Basically a rapidly rising PSA but so far PSMA-negative scan (Ga-68). I’ve been assuming I’ll eventually have Pluvicto as a backstop, but if I actually have PSMA-negative disease, the Pluvicto wouldn’t help me. But I’ve stumbled across a new imaging agent that may also prove useful in theranostics for PSMA-negative disease.
Cu-64 has been discussed in previous posts on this forum. There are various trials using Cu64 (recruiting, not yet recruiting) for 64Cu in US and Australia as per this list:
Several of these trials are using 64Cu-SAR-bisPSMA while one, at the moment, uses 64Cu-SAR-BBN.
Judging by the name, the bisPSMA agent targets PSMA. If I’m correct, then this doesn’t help if someone has PSMA-negative disease. I would lobby Clarity Pharma to change the name, but I’m pretty sure that won’t help either.
However, the upcoming SABRE trial uses 64Cu-SAR-BBN, which, according to the following article, targets Gastrin Releasing Peptide receptor (GRPr) instead of PSMA (the name used in article is 64Cu-SAR-Bombesin):
As per the article, SABRE investigates detection of cancer in PSMA-negative disease. Subsequent theranostic treatment might apparently be done with a different isotope that also targets GRPr, namely 67Cu.
Interestingly, GRPr is also expressed on other types of tumors, not just prostate.
As brought to our attention some years ago by tango65 , Bombesin has been under investigation for low-PSMA expression, and he points us to this excellent article that elaborates on the bigger picture:
“GRPR is found in prostate cancer cells but is also highly expressed in gastrointestinal and CNS tissues. This limits its usefulness as a therapeutic target.”
…which suggests that the Cu64/67 approach is not the silver bullet I’d hoped. Next we have FAPI:
“Fibroblast Activating Protein (FAP) seems to be particularly useful. It is highly specific - it has only been found in cancers of epithelial origin (like prostate cancer), and never in healthy tissue. Immunohistochemical analysis of tumors has demonstrated a strong correlation between high FAP expression and worse prognosis. It has also been found in damaged tissue: inflamed tissues as in rheumatoid arthritis, myocardial infarction, liver cirrhosis, and atherosclerosis.”
So, my understanding is that we want to inhibit the FAP. The article talks about previous studies with decent FAPI imaging where PSMA was not so good, and a FAPI-based theranostic experiment in Germany.
But in a FAPI post by TA , three years ago but updated recently:
“It doesn't seem to be as good with PCa as it is with other cancers. MD Anderson has been focussing on fibroblast growth factor inhibitors like erdafitinib.”
And GP24 ’s n = 1 story does not endorse FAPI wrt diagnosis.
So, FAPI appears a mixed bag. Trials right now are limited to two, with only one in US (which I don’t qualify for).
My takeaway so far, for my particular situation, is (1) get another PSMA-based scan when PSA is higher, and/or get an F-18 scan sooner on the assumption it’s more sensitive at low PSA (mine at the moment is ~2); (2) investigate 64Cu trials to cover things if in fact I have PSMA-negative disease; (3) keep an eye on future alternate theranostics as complement to PSMA-based. For now it appears #3 is elusive - I welcome corrections to my read of things.
I wonder if FAPI requires a higher PSA to be as sensitive as the PSMA…? So you found the mets four months later b/c of that, and/or b/c they simply got “large enough” to be spotted over that time frame?
I believe this clinic is starting FAPI treatment privately. I dont know if they will offer it for prostate or other cancers but you could ask them if they think it is feasible for prostate. They have been very responsive to my enquiries about LU177 in the past
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Best alternative PET for PSMA negative PCa
Highly effective targeted therapy for metastatic prostate cancer, using 177Lu-PSMA Radioligand 
Advanced recurrent PCa, rising PSA, 2 negative PSMA PET Scans
looking for input - RIsing PSA with Negative PSMA Pet scan
Bone met biopsy = [b]PSMA-POSITIVE, PSA-NEGATIVE TUMOR[/b]
