Targeted Alpha-emitter Therapy (TAT) – the wave of the future in nuclear oncology/PRRT?


What is Targeted Alpha-emitter Therapy?

Regular PRRT which is authorised for use now, i.e. Lutathera/Lu177 is a beta therapy.  Targeted Alpha Therapy is based on the coupling of alpha particle emitting radioisotopes to tumour selective carrier molecules, such as monoclonal antibodies or peptides. These molecules have the ability to selectively target tumour cells even if they are spread throughout the body. They recognize the targeted cancer cells through antigens that are expressed on the cell surface and can bind selectively to these cells, similar a key fitting into a lock. In targeted alpha therapy these carrier molecules serve as vehicles to transport the radioisotopes to the cancer cells. This is called the “magic bullet” approach. Radioisotopes that emit alpha particles seem particularly promising to selectively destroy cancer cells. Alpha particles have a high energy in the range of 5-9 MeV and at the same time a very short path length in human tissue below 0.1 mm, corresponding to less than 10 cell diameters. Consequently, the use of alpha emitters allows the specific targeting and killing of individual malignant cells, while minimizing the toxicity to surrounding healthy tissue. Extracted from EU Science Hub

According to the clinical trials document, this drug addresses an unmet need in the field of peptide receptor radionuclide therapy (PRRT) for NETs. Substitution of an alpha emitter (²¹²Pb) for the beta emitters currently being used (i.e., 177Lu or 90Y) will provide significantly higher Linear Energy Transfer (LET) and a shorter path length. Higher LET particles should cause more tumor cell death. Shorter path length should result in less collateral damage of the normal tissue and therefore less side effects for subjects receiving the drug.

What is the difference between ‘regular’ PRRT and the Alpha version?

From the scant ‘patient understandable‘ information currently available, it would appear that alpha therapy has the potential to be more targeted and less toxic than beta PRRT – to me that seems like it would be able to target smaller tumours.  I also noted that alpha therapy is sometimes described as a ‘radioimmuotherapy’ or ‘alpha immunotherapy’, indicating the mechanism of action is significantly different to that of conventional PRRT. It was also described as a ‘Trojan Horse’ which would seem to hint at its immunotherapy credentials. I noted that TAT is also being studied for use in Prostate Cancer and Leukaemia. The main effort for NETs is based on the use of two TAT radionuclides – 225Actinium and 212Pb

Update 27th July 2022

This real-world study from India using 225Ac and Capecitabine chemotherapy is interesting.  Read more by clicking here or on the photo below:

Update 15th June 2022

SNNMI Abstract of the Year: Targeted Radionuclide Treatment Achieves High Response Rate, Minimal Toxicities for Advanced-Stage Neuroendocrine Tumors

June 14, 2022

Reston, VA — A targeted radionuclide alpha therapy, 225Ac-DOTATATE, has been shown to have long-term anti-tumor effects in patients with advanced-stage gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Results from the Phase II study showed promising survival rates, high response rates and an acceptable toxicity profile, making 225Ac-DOTATATE a potential treatment option for patients who have exhausted other forms of therapy. This research was presented at the Society of Nuclear Medicine and Molecular Imaging 2022 Annual Meeting and was selected as the meeting’s Abstract of the Year.

Each year, SNMMI chooses an abstract that best exemplifies the most promising advances in the field of nuclear medicine and molecular imaging. This year, the SNMMI Henry N. Wagner, Jr., Abstract of the Year was chosen from more than 1,000 abstracts submitted to the meeting and voted on by reviewers and the society leadership.

GEP-NETs are rare malignancies that arise from neuroendocrine cells and can be present all along the gastroinstesinal tract. While patients with early-stage GEP-NETs can undergo surgery to cure the disease, the majority of patients are diagnosed with metastatic disease, making systemic treatment—such as targeted radionuclide therapy—their only option. 177Lu-DOTATATE has been proven to be an effective targeted beta radionuclide therapy; little evidence, however, is available on targeted alpha radionuclide therapies for GEP-NETs.

In the study, researchers aimed to evaluate the long-term efficacy, survival outcomes, and safety of the targeted radionuclide alpha therapy 225Ac-DOTATATE in GEP-NET patients. Eighty-three GEP-NET patients (including 56 patients with prior 177Lu-DOTATATE treatment and 27 177Lu-DOTATATE-naïve patients) received systemic treatment with 225Ac-DOTATATE intravenously at eight weekly intervals.

Hematologic, kidney and liver function tests were performed before and after each cycle. Tumors were measured using RECIST 1.1 criteria at baseline and after two cycle intervals. Overall survival, radiographic progression-free survival, objective tumor response, and treatment-related adverse events were assessed.

After the treatment course, two patients (2.7 percent) had complete response, 32 (43.2 percent) had a partial response, 25 (34 percent) had stable disease, and 15 (20 percent) had progressive disease. Minimal toxicities were noted after treatment with 225Ac-DOTATATE.

225Ac-DOTATATE is a promising therapy option that adds a new dimension to the treatment of end-stage GEP-NETs, especially for patients who have tried all other standard therapy options,” said Chandrasekhar S. Bal, MD, DNB, DSc (HC), FAMS, FNASc, FASc, professor and head of the Department of Nuclear Medicine and PET at the All India Institute of Medical Science in New Delhi, India. “These results warrant a Phase III randomized control trial to assess the true efficacy of 225Ac-DOTATATE versus 177Lu-DOTATATE.”

“The results from this study not only emphasized the promise and success of targeted alpha therapies but also reflected growing global interest in these life-extending treatments,” said Heather Jacene, MD, SNMMI Scientific Program Committee chair. “We look forward to further research on this topic in the future.”

Source.  SNMMI 2022 conference

Update 9 January 2022


Peptide receptor radiotherapy (PRRT) with somatostatin analogs has been successfully utilized as a treatment for somatostatin overexpressing tumors for years. Treatment of neuroendocrine tumors (NETs) with the beta particle emitter 177Lu-DOTATATE is currently considered the standard of care for subjects with gastroenteropancreatic NETs. Despite the overwhelming success of 177Lu-DOTATATE, there remains significant room for improvement in terms of both safety and efficacy. Targeted alpha-emitter therapy with isotopes such as lead-212 (212Pb) has the potential to improve both. Herein, we present the preliminary results of the phase 1 first-in-human dose-escalation trial evaluating 212Pb-DOTAMTATE in patients with somatostatin receptor positive NETs. Methods: A total of 20 subjects with histologically confirmed NETs, prior positive somatostatin analogue scans, and no prior history of 177Lu/90Y/111In PRRT, with different primary sites of the disease, were enrolled. Treatment began with single ascending doses of 212Pb-DOTAMTATE, with subsequent cohorts receiving an incremental 30% dose increase, which was continued until a tumor response or a dose-limiting toxicity was observed. This was followed by a multiple ascending dose regimen. The recommended phase 2 dose (RP2D) regimen consisted of 4 cycles of 2.50 MBq/kg (67.6 µCi/kg) of 212Pb-DOTAMTATE administrated at 8-week intervals, intravenously. Results: Ten subjects received the highest dose of 2.50 MBq/kg/cycle (67.6 µCi/kg/cycle). Treatment was well tolerated, with the most common treatment-emergent adverse events (TEAEs) being nausea, fatigue, and alopecia. No serious TEAEs were related to the study drug, and no subjects required treatment delay or a dose reduction. An objective radiological response (ORR) of 80% was observed for the first 10 subjects treated at the RP2D. Conclusion: Targeted alpha therapy with 212Pb-DOTAMTATE has been shown to be a well-tolerated and highly effective treatment in patients with metastatic NETs. With an ORR of 80%, further development of 212Pb-DOTAMTATE is warranted as it represents a significant improvement over the current standard of care and has the potential to be a breakthrough alternative for the treatment of metastatic NETs.


Targeted Alpha-Emitter Therapy With 212Pb-DOTAMTATE for the Treatment of Metastatic SSTR-Expressing Neuroendocrine Tumors: First-in-Human, Dose-Escalation Clinical Trial

Ebrahim S DelpassandIzabela TworowskaRouzbeh EsfandiariJulien TorgueJason HurtAfshin Shafie and Rodolfo Núñez

Update 03 January 2022

Radiomedix and Orano Med Announce the Initiation of the Phase II Multi-Center Clinical Trial of Alphamedix™ for Targeted Alpha-Emitter Therapy of Neuroendocrine Cancers

Houston, TX and Plano, TX, Jan. 03, 2022 (GLOBE NEWSWIRE) — RadioMedix and Orano Med are pleased to announce the initiation of the Phase II clinical trial of AlphaMedix™ with the treatment of the first patient on December 21st, 2021.  This trial will evaluate the safety and effectiveness of 212Pb-DOTAMTATE (AlphaMedix™) in Peptide Receptor Radionuclide Therapy (PRRT) of naive patients with somatostatin receptor-expressing neuroendocrine tumors (NET). 

“The initiation of the Phase II trial is a significant milestone in the clinical development of our innovative targeted alpha-emitter radiotherapy and brings us one step closer to having this drug available for our patients”, said Ebrahim Delpassand, MD, Chairman and Chief Executive Officer of RadioMedix. “Targeted alpha therapy (TAT) with 212Pb-DOTAMTATE has been shown to be well-tolerated and preliminary efficacy results are highly promising. If these results are confirmed in the Phase II trial, it could potentially provide substantial benefit over currently FDA approved therapies for patients with metastatic or inoperable SSTR-expressing NETs regardless of the grade and location of the primary tumor”,  added Dr. Delpassand.

“This milestone highlights the strength of collaboration between RadioMedix and Orano Med teams dedicated to making targeted alpha-emitter therapy with AlphaMedix™ available to NET patients”, said Dr. Izabela Tworowska, Chief Scientific Officer of RadioMedix.

Additionally, Julien Dodet, President and Chief Executive Officer of Orano Med, noted “We are excited to have this Phase II trial underway and we are confident that this trial will confirm the very promising results from Phase I. It would be yet another demonstration of the interest of the combination of 212Pb and fast-PK targeting agents like DOTAMTATE. This reinforces Orano Med’s commitment to make innovative 212Pb-based therapies available to the medical community and patients worldwide.”

The Phase II trial will enroll a total of 34 patients with histologically confirmed NETs and positive somatostatin analogue imaging who have not received prior PRRT.  Treatment will consist of up to 4 cycles of AlphaMedix™.  We would like to thank Dr. Rodolfo Nunez, principal investigator, and the research team at Excel Diagnostics and Nuclear Oncology Center in Houston for enrolling our first patient in Phase II”, added Jason Hurt, MD, Chief Medical Officer of Orano Med.

Click here to read the clinical trial document for 212Pb-DOTAMTATE. 

Clinical trials – 212Pb-AR-RMX

Update 3 Jan 2022.  See Phase 2 clinical trial news in the lead box

Update 3 Jan 2020.   RadioMedix Inc. is pleased to announce that the company has been selected for the 2019-2020 Commercialization Accelerator Program (CAP) by the National Institute of Health (NIH) SBIR/STTR (Small Business Innovation Research/Small Business Technology Transfer) program office. This award is following our two-years, $2.0 M Phase II SBIR funded in part with Federal funds from the National Cancer Institute, National Institutes of Health and Human Services, under Contract No HHSN261201800048C. The Contract focuses on the clinical development of 212Pb-AlphaMedix™ for the targeted alpha-emitter therapy (TAT) of neuroendocrine tumours.

Original Article

In 2018, RadioMedix Inc. and Orano Med initiated the Phase 1 trial for AlphaMedixTM in patients with somatostatin receptor (SSTR) positive Neuroendocrine Tumors (NETs) – an NIH supported trial.

AlphaMedixTM is composed of a somatostatin analogue radiolabeled with 212Pb, an isotope used for Targeted Alpha-emitter Therapy (TAT).  This open-label, dose escalation study’s objective is to determine safety, bio-distribution, and preliminary effectiveness of 212 Pb-AR-RMX in adult patients with differentiated (sic) NETs. “Targeted Alpha-emitter Therapy (TAT) is the wave of the future in nuclear oncology and has a tremendous potential to treat patients with NET and overcome some of the limitations of current Peptide Receptor Radionuclide Therapy (PRRT)” said Dr. Ebrahim S. Delpassand, Chairman and CEO of RadioMedix, sponsor of the trial. They further announced on 21 Feb 2018 that the first patients had undergone some treatment.


Related articles:

Phase 1 Clinical Trial Document Phase 1 Study of AlphaMedix™ in Adult Subjects With SSTR (+) NET – click here

Phase 2 document – Targeted Alpha-emitter Therapy of PRRT Naive Neuroendocrine Tumor Patients (ALPHAMEDIX02) click here 

Ornamed Website – click here

RadioMedix Inc Website – click here

Some advance info on the data from the Phase 1 trial results (quote from Dr Strosberg)

“Some exciting data on peptide receptor radionuclide therapy have been released with regard to the alpha particle–emitting isotope 212Pb–DOTATATE; this [treatment] was associated with exceptionally high response rates with the maximum-tolerated dose, which was discovered in the phase 1 study. Alpha emission is completely different from beta-emitting [radionuclide therapy], such as lutetium-177 (Lutathera)or yttrium-90; it delivers a much higher energy over a much shorter particle length. Although development may take more than a few years, I believe this [approach] has the potential to improve the therapeutic index that we are currently seeing with lutetium-177” Read the quote reference here.

This has been taken from the Radiomedix website:

Caption. AlphaMedix™ : First Pb212 labeled Somatostatin analogue Targeted Alpha-emitter Therapy (TAT) agent for treatment of metastatic or inoperable Somatostatin expressing Neuroendocrine Tumors (NET) with highly encouraging safety and efficacy results. Below images show an example of impressive response to therapy in a patient with stage IV Pulmonary NET after 4 cycles of AlphaMedix therapy. The clinical trial has completed dose escalation phase and entering expansion cohort phase, in preparation for the registration trial. This drug has received Orphan Drug Designation by U.S. FDA. Pb-212 is an alpha emitter with high linear energy transfer accommodating maximum malignant cell kill. This project is performed in collaboration with Oranomed corporation.

This summary was presented at ASCO 2021 as an abstract:

DOI: 10.1200/JCO.2021.39.15_suppl.4117 Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021) 4117-4117.

Conclusions: This F-I-H clinical study of AlphaMedix shows that PRRT with 212Pb is feasible, well tolerated, and provides substantial reduction in tumor burden to patients with unresectable, metastatic SSTR-expressing NETs. Dramatic improvement in tumor burden and a positive impact on quality of life were seen in all of the PRRT naïve subjects who AlphaMedix at the highest dose tested. 

Clinical trials – 225Ac

There seems to be quite a bit of use in India, not much is known if the Indian Drug Approval authorities have authorised it or it’s being used on a clinical trial basis (see more below).  Anecdotally being used in German studies too.  Searching “AC225” on the clinical trials database brings up trials in prostate, colorectal and melanoma only. 

However, I did find this from the same company involved in the 212Pb trial above.  “Excel Diagnostics and Nuclear Oncology Center Announces FDA Authorization of IND for 225Ac-PSMA I&T Targeted Alpha Therapy for Castration Resistant Prostate Cancer.  This would be in line with my searches above”. 

From the CNETS India website.  Two nuclear medicine centres in India have started Alpha PRRT for NET patients.  World over, many clinical trials have established the benefit of PRRT for metastatic NETs. Alpha PRRT uses the more powerful alpha particle emitting agents, Actinium 225 or Bismuth 213, in place of Lutetium 177 or Yttrium 90, which are the commonly used beta emitters for PRRT, to target the somatostatin receptors expressed by the tumor cells. According to CNETS India, Alpha PRRT holds higher energy leading to higher efficacy and lower toxicity to normal tissues and hence lesser side effects as compared to the currently available Lu177 based PRRT. Currently Alpha PRRT is already available at two superspecialty hospitals in Delhi and Bengaluru in North and South India, respectively.

Targeted Alpha Theranostics

Read about the involvement of Viewpoint Molecular Targeting (VMT) who are involved in a theranostic approach using TAT.  Presumably working with alongside Radiomedix 212Pb approach.  Read more here:

Interest point – Cu64 Dotatate PET for NETs

Click to read

The same company is involved in this approved somatostatin receptor PET for NETs.

General Clinical Trials Disclaimer

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided in the clinical trials document. It’s very important to check the trial inclusion and exclusion criteria before making any contact. 

Inclusion of any trial within this blog should not be taken as a recommendation by Ronny Allan. 



Whenever I post about a trial or study, some people get excited without understanding that these new treatments and capabilities can very often take years to come to fruition and it’s also possible that clinical trials can be halted, or that national approval agencies will not approve the final product.  Plus, not everyone will be eligible, so always check the exclusion and inclusion criteria in the relevant clinical trials document.   Please bear that in mind when reading studies/clinical trials posted on RonnyAllan.NET

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10 thoughts on “Targeted Alpha-emitter Therapy (TAT) – the wave of the future in nuclear oncology/PRRT?

  • Frank Geleyn

    Hi everybody! I live in Belgium and I have been diagnosed with SiNets in 2013. I am currently being treated with Sandostatin LAR 30 mg. First 1 every month, now 1 every 3 weeks. Recently, they’ve found progression (increase in size and number of peritoneal and liver metastastases) and my doctor suggests to start PRRT. The TAT 212 Pb-AR-RMX trial seems a very promising alternative. Would this treatment be better for me than PRRT? Or would it be recommended to ‘try’ PRRT first? Can I have this TAT 212 Pb-AR-RMX treatment afterwards? The ‘exclusion criteria’ mention that the patient can’t have had PRRT previously… What would be the right choice for me? Thank you for your help.

    • Hi Frank, you’ve come through on my blog article – this would have been a better topic inside my group. I think TAT will be a while yet and is not yet approved. |Perhaps when it is approved there will be another trial of something even better? Something to think about. There’s always an issue with previous radiotherapy treatment and there is certainly risk involved. However, I spoke to a lady yesterday who was on PRRT treatment number 11.

      • Frank Geleyn

        I’ve indeed read your blog article and I found it very interesting. I’m a bit afraid of PRRT treatment because of the radioactivity/toxicity. 11 PRRT treatments? As far as I know, you can have 4 treatments (every time with 8 weeks in between) and eventually 2 extra treatments (after 1 1/2 year), but not more…
        So, TAT is too early… but are there other alternatives than PRRT? My doctor said Afinitor is for pNets but there seems to be a new medicine (Lenvatinib)…that is very promising. Does anyone know more about that medicine?

      • afinitor is out there and side effects seem to be tolerable – that stats are not as good as PRRT. Lenvatinib is on trial – not enough data to comment (no data yet).

  • Betty

    has anyone already undergone PRRT treatment? My spouse is looking at that once the insurance company okays it, and I was wondering what the after effects are like…. any info would be great. He really had a month of pure exhaustion after his bland embolisation procedure, and some heart abnormalities to deal with….

  • Tony McGrory

    Great stuff, onwards & upwards. T

    On Wed, 10 Jan 2018 at 19:32, Ronny Allan – Living with Neuroendocrine Cancer wrote:

    > Ronny Allan posted: ” RadioMedix Inc. and AREVA Med today announced the > initiation in the United States of Phase 1 trial for AlphaMedixTM in > patients with somatostatin receptor (SSTR) positive Neuroendocrine Tumors > (NETs). AlphaMedixTM is composed of a somatostatin analogue ” >

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