Properties:
Tin-117m (117mSn) is both a gamma (SPECT) emitter with a photon at 159 keV (86%) and a therapeutic radionuclide through conversion electrons at about 140 keV with a range below 300 µm in tissue. It is also a conversion electron emitter. 117mSn has a half-life of 13.6 days and decays into stable Tin-117. Maximum specific activity is 82.0 Ci/mg.
Manufacturing:
117mSn can be produced by several methods but the only useful commercial methods include:
- Irradiation of Tin (116Sn or 117Sn) in a reactor [116Sn(n,γ)117mSn] or [117Sn(n,n’γ)117mSn];
- Irradiating of an Antimony target with a proton accelerator [natSb(p,x)117mSn] at about 50-55 MeV; or
- Irradiation a Cadmium-116 target with an alpha accelerator [116Cd(α,3n)117mSn] at 47 MeV / 60-80 µA for 20 h (production 10 mCi/h).
The methods using reactors or proton accelerators to irradiate 116Sn [116Sn(n,γ)117mSn]) do not provide high specific activity radionuclides (about 1 Ci/g). Electromagnetic separators can increase the specific activity up to 1,000 Ci/g. The method using the cadmium precursor is the only one suitable for producing very high activity 117mSn (specifically up to 25,000 Ci/g).
Alpha irradiation is the only realistic method to produce 117mSn at the level of quality needed for medical application (labeling). This irradiation can take place in cyclotrons (>50 MeV) or Linac accelerators and uses the route [116Cd(α,3n)117mSn]. These devices are very rare and dedicated to specific applications. The development of 117mSn-labeled drug for worldwide supply would need an investment in at least two of these instruments (minimum investment EUR 30 million – US$ 39 million each).
Source and availability:
The alpha irradiation technology was mainly developed in Russia, in collaboration with Clear Vascular Inc., then transferred to the US. Intellectual property for most of the production routes, and particularly the high specific activity irradiation route, is owned by Clear Vascular Inc. (now Serene). Serene LLC (with its subsidiaries Convetra, NeuroSn, Clear Vascular Inc. and Exubrion Therapeutics) is the only company presently interested in the medical development of this radionuclide; they routinely produce 117mSn with a specific activity above 15,000 Ci/g, which is approximately one fifth of theoretical specific activity.
Supply to perform the clinical trials is presently sufficient. The deployment of new 70 MeV cyclotrons for the production of 82Sr could be a good source of new 117mSn manufacturing sites in the near future. Specific equipment with sufficient high energy alpha beam from cyclotron or linacs could produce between 300 and 1,500 Ci pure 117mSn per year.
Derivatives:
All 117mSn-labeled compounds are still under development. The most advanced product is 117mSn-Tin-Annexin (117mSn-DOTA Annexin V) developed by Serene Inc. 117mSn can also be used to electroplate stents or wires for a number of non-nuclear medicine applications.
In particular Serene through its subsidiary Exubrion Therapeutics launched by mid of 2018 a formulation of 117mSn-HTC (microparticles) for veterinary use in radiosynoviorthesis applications in dogs, cats, horses and camels. The maximum tissue penetration for 117mSn in radiosynoviorthesis applications is estimated at 0.3 mm compared to 11.0, 4.4 and 1.1 mm respectively for the three marketed radiosynovectomy agents based on 90Y, 186Re and 169Er. As a consequence, this short penetration reduces considerably side-effects and irradiation of healthy tissues.
Other 117mSn-labeled drugs under development include 117mSn-DTPA (bone metastases therapy) and 117mSn-RAGE (Alzheimer’s Disease).
Price:
As a consequence of the limited supply and high-quality requirements of Tin-117m, this radionuclide will probably remain expensive. As the radionuclide is not produced routinely, no figures can be provided, but the cost of a single dose per patient is probably higher than EUR 2,000 (US$ 2,600). Fortunately, very low amounts are needed per patient, even for therapeutic use. In the future it is expected than 117mSn will cost below EUR 100/mCi (US$ 130/mCi) and probably around EUR 50/mCi (US$ 65/mCi). Therapeutic doses for the treatment of vascular plaques will need about three to five mCi/patient while labeling a peptide or an antibody for cancer treatment could reach 100 mCi/patient.
Issues:
Besides access to the Tin-117m production centers and adequate tools, users of this radionuclide should also make sure that, next to the specific activity, the chemical and radiochemical purity is adequate. In particular, some manufacturing process may include 113Sn as an impurity (half-life 115 d) which may generate waste issues and higher patient dosimetry issues.
Comments:
Tin-117m is a gamma conversion electron and Auger electron emitter that is supported by a single company (Serene). The radionuclide shows a nice profile, but is lacking access to high-capacity manufacturing sites. Serene is presently looking to create a network of manufacturing sites in order to overcome the present limiting factors which are availability, power of existing alpha accelerators and targetry. The technology is available, but there is a need for large-scale investment. Fortunately, there are several investments in larger accelerators for the production of 82Sr that have been started. These tools could be used to produce 117mSn as well.