The panel explains the science behind PSMA PET scans and reviews the different positron-emitters used in the scans.
Neal Shore, MD, FACS: Larry, maybe you’d like to elaborate on PSMA [prostate-specific membrane antigen]. What exactly is PSMA, and how does it differ from PSA [prostate-specific antigen]?
Lawrence Saperstein, MD: To summarize it briefly, we’re targeting the cancer cell. We weren’t doing that before, so that’s a nice way of putting it together. But PSMA is a transmembrane protein on the surface of prostate cancer cells, which is helpful in imaging live cells. The majority of the protein resides outside the cell, and it’s markedly overexpressed in prostate cancer cells than normal cells. That’s the key. For a number of reasons, it’s an attractive target for imaging and therapeutics, and there are different ways of labeling the compound. We can go into the different isotopes used and the pros and cons of that, but this illustrates what it is and where it is on the cell, and that’s our target.
Neal Shore, MD, FACS: Yes, this last bullet is remarkably important. It has dual purposes, doesn’t it? It’s to enhance our imaging capability, the overall accuracy for imaging, yet at the same time it brings in a therapeutic option or what we now call theranostics. I know we’re going to get to that. This is an important area for our colleagues to recognize. This is going to add a sixth novel mechanism of action to the 5 categories we have for patients with advanced prostate cancer. Exploiting the fact that this is a transmembrane protein is the key to the theranostic leverage. To go from extra to intracellular has real advantages. Larry maybe you can further walk us through this as it relates to the United States. There are other PET [positron emission tomography] radiotracers outside the United States, but maybe you want to first comment on Gallium-68 and 18F-DCFPyl.
Lawrence Saperstein, MD: Without going into too much of the physics, it’s important to recognize some of the differences with these positron-emitting agents. Gallium-68 is a positron emitter as is F-18. It’s probably important for this audience to understand that the energy level of the positron that’s emitted with Gallium-68 is higher than that of fluorine-18. What that means is that there’s a potential for lower-resolution images using Gallium-68. This is theoretical. There are no large-scale studies comparing the 2, but that’s something to think about in terms of image resolution and lesion detection. The half-lives are different—Gallium, 68 minutes; fluorine, 110 minutes—so that introduces some challenges with respect to distribution. F-18 is produced in a cyclotron, and Gallium-68 is produced in a generator. In terms of the half-life and the generating capabilities, there may be some challenges with agents, or 1 [may be better than] the other. But it depends on geographic location, the size of the institution, and the volume of cases that need to be performed.
Neal Shore, MD, FACS: I was on an advisory board recently, and 1 of the European colleagues said that the United States typically always led on having access to therapeutics. We’ve been lagging behind the rest of the world on the next-generation imaging, specifically these PSMA PET scans. They asked me, “How do you square that? How do you rationalize that?” I gave an answer, but I’m curious, Steven Finkelstein, do you have any thoughts on why we’ve had this delay in getting these state-of-the-art imaging PSMA PET scans so slowly in the United States compared with other parts of the world?
Steven Finkelstein, MD, DABR, FACRO: It’s a wonderful question. First, it’s a pleasure to be here with such luminaries. In the community setting and even the academic setting, what determines if an imaging modality is going to be used is whether it’s going to be reimbursed. There are some challenges in the United States about the timing it takes. We have a great imaging modality, and we know that there’s the appropriate billing codes. Those imaging modalities that we’re employing will both patients and be reimbursed by those providing it. Some other nations have been much more suited and more forward thinking about getting these modalities to the patients than we have. That should change.
Neal Shore, MD, FACS: It’s always fascinating and interesting to see the global disparities and the different methodologies for agency approval, for reimbursement, and for having facilities. To your point, Steven—you hit it squarely—these are all factors that come into play. Ultimately, organizations like AUA [American Urological Association], SNMMI [Society of Nuclear Medical and Molecular Imaging], ASCO [American Society of Clinical Oncology], EAU [European Association of Urology], and ESMO [European Society for Medical Oncology] are all trying to address accessibility disparities.
Transcript edited for clarity.