The evolution of nuclear imaging in the management of prostate cancer

What is properly known as “nuclear imaging” is the use of (usually injectable) radioactive compounds into the body that have no known clinical effects but which can be targeted to “light up” and demonstrate the presence of specific types of tissue. Patients ask constantly whether there are new imaging tests that can be used to find prostate cancer early or to identify areas of prostate cancer recurrence.

In the management of prostate cancer the oldest and still the most common form of nuclear imaging in use today is radionuclide bone scanning. This is based on  injection of a radioactive technetium-99m (99mTc) tracer chemical that accumulates in areas of bone where prostate cancer is present. Such scans are not perfect. They have a high sensitivity but low specificity for metastatic prostate cancer, so there is always a danger that areas of bone that “light up” on bone scans of this type are not actually metastatic prostate cancer at all. However, on the whole, this type of bone scan has had and probably will continue to have a long and very useful life as the primary tool for identification of risk for bone metastasis in prostate cancer patients with an elevated PSA level (> 20 ng/ml), a Gleason score of 4 + 3 = 7 or higher, and/or symptoms — such as low back pain — that might suggest the presence of prostate cancer.

In more recent years there have been a whole series of attempts to introduce new types of nuclear scanning technology that might be helpful in identifying the presence of smaller amounts of prostate cancer earlier and in other tissues. These techniques have involved new radioactive compounds and different scanning techniques such as CT scans and PET scans as opposed to traditional x-rays. Examples of some of the types of radioactive compound involved include things like [11C]choline, [18F]fluorocholine, [11C]acetate, [18F]fluoroacetate, [11C]methionine, and [18F]fluoride. And we are seeing some progress.

In September 2012 the U.S. Food and Drug Administration approved the use of [11C]choline PET/CT scans in the work up of men  at risk for progressive prostate cancer after first- and second-line therapy to try and identify the presence of micrometastatic prostate cancer in such tissues and lymph nodes and other soft tissues. The utility of [11C]choline PET/CT scans is constrained by the fact that the half-life of this tracer is extremely short and so every dose must be individually created and used immediately. In addition, it seems to work best only in men whose PSA levels have risen to 2 ng/ml or higher. In men with lower PSA levels, there is a significant risk for false positive and false negative results. Only once center in the USA is currently capable of providing this type of [11C]choline PET/CT scan: the Mayo Clinic in Rochester, MN.

Other radionuclear imaging tests that are regularly used (either clinically or investigationally) at a small number of centers are the following:

  • [18F]DCFBC-enhanced PET scanning within the Molecular Imaging Program at the National Institutes of Health Clinical Center in Bethesda, MD, where there is an ongoing, open, pilot clinical trial of this type of imaging to identify sites of localized, recurrent, and metastatic prostate cancer. [18F]DCFBC binds to a natural molecule in the body known as prostate-specific membrane antigen (PSMA) that is expressed by men with prostate cancer.
  • [11C]Acetate-enhanced PET and PET/CT scanning at what is now the Phoenix Molecular Imaging Center in Phoenix, AZ (formerly the Arizona Molecular Imaging Center), where there are at least three ongoing clinical trials to identify sites of residual and/or recurrent prostate cancer.
  • Similar tests at Sand Lake Imaging in Orlando and Maitland, FL, where we understand they are transitioning from older Feraheme (ferumoxytol)-based scans to identify prostate cancer in the lymph nodes to newer investigational scanning techniques.

A recent report by Rowe et al. in the Journal of Nuclear Medicine has suggested that [18F]DCFBC-enhanced PET scanning may be capable of detecting fast-growing  forms of primary prostate cancer and could prove significant in the care of patients with suspected prostate cancer that had not been confirmed by biopsy (see also this article on the HealthImaging web site). This is a small study in just 13 patients and so it needs to be interpreted with caution.

However, what is very important for patients to appreciate at this time is that there is a whole range of new agents in development that may be able to link to PSMA and thus be used in combination with various scanning techniques to identify small areas of prostate cancer in the not too distant future. These already include such agents as [18F]-DCFpyL, [68Ga]-labeled PMSA, and others that are in the very earliest stages of testing.

Dr. Stephen Cho, the senior author of the recent paper by Rowe et al., just mentioned, goes out of his way to point out that:

There are a number of PSMA-based PET agents currently being introduced into prostate cancer imaging, many with improved signal to background uptake and sensitivity from this earlier first-generation PSMA [18F]DCFBC PET radiotracer, which should further improve the detection of prostate cancer.

While it is difficult to predict which of the numerous prostate cancer molecular imaging agents being developed will ultimately become clinically adopted, this work, in aggregate with that of other groups, suggests there are important advantages to the PSMA ligands for prostate cancer molecular imaging.

The ability to accurately identify small areas of residual and recurrent prostate cancer — and aggressive primary cancers — with high levels of accuracy could revolutionize the treatment of prostate cancer in the future because it could allow us to target treatment with a much higher level of accuracy and lower the need for things like radiation therapy over wide areas of the pelvis for some types of patient.

Editorial note: The very long and proper name for [18F]DCFBC is N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-4-18F-fluorobenzyl-l-cysteine … which is why we’ll stick to [18F]DCFBC!

9 Responses

  1. Thanks for the great summary of the state of the art in the imaging world. It certainly coincides with my fragmented knowledge on the subject accumulated over the last few weeks as I embark on a search to locate the source of my rising PSA after failed RP, and SRT, when scans so far have been negative.

  2. Thank you for this review.

    I was especially interested in Sand Lake Imaging’s use of the Feraheme MRI scan, as I had that scan at Sand Lake as well the Na18F PET/CT bone scan locally to determine eligibility for radiation. (The scans were negative, and I had 78 Gy of Tomotherapy, including a 46 Gy pelvic boost, in 2013, with 18 months of supportive triple androgen deprivation therapy. My current PSA is < 0.02.)

    Sand Lake had not posted information about its Feraheme work in the past. Now I see a link to an interesting article. Here is a key sentence:

    ‘…“With the tools that we are using now, we have data demonstrating accuracy, sensitivity, and specificity of approximately 96 percent in detecting lymph node invasion down to the size of two millimeters,” says Bravo.’

  3. As I pointed out earlier Sand Lake is not using Feraheme any longer, due, as I was told by a nurse there, to the cost to the patient of the Feraheme. But I still have an appointment to be scanned there on September 9 — hoping that any mets can be located.

  4. Just to provide an update: I was able to get into a trial at the National Institute of Health in Bethesda, MD, and had the DCFBC PET/CT. It was an interesting process where they do two scans for the DCFBC followed by an 18F sodium PET/CT bone scan. They do another set of scans 4-6 months from now.

    Just so I understand something. … Is the theory that there might be therapies developed down the road that go directly to where spots might show up on these special types of scans?


  5. Jerry:

    The theoretical possibility that one might be able to use similar technology to target treatment is — as far as I am aware — just that at the moment: theoretical.

  6. No Longer Just “Theory” (though far from standard)

    Actually a few doctors are now doing just that in favorable circumstances: going after the spots revealed by the imaging and wiping them out.

    That is a key goal in putting the concept of “oligometastatic prostate cancer” to use. If there is a small number of bone mets, such as 5 or fewer, and limited additional soft tissue mets, if any, and if they are in places that can be hit safely with radiation or taken out with surgery (or both), these doctors are treating the mets with the hope that no others occur, or that they too can be eliminated. For instance, Dr. Michael Dattoli, a radiation oncologist in Florida, has been doing that on an investigational basis for several years now, and Dr. Charles “Snuffy” Myers has a number of patients he is overseeing who are following this strategy. I expect that drugs like Xofigo may also find a role in this approach to oligometastatic disease.

    My own hope in 2011/2013 was that my feraheme scan and NaF18 PET/CT bone scans would show that I had just a few mets in accessible places so that I could have the prostate and pelvis targeted followed by the spot treatment; it turned out I had no detectable mets, and I was able to get radiation done locally in 2013 for the main cancer sites.

    I have known several men who have had the spot treatment. One required a retreatment for new mets in different places, but he has done well. The proportion of successful results for this new approach remains to be seen.

  7. Dear Jim:

    I don’t think you understood Jerry’s question. He was asking whether a goal was to be able to use the same targeting agents that are used to produce the results of sophisticated PET/CT scanning technology to actually deliver therapeutic agents directly to areas of metastasis.

    While this is theoretically possible, the only agent of which I am aware which might have this capability in the reasonably near future is one like Lu-177 anti-PSMA, and as yet I have seen no good data on the therapeutic use of this agent beyond a small number of men with very late stage disease (which is not the group of men that Jerry or you are referring to).

  8. Thank you both for your comments.

    Jim — I guess I fall into that camp where I’ve used imaging (both traditional and advanced scanning) to locate areas and radiate those spots. I’ve done it a few years ago on my pelvis.

    But, yes, I was referring to the PSMA-based scans and was wondering what high tech therapies are being worked on in association with the type of scan that I just had. I guess I’m looking for Dr. McCoy from Star Trek to wave the DCFBC wand and do a search and destroy. Ironically, his nickname was Bones, but in my version of Star Trek it also works for soft tissue.

    Lu-177 is interesting, but I think they are trying to determine what dose is effective and not harmful. Done mainly in Germany if I’m not mistaken.

  9. I’m heading down for a consult with Dr. Dattoli next week for exactly that reason: to try to kill recurrent prostate cancer with more HT and RT after a failed RP (Gleason 9, stage pT3b) and SRT (< 3-month PSA doubling time) which heretofore has been undetectable with scans.

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