sensitive or specific as PyL and often miss lesions that PyL can easily spot. “With PyL, in one fell swoop you prevent two largely imprecise tests with one exceptional test, and you get a definitive answer in the process,” Pomper says. “It’s the best of both worlds.”