PSMA imaging in prostate cancer

[pjoshea13]

New paper below [1].

This ties in with a recent post by Alan Meyer. Not least because of the involvement of Clemens Kratochwil.

Prostaglandin was discovered over 80 years ago & named for the prostate. It isn't actually made in the prostate, but in the seminal vesicles - & almost everwhere else. So much for a name.

Prostate-specific antigen [PSA] is not actually specific to the prostate.

So what about prostate-specific membrane antigen (PSMA)?

The Wikipedia page for PSMA is titled Glutamate carboxypeptidase II [2]:

"GCPII is mainly expressed in four tissues of the body, including prostate epithelium, the proximal tubules of the kidney, the jejunal brush border of the small intestine and ganglia of the nervous system."

Oh, & don't forget the salivary glands [3]. Which explains the dry mouth (Xerostomia) nentioned in Alan's post.

In the current paper, the subject is imaging, but in Alan's paper PSMA was targeted for destruction. Not sure how I feel about that.

"To improve clinical diagnostics of PCa, 68Ga-PSMA-11 was recently introduced as a new PET tracer. 68Ga-PSMA-11 is able to specifically bind to the prostate-specific membrane antigen (PSMA), which is upregulated on the surface of prostate cancer cells in most patients."

"In biochemical recurrence, 68Ga-PSMA-11 PET/CT shows significantly higher detection rates in comparison to choline PET/CT, especially in patients with low PSA values."

One month ago, Kratochwil was co-author of "PSMA-targeted radioligand therapy in prostate cancer" [3]:

"Radioligand therapy (RLT) directed against prostate-specific membrane antigen (PSMA) enables tumor-specific treatment directed against PSMA-overexpressing prostate cancer cells. Several PSMA ligands such as PSMA-617 or PSMA-I&T have been developed that can be labeled with β‑radiating lutetium-177. These are currently applied in compassionate use programs to treat metastatic castration-resistant prostate cancer (mCRPC). PSMA-directed RLT is currently being offered in several nuclear medicine departments throughout Germany. Several retrospective case series demonstrate its activity with a prostate-specific antigen (PSA) decrease >50% in 30-60% of mCRPC patients. The toxicity seems to be low. "

"... a survival benefit over approved standard therapies such as abiraterone, enzalutamide, radium-223-dichloride, docetaxel or cabazitaxel has not been shown. PSMA-targeted RLT should therefore currently only be offered after critical evaluation in patients who exhausted the approved standard therapies."

In another paper from last month [4]:

"The prostate-specific membrane antigen (PSMA) targeted positron-emitting-tomography (PET) tracer 68Ga-PSMA-11 shows great promise in the detection of prostate cancer. However, 68Ga has several shortcomings as a radiolabel including short half-life and non-ideal energies, and this has motivated consideration of 18F-labelled analogs. 18F-PSMA-1007 was selected among several 18F-PSMA-ligand candidate compounds because it demonstrated high labelling yields, outstanding tumor uptake and fast, non-urinary background clearance. Here, we describe the properties of 18F-PSMA-1007 in human volunteers and patients."

"18F-PSMA-1007 performs at least comparably to 68Ga-PSMA-11, but its longer half-life combined with its superior energy characteristics and non-urinary excretion overcomes some practical limitations of 68Ga-labelled PSMA-targeted tracers."

The paper mentioned in Alan's post is [5]:

"Prostate-specific membrane antigen (PSMA) is a promising target in prostate cancer. Recently, we started the first-in-human treatment with an α-radionuclide–labeled PSMA ligand. Although the case series is still ongoing, we here report in advance about two patients in highly challenging clinical situations who showed a complete response to 225Ac-PSMA-617 therapy. Methods: 68Ga-PSMA-11 PET/CT validated the presence of the PSMA-positive tumor phenotype. A 100-kBq activity of 225Ac-PSMA-617 per kilogram of body weight was administered bimonthly. Prostate-specific antigen response and hematologic toxicity were measured at least every 4 wk. Restaging was performed with 68Ga-PSMA-11 PET/CT. Results: Both patients experienced a prostate-specific antigen decline to below the measurable level and showed a complete response on imaging. No relevant hematologic toxicity was observed. Xerostomia was the only mentionable clinical side effect."

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/280...

[2] en.wikipedia.org/wiki/Gluta...

[3] ncbi.nlm.nih.gov/pubmed/278...

[4] ncbi.nlm.nih.gov/pubmed/278...

[5] jnm.snmjournals.org/content...

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That sounds like a promising area of research. I didn't understand much of it but I bookmarked your post. Thanks for continuing efforts to keep us all informed.