2015 PCRP Investigator Vignette

Title: Hyperpolarized Molecular Imaging Biomarkers in a Novel Prostate Tissue Slice Culture Model

Investigator: John Kurhanewicz, PhD, University of California, San Francisco

My current grants are really focused on the development and translation of new imaging biomarkers to help people with prostate cancer, in particular, decide what to do next.

The Prostate Cancer Research Program has funded the area of hyperpolarized magnetic resonance imaging, and that technique may really change the way we image prostate cancer-because it gives us the ability to overcome some of the really intrinsic limitations of MRI, which is sensitivity and specificity.

We can take a probe, an endogenous thing like Pyruvate, which is a downstream metabolic product of glucose, and enhance this signal from it so that we can follow it all around the body-so we can just monitor where it goes. But more important, where it's metabolized, and where it goes-branches off to. And from that metabolism, we can figure out the answers to some really important questions-and the top one is, "Is it an aggressive cancer?" Do we need to treat it, or is it a disease that we can watch and wait?

You know it's a very difficult disease because prostate cancer, there's huge proportions of patients who have indolent disease, that should probably not be treated immediately maybe? And people go, "Oh, why would you want to do that?" And the answer is, is that all the treatments we have, have side effects right now, and we're figuring out better ways of doing this. And so this watchful waiting period not only helps the person through maybe a period of their life that they don't want some of these side effects, but also opens the door that we might be able to treat it better tomorrow.

So, all the imaging I'm talking about is magnetic resonance imaging, which is available on every clinical scanner across the country. What our involvement is, is improving the techniques that specifically can identify prostate cancer, as well as to more specifically assess its aggressiveness. Because we know we're identifying a lot of indolent disease right now, so the $1,000 question to the patient and their doctors is whether it's aggressive or not.

And that's what imaging is all about-it's detecting clinically significant disease. And can we do it non-invasively, and can we help the patients decide whether they need to have the whole prostate taken out, and all the consequences of that?

The DoD really played a big role in funding the preclinical studies to show that there is value to the research. Then we propose a very unique human tissue model that was based on correcting some of the limitations of previous mouse models and cell models that have been used in prostate cancer. And that's very hard to get funded by the NIH, and the DoD went out with a synergistic award and funded us on this. And we developed the platform where we could look at living, human prostate tissue, taken out of men at the time of surgery-radical prostatectomy-that we could inject these probes into and look at the efficacy of how well they reported the parameters we were interested in, such as aggressiveness, response to therapy, and things of that sort. And that was huge because that, I think, was one of the really big parameters that pushed us over the edge to get this FDA IND approval for our first clinical trials.

Any time we see things that are taken from the bench top into the clinic and actually help patients is so gratifying. And particularly for me, I've seen several imaging techniques in the setting of prostate cancer taken into the clinic and directly help patients. Now with this new technique, I think we could change things and make them-I mean very much faster and much more specific. So you know, it's kind of fun being involved a second time around in a technique going into patients. And you know the DoD funding was so critical to get the initial data to make this happen.