Among the more interesting developments in radiation oncology/nuclear medicine in recent years are novel therapies created by attaching radioactive isotopes to molecules (called ligands) that attach to the prostate-specific membrane antigen (PSMA) that is found on the surface of most metastatic prostate cancer cells.
We have seen several small studies conducted throughout Germany using Lu-177-PSMA (see this link for latest update). Lu-177 is a beta (β) particle emitter – its radioactivity is produced when a neutron decays into a proton and an energetic electron – a beta particle. Xofigo is an alpha (α) particle emitter – its radioactivity occurs when the radium 223 nucleus releases 2 protons and 2 neutrons – an alpha particle or helium nucleus. There are advantages and disadvantages to each (see table in this link).
Lu-177-PSMA was developed at the University of Heidelberg. Those researchers have developed a targeted therapy using an alpha emitter called actinium 225. Ac-225-PSMA-617 can potentially be used in some situations where Xofigo or Lu-177-PSMA cannot. Xofigo only treats bone metastases because radium is biologically similar to calcium and replaces it in areas of active bone growth, like metastases. Ac-225-PSMA-617 has several theoretical advantages:
- · It can target metastases in any tissue or fluid, including undetectable, systemic micrometastases.
- · Because its alpha particles are very short range, it doesn’t destroy very much healthy bone marrow.
- · Because the alpha particles are highly energetic, they destroy nearby cells very effectively.
- · Because it attaches to PSMA instead of calcium-active sites in bone or other tissue, it may be less toxic to other healthy tissue.
Kratochwil et al. report a proof-of-concept in two patients treated with Ac-225-PSMA-617. They used Ga-68-PSMA-11, which shows up on a PET scan, to detect metastases that were positive for PSMA and to detect response to the alpha- emitter. The two patients selected had progressed under other treatments and were in “highly challenging clinical situations,” which included tumor infiltration into the red bone marrow. After bi-monthly treatments, both patients:
- · Exhibited complete PSA response, becoming undetectable
- · Exhibited complete tumor response on PET imaging
- · Exhibited no hematological toxicity; that is, no bone marrow suppression
- · Exhibited dry mouth from decreased saliva (xerostomia)
This is a first-in-human trial, and larger trials will be needed to prove efficacy and safety. However, it is an early encouraging development worth taking note of.