Let’s talk about the future. Do you see new radionucleotides or new tracers coming out for PET scanning or imaging in general?
There are two aspects of the future: therapeutic and further imaging. With regard to further imaging, I think there will definitely be a swing toward using a fluoridated PSMA tracer rather than gallium. Fluoridated PSMA is a little more difficult to manufacture because it requires a cyclotron, but it has a very long half-life, which means it can sit on the shelf for quite a long time and can be made in large batches. Thus, a lot of nuclear medicine departments can store it on site. The advantage for me is that there is no urinary excretion, and the ureteric peristalsis mimicking a pelvic node won’t occur. It should be much better at picking up the local recurrences at the bladder neck after radical prostatectomy.
Interestingly, we’ve found in Australia that a multiparametric MRI of the pelvis probably actually identifies local recurrences often a lot better than a PET PSMA scan, purely because of the problem with urinary excretion. You can still pick them up on the PET scan, but an MRI is often better.
The other future direction relates to theranostics or treatment of advanced disease. We’ve been running some trials in Australia using lutetium as the agent, which is bound onto the PSMA and has effectively been used to treat castrate-resistant prostate cancer when all therapeutic options have been exhausted. There have been some very impressive results; we’ve had at least 50% PSA drops in well over 50% of patients and about 10% to 20% have extraordinary drops where the disease virtually melts away with a couple of treatments with lutetium. It’s generally relatively well tolerated. This is another very ripe area of research.
What you’re talking about is what some say is “calling in the fire department after the house has burned down.” Do you see a future where we take a nuclear tracer and attach a therapeutic molecule of some type at an earlier stage—perhaps biochemical recurrence with nothing showing up beside a small area?
I would agree with you. I think there’s a real chance of bringing these in much earlier in the treatment paradigm compared to where we are. In the current trials, we are using lutetium to look at toxicities and make sure it’s safe, and it appears to be very well tolerated. Once we confirm that it’s safe, it would make sense to be using it earlier.
Also, in patients with widespread metastatic disease, we often have to do a PET 18F-fluorodeoxyglucose (FDG) scan with glucose as well as the PET PSMA scan. In fact, we’re finding that some patients will have completely separate sites of disease and the PSMA and the FDG sometimes don’t match, and if this is the case the effectiveness of lutetium theranostics is reduced.
That’s interesting because we’ve always thought that it’s not glucose avid.
I think as it dedifferentiates, it actually becomes glucose avid. So when you’re using lutetium PSMA as a therapeutic target, it will track to the PSMA-positive sites, but if there is non-concordant FDG-avid disease those areas will not be well treated. Those patients actually don’t do well with lutetium PSMA because you’re not actively treating all of their disease, but you only see that in very end-stage disease.
Is there anything you’d like to add regarding imaging in prostate cancer?
I think it’s an exciting time. Both the advent of MRI and these new PET tracers like PSMA have altered the way we stage and restage prostate cancer. It does create a number of questions that we have to answer, including whether or not it ultimately leads to improved survival. Hopefully further trials will help answer the questions that have arisen.