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Actinium et Lutetium

In the therapeutic field Global Morpho Pharma anticipates very soon a massive need for high quality pharmaceutical grade radionuclides from alternative sources such as non-carrier-added Lutetium-177, Actinium-225 or even Copper-67.

Lu
Lutetium-177
nca

Lutetium-177 (177Lu), is a beta emitter (β-) at 498keV (78.6%) and 177 keV (12.2%) decaying into stable Hafnium-177. It has a half-life of 6.73d. 177Lu shows a major advantage in also emitting gamma rays at 208 keV (11.0%) and 113 keV (6.3%) which allows also imaging for this therapeutic radionuclide. 100 mCi of 177Lu corresponds to approximately 1 µg of lutetium. The mean path length is 0.7 mm. Maximum specific activity of 177Lu is 109 Ci/mg.

177Lu is a reactor-produced radionuclide that can be obtained via two different routes, one based on irradiation of natural Lutetium-176 [natLu or 176Lu(n,γ)177Lu], the direct route, the other on Ytterbium-176 [176Yb(n,γ)177Yb→177Lu], the indirect route (half-life of the intermediate 177Yb: 1.9h). The two different routes correspond to two different qualities of lutetium. The indirect route provides high specific activity 177Lu (also called nca – non carrier added) which will allow the manufacturing of higher quality and even carrier-free radiolabeled drugs. The direct route does not allow separation of 177Lu from 176Lu and the use of this radionuclide can have some limitations (e.g., antibody labeling).

On top of this, the carrier-added route also generates a long half-life impurity 177mLu, a by-product generated by the irradiation of the 177Lu that is produced. 177mLu cannot be separated from the final product. This impurity has a half-life of 160.4d. Global Morpho Pharma provides only the non-carrier added 177Lu quality.

Ac
Actinium-225

Actinium-225 is a radioactive element with a half-life of 9.91 days emitting alpha particles with emissions at 5,830 keV and 5,792 keV. It decays first into Francium 221, then successively in Astatine-217, Bismuth-213, Thallium-209 and Lead-209 before leading to the stable Bismuth-209.

Actinium 225 is the parent radionuclide of Bismuth-213 in the 225Ac/213Bi generator. Its maximum specific activity is 58,000 Ci/g.

There are six ways possible to produce 225Ac:

1) 225Ac has historically been produced at an annual volume of between 600 and 800 mCi through the natural decay of Thorium-229 (half-life 7,340 years).

2) The neutron irradiation of 226Ra is another production route but leads to a mixture of 229Th (half-life 7,340 years) and 228Th (half-life 1.9 years).

3) Cyclotron production is possible by irradiating 226Ra targets via [226Ra(p,2n)225Ac] at about 15 MeV, but is cumbersome.

4) Another method starts from Thorium-232 [232Th(p,x)225Ac] but needs at least 100 MeV accelerators which are currently only available at BNL (USA), LANL (USA) or INR (Russia).

5) The use of linear accelerators is presently under final stage evaluation and 225Ac production needs accelerator produced 15 MeV deuterium beams and is based on the route [226Ra(d,3n)225Ac].

6) The most recent technology is based on the use of Rhodotron, an electron accelerator that generates gamma and X rays close to the target which can transform 226Ra in 225Ac through the reaction [226Ra(γ,n)225Ac]. It has a potential to generate as much 225Ac as a linear accelerator. The first prototype is under construction.

Global Morpho Pharma is relying on sources that can produce 225Ac of high quality and without contamination with other actinium isotopes and therefore proposes radionuclides based on either Thorium-229 generators or Linear accelerator/Rhodotron routes.

“Global Morpho Pharma aims at guaranteeing backup solutions for all its sources and over the next month will continue creating a network of additional sources. This information will be available on the News page.”

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