Alpha particles are highly effective at destroying tumor cells, but their therapeutic use has been limited by the short range in which these particles can travel in tissue. A novel mechanism called Alpha DaRT is exploring the possibility to diffuse atoms that emit alpha particles directly within solid tumors, thus overcoming the short travel distance limitation.1 This opens the door to new therapeutic approaches in radiation therapy beyond conventional modalities that rely on beta or gamma emissions.
Alpha DaRT is currently being assessed across a broad range of malignancies, including lung cancer, pancreatic cancer, and skin cancer. In the genitourinary (GU) cancer space, the technology shows particular promise in prostate and bladder cancer, where highly targeted treatments are critical for sparing surrounding organs while maintaining oncologic control.
Currently, Alpha DaRT is under investigation in a feasibility study (NCT04543903) as a neoadjuvant therapy in patients with prostate cancer. In total, the study plans to enroll 10 adult patients with pathologically confirmed prostate adenocarcinoma. The primary end points for the study are feasibility and safety, and primary completion is expected in December 2026.2
In the following interview, Robert B. Den, MD, outlines the exploratory applications of the Alpha DaRT technology across the prostate and bladder cancer landscapes. Den is the Chief Medical Officer at Alpha Tau Medical as well as an associate professor of radiation oncology, cancer biology, and urology at Thomas Jefferson University in Philadelphia, Pennsylvania.
Urology Times®: By way of background, could you explain what Alpha DaRT is for those who don’t know? What is the mechanism of action for this agent?
Den: Alpha DaRT is a small stainless steel or titanium seed that we coat with a radiopharmaceutical, radium-224. Radium-224 is an unstable element, meaning it has too much energy, and it will release that energy naturally through radioactive decay. That process of radioactive decay releases the radiopharmaceutical radium-224 as it decays to become radon-220 from the physical seed. Therefore, what we’ve done is we’ve used a seed as a scaffold to introduce a radiopharmaceutical locally, intratumorally. Now, radon and the subsequent daughter atoms will continue the decay process, spreading Alpha dose approximately 5 mm from where we place the seeds. What we’ve figured out is a way to deliver the most potent form of radiation, which is alpha particles, and overcome the natural limitation of the alpha particle itself.
Urology Times: How is this treatment approach being applied in the genitourinary oncology space? What have preclinical data shown?
Den: We are currently utilizing this technology in the setting of prostate cancer, and we are moving toward utilizing it as well in bladder cancer. One of the main challenges in prostate cancer is that you want to maximize the amount of damage that you cause to the tumor and minimize it to the bladder, rectum, and urethra. The unique aspect of the Alpha DaRT and alpha technology is that the Alpha dose is very conformal, much more so than standard treatments that are available today. What that means is that we can put our sources touching the rectal wall or touching the bladder wall and not see damage to those structures because the dose falls off so quickly.
We’ve shown in preclinical studies that we can have just as potent, if not a more potent, effect on stalling and reversing tumor growth. We also have the ability to activate an immune response in a much more brisk and robust manner than [with] standard therapy. We think that with the Alpha DaRT technology, we can not only augment the role of immunotherapy in bladder cancer, but we may also be able to trigger it even more in patients who are currently refractory to that type of therapy. There are multiple ways in which we see the Alpha DaRT being utilized for these patients.
Urology Times: Alpha DaRT is currently being explored in a clinical trial in the prostate cancer space. How is that study designed? What are the key end points?
Den: That study right now is a pilot study. It’s a feasibility and safety study. We are specifically studying it in the context of patients with recurrent prostate cancer who have had prior radiation to the prostate. We know that this can be a really challenging patient population. Surgical resection is more complicated in these patients, and reirradiation causes an increase in potential [adverse] effects.
So, we’re doing 2 things in this study. First, we’re ensuring that we are able to safely deliver the Alpha DaRT technology to these patients. Second, we are also evaluating how to optimize the delivery in this patient population. We’ve built out a unique treatment planning software, as well as a new grid format in which we deliver the sources directly into the prostate itself. Of course, secondary end points are efficacy in terms of [prostate-specific antigen] control.
Urology Times: If the data shows that this approach is feasible and effective, how do you see Alpha DaRT fitting into the current treatment paradigm?
Den: In truth, Alpha DaRT can fit across the treatment paradigm. We anticipate that we will show the safety of this device in this population where there is a high propensity for adverse events to occur. [The agent could] then be utilized either in combination with current standard therapies or in lieu of certain standard therapies, and we can deliver it in such a way that we can make it a much more attractive option for patients who would otherwise not have as many options available to them. What I would also say is that with the ability to utilize it in combination with immunotherapy, it opens up a huge opportunity for a very diverse patient population, potentially even in the metastatic setting, setting us apart from what current technologies have available.
Urology Times: We talked about the applications of Alpha DaRT across prostate cancer and bladder cancer. Looking at those 2 avenues, what are the next steps for this agent?
Den: We plan on opening up US trials in both of these spaces, but prostate space will open up first. This will introduce the technology not only to the patients, but also to the different providers. Our technology is unique in that it can be delivered by urologists directly in conjunction with radiation oncology, and we can do this in multiple different settings. We currently have the product being utilized in the setting of non-GU cancers, as diverse as GBM
[glioblastoma], pancreatic cancer, skin cancer, and these are being delivered by many different providers, whether it’s neurosurgeons, endoscopists, or dermatologists. We see this as a product that can be utilized across multiple specialties, and it is not only in the domain of one.
Urology Times: Is there anything else that you wanted to add?
Den: I think that this technology is unique in that it’s allowing us to access a very potent form of radiation, the alpha technology, which previously had been prohibitory, except in the setting of systemic therapy. We can utilize systemic therapy as precedent. In prostate cancer, we have product Xofigo, which is an alpha radium-223, and we have a similar product called samarium-153 that used to be on the market. One of the unique aspects and differences between samarium and radium is that although samarium showed a progression-free survival advantage, radium ultimately showed a survival advantage later on when there were more drugs available at the time. So, clearly, we see a unique difference between alpha vs beta in the context of prostate cancer and GU cancer. The thought is that we can replicate this as well in the intratumoral and in the localized setting.
REFERENCES
1. Alpha DaRT technology. Accessed August 21, 2025. https://www.alphatau.com/alpha-dart-radiotherapy
2. Neoadjuvant interstitial brachytherapy using diffusing alpha emitters radiation therapy in men with prostate cancer. ClinicalTrials.gov. Last updated February 7, 2025. Accessed August 21, 2025. https://clinicaltrials.gov/study/NCT04543903