An Job interview with Andrei Iaguru, MD
Andrei Iagaru, MD, Professor of Radiology – Nuclear Drugs and the Main of the Division of Nuclear Medication and Molecular Imaging at Stanford Overall health Care, discusses recent trials checking out new indications for prostate specific membrane antigen (PSMA) and GRPR, as effectively as what is presently in the prostate cancer therapy pipeline and some vital distinctions between Axumin and PSMA.
Read through an additional job interview with Dr. Iagaru on breakthroughs in prostate cancer imaging on website page 8.
GU Oncology Now: Could you examine the premises of the trials currently underway at your establishment evaluating PSMA and GRPR imaging for indications further than biochemical recurrence and the presurgical setting?
Dr. Iagaru: 1st of all, thank you for the invitation to be a part of your collection. This is a quite vital spot, imaging and therapy of prostate cancer, and it’s excellent that Nuclear Drugs now plays a considerable function in equally imaging and remedy.
We begun at our institution offering expanded entry application to PSMA radiopharmaceuticals for diagnosis. We at the moment use F-18 DCFPYL for these uses, both equally biochemical recurrence and pre-prostatectomy. But as you questioned about other indications past these, we do have trials with Gallium-68 PSMA-11 below an IND, as well as Gallium-68 RM2, a gastrin-releasing peptide receptor antagonist also on below an IND for the indications of biopsy steering, as properly as steerage in patients with either suspected prostate cancer in the circumstance of pre-biopsy or newly diagnosed prostate most cancers in the situation of treatment method steerage.
What are some of the preliminary conclusions of these trials?
As considerably as biopsy advice, we just finished examining the details from the initial 10 individuals who had been included, so it is a pilot research, but total, both equally PSMA and RM2 had precision in the mid-80% vary. We saw a sensitivity of 100% for both equally of them and specificity of also mid-80%. What we’ve observed is that in this cohort, the sensitivity of multiparametric MRI of the prostate was 50%. And this is not surprising since we are selecting patients who experienced equivocal or destructive MRI. So not absolutely everyone with suspected prostate most cancers need to get these tests, but those people wherever MRI and prior biopsies are inconclusive are most likely to profit from PET imaging, both with PSMA or gastrin-releasing peptide receptor, or both of those.
How can extra indications for PSMA and GRPR imaging fill an unmet need to have in prostate most cancers treatment?
Outside of biopsy steering, as I indicated earlier, guiding what spot of the prostate to take care of with substantial depth centered ultrasound (HIFU) or higher-dose amount brachytherapy are of excellent desire to our team. And not only to information what requires to be taken care of, but also 6 months later on just after remedy to see if we can stay away from biopsying these clients all over again to evaluate the response to cure.
And then if we increase outside of that, the spectrum of the prostate cancer patient handles many many years. So we can glance at earlier levels of biochemical recurrence like oligometastatic illness. We can feel of blend with radioligand treatment. So Lutetium-177 or alpha emitters labeled PSMA mixed with immunotherapy, for example. Or we can consider of combining condition specific therapies with external radiation therapy. At my establishment we put in the initial biology guided radiation remedy from a enterprise known as RefleXion. So as an alternative of applying the anatomical sign to guidebook the X-ray beam for external radiation you use the PET signal to do that, which has a lot of positive aspects.
What are some solutions for prostate cancer now in the pipeline that you are interested in?
On the side of radiopharmaceuticals, there are numerous variations of PSMA agents every single with their possess likely rewards. In addition to beta emitters like Lutetium-177, we also have alpha emitters that are in the pipeline. Individuals are of fantastic fascination as nicely, but we also have to continue to keep in brain that there are also prescription drugs that are non-radioactive, that are expected to, for example, concentrate on PSMA and block those most cancers cells in other techniques than radiation does. So the field is evolving quickly and there is a lot of exhilaration about all of these solutions.
I would also increase again that the mixture of biology guided radiation remedy via a machine like RefleXion and intravenous radiopharmaceutical treatment holds a great deal of promise for numerous of these clients.
What are the most sizeable distinction between
Axumin and PSMA?
Perfectly, there are a lot of and I do not know if we have time to discuss all of them, but Axumin (fluciclovine) has an advantage of minor-to-no urinary excretion. For several of the PSMA agents, analysis of the prostate mattress may well be minimal by the reality that the urine is made up of the drug. So a single likely reward for Axumin is evaluating the prostate bed. There are PSMA agents like PSMA-1007 with much less urinary excretion that do not have the drawback. However, I would say that the PSMA agents have significant benefits in excess of fluciclovine in phrases of detection of disease at low PSA stages, this sort of as <1 ng/ml. So it’s there where PSMA has significant advantages. If you go to levels of PSA greater than five, the positivity rate between the two I think is comparable. PSMA targets an enzyme that’s overexpressed in many prostate cancers, while Axumin targets the amino acid transporter present in cancer, but also other cells.
I think that as far as image interpretation, PSMA scans are likely to be easier to interpret than Axumin scans because of less non-specific activity. My prediction (and of course you have a 50% chance of being correct when you make a prediction about the future, but I think in this case it’s higher than 50%) is that PSMA would largely replace Axumin in the United States after FDA approval, but Axumin will retain a role for certain patients. Remember PSMA is a great tool but not 100% sensitive or specific.