Method for production of radioisotope preparations and their use in life science, research, medical application and industry
The present invention relates to an universal method for the large scale production of high-purity carrier free or non carrier added radioisotopes by applying a number of “unit operations” which are derived from physics and material science and hitherto not used for isotope production. A required number of said unit operations is combined, selected and optimized individually for each radioisotope production scheme. The use of said unit operations allows a batch wise operation or a fully automated continuous production scheme. The radioisotopes produced by the inventive method are especially suitable for producing radioisotope-labelled bioconjugates as well as particles, in particular nanoparticles and microparticles.
1. A method for the large scale production of a high-purity carrier-free or non-carrier added radioisotopes in a quantity suitable for medical applications comprising the following steps:
(a) activation of a target by a particle beam,
(b) separation of the isotope from the irradiated target under vacuum or in an inert atmosphere,
(c) ionisation of the separated isotope in an ion source,
(d) extraction of the ionized isotope from the ion source in an ion beam and acceleration of the ion beam,
(e) mass-separation of the isotope, and
(f) collection of the isotope including implanting,
the isotope in the mass-separated ion beam into an implantation substrate and separating the isotope from the implantation substrate containing the isotope, wherein separating the isotope from the implanation substrates includes dissolving the implantation substrate in a small volume of water or an eluting agent.
2. The method according to claim 1 , wherein the mass separation process is controlled by mass marking.
3. The method according to claim 1 , wherein before step (c) the isotope of interest is introduced into an oven from where a sample is fed into the ion source.
4. The method according to claim 1 , wherein the ionisation in step (c) is surface ionisation, laser ionisation or plasma ionisation.
5. The method according to claim 1 , wherein the mass separation of step (e) is an on-line or an off-line mass separation.
6. The method according to claim 1 , wherein in step (f) the isotope of interest is collected by implantation into a prepared chemical substrate.
7. The method according to claim 1 , wherein radioisotopes in carrier-free or non-carrier added form are produced.
8. The method according to claim 1 , wherein an implantation energy is selected in order to adjust the implantation depth.
9. The method according to claim 1 , wherein the implantation is performed through a thin cover layer into the implantation substrate.
10. The method according to claim 1 , wherein the implantation substrate is a salt layer, a water-soluble substance, a thin ice layer of frozen water or another liquid, or a solid matrix.
11. A method for direct radioisotope-labelling of a bioconjugate, comprising
(i) performing a method according to claim 1 ,
(ii) obtaining the product fraction containing the radioisotope of interest in a small volume, and
(iii) direct radioisotope-labelling of the bioconjugate and/or direct injection into a chromatographic system for further purification,
wherein the bioconjugate is an immuno-conjugate, antibody, protein, peptide, nucleic acid, oligonucleotide, or fragment thereof.
12. The method according to claim 11 , wherein the bioconjugate further comprises a nanoparticle, microsphere or macroaggregate that is conjugated with, or covalently or noncovalently attached to, said immuno-conjugate, antibody, protein, peptide, nucleic acid, oligonucleotide or a fragment thereof.
13. The method according to claim 1 , wherein the implantation substrate is a nanoparticle, macromolecule, microsphere, macroaggregate, ion exchange resin, or other matrix used in a chromatographic system.