Lutetium 177 PSMA radionuclide therapy for men with prostate cancer

[Giorgos]

Lutetium 177 PSMA radionuclide therapy for men with prostate ca is proposed to me. 56age , castrate resistant pr ca with neuroendocrine differenciation and bones and lymph nodes involvment resistant to all therapies tried until now. Any information, suggestion is wellcoming. Thank you

[Hidden]

LU-177 is showing a lot of promise as a treatment if you have a significant expression of PSMA. Have you had any imaging done for that?

"Currently PSMA activity is measured by assessing intensity of activity on a 68Ga‐PSMA staging PET/CT and is a requirement for treatment in all currently published studies."

Here's more information on that:

ncbi.nlm.nih.gov/pmc/articl...

[Tall_Allen]

It's not the Lu-177 so much as the ligand it's attached to. The ligand is what attaches to the PSMA on the surface of prostate cancer cells. However, neuroendocrine PC does NOT express PSMA, so in Germany they are experimenting with a different ligand called DOTATOC that attaches to the somatostatin receptor instead. They attach to it Bi-213, which emits powerful alpha particles as it undergoes radioactive decay. Here's some more info:

pcnrv.blogspot.com/2016/12/...

[JLS1 in reply to Tall_Allen]

So neuroendocrine tumors originating from PC are different?:

FDA Approves New Treatment for Certain Neuroendocrine Tumors

cancer.gov/news-events/canc...

“This is a major advance for patients with neuroendocrine tumors and provides a new treatment alternative for a good number of patients who don’t respond to other treatments,” said Electron Kebebew, M.D., chief of the Endocrine Oncology Branch in NCI's Center for Cancer Research.

The new drug consists of a radioactive isotope, Lu-177, ...."

[Tall_Allen]

Yes, neuroendocrine prostate cancer is certainly an entirely different animal from acinar adenocarcinoma of the prostate. Unfortunately, the FDA only approved Lu-177-DOTATATE for neuroendocrine tumors of the pancreas and GI tract, but not for neuroendocrine prostate cancer. It is the ligand that determines whether it will be effective against neuroendocrine tumors or ordinary prostate cancer. DOTATATE=DOTATOC

[Hidden in reply to Tall_Allen]

There are trials in the US, and I think he is in Germany, anyway.

[Hidden]

You have neuroendocrine differentiated PCa, but we don't what percentage it is. If they are proposing LU-177 to you, I'm guessing they suspect there may be enough PCa cells expressing PSMA. The original biospy was Adenocarcinoma so it's probably treatment related and some percentage of neuroendocrine. The best way to determine how much PSMA expression would be with imaging.

We are not doctors here, so ask your doctor about these things and please let us know what he or she says about it.

[Hidden in reply to Hidden]

Well, the 177Lu is the warhead. The warhead is going to blow up, no question about that.

The question is where is it going to be when it blows up? That depends on the guidance system. What is the guidance system targeting?

Should it target the somatostatin receptor or should it target the PSMA cell surface antigen.

These drug conjugates are even a little bit more involved: The target of the ligand part of the drug conjugate can be PSMA (or something else), but the ligand itself can be a full antibody (like J591 is) or can be an analog of a subset of it. This is called "small molecule".

Example of use: ncbi.nlm.nih.gov/pmc/articl...

What you would love, is to target something that is taken into the nucleus, so that each detonation is fairly certain to destroy the DNA. This however, is still a dream, as far as i know. A virus-based guidance would be nice; one that targets cancer stem cells.

[Hidden in reply to Hidden]

He did not actually say that it is "treatment induced" NET. That is a factor. Oh he did say "castrate resistant" so it sounds like he has gotten ADT. Yea.

Also, the University of Iowa is replicating a lot of the experimments done in Europe on neuroendocrine cancers. PRRT in the acronym for the treatment. It does have somatostain as the target, as you mention. They might have something to say. They got a giant grant last year, so it has their attention.

Oh! He has been in Germany. The University of Heidelberg is doing this.

[Hidden in reply to Hidden]

Heidelberg is reluctant to do 225Actinium, I think because of toxicity to the saliva glands. Problems, problems....

Heidelberg: ncbi.nlm.nih.gov/pubmed/286... click on Author Information. Dr C Kratochwil

[Giorgos]

Thank you for the informations. Very usefull!

[j-o-h-n]

Giorgos,

Yassou, me tin ygeía.

Good Luck and Good Health.

j-o-h-n Monday 04/02/2018 11:15 PM EDT