Novel Imaging Techniques for Metastatic Prostate Cancer Advance

Daniel P. Petrylak, MD

Improved imaging modalities are needed to help advance treatment of men diagnosed with metastatic prostate cancer, and several novel techniques are under study, Daniel P. Petrylak, MD, said during a presentation at the 7th Annual Interdisciplinary Prostate Cancer Congress™.

Petrylak, a professor at the Yale School of Medicine and director of the Genitourinary Translational Program at Yale Smilow Cancer Hospital at Yale-New Haven, sat down with OncologyLive to discuss the top-line information from his talk in an interview during the conference, which was held March 15 in New York City.

OncologyLive: Ideally, what benefits can novel imaging techniques offer when it comes to diagnosing and treating prostate cancer?

Petrylak: As far as metastatic disease is concerned, important questions in imaging are: What are you seeing, is it real, and is this going to impact the patient’s treatment decision?

We have patients who have a rising PSA with no detectable metastases based upon CT scan, MRI, or standard 99mTc-MDP bone scan. That makes the decision to treat difficult, because several therapeutic options are not open to these patients—particularly sipuleucel-T, enzalutamide, or abiraterone.

Some of the focus now has been trying to detect disease earlier by using more sensitive methods, such as sodium fluoride PET scanning or choline PET scanning, or the other new PET imaging agents. It’s reasonable to use sodium fluoride PET to look at the bones, since 90% of prostate cancer metastases come from the bone, and this is a more sensitive way of detecting bone metastases. The problem is that you start to detect things that may not have clinical relevance or may not actually be disease, so you need confirmation over time, of course, as to whether this is a metastatic lesion.

What other novel imaging options are out there?

Some of these are not yet ready for prime time. MRI fusion biopsy techniques, when you’re fusing 3D MRI results with 3D ultrasound images—this is called Artemis—are helping us detect prostate cancer in localized biopsies, so that’s being clinically investigated at this point. Sodium acetate PET, some of the amino acid imaging I talked about today—those are still investigational.

What is going to be fairly interesting, as we’re starting to develop targeted therapies, is imaging for those particular targets and using that as a companion to check for drug activity and eligibility for different drugs. One thing that comes to mind is PSMA, for which there are small molecules available that image better than the monoclonals that are out there at this point. That may be one way of saying, “This is a reasonable patient to target with PSMA-directed therapy,” and then if they start progressing, you can see if they’ve changed their expression profile.

Please explain a bit more about PSMA and why it is relevant in imaging.

PSMA is prostate-specific membrane antigen, a protein isolated a number of years ago. That’s distinct from PSA. This is a protein that is thought to be a folate transporter or transporter of other molecules. It’s expressed in about 90% of prostate cancer specimens, at all stages of disease. It seems to be upregulated after hormone therapy, but there may be some evidence that it’s downregulated as patients progress in the pathway of castration resistance. In other words, it may be a little bit less expressed as you de-differentiate the tumors, but that’s the same with PSA, as well.

PSMA is the target of ProstaScint, an FDA-approved agent for imaging prostate cancer that is still used, but not frequently. The problem with that antibody is that it recognized the internal portion of PSMA, possibly imaging only dead cells. There are other antibodies that have been developed targeting the external portion.

PSMA is being used as an imaging agent as well as a therapeutic target, so we’ve been looking at a combination of an anti-PSMA antibody combined with an auristatin drug that targets tubulin. The drug, called a PSMA ADC [antibody drug conjugate], is a way of delivering chemotherapy potentially more effectively than giving it systemically. We’ve completed our phase I trial, and we have a phase II trial we just presented at the Genitourinary Cancers Symposium this year that’s showing activity in patients who failed both docetaxel as well as cabazitaxel. It’s an interesting drug, and we’re looking forward to moving it up higher in the pathway, potentially to pre-docetaxel patients.

Imaging Techniques in Prostate Cancer

Technique

Description

ProstaScint^a

(¹¹¹In-capromab pendetide)

Radiolabeled murine monoclonal antibody against intracellular epitope of PSMA

¹⁸F-FDG PET^a

Positron-emitting radiopharmaceutical transported by glucose proteins

Diffusion-weighted MRI

Detects images based upon the motion of water molecules between tissues

Multiparametric MRI

Combines T2-weighted MRI plus dynamic contrast-enhanced MRI plus magnetic resonance spectroscopy

MRI SPIO

Uses intravenous lymphotropic ultrasmall SPIO particles to differentiate benign from malignant nodes

¹⁸F-NaF (sodium fluoride PET)^a

Chemisorption occurs with exchange of 18F-ion for OH-ion to form fluoroapatite,which then migrates into crystal matrix of bone for recognition via PET scan

¹¹C-sodium acetate PET scan

Uses carbon and acetate to recognize fatty acid synthase upregulated in prostate cancer

Choline PET scan

Recognizes choline kinase overexpressed from cell proliferation in prostate cancer

Amino acid-based imaging

Detects upregulated amino acid transport in tumors

Tc-99m MIP-1404

Radiolabeled with the gamma-emitting isotope technetium-99m to target PSMA extracellular domain

FDG indicates fludeoxyglucose; MRI, magnetic resonance imaging; PET, positron emission tomography; PSMA, prostate-specific membrane antigen; SPIO, superparamagnetic iron oxide.

^aFDA-approved agent