New fluorine-18-based imaging agent approved in USA

Last Friday the US Food and Drug Administration (FDA) last Friday approved a new type of imaging agent for use in PET/CT scans for men with suspected prostate cancer recurrence after earlier treatment.

The new imaging agent is known as [18F]fluciclovine or Axumin®. It contains radioactive fluorine-18 as a key element. And according to a media release issued by the FDA, the new agent was evaluated in two different studies for its value in imaging prostate cancer in men with a rising PSA suggestive of prostate cancer recurrence after prior treatment.

In the first study, based on 105 scans using [18F]fluciclovine, the on-site radiologists read the scans and compared them to data prostate biopsies and biopsies of suspicious imaged lesions. The same data were then re-read by three independent radiologists in a blinded study.

The second study was designed to compare the results of [11C]choline scans and [18F]fluciclovine scans in 96 men with average (median) PSA levels of 1.44 ng/ml after prior treatment. Radiologists on-site again read the scans initially, and the same three independent radiologists who re-read the scans in the first study also re-read the [18F]fluciclovine scans in this second blinded study.

In each of the two studies, the results of the independent scan readings were generally consistent with one another, and, according to the FDA, they confirmed the results of the on-site scan readings. The FDA concluded that these studies supported the safety and efficacy of Axumin for imaging prostate cancer in men with elevated PSA levels following prior treatment.

[18F]fluciclovine is a more stable compound than [11C]choline, which will make it a lot easier for radiologists and nuclear medicine specialists to use. However, what we really do not seem to know at the present time is whether the rsults that can be obtained with this compound are any better than those that can be obtained using [11C]choline, let alone agents like gallium-68 and others that are currently still in development here in the USA.

The developer of this new product (Blue Earth Diagnostics, which is a UK-based company) has opened offices here in the USA, but it is unclear, as yet, whether they will be marketing this product on their own or working with other established US companies to make this product available to US-based radiologists and nuclear medicine specialists.

6 Responses

  1. Fluciclovine (aka F18-FACBC) has been in tests for a long time by David Schuster at Emory and in Europe, and I’m glad it finally got approved .

    FACBC is a synthetic amino acid that is preferentially metabolized by prostate cancer cells. Unfortunately, it is also highly absorbed by BPH cells, so it can only be used post-prostatectomy. Like [11C]choline, it also seems to have a high false negative rate.

    It has proved superior to [11C]choline PET (see here) and to Prostascint (see here). I haven’t seen any comparisons with the PSMA PET tracers.

    It’s still in trials at Emory (see here) and in the UK and Norway. I’ve heard there will be an expanded trial in the US as well, but recruiting has not yet begun.

  2. Thanks for this report and comment. I have a few questions and am wondering if anyone has some answers.

    I have looked at the links and am a bit confused at this point. It is not clear that this is a soft tissue scan, or a soft tissue plus bone scan, rather than a bone scan, but I’m thinking that is not solely a bone scan especially because the agent is taken up by non-cancerous BPH tissue.

    The Emory study mentions an 18F bone scan, and I’m wondering if that is the same as the Na18F PET/CT bone scan; I’m thinking it is not, as leaving off the Na seems like a major part of the descriptor.

    There was no mention of comparison with the [18C]acetate scan (which is done in the US at least in Phoenix). I’m wondering why that was omitted as a comparison technology. My recollection is that [18C]acetate has a substantially longer half-life than [18C]choline, and it would be helpful to have numbers to put these two agents and the new agent in perspective. I’m wondering if the half-life of the new agent is long enough so that it could be used after air transport to distant locations.

  3. Jim:

    (1) I know that fluorine-18 is a great deal more stable than carbon-11, so I have little doubt that this product can be delivered to users from a centralized production facility (in the same way that a product like radium-223/Xofigo can).

    (2) I don’t believe that any carbon-11 product ([11C]acetate or [11C]choline) can have a significantly different level of stability. It is the radioisotope that is unstable, regardless of what molecule it is being used in.

    (3) I suspect that the reason that there was no comparison to [11C]acetate is quite simply because availability of this form of scan is extremely limited.

    (4) There is no doubt in my mind that the new product can identify cancer in both soft tissue and bone. What is less clear from the available data is exactly how well it can do that. I’m not sure that we have a good handle yet on the false negative and false positive data.

  4. To your other question, NaF18 is the same as F18 (only the fluoride ion is important). Unlike FACBC, it is only taken up by bone. All C11-based agents have exactly the same half-life of 20 minutes. All F18-based agents have exactly the same half-life of 110 minutes, so it doesn’t have to be manufactured on site, but it must be nearby. Ga-68 has a half-life of 68 minutes.

  5. Sitemaster – Thanks very much for your informative reply.

    I’m hoping this new imaging agent has a kinder fate than feraheme for USPIO (Ultra Small Super Paramagnetic Iron Oxide) imaging. The feraheme scan worked very well for me, but I’ve learned that it is no longer available due to a rare risk of death from allergic reaction that can not, in some patients, be controlled by the standard emergency measures.

  6. The question of detection efficacy of FACBC vs [11C]choline is addressed in the paper by Nanni et al. cited above by Allen. It reports on 89 post-RP patients who received both scans — not a lot to base conclusions on, but for what it’s worth they report results as follows.

    For [11C]choline and [18F]FACBC respectively, sensitivities were 32% and 37%, specificities 40% and 67%, accuracies 32% and 38%, PPVs 90% and 97%, and NPVs 3% and 4%. So it would seem FACBC has fewer false positives (false positive rate 33% versus 60%).

    They break down the number of true positives (NTP) by PSA value as follows:

    — PSA = < 1 (N = 28): NTP(FACBC) = 6; NTP([11C]choline) = 4
    — PSA = 1 to < 2 (N = 28): NTP(FACBC) = 8; NTP([11C]choline) = 8
    — PSA = to < 3 (N = 11): NTP(FACBC) = 5; NTP([11C]choline) = 4
    — PSA = 3+ (N = 22): NTP(FACBC) = 13; NTP([11C]choline) = 11

    Their standard of reference (criterion for "true" versus "false") was follow-up at 1 year, including correlative imaging, PSA trend, and pathology when available.

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