SABCS 2012

Use of FDG PET imaging

Dr David Mankoff – University of Pennsylvania, Philadelphia

We looked at PET from a number of aspects. We spent a lot of time on FDG PET which images glycolysis and is widely used. We actually spent some time on the preclinical portion of the talk trying to understand what are the molecular determinants of FDG uptake. We use it every day in the clinic and routinely for breast cancer patients and I would still say we have relatively little idea biologically what leads to high glycolysis and FDG uptake. So in the talk today Lewis Chodosh presented data from his fairly elegant animal models that were imaged with FDG PET that shed a lot of light on that.

I think what we’ve learned about that is that FDG uptake is quite variable across breast cancer and seems to favour more aggressive and often recurrent breast cancer. It’s not by coincidence that’s where it’s had its greatest impact in the clinic.

We are taking advantage of the ready availability of FDG PET as a way to measure tumour glucose consumption to better understand this biology, both in humans and in animals. Then we’re beginning to really take advantage of other PET tracers that image other facets of breast cancer biology to make those same discoveries and translation into the clinic for other aspects of breast cancer biology ranging from proliferation to hypoxia to the expression of ER and HER2 and therapeutic targets.

Could you discuss how hypoxia is involved with this?

Hypoxia is something that’s been known about in tumours for quite a while but has always been relatively difficult to measure. In general while you would think that the absence of oxygen would kill tumours, those that survive it actually become quite resistant and through a variety of mechanisms demonstrate rather clinically aggressive features. Up until recently the measurement of hypoxia required invasive electrodes but non-invasive measurements using a variety of techniques that include both PET and MR may be quite helpful in that regard. It’s probably a subset of those breast cancers that are hypoxic but it may be a significant resistance factor in ones that are.

And in regards to response to therapy?

I think in general the idea of using quantitative molecular characteristics that you can take from imaging should offer much earlier windows into response than what we do now which is simply to look for decreases in size as evidence of efficacy. That’s already happened, to a certain extent, in the clinic using FDG PET but there may be advantages to using other markers, in particular FLT PET, which is a marker of cellular proliferation, may provide some of the earliest signals that we would expect to see in response to treatment where we would expect to see an early decline in tumour growth.

Do you see this being used in very small tumours?

There is work going on right now, especially using PET detection systems that are designed primarily for breast cancer that have investigated that with some interesting results and some people are beginning to use them in the clinic. To my way of looking they are still pretty early results and I think that while FDG looks like a very good marker for more advanced disease, it’s not clear that that’s the best marker for early breast cancer. So again, as our understanding of the biologic events of breast cancer development and early breast cancer emergence get better, we’re going to be able to design better molecular tracers to identify that.