VIOLET Study – First Results

Coinciding with the launch of the therapy at our center, the early results of the VIOLET study, the first-in-human trial of ¹⁶¹Tb-PSMA, are being published. And they are highly promising! No dose-limiting toxicities were observed across six treatment cycles (up to 7.4 GBq) in 30 patients. Encouraged by these results, a new cohort at 9.5 GBq has been initiated.

¹⁷⁷Lu-PSMA radioligand therapy has proven highly effective for prostate cancer, but some patients eventually experience disease progression. A likely reason is the presence of energy-sheltered micrometastases and single tumor cells, which absorb very little radiation due to their small size and limited mass. The beta particles emitted by ¹⁷⁷Lu have a mean pathlength of ~0.7 mm (range: 0.04–1.8 mm), which far exceeds the size of single tumor cells measuring only a few micrometres (7–13 μm). As a result, most radiation overshoots these tiny cancer cells, failing to deposit lethal energy and allowing disease progression.

In contrast, ¹⁶¹Tb emits abundant Auger and conversion electrons, which have much shorter pathlengths (nanometers to micrometers). This enables precise, high-energy deposition directly into single tumor cells and micrometastases, making it potentially more effective than ¹⁷⁷Lu at eradicating these resistant cancer cells. Additionally, ¹⁶¹Tb may further reduce radiation-related toxicity by limiting unnecessary exposure to surrounding healthy tissue.

¹⁶¹Tb-PSMA radioligand therapy is already available at our center.

The VIOLET study is named in honor of the late Dr. John Violet, a radiation oncologist at the Peter MacCallum Cancer Centre in Melbourne, Australia, who had a keen interest in Auger electron therapy. The study aims to determine the maximum tolerated dose, safety profile, and antitumor activity of ¹⁶¹Tb-PSMA in patients with mCRPC. The therapy is administered in an outpatient setting, with key objectives including measuring absorbed radiation doses, PSA response, survival outcomes, and patient-reported quality of life.