Theranostics: Functional imaging with PCa

Behind this word lies a new method that combines diagnostics and therapy. In prostate cancer, a PSMA ligand, such as that used in PET/CT, is linked to a radioisotope such as 177 lutetium. This achieves site-specific tumor therapy.

Radioisotope-labeled PSMA ligands help to kill tumor cells in a targeted manner

Theranostics. Behind this artificial word lies a new method that functionally combines diagnostics and therapy. In the case of prostate cancer, a PSMA ligand, such as that used in PET/CT, is linked to a radioisotope such as 177 lutetium. This makes it possible to achieve site-specific tumor therapy.

The combination of a diagnostic marker such as prostate-specific membrane antigen (PSMA) and a therapeutic agent is known in radiology as theranostics. This approach is not so new, but it is being rediscovered for the treatment of metastatic prostate cancer.

As early as 1941, Seidlin and his colleagues developed the first radioiodine ligand for the treatment of thyroid adenocarcinoma. Based on the good results in the imaging of prostate carcinoma (PCa) using PSMA, it was now probably a short step towards PSMA-theranostics.

PSMA in Theranostics

In many studies, PSMA has already proven its superiority in PCa imaging over choline or fluciclovine. In addition, in their systematic review of various current imaging procedures, Visschere and colleagues showed that PSMA had higher detection rates than TRUS, CT, mpMRI or choline PET, for example, especially with low PSA values < 0.5 ng/ml.

PSMA imaging in patients with metastatic Castration-resistant prostate cancer (CRPC) helps localize a large portion of metastases. The binding of the PSMA ligand is specific so that the path to a radioisotope-coupled PSMA ligand was not far away. 177Lutetium (177Lu) is now of particular interest as a therapeutic agent in this context. This is due in particular to its properties as a beta emitter. Studies showed that 44% of CRPC patients achieved a PSA drop of more than 50% when treated with a 177Lu-PSMA ligand. The overall survival of these men increased to about 14 months.

Since the introduction of radium-223 in the treatment of advanced metastatic CRPC, however, it is known that alpha emitters, such as Ra-223, have fewer side effects than e.g. 177Lu. The 177Lutetium, for example, radiates much further than a narrowly confined alpha emitter. As a result, damage to the bone marrow in beta radiators can be observed much more frequently, resulting in their hematological toxicity.

For this reason, a working group from Heidelberg recently tested 255Actinium, an alpha emitter, together with a PSMA ligand. The first preliminary data from this series of experiments are indeed positive.

Conclusions

PSMA is not only a promising molecule in imaging but is also likely to be equally well suited as a therapeutic target in men with advanced metastatic CRPC. Nevertheless, further studies must show which radioligands will provide the most promising results in PCa diagnostics. With 177Lu and the somewhat gentler 255Ac alpha emitter, two candidates have already been found who have delivered convincing results in the first series of tests.

Source: Plenary Session 3 "EANM lecture: Theranostics - The future of functional imaging", EAU 2019, Barcelona

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