Yttrium-90 is a radioactive isotope of the element yttrium with a half-life of approximately 64 hours. It is commonly used in targeted radiation therapy, known as radioembolization, for the treatment of certain types of liver cancer, such as hepatocellular carcinoma and metastatic liver tumors.
In radioembolization, tiny resin or glass beads containing yttrium-90 are injected directly into the blood vessels that supply the liver tumors. The beads become lodged in the small blood vessels near the tumors, where they deliver high doses of radiation to the cancer cells while sparing the surrounding healthy liver tissue.
The beta radiation emitted by yttrium-90 has a short range in tissue, making it effective for targeting tumors while minimizing damage to nearby healthy tissues. This targeted approach allows for a higher radiation dose to be delivered to the tumor, potentially leading to better tumor control and fewer side effects compared to traditional external beam radiation therapy.
Yttrium-90 radioembolization is typically used as a palliative treatment for patients with inoperable liver tumors or as a bridge to liver transplantation. It can help shrink tumors, relieve symptoms, and improve overall survival in certain patients with liver cancer.
Overall, yttrium-90 is a valuable radioisotope used in targeted radiation therapy for the treatment of liver cancer. Its ability to deliver localized radiation to tumors makes it an important tool in the management of certain types of liver cancer, providing a treatment option for patients who may not be candidates for surgery or other forms of therapy.
Properties:
Yttrium-90 (90Y) is a radionuclide for therapy with a half-life of 64.0 hours. It is a pure beta emitter with energy of 2,280 keV (100%). Its effective path length (90% of the distribution of the radioactivity) is 5.3 mm and the mean path length is 3.9 mm. Unfortunately, 90Y has no gamma emission. It is easily chelated with DOTA and can be attached to almost any organic molecule. Maximum specific activity of 90Y is 543 Ci/mg.
Manufacturing:
Two grades of 90Y are commercially available. Carrier-added (ca) 90Y is produced via a direct neutron irradiation of 89Y via the route [89Y(n,γ)90Y].
Carrier free (or no carrier added, nca) 90Y is obtained in a two-step production route, first as a fission product from Uranium-235 that leads to Strontium 90 which decays slowly into 90Y: [235U(n,f)90Sr]→90Y. The 90Sr decay and separation of 90Y from 90Sr takes place in a kind of industrial generator. Due to the long half-life of 90Sr (half-life 28.79 years; β– 546 keV, 100%) such a generator lasts for years and cannot be provided to individual radiopharmacies.
Source and availability:
The two sources of 90Y (carrier free – cf or nca – and carrier added – ca) are available readily but are used for distinct applications.
- There is already high competition with centers running 90Sr/90Y generators. High- quality pharmaceutical-grade nca 90Y can be obtained from IBA Molecular (Curium) (Yttracis®), Eckert & Ziegler (Yttriga®) and POLATOM (RY-1/ItraPol™). Until 2016, IRE-ELiT was also commercializing the product Yttri-Eo™ (90Y), but stopped the production in June 2019 due to low perspectives. In February 2020, Eckert & Ziegler announced the building of a radiopharmaceutical production site in the Boston area and has signed a long-term rental contract for a suitable building in Wilmington, Massachusetts (USA) for the production of nca 90Y (opening expected by end of 2021). In July 2019, Eckert & Ziegler had already agreed to bring its 90Y production technology to a partner in Chengdu, China.
- In fact, as a generator is considered by regulations as a drug, in order to use 90Y solution for labeling of drugs, this radionuclide needs an official marketing authorization (through the filing of an NDA) that includes the full description of the generator. Yttracis® obtained its EU MA in March 2003 and Yttriga® in January 2006. Yttri-Eo never had a MA.
- Carrier free 90Y is also used in the SIR-Spheres microspheres for hepatic cancer therapy and represents now the largest part of the market of nca 90Y.
- The carrier-added 90Y quality is available from the main radionuclide producers (IBA Molecular and Mallinckrodt – Curium, Perkin Elmer, PNNL). It is used for radiosynovectomy (90Y-Citrate or 90Y-Silicate) or in microspheres for hepatic cancer therapy (TheraSpheres®).
Derivatives:
Carrier-added 90Y produced directly with a reactor is used in the radiosynovectomy application. This radionuclide quality cannot be used for labeling of molecules. The carrier free product is used in 90Y-labeled products such as 90Y-Zevalin.
In brachytherapy, 90Y is used only in microspheres for the treatment of non-resectable liver tumors or metastases using the radioembolization technique (SIR-Spheres® microspheres from SIRTeX and TheraSphere® microspheres from BTG/Boston Scientific). In the liver, these microspheres are considered to have a maximum range of emission and, therefore, of efficacy, of 11 mm, with a mean of 2.5 mm. 94% of the radiation is delivered to the tumor within 11 days. Doses used in single patients vary between 3.0 and 20 GBq (80–540 mCi).
Price:
The carrier-added 90Y used in brachytherapy and radiosynovectomy is the cheapest form, at less than EUR 10/mCi (US$ 11/mCi). A patient dose of nca 90Y for labeling is estimated to be about EUR 1,000 (US$ 1,100) which brings the mCi in the range of EUR 30 (US$ 33). The dose used in NHL patient therapy is around 30 mCi.
Issues:
- No gamma emission.
- High energy.
Comments:
So far, drugs developed with 90Y have been associated with imaging analogues labeled preferentially with 111In. This is a consequence of the absence of gamma emission which disadvantages 90Y when compared to 131I or 177Lu. Iodine-131 (like all iodine radioisotopes) suffers from its high volatility, obliging high investments in radioprotection and radiomonitoring equipment. As a result, industry becomes more and more reluctant to produce larger amounts of new 131I-iodinated compounds and in fact to invest in iodine radioisotopes in general. 177Lu has a better profile for therapeutic applications, and beside the existence of a gamma emission, 177Lu also has a less energetic beta emission which favors treatment of smaller tumors. The mean path length of 177Lu is 0.7 mm compared to 3.9 mm for 90Y. In summary 90Y has declining interest except in the brachytherapy use of microspheres.