Showing posts with label PET. Show all posts
Showing posts with label PET. Show all posts

Sunday, September 2, 2018

Free Randomized Clinical Trial of Ga-68-PSMA-11 PET indicator at UCLA

UCLA is now running a randomized clinical trial of the Ga-68-PSMA-11 PET indicator for men  with a recurrence (PSA≥ 0.1 ng/ml) after prostatectomy who are considering salvage radiation therapy (SRT). They are expanding and adding a control arm to the trial they did earlier (see this link) that found that the PSMA-based PET scan was able to change treatment decisions in about half the men.

Here are the trial details and the contact info:
https://clinicaltrials.gov/ct2/show/NCT03582774

UCLA normally charges $2650 for the PET indicator, so this is an opportunity to save some money. If a patient is randomized to the control group, he may still get an Axumin PET scan when his PSA is confirmed above 0.2 ng/ml, which is covered by Medicare and most insurance. The Axumin PET scan only detects cancer in 38% of patients if their PSA is in the range of 0.2-1.0 ng/ml, while the Ga-68-PSMA-11 PET scan detects cancer in about 27%-58% of recurrent men whose PSA is between 0.2 and 0.5. UCLA recently completed another free clinical trial comparing Axumin to Ga-68-PSMA.

I'm told that the NIH trial of another PSMA PET indicator, DCFPyL, has a waiting list of 2-3 months, and they are no longer taking patients whose PSA is below 0.5 ng/ml. It is possible to pay for PSMA-based PET scans in Germany and Australia. The newest and perhaps most accurate PSMA-based PET indicator, F(18)-PSMA-1007, is in clinical trials in Germany (see this link).

This trial is not open to men who have already had SRT, have known metastases, have had ADT within the last 3 months, or who cannot have radiation for any reason.

Thursday, July 26, 2018

F18-PSMA-1007 - the latest PSMA-based PET indicator

The development of new PET indicators for prostate cancer continues. As we've seen, the Ga-68-PSMA-11 indicator is already making a difference in clinical practice. Many of the new PET indicators have been developed in Germany, although the best one so far before this, F18-DCFPyL was developed at Johns Hopkins.

Researchers in Germany have developed a new PSMA-based PET indicator, F18-PSMA-1007, that seems to be even better. They tested it on 251 biochemically recurrent (after prostatectomy) patients at 3 academic centers.

  • 81% had a recurrence detected
  • 44% had a local (prostate bed) recurrence
  • 41% had a pelvic lymph node recurrence
  • 20% had a retroperitoneal lymph node recurrence
  • 12% in lymph nodes above the diaphagm
  • 40% had bone metastases
  • 4% had visceral organ metastases


Detection rates varied by PSA:

  • 62% in those with PSAs from 0.2-<0.5
  • 75%  in those with PSAs from 0.5-<1.0
  • 90%  in those with PSAs from 1.0-<2.0
  • 94%  in those with PSAs >2.0


Interestingly, those who had ADT in the last 6 months had higher detection rates (92%) compared to those who'd had no ADT recently (78%). This may be because those who had ADT recently had more advanced tumors. There was some early evidence in mice and lab studies (like this one and this one) that ADT upregulated PSMA. One clinical study indicated that ADT improved detection of PSMA. Two studies  (this one and this one) showed no effect of ADT on PSMA detection. More recent evidence indicates use of ADT negatively impacts detection rates. The patient should avoid ADT before getting a PSMA-based PET scan, if possible.

The detection rate among those with PSAs between 0.2-2.0 was 78%, which is comparable to the 88% detection rate reported for men with PSAs between 0.2-3.5 for F18-DCFPyL and much better than the detection rate of 66% reported for Ga-68-PSMA-11 in that PSA range. F18 has an advantage over Ga-68 in having a longer half-life (118 minutes vs 68 minutes) and is more tightly bound to the ligand. Because it is not appreciably excreted through the urinary tract, it can be seen more easily around the prostate - important when the recurrence is near the site of the anastomosis, as most recurrences are. In a mouse study, it was superior to F18-DCFPyL. In a clinical pilot study, they both detected the same tumors.

As of now, the F18 PSMA-based PET indicators seem to be superior, but others are working on ligands that detect other prostate cancer proteins more sensitively and more specifically. Leading candidates are hK2, FMAU, Citrate, Prostate-Stem-Cell-Antigen, , DHT/androgen receptor, uPAR receptor, VPAC receptor, or multiple ligands.

Also see:




Saturday, February 24, 2018

A PSMA-based PET scan can change salvage radiation treatment decisions

The new PSMA-based PET scans provide a way to locate exactly where the cancer has spread to after an unsuccessful prostatectomy. Formerly, the only tools we had were scans that could only detect very large or rapidly growing tumors at PSAs well above the levels most radiation oncologists would be comfortable treating with salvage radiation; that is, there is widespread agreement that success rates improve the lower the PSA is when SRT is used. Even the newly approved Axumin PET scan only detects cancer in 38% of patients if their PSA is in the range of 0.2-1.0 ng/ml. By contrast, as we saw recently, the Ga-68-PSMA-11 PET scan has detected cancer in half of men when their PSA was still below 0.2, and in about two-thirds of men whose PSA was 0.2 - 0.4. The PSMA-based PET scan has the power to change SRT treatment decisions.

Calais et al. reported the results of a multi-institutional study of the Ga-68-PSMA-11 PET/CT in 270 men with biochemically recurrent prostate cancer after prostatectomy while their PSAs were still below 1.0 ng/ml (median 0.44). The institutions comprised UCLA, Technical University of Munich, Ludwig-Maximillian University of Munich, and University of Essen. Patients received PET scans from 2013-2017. Researchers painstakingly mapped all sites of cancer to find the locations of cancer that would have been missed if they had just blindly treated the prostate bed and/or the pelvic lymph node field recommended by RTOG guidelines.

The following table shows how treatment decisions might change based on their findings.

So, all in all, about half of treatment decisions might change - 30% in a minor way, 19% in a major way. The major changes would be: 
  • forgoing SRT entirely in up to 12%
    • consider metastasis-directed radiation in 8% - a treatment of unknown significance
  • changing from prostate bed-only to whole pelvic SRT in 11%, so as to potentially render curative what would have been a non-curative treatment
  • expanding the pelvic treatment field in 7%, so as to potentially render curative what would have been a non-curative treatment
At the above institutions, extended pelvic lymph node dissection (ePLND) is common practice - 81% of patients had a PLND. Consequently, 20% of patients already had detected pelvic LNs (N1) before the scan. At many institutions in the US where ePLND is less common in intermediate and high risk patients, this can cause a much larger and potentially curative change in the treatment plan from prostate bed-only to whole pelvic radiation. The researchers are to be congratulated for the painstaking work in contouring and comparing so many pelvic scans.

As one might expect, PSMA-based cancer detection was higher for those with Gleason score more than 7, and those with pathological stage N1 and T3. The patient's PSA at the time of the scan played a major role. While almost two-thirds had a PSA ≤ 0.5 ng/ml, the detection rate was 41% for those patients vs. 60% for those with higher PSAs. While detection improves with higher PSA, it is important for patients to understand that it is unwarranted (and potentially unsafe) to wait for PSA to rise just so that more cancer can be detected. That would be a self-fulfilling prophecy: by waiting for the cancer to put out more PSA, one is virtually ensuring that the cancer will grow, spread, and possible metastasize. Although we await definitive clinical trial data, most radiation oncologists recommend early treatment (before PSA reaches 0.2 ng/ml) for men with adverse pathology or for those evincing a distinct pattern of PSA progression after prostatectomy.

While a previous analysis showed that the Ga-68-PSMA PET had little effect on SRT decisions, and no patients were upgraded from incurable to potentially curable, this larger, more detailed study indicates that about 1 in 5 patients can be upgraded, and 1 in 6 can be spared SRT. This would seem to justify the cost. UCLA charges $2650 for recurrent (and high risk) patients. NIH is recruiting recurrent and high risk patients for an improved PSMA-based PET scan (called DCFPyL) that  is free (and transportation to Washington D.C. is covered as well).

Friday, March 10, 2017

Are two PET radiotracers better than one?

There seem to be clinical trials of new PET radiotracers for the detection of prostate cancer all the time. In addition to the FDA-approved C-11 Choline, NaF18, FDG, and fluciclovine PET scans, most of the new PET scans target the PSMA protein on prostate cancer cells. On the horizon, we have seen some encouraging reports on PET radiotracers that target the Gastrin Releasing Peptide Receptor (GRPR) with a peptide called bombesin. GRPR, as the name implies, is ubiquitous in the stomach and intestines, but seems to show up in several different kinds of cancer cells as well.

Zhang et al. reported the results of a very small pilot study using a synthetic molecule that targets two different receptor proteins at the same time (also see this link). One part of the molecule (bombesin - BBN) targets the GRPR protein. The other part, called RGD, targets a protein called αvβ3. αvβ3 is a member of a family of proteins called integrins. These proteins are responsible for maintaining the structural integrity of cells. αvβ3 promotes cell adhesion, spreading and blood supply -- qualities vital to metastatic progression.

They used both the single Ga-68-BBN PET/CT and the dual Ga-68-BBN-RGD PET/CT to detect prostate cancer among 13 patients (4 newly diagnosed, 9 recurrent) with biopsy-proven prostate cancer. The dual PET radiotracer found cancer:

  • In the prostates of 3 of the 4 men with newly diagnosed prostate cancer vs. 2 of the 4 men using the BBN-only radiotracer.
  • 14 metastatic lymph nodes vs. 5 metastatic lymph nodes using the BBN-only radiotracer.
  • 20 bone metastases vs. 12 metastatic bone metastases using the BBN-only radiotracer.

There were no toxic reactions.

While encouraging, it is still very early to draw conclusions. There is no confirmation that the extra "metastases" discovered were indeed metastases - they may be false positives. And there are no clues as to which kinds of prostate cancer the dual PET radiotracer is sensitive to, and which kinds are undetectable.

If confirmed by larger studies, it may be possible to not just detect the cancer, but to kill the detectable cancer cells as well with beta emitters like Lu-177 or alpha emitters like Ac-225.

Sunday, December 11, 2016

PET scans for prostate cancer

In the last few years there has been an explosion in the number of new PET scan indicators. I thought it a good idea to provide some background and an update.

Bone scans

PET scans may be understood as an improvement over bone scans. The traditional way of finding distant metastases is to use a technetium bone scan and CT. There are several problems with bone scans:
  • they show bone overgrowth, which may be bone metastases, but may just be arthritis or old injuries
  • only a bone biopsy can tell for sure, and it's not often feasible when the suspected mets are small or inaccessible
  • they reveal few mets when PSA is below 10-20 ng/ml or when PSA is stable
  • they only show bone mets, not soft tissue
The main advantage is that they are relatively inexpensive.

The principal uses are: 
  • to rule out bone mets in high risk patients prior to curative treatment
  • to diagnose metastases that may respond to chemo, Xofigo, or spot radiation
  • to track response to treatment among metastatic patients.

PET SCAN USES

Inherent limitations

The new PET scans are better than previous ones in terms of the size of the metastases they can detect, but they do not detect all metastases.
  • A cancer cell is many times smaller than the resolution of the CT or MRI. 
  • The activity of the cancer cell seems to influence whether it is detectable on any of the scans. 
  • There is "noise" in even the most specific tracer, with no sharp delineation between signal and background.
Salvage Radiation

The most important use of these new PET scans is to rule out salvage treatment when it would be futile. For men who have persistently elevated PSA after prostatectomy, or who have had a recurrence (nadir+2) after primary radiation treatment, a PET scan showing distant metastases can spare the man the ordeal and side effects of salvage treatment.

The FDA has approved Ga-68-PSMA-11 PET/CT for detection of recurrences after prostatectomy or radiation. They have also approved Axumin PET scans and C-11 Choline PET scans (at Mayo) for this purpose.

For salvage after primary radiation failure, it is necessary to locate areas within the prostate where the cancer may still be localized.  Memorial Sloan Kettering and the Mayo Clinic have effectively used PET scans to target areas within the prostate for salvage focal ablation or brachytherapy.

For salvage radiation after prostatectomy, it may be possible to identify areas of the prostate bed where spread is evident. While the entire prostate bed must be treated (most of the prostate cancer is below the limit of detection of even the most accurate PET/MRI scan), some radiation oncologists like to provide an extra boost of radiation to the detected cancer foci.

For salvage radiation after primary radiation therapy, whether focal or whole gland (see this link), a PSMA PET scan combined with an mpMRI may be able to detect areas within the prostate that still have cancer. PSMA PET scans may cause false positives if used alone to detect cancer in and around the prostate, because they are excreted in the urine. Some of the newer PSMA PET scans (e.g., F18-PSMA-1007 and F18-rh-PSMA-7) have less renal clearance.

There has been accumulating evidence in the last few years (see this link) that very early salvage radiation treatment may improve salvage radiation outcomes over waiting until the PSA has risen above 0.2 ng/ml. Unfortunately, none of our PET indicators are any good at detecting metastases when PSA is below 0.2 ng/ml. It is unlikely that there are any distant metastases when PSA is that low, but there are some relatively rare forms of prostate cancer that metastasize without putting out much PSA. This leaves the patient without any assurance that salvage radiation will be successful. Perhaps the new PORTOS genetic test will be able to detect distant metastases biochemically, but this remains to be proven.

Pelvic Lymph Node (LN) Treatment

For men diagnosed with high risk prostate cancer, a difficult question is whether the pelvic lymph nodes ought to be treated, either with radiation or with pelvic lymph node dissection. Nomograms based on disease characteristics are used to determine whether the pelvic LNs merit treatment, but such nomograms are often inaccurate. A CT scan can sometimes identify lymph nodes enlarged (>1.2 cm) due to cancer. However, some LNs are only slightly enlarged (0.8-1.2 cm), and some cancerous LNs are not enlarged at all (<0.8 cm). LNs are usually enlarged by infection, so size alone is not a good indicator of cancer. An advanced PET scan can sometimes detect cancerous LNs. This may aid the decision on whether to have whole pelvic treatment for men with high risk cancer. Men who have already had radical prostate therapy that may have included radiation (primary or salvage) to other areas (i.e., the prostate or prostate bed) may face a similar decision as to whether to treat the pelvic LNs with radiation.

Just as it is necessary to irradiate the entire prostate bed and not just the detected foci when giving salvage radiation after prostatectomy, it is probably necessary to treat the entire pelvic LN area, and not just individual LNs, when cancer is detected anywhere in the pelvic LN area. Of course, such a decision must be balanced against the risk of side effects. There are ongoing clinical trials (RTOG 0534 for salvage therapy and RTOG 0924 for primary therapy) to determine whether such treatment provides any survival advantage when LN involvement is suspected. The STAMPEDE trial included an arm where patients were node positive (but negative for distant metastases) and were treated with radiation. Short term follow-up demonstrated an improvement in failure-free survival of 52% among those who had treatment.

Ruling out distant spread where it seems to be localized

PSMA PET scans have been approved to detect prostate cancer in high-risk patients. PSMA PET scans provide a critical decision-making tool because it may be able to answer the following questions for the first time:
  1. Is the cancer still confined to the prostate capsule?
  2. Has the cancer spread to the prostate bed or to surrounding organs?
  3. Has the cancer spread to pelvic lymph nodes?
  4. Has the cancer spread to non-local lymph nodes, bone, or visceral organs?
Giving extra radiation to known tumors

While modern dose-escalated doses of radiation of very good at eradicating tumors, results can be improved even further if focused boost doses are given to areas in the prostate, the prostate bed, and pelvic lymph nodes that are proven to be cancerous with a PET scan. The excellent results are described here.

Oligometastatic radiation of distant metastases

Although some have theorized that there is a stage in prostate cancer metastatic progression where the cancer is still curable, or where it can be delayed by removal of 1-3 detectable metastases, this theory has never been proven. In fact, a meta-analysis this year (see this link) showed that metastatic progression continues in almost all men despite such treatment. The possibility remains that progression may be slowed by spot treatment, although this remains uncertain as well. The natural history of metastatic progression is often very slow in early stages, with years between the first few metastases. The reason for this may be because the tissue in metastatic sites must first be biochemically transformed by signals from micrometastases in order to accommodate the growth of larger metastases. This preparation of fertile "soil" in which metastatic "seeds" can grow may take some time. PET scans for detection undoubtedly introduce lead-time bias into the calculation; i.e., the time between the first and second detected metastasis is certainly longer because a more sensitive PET scan was used, and not necessarily because the first detected metastasis was spot-treated.

In spite of the uncertainty concerning efficacy of spot treatment, patients often want to treat whatever can be detected. When such metastases are detected with sensitive PET scans and are in locations amenable to spot treatment with SBRT, and there is minimal risk of radiation damage to nearby organs, it is hard to argue against such use. However, the patient should understand that there is so far no evidence that such treatment will provide any benefit. He should also understand that detectable metastases in distant sites means that his cancer is systemic. There are thousands of circulating cancer cells and undetectable cancer cells already lodged in tissues. For this reason, it is never a good idea to delay systemic therapy (e.g., hormone therapy) in order to wait for PSA to increase to a point where metastases become detectable on a PET scan. 

Palliative treatment of metastases

Metastases can cause pain and interference with organ function. Bone scans can find larger bone metastases, and they are the ones most apt to cause pain, fracture, or spinal compression. Metastases in weight-bearing bones may be spot-radiated with SBRT to prevent such problems and to relieve pain. In the unusual event that a bone scan can't locate them accurately enough for SBRT treatment, a PET scan may be used.

Bone scans do not detect metastases in soft tissue, while most PET scans (other than the NAF18 PET) can. A PET scan may locate metastases in organs that may be biopsied or treated with radiation or other therapies, like embolization or ablation.

Multiple metastases

The CHAARTED study has taught us that prostate cancer with multiple distant metastases behaves in a different way and reacts to different therapies compared to prostate cancer with a low metastatic burden. Although the metastatic burden in the CHAARTED study was based on bone scan and CT, there may be a potential to identify patients who may respond to earlier systemic therapy if a PET scan were to be used. This use has yet to be explored.

Tracking success of treatments (radiographic progression)

PSA is not always the best measure of whether a treatment is successful and ought to be continued. Because they destroy cancer cells, some therapies may actually raise the PSA level for some time immediately following treatment. Chemotherapy does not always immediately reduce PSA, but the patient wants to know whether the potentially toxic treatment should be continued. Most of the time, serial bone scans can provide an adequate radiographic assessment. However, in patients with low PSA or low metastatic burden, serial PET scans may sometimes provide a more accurate assessment.

Initial detection, active surveillance, focal therapy, dose painting

Just as multiparametric MRIs can be used to detect significant prostate cancer when suspicion remains after a first negative biopsy, a PET scan can conceivably be used for such a purpose (as in this clinical trial). PET scans can also be used to track progression of prostatic foci in patients on active surveillance. It is hard to justify the cost for such purposes, and there is as yet no evidence that it is any better than a multiparametric MRI. In light of the recent evidence that multiparametric MRI may fail to delineate up to 80% of detected prostatic index tumors, they may find future use of PET/MRI in contouring treatment areas for focal ablation and for dose painting (see this link).

The FDA has approved Ga-68-PSMA-11 PET/CT at UCLA and UCSF for unfavorable risk prostate cancer.


How PET scans work

Positron Emission Tomography (PET) is a way of creating a 3D anatomical image. Instead of using X-rays, as a Computerized Tomography (CT) scan does, it detects positrons, which are positively charged electrons (which do not exist in nature). When a positron encounters a normal negatively-charged electron, they annihilate each other and release 2 gamma rays in opposite directions. When the machine detects such a pair of gamma rays, it extrapolates their source position, putting an image together. The PET scanner is combined with a CT scanner in the same device in order to provide anatomic detail.

As a cautionary note, PET scans do expose the patient to significant amounts of ionizing radiation from both the PET indicators and the simultaneous CT scan. It is not something one wants to do frequently.

PET emitters are short-lived radioisotopes that are created in a nearby cyclotron. Commonly used ones include carbon 11 (C11), fluorine 18 (F18), gallium 68 (Ga68), copper 64 (Cu64), zirconium 89 (Zr 89), and iodine 124 (I124). The choice of which one to use is based on cost, access, half-life, strength of signal, and ease of integration with the ligand. C11, for example, has an extremely short half life of only 21 minutes. This means it has to be manufactured very nearby where it will be incorporated into a ligand (like acetate or choline), and must be used immediately. F18 has a longer half-life (118 minutes) and has excellent detectability, but interferes somewhat with metabolism of acetate or choline. I124 has a long half-life (4.2 days) which may be too long for a patient who may have to remain isolated for the duration.

PET emitters are often chemically attached (chelated) to molecules, called ligands, that have particular affinity for prostate cancer cells. Some ligands are metabolically active, meaning they are food for the cancer cell, but not as much for healthy cells. Other ligands are created to attach to specific binding sites on the surface or inside prostate cancer cells. 

NaF(18) PET for bone metastases

Sodium fluoride (NaF18) replaces hydroxide with positronic fluoride when hydroxyapatite, the mineral that constitutes our bones, is actively accumulating in bone metastases. It is our most sensitive tool for detecting bone metastases. Fourquet et al. found that in the same patients, NaF18 detected 91% of bone metastases while DCFPyL detected only 46%.

Metabolic ligands

Because rapidly growing cancer cells metabolize a lot of glucose, fluoro-deoxy-glucose (FDG) has long been used in PET scans for cancer. Prostate cancer in its early stages does not metabolize glucose readily, so FDG can't be used until later stages.

Prostate cancer cells do metabolize fats, consuming choline and acetate. C-11 choline and acetate overcomes the interference problem of F-18 choline and acetate, but is very difficult to work with. Although the FDA has approved the C-11 Choline PET, only the Mayo Clinic offers it in the US. A few sites offer the C-11 Acetate PET, but it is expensive. It also requires a fairly high PSA, ideally ≥ 2.0 ng/ml, or fairly large metastases, to detect anything.

Fluciclovine has recently been FDA approved. It is incorporated into prostate cancer cells as part of amino acid metabolism. It can detect somewhat smaller metastases at lower PSAs.

PSMA ligands

95% of prostate cancers express a protein called Prostate-Specific Membrane Antigen (PSMA) on the surface of cells. There are a variety of ligands that are attracted to it. Some of the ligands are antibodies (like J591), some are shortened antibodies (called minibodies, like Df-IAb2M), and some are small molecules (peptides, like PSMA-HBED-CC or DCFPyL). PSMA-targeted ligands may accumulate in salivary glands, tear glands and kidneys, and urinary excretion may interfere with readings in the prostate area. PSMA has also been found on the cell surface of some other kinds of cancer. New PSMA ligands are still being developed and tried. So far, the one that seems to have the highest specific affinity for PSMA are the F18-based ligands (F18-DCFPyL, F18-PSMA-1007, and F18-rh-PSMA-7). They detect more metastases at lower PSA than the others. 

As prostate cancer progresses, PSMA expression reduces and the cancer metabolizes glucose to a greater extent. Then, it will be detected by FDG PET scans.


Other ligands

There are other prostate cancer-specific molecules for which ligands have been developed and to which positron emitters have been attached.  One of the most promising is the bombesin or RM2 ligand that attaches to the gastrin-releasing peptide receptor (GRPR) on the prostate cancer cell. In pre-clinical studies, it outperformed C-11 Choline. Clinical trials have started. Clinical trials have begun on several PET ligands that are designed for other receptor sites: human kallikrein-related peptidase 2 (hK2), FMAU, Ga-68-Citrate, I-124-Prostate-Stem-Cell-Antigen, Ga-68-DOTATATE (Somatostatin receptor), F18-DHT (androgen receptor), Cu-64-DOTA-AE105 (uPAR receptor), Cu-64-TP3805 (VPAC receptor). or multiple radiotracers.

The winner (so far) is...

Based on clinical trials, below are various PET indicators in approximate rank order of their sensitivity to detect recurrent prostate cancer, and their specificity for detecting it exclusively:
  1. F18-PSMA-1007
  2. F18-rhPSMA-7
  3. F18-DCFPyL
  4. F18-DCFBC
  5. Ga68-PSMA-HBED-CC (Ga68-PSMA-11)
  6. Fluciclovine (F18 - FACBC)/ Axumin
  7. C11-Choline/ C-11-Acetate
  8. F18-Choline
  • NaF18 (note: best for detecting bone metastases)
  • F18-FDG (note: better in late-stage PCa)
The following table shows the percent of patients who had metastases detected at various PSAs. F18-PSMA-1007 and F18-rhPSMA-7, are experimental PET indicators that are cleared quickly from the bladder, and are the best so far. F18-DCFPyL is much better than Ga68-PSMA at low PSA.  At PSAs between 0.5-3.5 ng/ml. it detected prostate cancer in 88% of recurrent patients, while Ga68-PSMA-11 only detected prostate cancer in 66% of the same patients - an improvement in sensitivity by a third. Next in line is fluciclovine, which was recently FDA approved. In 10 patients screened for recurrence at a median PSA of 1.0 with both Ga68-PSMA-11 and fluciclovine, the PSMA scan detected cancer in 5 of the 10 men that were negative on fluciclovine. In addition, positive lymph nodes were detected in 3 of the men using the PSMA scan that were undetected with fluciclovine (see this link). Most other PET indicators, like C-11 Choline or Acetate, or NaF18 are not at all reliable when PSA is less than 2.0.


Percent of patients in whom prostate cancer was detected by the PET indicator, broken down by the PSA of the patients


PSA range

Source

PET Indicator

<0.2 ng/ml

0.2- 0.5 ng/ml

0.5 -2.0 ng/ml

> 2.0 ng/ml


F18-DCFPyL



88% (0.5-3.5)



(1)

Ga68-PSMA-HBED-CC



66%  (0.5-3.5)


F18-rh-PSMA-7 (experimental)


71%

86% (0.5-1.0)

86% (1.0-2.0)

95%

(11)

F18-PSMA-1007 (experimental)


86%

89% (0.5-1.0)

100% (1.0-2.0)

100%

(12) (13)

F18-DCFPyL


48%

50% (0.5-1.0)

89% (1.0-2.0)

94%

(9)

F18-DCFPyL


38%

63% (0.5-1.0)

83% (≥ 1.0)


(14)

Ga68-PSMA-HBED-CC

31%

54%

88%

(2)

Ga68-PSMA-HBED-CC


58%

73% (0.5-1.0)

93% (1.0-2.0)

97%

(3)

Ga68-PSMA-HBED-CC


50%

69%

86%

(4)

F18-FluoromethylCholine


12.5%

31%

57%

Ga68-PSMA-HBED-CC



36% (PSA<1, PSADT>6 months)

95% 

(PSADT<6 months)

(5)

Ga68-PSMA-HBED-CC

11.3%

26.6%

53.3% (0.5-1.0)

71.4% (1.0-2.0)

95.5%

(6)

Ga68-PSMA-HBED-CC

33.3%

41.2%

69.2% (0.5-1.0)

86.7% (1.0-2.0)

94.4%(2.0-5.0)

100% (>5.0)

(7)

Ga68-PSMA-HBED-CC

43%

58%

72% (0.5-1.0)

84% (1.0-2.0)

90% (2.0-5.0)

(13)

Fluciclovine


37.5% (0.2-1.0)    77.8% (1.0-2.0)

88.6%

(8)

C-11 Choline


28%

46% (0.5-1.0)

62% (1.0-2.0)

81%

(10)


PET/MRI

PET scans are usually combined with simultaneous CT scans for image resolution. Siemens has a device that simultaneously provides a PET scan and an MRI. This enables  greater image resolution and the detection of smaller metastases than is possible with a PET/CT. (GE and Philips manufacture dual scanners rather than an integrated single scanner). The PET/MRI exposes the patient to a much lower dose of ionizing radiation than the PET/CT. These devices are expensive, and are only available at a few large tertiary care facilities. In one PET/CT vs. PET/MRI comparison using Ga-68-PSMA, the PET/MRI was able to detect 42% more metastases in recurrent patients, 10% more lymph node metastases, and 21% more bone metastases. In the US, PET/MRIs are in use at Mass General, Johns Hopkins, Stanford, UCSF, Washington University, Cleveland Clinic, and Memorial Sloan Kettering and several others.

Cost/Availability

So far, only Ga-68-PSMA-11, FDG, C11-Choline, and Fluciclovine are FDA approved for prostate cancer detection. NaF is approved for clinical trials and registries only. FDA approval opens the way for Medicare and private insurance to approve and pay for them. Sometimes, insurance plans will agree to pick up the cost. Otherwise, patients who want them must pay out of pocket, if they are available. Ga68-PSMA-11, while FDA-approved at UCLA and UCSF so far, costs $3,000  out of pocket. Hopefully, Medicare/insurance will reimburse soon.

Clinical trials

All of the newer PET tracers require validation with larger sample sizes. While there are some diagnostic tests that have a "gold standard" against which performance can be evaluated, this is problematic for detecting metastases. A positive finding can often be confirmed with a biopsy, so a PET scan's positive predictive value (true positives and false positives) can be ascertained. But there is no easy way to determine whether negatives were true or false in live patients.

F18-DCFPyL is available for free in a trial at NIH for free among any men who are (1) high risk or (2) recurrent (see this link). It is available as a PET/MRI for specific purposes at the  Northwestern University.

It is also available at Johns Hopkins, where it was first developed, for a wide range of indications if ordered by any of their physicians Contact details are available here, There are several studies in Canada: in BC.

Ga68-PSMA-11 is approved at UCLA and UCSF and is available in a clinical trial in the US, including one with a PET/MRI, at  Cleveland Clinic

Fluciclovine is available almost everywhere in the US, and is covered by Medicare for recurrent patients.

If you are interested in one of those PET scans for an indication outside of the clinical trial, call the contact anyway. Some are planning clinical trials for expanded indications shortly, and some may make the PET scan available for purchase outside of the clinical trial. Inquire about cost and get pre-authorization from your insurance company if you can. These can be very expensive.