Our medical isotope production process is enabling treatment options that have the potential to improve outcomes for patients being treated for a range of cancers. Our current focus includes production of non-carrier-added lutetium-177 with additional therapeutic isotopes in the pipeline. We believe the unique advantages of our production process to produce and extract n.c.a. Lu-177 and other radioisotopes give us the potential to become the largest manufacturer of these therapeutic isotopes in the world.
Lutetium-177 is a radioactive isotope of lutetium, a rare earth metal, with a half-life of about 6.7 days. Like molybdenum-99, it is a somewhat short-lived isotope with enormous applications in the medical industry. However, unlike Mo-99, which enables powerful diagnostic procedures such as SPECT scans that can diagnose diseases, Lu-177’s radioactive properties make it a powerful tool for directly treating certain cancers.
Due to Lu-177’s radioactivity and half-life, it is a very useful tool for treating cancers. The radiation emitted by low-specific-activity Lu-177 as it decays can destroy cancer cells when properly applied by medical professionals in the form of a radiopharmaceutical drug. In particular, Lu-177 is especially useful for treating prostate cancer, one of the most common forms of cancer.
Lutetium-177 is a beta emitter, meaning that as it decays it releases beta radiation—high-energy electrons the unstable atom can no longer contain. Beta radiation is particularly useful for cancer treatment because of how effectively attenuated it is by biological soft tissues. By applying radioisotopes like Lu-177 to the right area, the beta radiation released can destroy tumors while causing minimal damage to the surrounding healthy tissue. Lu-177 also emits gamma radiation.
Radiopharmaceutical cancer therapy using radionuclides like lutetium-177 is one of the fastest growing markets in oncology. Various radioisotope-derived drugs are critical for the treatment of many types of cancers impacting tens of millions of patients globally every year. To treat conditions such as advanced prostate cancer, Lu-177 is used as an essential part of radionuclide therapy.
Currently, lutetium radionuclide therapy is used to treat prostate cancer, the most common form of cancer in men over 50. Research has shown Lu-177 therapy to be extremely effective in reducing the size of tumors and preventing them from multiplying.
Lutetium-177 prostate-specific membrane antigen therapy is one of the best methods for treating advanced prostate cancer, such as metastatic prostate cancer or prostate cancer with treatment-resistant tumors. Lu-177 PSMA therapy relies on PSMA, a type of protein that exists in highly elevated levels in the prostate around tumors. By pairing the Lu-177 with a molecule that seeks out and binds to PSMA, the isotope can be delivered to the appropriate parts of the body where its radioactive emissions will damage and destroy prostate cancer cells.
Lu-177 peptide receptor radionuclide therapy works in much the same way, but is more effective in treating advanced stage neuroendocrine tumors. In PRRT, a cell-targeting protein similar to naturally occurring hormones is bonded with Lu-177 to create a radiopeptide, a special kind of radiopharmaceutical. The radiopeptide is injected into the patient’s bloodstream, where it binds to neuroendocrine tumor cells. PRRT can also be done with yttrium-90, another radioisotope with similar medical properties to Lu-177.
Lutetium treatment costs on average $10,000 per course, and a patient undergoing lutetium-177 PSMA therapy will typically undergo three or four courses. Lu-177 treatments such as PSMA and PRRT therapy are a last resort for advanced cancer treatment, usually prescribed to fourth-stage cancer patients if other methods of treatment have failed. These treatments increase the patients’ longevity and quality of life, drastically increasing survival rates.
In the advanced stages of cancer, urgency of treatment is paramount. Critical medical isotopes such as Lu-177 must be readily available at advanced radiopharmaceutical facilities to provide these radionuclide treatments to patients in need. Like molybdenum-99, though, Lu-177 cannot be stockpiled due to a short half-life on the order of days, which means it must be constantly in production and the supply is constantly running out. This makes Lu-177, like most medical radioisotopes, incredibly valuable. Lutetium-177 dotatate, the radiopeptide drug used in PRRT, costs over $54,000 per unit.
Lu-177, like many medical radioisotopes, is not naturally occurring and must be synthesized using nuclear technology. There are two methods for producing lutetium-177, resulting in two types of Lu-177: carrier-added and non-carrier-added. Generally, n.c.a. Lu-177 is far more useful than carrier-added Lu-177.
Carrier-added lutetium-177 is produced using the “direct” method of Lu-177 production. In the direct method, Lu-177 is produced by irradiating a naturally occurring lutetium isotope, Lu-176, with neutron radiation. When Lu-176 atoms absorb neutrons, they become Lu-177 and another daughter isotope, Lu-177m. The presence of Lu-177m is what makes directly produced Lu-177 “carrier-added.”
While this is conceptually the simplest method to produce Lu-177, carrier-added Lu-177 is less desirable than non-carrier-added Lu-177 due to the presence of Lu-177m. Lu-177m is an impurity byproduct of the production process. Further separating the Lu-177m from the Lu-177 is difficult and results in a lower therapeutic concentration of medically useful Lu-177. Lu-177m also leads to more radioactive post-procedure medical waste that must be contained.
Though it sounds counter-intuitive at first, the indirect method for producing lutetium-177 is ultimately the more powerful method. It is more difficult to produce n.c.a. Lu-177 compared to carrier-added Lu-177, but the “indirect” method leads to a much more useful end result with far fewer drawbacks. To produce n.c.a. Lu-177, we bombard highly pure ytterbium-176 with neutrons to produce Yb-177, which decays quickly into Lu-177 by releasing beta particles.
The indirect method of Lu-177 production results in pure Lu-177 without the presence of Lu-177m, making it non-carrier-added. Without Lu-177m to contend with, Lu-177 can be more readily used, has a stronger therapeutic concentration, and reduces post-procedure radioactive waste.
Therapeutic applications of Lu-177 are more effective and easier to administer with n.c.a. Lu-177. The downside of n.c.a. Lu-177, though, is that it requires Yb-176, which is a rare raw material.
Currently, n.c.a. Lu-177 is produced in nuclear fission reactors, similarly to molybdenum-99. However, unlike Mo-99, which is produced by irradiating uranium, Lu-177 is produced by irradiating ytterbium. Like with Mo-99, these few reactors are all aging and many are scheduled to be permanently decommissioned within the next ten years with no replacements lined up. New methods for producing this vital therapeutic isotope are necessary.
Currently, we source highly pure ytterbium-176 from fission reactors, which we then apply to our medical isotope production process using our accelerator-driven fusion neutron generators. Similarly to how our neutron generators irradiate uranium to produce molybdenum-99, by irradiating ytterbium we can produce highly pure lutetium-177.
Over the next few years, we plan on phasing out externally sourced ytterbium in favor of our own proprietary method for producing Yb-176. We believe that producing our own source of highly pure Yb-176 will lower the cost and simplify the manufacturing logistics associated with producing n.c.a. Lu-177.
Our therapeutics division, SHINE Therapeutics, will be commercially producing Lu-177 out of our new production facility Cassiopeia in Janesville, Wisconsin. Our medical isotope production process and facilities are designed to produce n.c.a. Lu-177 in accordance with good manufacturing processes. Due to our uniquely scalable and efficient nuclear separation technique to extract medical radioisotopes, we believe this process will provide a sustainable and cost effective option for therapeutic radioisotope production.
As the nascent radiopharmaceutical therapy market develops with additional therapeutic approvals outside of Lu-177, we believe our core competencies support future expansion into other therapeutic radioisotope production, such as Iodine-131, Actinium-225 and Copper-67.
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