PSA, MRI, Biopsy why doesn't PSMA Pet Scan

Following to learn. Sure seems odd to me.

For what it's worth, there was no sign of cancer in my prostate via MRI or CT+contrast scan in 2021, even though it had already metastasised to my spine and formed a lesion large enough to compress my spinal cord and render me temporarily paraplegic. All scans, including PSMA-PET, have a resolution limit, and can miss very small clusters of cancer cells. In my case (and possibly yours???), the cancer had escaped my prostate early, before it had time to develop any detectable tumours in the prostate itself.

It's rare, but it happens (my oncologist told me "1 case in 20" at the time, but that might have been a ballpark rather than a hard stat). We don't all follow the standard path of cancer staying in the prostate and growing until the gland enlarges visibly or forms detectable lumps, and only then possibly escaping into the rest of the body.

Here’s info directly from Mayo

It's possible for a PSMA PET scan to miss cancer confirmed by biopsy because not all prostate cancers produce enough PSMA protein, or the cancer cells might be in an area hard to see, leading to a false negative, even though PSMA scans are highly accurate for detecting cancer spread, with about 10% of cancers not showing up. If a biopsy confirms cancer but the PSMA scan is clear, it suggests the cancer might be an "under-producer" of PSMA or located where detection is difficult, requiring further discussion with your doctor about other imaging (like MRI) or treatment strategies, say the Mayo Clinic and WebMD.
https://www.mayoclinic.org/tests-procedures/psma-pet-scan/about/pac-20582225.

(Remember that every test has its limitations - PSA, MRI, biopsy, biomarker, and yes even PET scans.)

As @jeffmarc mentions, some prostate cancers (said to be in the range of 10%-15%) are PSMA-negative (or PSMA-naive), such that the prostate cancer does not express the PSMA protein on its cell surface (or too little to be detected), in which case a PSMA PET scan will not "see" the tumors, even if other tests (like a rising PSA or biopsy) confirm the cancer is present and growing.

Also consider that prostate cancer is very heterogeneous, not just from person to person, but also sometimes within one person; some prostate cancer cells may express PSMA while others may not.

PSMA PET scans outperform the other (older) types of PET CT scans (like FDG, NaF, Choline C11, and Axumin) - just as long as the prostate cancer cells are producing enough PSMA to be detected.

In the cases when it isn’t, the older types of PET scans, ones that aren’t dependent on PSMA - like the older Axumin or Choline C11 PET scans - might be able to detect the location of the prostate cancer. (Mayo Clinic often uses the older C11 Choline PET scan for this purpose.)

For prostate cancers that may be PSMA-negative, Axumin®
(F18-Fluciclovine) is often used. (Insurance still covers it.) Axumin PET scans don’t rely on PSMA.

Axumin works by exploiting the fact that prostate cancers absorb amino acids at a much more rapid pace than normal cells. Axumin is made up of a radioactive tracer linked to an amino acid. Cancer cells absorb the amino acids more avidly than normal cells, so when Axumin is used, the radioactive tracer concentrates inside the tumor cells. Then during imaging, the areas that have a high concentration of the imaging agent signal the location of the cancer.

Just something to consider in the future if needed (which hopefully it won’t be!)

PS: The Mayo HQ in Minnesota is the only site that uses choline because the half life is minutes. There the source is made a la carte.

@brianjarvis
Neuroendocrine prostate cancer is another exception

FDG can be good for highly aggressive NEPC due to its high glucose metabolism, though PSMA or other tracers like Gallium-DOTATATE (not Axumin) might be better for targeting neuroendocrine features, meaning the best choice depends on the cancer's specific biology, with no single "easiest" scan for all scenarios.

I have heard doctors at PCRI say that the choline PET scan is not worth doing. That could be the reason it’s only available at one place in the USA. Makes me wonder why it is used in place of a PSMA PET scan

in this video Mark Scholz discusses what he does when a PET scan on one of his patients shows no uptake in the prostate

@jeffmarc The reason why Choline C-11 (Carbon-11) isn’t used in but one place in the U.S. - Mayo Clinic Rochester - is more about logistics (& perhaps financials) than anything else.

The half-life of Choline C-11 is very short, about 20 minutes, which means it has to be used very quickly after its generation. This rapid decay makes its use limited elsewhere. (Plus, I’ve read that there are still patents related to Choline C-11 for its use in medical imaging.)

If you recall, this was the same challenge when PSMA was first FDA-approved in late 2020. The clinical trials using Gallium68 (68Ga-PSMA-11 - later trade-named Illuccix) were all done at UCLA and UCSF. With the half-life of Gallium68 being just 58 minutes, there was no way to access it unless you travelled to either of those universities.

These days there are a number of “kits” that are used to generate not only Gallium68 for PSMA PET scans, but also F18-DCFPyL (trade name: PYLARIFY®) and F-18-Flotufolastat (trade name: Posluma®). So, if a Facility has the proper ‘kit’ they can generate the isotope on-site.

Mayo Clinic had been using Choline C11 in clinical trials for almost a decade before it was FDA-approved for prostate cancer diagnosis in 2012. So, they’re the recognized experts in its use, the only one that uses it, and probably has a vested (financial) interest in its continued use.

It’s said that the Choline C11 PET scan is on-par with the Axumin PET scan.
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Many PET scans have been developed over the past 25 years to diagnose prostate cancer:

> F18-FDG (Fluoro-2-Deoxyglucose) PET/CT: FDA approved in August 1999

> F18-NaF (Sodium Fluoride) PET/CT: FDA approved in February 2011

> Choline C11 (Carbon 11) PET/CT: FDA approved in September 2012

> F18-Fluciclovine PET/CT: (trade name: Axumin®): FDA approved in May 2016

> 68Ga-PSMA-11 (Gallium68) PSMA PET: (trade name: Illuccix®): FDA Approved in December 2020

> F18-DCFPyL (Piflufolastat) PSMA PET: (trade name: PYLARIFY®): FDA approved in May 2021

> F-18-Flotufolastat PSMA PET: (trade name: Posluma®): FDA approved in June 2023.

More are coming…….
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@brianjarvis
The fact that choline has not been used anywhere else in the USA is because it is not an effective PET scan is what I have heard.

There are much better options.

Heard a doctor PCRI said it’s not even worth doing that scan.

I still haven’t heard any reasoning why that scan is useful compared to Axumin, FDG or PSMA pet scans.

@brianjarvis
Here are scans done from various pet types

The Choline scan compared to the PSMA misses possible metastasis in the spine And shows a big Blob where the Prostate bed is and only highlights the salivary glands.

Still not sure why it is used.