Dr. Peter Choyke, Director of the Molecular Imaging Program at the National Institutes of Health’s National Cancer Institute, is keenly interested in translating molecular imaging methods like MRI and PET into practice.
Prostatepedia spoke with him about his clinical trial on 18F-DCFPyL PET/CT imaging in high-risk prostate cancer.
Why did you become a doctor?
Dr. Peter Choyke: I was always interested in science. I came from a family of scientists. It just seemed that medical problems were the kind of problems that I needed to do work on. A lot of the problems in physics and chemistry had been solved, but in biology and medicine we really needed a lot more effort. I wanted to devote my life to that.
Can you explain the thinking behind your clinical trial on 18F-DCFPyL PET/CT imaging in high-risk prostate cancer?
Dr. Choyke: Prostate cancer imaging has been very limited. We’ve only had access to CT and bone scans, both of which had limited sensitivity for picking up prostate cancer. In the beginning of the 2000s, a number of new PET agents—or Positronemission tomography labeled agents—emerged. We started looking at them as they became available. They showed better and better sensitivity and specificity.
About three or four years ago, we accessed a first generation PSMA-targeted PET agent named F-18 DCFBC in collaboration with the person who invented this whole field, Dr. Martin Pomper at Johns Hopkins University.
We formed a collaboration and scanned 135 patients in an earlier protocol. We showed that even though this was a first generation PSMA agent, it was really promising and had much better sensitivity and specificity for prostate cancer than any other agent we had ever looked at.
Then Dr. Pomper, who is partly an imaging specialist and partly a chemist, further developed the compound into F-18 DCFPYL. This is the agent we’re now using in this trial.
F-18 DCFPYL has probably 10 times better sensitivity than the first-generation agent because of the higher affinity of the agent for PSMA and because of lower background. We started using that in the end of the summer of 2017 in a trial looking at high-risk primary cancer and recurrent disease.
If a man enrolls in this trial, what can he expect to happen from beginning to end?
Dr. Choyke: First of all, it’s important to talk about who qualifies for the trial. We have two arms.
In one arm, we’ll have men with high risk cancers, meaning they’re at high risk for metastatic disease or spread outside the prostate. Such men would come to our center and get the scan. They’d also get an MRI of their prostate, because we always correlate the findings of the DCFPyL scan with MRI to anatomically locate where the uptake is occurring. The anatomy is very complex in the low pelvis.
With the MRI in hand, the patient would get an injection of a small amount of radioactivity in the form of this F-18 DCFPyL. About an hour later, they go onto the scanner and simply lie flat for about 20 to 30 minutes until the entire body is scanned from head to toe. Then we’ll report the findings back to his physician.
Part of the reason why this is a research study is that we try very hard to correlate the findings that we see with biopsy specimens. This is still a research agent. We don’t know for sure that the areas of uptake are actually cancer. We can only confirm that with biopsy. We insist that patients undergo biopsy of PSMA-positive lesions as seen on the scan.
We say insist, though of course it may not be medically safe for some people to undergo a biopsy. It may not be feasible. There are exceptions. It’s not an absolute rule. We certainly want to get as much histologic correlation as possible. Otherwise, we could end up in a situation where we think we’re seeing disease, but we are in fact not. That would be very misleading and could possibly cause more harm than good. It’s very important at this stage of development to get as much information as possible.
In the second arm of this trial, we are scanning patients who have already undergone radical prostatectomy or radiation therapy and who now have a rising PSA, which indicates recurrent disease. We would do the scan in the same way as in the first arm with correlation of the MRI. Again, we’re trying to get as much histologic confirmation as possible.