Properties:
Thorium-227 (once called Radioactinium) is an alpha emitter with a half-life of 18.7 days that decays into 223Ra (half-life 11.4 d; α, 76% at 6,336 keV and 23% at 6,234 keV; γ, 3% at 111 keV). In other words, 227Th is the parent isotope of the radionuclide used for 223Ra-Xofigo.
Toxicity: Unbound 227Th accumulates in bones
Manufacturing:
227Th is obtained indirectly by neutron irradiation of 226Ra (1,600 years half-life) which first leads to 227Ac (half-life 21.8 years; 100% α at 4,953 keV, 48% and 4,940 keV, 40%) which decays into 227Th (98.6%) and 223Fr (half-life 21.8 min, 1.4%; with β–-emission at 1,098 keV and 1,690 keV, 16%). This separation process which leads also to 223Ra in a further step can also be considered as a kind of industrial generator.
Source and availability:
For research purpose NIDC (DoE, USA) is proposing hundreds of mCi 227Th (and 223Ra) per month from their 227Ac cows.
In May 2018, Bayer signed a 10-year supply agreement with DoE for access to 227Ac, the precursor of 223Ra, and 227Th. In June 2018, Bayer signed an agreement with Eckert & Ziegler which will become the European partner for the production of 227Th labeled products.
Derivatives:
227Th is already part of some development programs involving Algeta and other companies such as Sanofi/Genzyme, Ablynx (since January 2018 acquired by Sanofi) or Affibody with first drugs in preclinical stage such as 227Th-Trastuzumab or 227Th- Rituximab.
Bayer in collaboration with Immunomedics was developing 227Th-BAY1862864, a CD-22 targeting thorium conjugate targeting relapsed or refractory CD-22 positive non-Hodgkin’s lymphoma, but Immunomedics stepped out.
The best chelator for 227Th seems to be 3,2-HOPO (3,2-hydroxypyridinone).
Price:
Unknown at this stage.
Issues:
Apparently, the chemistry of 227Th is more favorable than 223Ra but the direct use of the parent compound 227Th adds a new step in the long alpha decay chain. The company Lumiphore has developed a specific ligand for 227Th that is used by Bayer in the development of 227Th-BAY1862864.
The negative data and unexpected side-effects (bone fractures and deaths) observed with 223Ra-Xofigo in combination with Abiraterone restricted the use of 223Ra-Radium Dichloride but will also impact all Thorium-227 research programs. With 223Ra being the first decay product from 227Th the risk of observing the same side effects at least when bone metastases are present may appear also with this radionuclide.
Comments:
227Th is a new radionuclide that has already triggered some interest from companies for further evaluation, actually mainly Bayer. Algeta SAS and Sanofi have started investing also in associated radiolabeled compounds, the chemistry of this atom and its manufacturing. With the acquisition of Algeta by Bayer (first quarter of 2014), the evolution of these competitor research programs will have to be closely observed. Surprisingly, no evolution of this 227Th-radiolabeled molecules (new clinical trials) has been observed since 2018.