Ac-225-PSMA-617 vs LU177

[cesces]

Why would one choose Ac-225-PSMA-617 over LU177 or vice versa?

[Hidden]

The main reason is that when each radioactive isotope decays, it releases certain types of particles at certain energies.

AC-225 releases alpha particles (helium nuclei) which are much heavier and thus higher energy than the beta particles (electrons) emitted by LU-177. Alpha particles have higher energy, but also shorter range so they do damage to a smaller range of tissue. They predominately cause double strand DNA breaks to the cells they hit.

The problem with AC-225 is the side effects from damage to the salivary gland which also happens to produce PSMA. I think it's still a better treatment, but they are working on that problem to make it even better.

Just for comparison, LU-177 has an energy (75% of particles) of 497 thousand electron volts. The other 25% are lower. AC-225 has an energy of 6 million electron volts for all of its emissions.

[cesces in reply to Hidden]

Don't LU177 and ac 225 have the same salivary gland problem?

[Hidden in reply to cesces]

Yes, but Ac-225 does more damage.

[cesces in reply to Hidden]

Hmm that's not so good.

And they also do kidney damage as well, for the same reason. But no one seems to talk about that. Anyone know why.

[Hidden in reply to cesces]

I do know that many of the patients that have been treated are pretty much out of options and don't have a very long life expectancy. (see Ac-225 trial result post from TA) So I think the SEs are probably weighed against that, but that's just a guess.

[tango65 in reply to cesces]

No, Lu 177 can cause xerostomia but it is transitory and less severe than Ac 225. Ac 225 may cause permanent xerostomia which could decrease quality of life.

[cesanon in reply to tango65]

It would seem to me that loss of saliva is pretty horrifying. Perhaps as bad as going on kidney dialysis. But I guess not as bad as end stage bone metastases.

[Seasid in reply to cesanon]

No, you can use biotene mouth wash. And maybe it can be better slowly.

It is not like going to have a hemodialysis.

But agree not something very desirable. Very soon this problem could be solved. I hope so.

[mperloe in reply to Hidden]

AMG160 may be a better approach that binds to PSMA and CD3 tagging the cells for T-cell destruction. This approach targets the PCa cell and does not seem to require a genetic DNA repair defect to trigger an immune response.

amgenoncology.com/clinical-...

[CantChoose]

If I understand fully (and I may not), 225 is an alpha-emitting small molecule that doesn't need a monoclonal antibody for delivery. It binds directly to the PSMA membrane, to an area that is expressed at a much higher rate in cancer cells. That results in less cell damage. It also clears the system faster than LU177, a beta emitter. Here's from an article comparing the two:

In nuclear medicine practices, two different approaches have been used for targeting PSMA. The first approach takes advantage of the macromolecular protein structure of PSMA to provide specific monoclonal antibodies as targeting vectors [45]. The second approach relies on the enzymatic activity of PSMA and uses radiolabeled enzyme inhibitors or binding agents as target seeking agents [46]. Though both these approaches have been successfully demonstrated for the development of diagnostic and therapeutic radiopharmaceuticals for targeting prostate cancer, the second approach, which utilizes radiolabeled small molecules targeting the enzyme activity of PSMA, is gaining overwhelming popularity recently. This is because smaller molecules show rapid blood clearance compared to monoclonal antibodies. This leads to a desirable higher target-to-nontarget ratio.

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

[cesces in reply to CantChoose]

Nice article. I couldn't understand it all.

I did notice that one of the problems with actinium is that there is a very very limited supply of it in the world.

If this becomes a widespread treatment it will have to be produced by scratch in cyclotrons. At very high cost it would seem.

[Fairwind]

Before you worry about the differences between these two experimental treatments, first you must figure out how and where you will receive either one of them...

[cesces in reply to Fairwind]

Actually it seems, if you are willing to travel, they are both getting more accessible by the month.

[Hidden in reply to Fairwind]

In the US, they are only available in trials. LU-177 in phase 3 and AC-225 in Phase 1. It could be a while before these are available outside of trials in the US. But as it has been pointed out, you can travel ouside the US for treatment. I don't think that is option for many due to the high cost with the exception of South Africa. AC-225 trial cost is low there.