RadioMedix Inc. and Areva (parent company Orano Med) 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 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.
What is Targeted Alpha-emitter 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 PRRT and TAT? From the scant ‘patient understandable‘ information currently available, it would appear that TAT has the potential to be more targeted and less toxic than PRRT – to me that seems like it would be able to target smaller tumors. I also noted that TAT 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.
Announcement of Phase 1 Clinical Trial – click here
Phase 1 Clinical Trial Document – Phase 1 Study of AlphaMedix™ in Adult Subjects With SSTR (+) NET – click here
Areva Med Website – click here
RadioMedix Inc Website – click here
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“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
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