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Radionuclide Therapy (RNT) or Radioligand Therapy (RLT) utilising alpha-particle emitters is a promising technology for cancer treatment with a strong growth. Some radiopharmaceutical products are in use and many pharmaceutical companies are in early stages developing radiopharmaceutical drugs with alpha-particle emitters.
However, alpha-particle emitters are in short supply.
Current production schemes for alpha emitters are dependent on irradiation in high-cost nuclear research reactors or charged particle accelerators with limited production volumes. Thus, the supply chain is immature and not ready for large scale industrial demands. There are only a few alternative alpha-emitters that can be used for cancer treatment and Radium-224 and Lead-212 are two of the best candidates. These two radionuclides belong to the radioactive decay chain of thorium and can therefore be produced in the Thor Medical process.
Radium-224 and Lead-212 are two of the best candidates for radionuclide cancer treatment.
Radioactivity is a process where an unstable nucleus in an atom transforms into another nucleus, thereby usually changing the identity of the atom. In this transformation radiation is emitted, either as alpha-particles, beta-particles, or gamma-rays. Alpha-particles are emitted when heavy unstable elements decay. An alpha-particle is composed of two protons and two neutrons (the same as the nucleus of helium gas). The emitted alpha particle has a 2+ elementary charge and carries a large amount of kinetic energy.
The alpha-particle is quickly slowed down by depositing its kinetic energy in the surrounding matter through ionizations.The range in water is a little less than 0.1 mm before it comes to an absolute stop. This is the key to its potential power in cancer treatment. The dense ionization is highly destructive for living cells and therefore opens for the possibility of effectivly killing cancer cells. Furthermore, the short range opens for the possibility of very selective treatment. If one deposits alpha-emitters selectively on small cancer clusters (micrometastasis), the cancer cells are killed and the nearby healthy cells more than 0.1 mm away will be unharmed, almost not receiving any radiation at all. Spread of cancer producing micrometastasis is one of the largest problems in cancer treatment today. By using alpha-emitters one can have the necessary tool to efficiently treat patients with metastatic spread of cancer.
Using alpha-emitters one can have the necessary tool to efficiently treat patients with metastatic spread of cancer.
This highly desirable goal in cancer therapy depends on the ability to deposit the alpha-emitters selectively on the cancer cells. This can now be done by chemically coupling the alpha-emitters to a targeting vector that selectively recognizes some structure on the cancer cells being different from the normal cells. The targeting vector then binds to the cancer cells and the alpha-particles irradiates the cancers cells selectively.
Due to the very high cell-destructive power of the alpha-particles, this treatment can be used for most cancers and stages thereof, also for irradicating radiation resistant cancers.
There are only a few alpha-emitters which can be used for RNT, due to considerations of half-life, purity, ability to stably conjugate to targeting molecules, radioactive decay products and not the least, availability. Based on these considerations, Radium-224 (Ra-224) and Lead-212 (Pb-212) are strong candidates, and both are currently the alpha-emitters of choice for many early-stage radiopharmaceutical products.
Ra-224 is an isotope of radium. It has a half-life of 3.6 days and undergoes four alpha decays and two beta-decay before it ends at stable Lead-208.
Pb-212 is a radioactive isotope of lead. It has a half-life of 10.6 hours and undergoes a beta-decay to Bismuth-212. Bismuth-212 decays with a 1 hour half-life through a branched decay with emission of one beta-particle and one alpha-particle before it ends as stable Lead-208.
Both radionuclides are decay products from Thorium-232. The difference in half-life and decay modes opens for many different uses in cancer therapy.
Th-228 is Thor Medicals‘ main product. It is a radioactive isotope of thorium with a half-life of 1.9 years and part of the Th-232 decay chain. It has 90 protons and 138 neutrons, once named Radiothorium. It decays to Ra-224, which undergoes further decay to Pb-212. This opens for the possibility of using Th-228 as a radionuclide-generator for Ra-224 and Pb-212.
