PRRT – The Sequel? – Targeted Alpha-emitter Therapy (TAT)

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Radioimmunotherapy

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 tumors.  I also noted that alpha therapy is sometimes described as a ‘radioimmuotherapy’ or ‘alpha immunotherpy’, 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 is baed on the use of two TAT radionuclides – 225Actinium and 213Bismuth.

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. 

Clinical trials – 212 Pb-AR-RMX

Latest 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 tumors. Read more here: Click here.

Original Article

In 2018, RadioMedix Inc. and Areva (parent company 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.

The funding for Phase 2 was granted by NIH on 22 Jan 2019.

Related articles:

Announcement of Phase 1 Clinical Trial – click here – results to follow.

Funding grant from NIH for Phase 2 – click here

Phase 1 Clinical Trial Document Phase 1 Study of AlphaMedix™ in Adult Subjects With SSTR (+) NET – click here – Phase 2 document to follow.

Areva Med Website – click here

RadioMedix Inc Website – click here

Thanks for reading. You may also enjoy my articles:

Lutetium Lu 177 dotatate (Lutathera®) – PRRT” – click here.
Expanding PRRT – Trial of 177Lu-Edotreotide (Solucin®) – COMPETE Trial” – click here.
Theranostics – a find and destroy mission” – click here
Ga68 PET Scans – into the unknown” – click here

Ronny

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10 thoughts on “PRRT – The Sequel? – Targeted Alpha-emitter Therapy (TAT)

  • 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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