RU2630475C2 - Radionuclide generator having first and second atoms of the first element - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention provides the first and second generator radionuclides of the same chemical element: isotopes of the same chemical elements have similar chemical properties and is therefore usually cannot be separated by conventional chemical methods; in this aspect the invention provides separation.

EFFECT: ability to receive carrier-free isotopes with high specific activity, the possibility of providing guaranteed availability of radionuclides with high specific activity for an extended period of time, for example, depending on the half-life of the parent radionuclide half-life of the subsidiary radionuclide instead.

15 cl, 2 dwg

Description

FIELD OF THE INVENTION

The invention relates to the field of radionuclide generators.

BACKGROUND OF THE INVENTION

A radionuclide is an atom with an unstable nucleus, and this nucleus is characterized by excess energy, which can be transferred either to a newly formed radiation particle inside the nucleus, or to the electron of the atom. In this process, a radionuclide undergoes radioactive decay and emits one or more of the following particles: a photon, electron, positron, alpha particle, directly or indirectly. These particles create ionizing radiation. Radionuclides can be natural or obtained artificially.

The amount of radionuclides is not exactly known. Some nuclides are stable, some break up. Instability is characterized by a half-life. Taking into account those obtained artificially, more than 3300 nuclides are known (among them ~ 3000 radionuclides), including those obtained artificially, and most of them (> ~ 2400) have half-lives of less than 60 minutes. Their number increases with the discovery of new radionuclides with very short half-lives.

Chemists and physicists often call radionuclides radioactive isotopes, or radioisotopes. Radioisotopes with suitable half-lives play an important role in many practically applicable technologies (for example, in nuclear medicine).

Radionuclide generators are devices in which a (daughter) radionuclide is formed from a parent radionuclide precursor and possibly separated from it. Maternal radionuclide is usually obtained in a nuclear reactor, which is a complex and expensive system. A typical example is the technetium-99m generator used in nuclear medicine. The maternal radionuclide is molybdenum-99, obtained in the reactor.

US patent 4782231 describes a ^99m Tc generator with elution of a standard design used for medical purposes. The invention additionally provides efficient production of ^99m Tc radionuclides by irradiation of molybdenum in a natural mixture of isotopes with an average neutron flux.

The generator of US Pat. No. 4,182,231 and related generators are not relevant to the present invention. US patent 4782231 describes a standard chemical separation of two radionuclides of chemically distinct elements.

Radionuclides are used in two main ways: in order to use their chemical properties and use as radiation sources. Radionuclides of known elements, such as carbon, can serve as indicators, since they are considered to be chemically identical to non-radioactive nuclides, so that almost all chemical, biological and environmental processes occur with them in a similar way.

In nuclear medicine, radioisotopes are used for diagnosis, treatment and research. Radioactive indicators emitting gamma rays or positrons can provide diagnostic information about the patient’s internal anatomy and the functioning of specific organs. It is used in some types of tomography: single photon emission computed tomography (SPECT) and positron emission tomography (PET).

Radioisotopes are also used to treat hematopoietic tissue tumors; less successful for the treatment of solid tumors. More powerful sources of gamma radiation are used to sterilize syringes and other medical equipment.

Other areas of use are, for example, biochemistry, genetics and food preservation.

When the excitation is removed by emitting gamma rays, the core gives off excess energy by emitting a gamma ray. At the same time, this element does not turn into another (there is no nuclear transformation).

There are many examples of the use of radionuclides.

For example, according to current practice, ¹⁷⁷ Lu (half-life of 6, 7 days) is obtained by neutron activation of a target containing stable ¹⁷⁶ Yb, according to the nuclear reaction ¹⁷⁶ Yb (η, γ) ¹⁷⁷ Yb (β-) ¹⁷⁷ Lu. Then ¹⁷⁷ Lu is chemically separated from the target ¹⁷⁶ Yb and the parent radionuclide ¹⁷⁷ Yb and get a carrier-free product with high specific activity. This approach exists along with the previously used production method, in which the activation of targets containing stable ¹⁷⁶ Lu occurs with the formation, according to the nuclear reaction ¹⁷⁶ Lu (η, γ) ¹⁷⁷ Lu + ^177m Lu, of a mixture of radionuclides ¹⁷⁷ Lu and ^177m Lu. The presence of a long-lived (161 day) radionuclide ^177m Lu, the formation of which cannot be avoided, is a significant drawback of this approach for nuclear medicine applications; Moreover, the presence of ¹⁷⁶ Lu atoms in the target material leads to lower specific activity.

To emphasize the importance of radionuclide production, we point out that 500 patients a year are currently being treated at the Erasmus Medical Center (EMC) in the Netherlands alone. EMC orders 2 batches of ¹⁷⁷ Lu with 1 Ki activity per week.

Some problems of the existing level of technology are associated, moreover, with the fact that:

a) Limited availability of ¹⁷⁷ Lu at the request of the medical center. Therefore, there is a need to regularly order new batches of ¹⁷⁷ Lu. However, deliveries may be interrupted, for example, due to failure of the supplier equipment.

b) It is not possible to obtain carrier-free ¹⁷⁷ Lu without the need for irradiation of the isotope-enriched ¹⁷⁶ Yb and the associated chemical separation.

Medical centers depend, for example, regarding the use of ¹⁷⁷ Lu-PRRT (Peptide Receptor Radiation Therapy) therapy, on the availability on the market and the operational readiness of industrial nuclear reactors. It should be noted that recently research reactors suddenly failed, and, in addition, the reactors are also stopped for scheduled maintenance.

Until now, medical centers must regularly order new batches of ¹⁷⁷ Lu and therefore depend on their availability and on the operating schedule of the reactor.

c) Irradiation of isotopically enriched ¹⁷⁶ Yb and chemical separation is not performed at the request of a particular medical center.

The deficiencies inherent in ¹⁷⁷ Lu are generally also characteristic of other radionuclides or isotopes.

The present invention thus relates to a method for manufacturing a radionuclide generator, wherein the generator, products containing said generator, and their use overcome one or more of the aforementioned disadvantages without sacrificing functionality and advantages.

SUMMARY OF THE INVENTION

A first aspect of the present invention relates to a method for manufacturing a long-lived radioisotope generator having high specific activity and / or carrier-free, according to claim 1, to a long-lived radioisotope generator, a product containing said radioisotope generator, to a single portion, to a kit and to their use.

The present invention, in particular, is intended for the manufacture of a ^177m Lu- ¹⁷⁷ Lu generator, as well as for the production of ^44m Sc, ^127m Te, ^129m Te, ^137ra Ce and ^186m Re. The following examples also apply specifically to the above. It should be noted that the example ^177m Lu- ¹⁷⁷ Lu generator is also generally well applicable to the other examples mentioned and is by no means limited to the example ^177m Lu- ¹⁷⁷ Lu.

The present invention solves one or more of the above problems. The risk of a lack of sales and interruptions in the operation of nuclear reactors is greatly reduced; the present invention provides the delivery on demand of the required number of radioisotopes for a significantly longer period of time. In the case of Lu, the period extends from multiples of 6.7 days (half-life of ¹⁷⁷ Lu) to values that are multiples of 160 days (half-life of ^177m Lu), in other words, it increases by about 25 times. A similar improvement is achieved for other atoms, namely for those mentioned above.

In addition, the need to use a carrier is reduced or absent.

Thus, the present invention provides a generator with high specific activity. The specific activity increases significantly, usually at least 10 times, compared with chemically identical atoms, such as ^177m Lu and ¹⁷⁶ Lu in an exemplary embodiment, where the magnification factor is at least 100.

As indicated above, the present invention provides a long-lived radioisotope generator. The term "long-lived" means that their half-life is longer than the half-life of the daughter nuclide. The service life of the generator usually increases at least 2 times, that is, the generator serves twice as long, although it is possible to achieve an increase of more than 1000 times.

The present invention provides for the production of highly active isotopes without the addition of a carrier, such as ¹⁷⁷ Lu, without the need to irradiate an isotope-rich target, such as ¹⁷⁶ Yb, and, depending on the isotope, without the need for their chemical separation. Therefore, the present invention is simpler than others in terms of, for example, process steps, and as a result, it is available upon request, unlike most of the isotopes of the prior art that need to be ordered.

It should be noted that the invention relates to a generator containing the first and second radionuclides of the same chemical element: isotopes of the same chemical element have basically the same chemical properties and therefore usually cannot be separated by traditional chemical methods; in this aspect, the invention provides separation.

The present invention gives medical centers the opportunity to widely use these isotopes, such as ¹⁷⁷ Lu for PRRT, allowing in most cases not to depend, for example, on their availability and the schedule of operation of nuclear reactors.

The present invention provides for continuous production, for example, in a ^177m Lu- ¹⁷⁷ Lu radionuclide generator, for example, the ¹⁷⁷ Lu isotope (half-life of 6, 7 days) from the parent radioisotope (in this example ^177m Lu (half-life of 160 days)) for a long time , in this example, the generator can run for at least six months. Moreover, the eluted radioisotope, for example ¹⁷⁷ Lu, is carrier free.

The prior art technologies provide the availability of a single portion of a radioisotope, such as ¹⁷⁷ Lu, for example, by neutron irradiation of ¹⁷⁶ Lu or ¹⁷⁶ Yb in this example, while the present invention provides, for example, a ^177m Lu- ¹⁷⁷ Lu-generator, in which, through intervals, portions of a daughter radioisotope, for example ¹⁷⁷ Lu, can be selected, can be removed from the available amount of a mother radionuclide, for example, ^177m Lu.

Namely, the generator of the present invention in this example allows to obtain carrier-free isotopes with high specific activity. This is required for various applications.

Under appropriate experimental conditions, the radionuclide generator of the present invention provides guaranteed availability of radionuclides with high specific activity over an extended period of time, for example, depending on the half-life of the parent radionuclide instead of the half-life of the daughter radionuclide.

In addition, the method of the present invention has no drawbacks, except for the need for access to a neutron source included in the radiochemical infrastructure.

DETAILED DESCRIPTION OF THE INVENTION

The first aspect of the present invention, according to paragraph 1 of the claims, relates to a method for producing a long-lived radioisotope, optionally integrated in the generator and allowing to achieve high specific activity without adding media.

In an example of the present method, activation is carried out by one or more of the following methods: a neutron reaction, such as neutron bombardment, a proton reaction, photonuclear reactions, such as with gamma or X-rays, a reaction with alpha particles, and reactions involving ion beams.

It should be noted that various methods of implementing the present invention are possible, starting with a target in which the first and second atoms of one element according to the present invention are obtained. Usually, activation is carried out in well-protected environments, thereby reducing the risk of environmental contamination with radioisotopes, such as, for example, in nuclear reactors. The present invention provides some advantage by using smaller particles, such as those indicated above, such as neutrons and protons.

In one example, neutron bombardment of the target compound is carried out in the reactor, while according to another example, bombardment outside the reactor is carried out by a neutron beam or proton beam, for example, from a cyclotron.

In one example of the present method, target atoms, such as natural or isotopically enriched atoms, and the production method are selected from the group consisting of ¹⁷⁶ Lu atoms, ⁵⁸ Co atoms, ⁸⁰ Br atoms, ¹⁸⁷ Re atoms, ²³² Th atoms, and ¹⁹⁸ Hg atoms.

The following are examples of ways to obtain the first (maternal) atoms:

^4m Sc: ⁴⁵ Sc (2, 2n) ^44m Sc and ⁴⁴ Ca (p, n) ^4m Sc

^80m Br: ⁷⁹ Br (n, γ) ^80m Br, ⁸¹ Br (n, 2n) ^80m Br and ⁸⁰ Se (p, n) ^80m Br

^121m Sn: ¹²⁰ Sn (n, γ) ^121m Sn _, ¹²² S (n, 2n) ^121m Sn, ¹²¹ Sb (n, p) ^121m Sn and ²³⁵ U (n, f) ^121m Sn

^121m Te: ¹²⁰ Te (n, γ) ^121m Te, ¹²² Te (n, 2n) ^121m Te and ¹²¹ Sb (p, n) ^121m Te

^127m Te: ¹²⁶ Te (n, γ) ^127m Te, ¹²⁸ Te (n, 2n) ^127m Te, ¹²⁷ I (n, p) ^127m Sn and ²³⁵ U (n, f) ^127m Te

^129m Te: ¹²⁸ Te (n, γ) ^129m Te, ¹³⁰ Te (n, 2n) ^129m Te, ¹³² Xe (η, α) ^129m Te and ²³⁵ U (n, f) ^119m Te

^137mCe:¹³⁶Ce (n, γ)^137mCe ¹³⁸Ce (n, 2n)^137mCe¹³⁸La (p, 2n)^137mCe and¹³⁹La (p, 3n)^137mCe

^177m Lu: ¹⁷⁶ Lu (n, γ) ^177m Lu and ¹⁷⁷ Hf (n, p) ^177m Lu

¹⁸⁶ Re: ¹⁸⁵ Re (n, γ) ^186m Re, ¹⁸⁷ Re (n, 2n) ^186m Re, ¹⁸⁶ W (p, n) ^186m Re and ¹⁸⁶ 0s (n, p) ^186m Re

^192m lr: ¹⁹¹ Ir (n, γ) ^192m Ir, ¹⁹³ Ir (n, 2n) ^192m Ir, ¹⁹² 0S (p, n) ^192m Ir and ¹⁹² Pt (n, p) ^192m Ir

^198m Au: ¹⁹⁷ Au (n, γ) ^198m Au, ¹⁹⁸ Pt (p, n) ^198m Au and ¹⁹⁸ Hg (n, p) ^198m Au

^242m Am: ²⁴¹ Am (n, γ) ^242m Am.

Thus, it should be noted that various methods of implementing the present invention are possible, starting with a target in which the first and second atoms of one element of the present invention are obtained.

In this example of the present method, the first atoms are selected from the group consisting of: ^44m Sc atoms, ^80m Br atoms, ^121m Sn atoms, ^121m Te atoms, ^127m Te atoms, ^129m Te atoms, ^137m Ce atoms, ^177m Lu atoms, ^186m Re atoms, ^186m Re atoms ^192m Ir, atoms ^198m Au and atoms ^242m Am, preferably ^177m Lu atoms, ^44m Sc, ^127m Te, ^129m Te, ^137m Ce and ^186m Re. Useful breakdown characteristics of maternal / subsidiary data are determined experimentally (e.g. for medical / research purposes).

In this example of the present method, the second atoms are selected in accordance with the first atoms from the group consisting of: ⁴⁴ Sc atoms, ⁸⁰ Br atoms, ¹²¹ Sn atoms, ¹²¹ Te atoms, ¹²⁷ Te atoms, ¹²⁹ Te atoms, ¹³⁷ Ce atoms, ¹⁷⁷ Lu atoms, ¹⁸⁶ Re atoms, ¹⁹² Ir atoms, ¹⁹⁸ Au atoms, and ²⁴² Am atoms, for example, ¹⁷⁷ Lu atoms.

It should be noted that the following improvements were obtained with respect to the lifetime (for long-lived isotopes). For ^44m Sc atoms, the half-life is about 15 times longer than for ⁴⁴ Sc atoms. For ^80m Br atoms, the half-life is about 15 times longer than for ⁸⁰ Br atoms. For ^121m Sn atoms, the half-life is about 17800 times longer than for ¹²¹ Sn atoms. For ^121m Te atoms, the half-life is about 9 times longer than for ¹²¹ Te atoms. For ^127m Te atoms, the half-life is about 280 times longer than for ¹²⁷ Te atoms. For ^129m Te atoms, the half-life is about 695 times longer than for ¹²⁹ Te atoms. For ^137m Ce atoms, the half-life is about 4 times longer than for ¹³⁷ Ce atoms. The half-life for ^177m Lu atoms is about 25 times longer than for ¹⁷⁷ Lu atoms. For ^186m Re atoms, the half-life is about 2 × 10 ⁷ times longer than for ¹⁸⁶ Re atoms. For the ^192m Ir atoms, the half-life is about 1100 times longer than for the ¹⁹² Ir atoms. For the atoms of ^198m Au, the half-life is about 0.8 times longer than for atoms of ¹⁹⁸ Au. For ^242m Am atoms, the half-life is about 7.7 × 10 ⁴ times longer than for ²⁴² Am atoms.

In one example, the present method further comprises the step of separating the first atoms to form second atoms, preferably by chemical separation.

According to the present invention, the separation is carried out taking advantage of the emission of highly converted gamma rays during the decay of maternal atoms. It is assumed that this emission leads to the Auger effect, in which the electrons of the orbit break out of their shells. As a result, many positively charged daughter atoms are formed. The Coulomb repulsion between these fragments of atoms can, in the case of a chemical compound, lead to the breaking of chemical bonds between the atoms of the compound and the daughter atoms, and, therefore, these daughter atoms will be separated from both the target material and the parent radionuclide. Another example would be a similar mechanism, when the target, mother and daughter atoms are in the solid state, for example, in the solid layer. The present invention leads to a high activity of daughter isotopes, which is usually at least 100 times higher than if the daughter isotope is not separated from the target.

Accordingly, the present invention relates to a method for producing carrier-free daughter atoms with high specific activity, such as ¹⁷⁷ Lu atoms, characterized in that atoms such as ¹⁷⁶ Lu atoms, when bombarded with neutrons, form radioactive atoms such as ^177m Lu (half-life 160 days) and radioactive ¹⁷⁷ Lu (half-life 6.7 days); the latter is formed directly from ¹⁷⁶ Lu, and also as a decay product of ^177m Lu), everything happens in the target. Due to bond cleavage, ¹⁷⁷ Lu radioactive atoms are separated from ¹⁷⁶ Lu and ^177m Lu atoms contained in the target.

In one example, a radionuclide generator comprises the following: neutron-activated ¹⁷⁶ Lu, plus its reaction products, ^177m Lu and ¹⁷⁷ Lu, for example, in solution. The solution is mixed with another solvent into which only ¹⁷⁷ Lu passes from the mixture of radioisotopes. Similar examples are intended for the other examples mentioned.

In one example, a generator, such as a ^177m Lu- ¹⁷⁷ Lu generator, is designed to load a 0.02-500 Ci radioisotope, for example 0.5-250 Ci, for example 1-100 Ci, for example 2-50 Ci, for example ^177m Lu. Such a generator can, in this example, provide 7-8 batches of a radioisotope, such as ¹⁷⁷ Lu, with an activity of 175-0.001 Ci for a period of 7-8 months. Weekly, as described above, EMC will need a 2-4 ^177m Lu- ¹⁷⁷ Lu generator (purchased sequentially over 2-4 weeks) in order to get a constant weekly availability of ¹⁷⁷ Lu for a period of 7-8 months, rather than ordering 80 batches of ¹⁷⁷ Lu for the same period, which is a clear advantage.

The fluid used may have oxidizing ability and / or have some ionic strength to facilitate the collection of second (daughter) atoms. The liquid should be chosen so that it can be used in the chemical separation of the second (daughter) atom from any chemical impurity. In the case of ¹⁷⁷ Lu, this may be the removal of ¹⁷⁷ Hf.

This rupture of communication also continues after irradiation, as soon as¹⁷⁷Lu on decay^177mLu. Separated Radioactive Atoms¹⁷⁷Lu is removed from said chemical compound or solution by a chemical process having high selectivity for¹⁷⁷Lu compared to chemically identical atoms^175/176Lu and maternal radionuclide^177mLu. After this removal, new atoms are formed.¹⁷⁷Lu on decay^177mLu, and the removal procedure¹⁷⁷Lu can be repeated after sufficient formation time. This creates^177mLu-¹⁷⁷Lu radionuclide generator to regularly remove volumes¹⁷⁷Lu from one volume^177mLu.

It should be noted that isotopes of the same chemical element have the same chemical properties and therefore usually cannot be separated by traditional chemical methods.

In one example of the present method, second atoms are released into a fluid such as gas, liquid, and supercritical fluid, or a combination thereof.

The fluid must be able to accept daughter atoms. In the case of its direct subsequent use, the liquid medium should also be acceptable for this application, for example, be non-toxic, close to biological fluid, etc.

In one example of the present method, the liquid medium is preferably water and contains one or more dissolved substances, such as salts, acids, bases, adjuvants, saccharides and stabilizers.

Such a fluid should be capable of simulating, for example, a biological fluid, for example, at typical concentrations of dissolved substances in it.

The second aspect of the present invention relates to a generator of long-lived, highly active and / or carrier-free radioisotopes, according to paragraph 8 of the claims.

It should be noted that the size of the generator can be adjusted, for example, by increasing or decreasing, thus potentially controlling the amount of emitted isotopes. For this, you can also adjust the amount of fluid supplied to the generator, the surface of the generator, etc.

A third aspect of the present invention relates to a product comprising a generator of long-lived, highly active and / or carrier-free radioisotopes according to the invention.

In one example of the present product, a radioisotope generator:

located on the surface and / or

is in a liquid and / or

is in the matrix, and / or

is in a chemical compound and / or

is in the complex and / or combinations thereof.

In one example, the present generator has a large surface area and a small volume, for example, is a layer with a thickness of 1 atom (~ 100 pm) -10 μm, such as 1 nm - 2 μm. This improves the release of daughter atoms.

As such a support layer / structure, a chemically inert layer, zeolite, etc. may be provided. Also, the generator may be in a compound, such as a chemical compound, capable of forming (chemical) bonds with the daughter and parent atoms, and, optionally, with the target atoms, or similarly in the complex. The generator may also be in a liquid, such as water, in a gas, such as nitrogen, and the like.

In one example of the present product, the radioisotope generator is on a chemically inert surface, such as the inner surface of the tubular structure, the surface of the particle, dissolved in a liquid, is in a 3D and / or 2D matrix, such as a zeolite, in a chemical compound, such as an organometallic compound , in a complex, such as a complex with one or more organic molecules, in a complex with one or more inorganic molecules, and combinations thereof.

In one example of the present product, it contains

- a tube, and the tube contains an inner surface formed by a chemically inert substance such as glass, Teflon, a suitable polymer, silicon, a metal such as copper, tantalum, titanium, a metal alloy or a combination thereof,

- inlet for starting fluid into the tube,

- an outlet for draining fluid from the tube,

- a protective sheath around the tube to prevent the influence of radiation on the environment, such as a protective sheath containing lead, and

- a generator of long-lived, highly active or carrier-free radioisotopes inside the tube.

Typically, fluid enters the generator through the inlet. The fluid collects a daughter radionuclide.

After collecting the required amount of the radioisotope, the liquid is discharged through the outlet. The amount of liquid withdrawn per unit time can be calculated, for example, in order to determine the residence time. In a similar manner, a continuous fluid flow can be provided, typically at a low flow rate, by supplying a fluid containing a daughter radionuclide. The flow rate can be 0.1 ml / h - 50 ml / h. In this way, a controlled amount of the radioisotope can be provided.

A fourth aspect of the present invention relates to a single portion of radioactive atoms, such as ¹⁷⁷ Lu atoms, which can be obtained by the method of the invention or provided by a product of the invention or a generator of the invention. A single serving is 0.02-5 Ci, for example 0.02-1.6 Ci, for example 0.1-1.0 Ci.

A fifth aspect of the present invention relates to a kit comprising a product of the invention and / or a single serving of the invention.

In this example, the kit contains the aforementioned generator. Additionally, the kit may contain a liquid, namely 0.1-1000 ml per received single serving. Preferably, the liquid contains additional components, namely the aforementioned solutes. In this case, the resulting single portion can be directly used for the intended (final) purposes. The kit may further comprise a syringe, namely a 10-250 ml syringe. Gloves are also usually included. The kit may further comprise a storage kit. In this example, the kit is substantially free of microorganisms.

A sixth aspect of the present invention relates to the use of a product of the invention and / or a single portion of the invention for the preparation of a medicament, namely for use in a therapy such as radiation therapy.

The invention will now be described in more detail using the accompanying drawings, which are given to illustrate and explain, but do not limit the scope of the invention. Specialists in the art will understand that many options are acceptable, obvious or not, falling within the scope of the claims defined by the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

Although the invention is described in detail in a context that clarifies its meaning, it will become more apparent in conjunction with the accompanying drawings.

FIG. 1-2 show a schematic representation of an example of a generator (such as claimed in the claims).

DETAILED DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a schematic illustration of a generator. The tube (1) is shown in the figure, the tube containing an inner surface formed by a chemically inert substance, such as glass, Teflon, a suitable polymer, silicon, a metal such as copper, tantalum, titanium, a metal alloy or a combination thereof. An inlet (2) for supplying fluid to the tube is also shown. Typically, the internal size of the inlet is 0.1-10 mm, for example 0.3-5 mm. The inlet is also made of chemically inert material. Perhaps it may also contain a protective layer. Also shown is an outlet (3) for draining fluid from the tube. Outlet and inlet usually have similar properties. To protect the environment from radiation, there is optionally a protective shell (6) around the tube, such as a protective shell containing lead. The product additionally contains a generator of long-lived, with high specific activity or carrier-free radioisotopes inside the tube. The generator may take any suitable form, such as described above.

FIG. 2 shows generator details.

In FIG. 2a shows a cross section of a coated tube containing element A: a deposited layer of first atoms (monoatomic or multilayer), the layer may include non-radioactive atoms of the same element); element B: a chemically inert surface (e.g. glass, tantalum, silicon, etc.), and element C: structural material; this material may include protective material (e.g., lead).

In FIG. 2b shows a further example in which the deposited layer contains spherical particles and the like, typically particles with a diameter of 0.2-10 nm.

In FIG. 2c, the generator is filled with coated granules having the same composition as above.

It will be appreciated that for commercial applications it may be preferable to use one or more varieties of the present system, similar to those disclosed in this application and not beyond the scope of the invention.

Claims (42)

1. A method of manufacturing a long-lived radioisotope generator capable of providing high specific and / or carrier-free radioactivity, comprising the steps of: (a) providing a target, (b) activating a target to produce a radioisotope generator, the radioisotope generator comprising (i) radioactive first atoms (maternal) of the first element having a first half-life, the first atoms being in a metastable state of the first element, (ii) second atoms (daughter) of the first element, which are radioactive and having a second half-life, the second atoms being in the second state of the first element, such as the ground state, moreover, the second atom is a radioactive daughter atom of the first parent atom, and this radioactive daughter atom is formed by emission of a gamma transition with high internal conversion, such as E2, E3, E4, E5, M2, M3, M4, M5, or a combination thereof, and the separation of the first atoms (parent) of the first element with the formation of the second atoms (daughter) of the first element. 2. The method according to p. 1, containing the stage (c) embedding an activated target, including first atoms, second atoms and inactive target atoms, by electrochemical or physical deposition on an inert surface, and / or in which the first half-life is at least 2 times greater than the second half-life, preferably at least 5 times more and more preferably at least 10 times more, for example at least 25 times more, and / or in which activation is carried out by one or more of the following methods: neutron reaction, proton reaction, photonuclear reactions, such as with gamma or X-rays, reaction with alpha particles and reaction involving ion beams. 3. The method according to claim 1 or 2, in which the target atoms, for example arising in nature or isotopically enriched atoms, and the production method are selected from the group consisting of: ¹⁷⁶ Lu atoms, ⁵⁹ Co atoms, ¹⁸⁷ Re atoms, ²³² Th atoms, ⁴⁵ Sc atoms, ⁴⁴ Ca atoms, ⁷⁹ Br atoms, ⁸¹ Br atoms, ⁸⁰ Se atoms, ¹²⁰ Sn atoms, ¹²² Sn atoms, ¹²⁰ Those atoms, ¹²² Those atoms, ¹²¹ Sb atoms, ¹²⁶ Those atoms, ¹²⁸ Those atoms, ¹²⁷ I atoms, ²³⁵ U atoms, ¹³⁰ Te atoms, ¹³² Xe atoms, ¹³⁶ Ce atoms, ¹³⁸ Ce atoms, ¹³⁸ La atoms, ¹³⁹ La atoms, ¹⁷⁷ Hf atoms, ¹⁸⁵ Re atoms, ¹⁸⁶ W atoms, ¹⁸⁶ Os atoms, ¹⁹¹ Ir atoms, ¹⁹³ Ir atoms, ¹⁹² Os atoms, ¹⁹² Pt atoms, ¹⁹⁷ Au atoms, ¹⁹⁸ Pt atoms, ²⁴¹ Am atoms and ¹⁹⁸ Hg atoms. 4. The method according to claim 1 or 2, wherein the first atoms are selected from the group consisting of: ^44m Sc atoms, ^58m Co atoms, ^80m Br atoms, ^121m Sn atoms, ^121m Te atoms, ¹²⁷ Sn atoms, ^127m Te atoms, ^129m Te atoms, ^137m Ce atoms, ^177m Lu atoms, ^186m Re atoms, ^192m Ir atoms, ^198m Au atoms, ²²⁹ Ra atoms and ^242m Am atoms, preferably ^177m Lu, ^44m Sc, ^127m Te, ^129m Te, ^137m Ce and ^186m Re atoms. 5. The method according to claim 1 or 2, in which the second atoms are selected in accordance with the first atoms from the group consisting of: ⁴⁴ Sc atoms, ⁵⁸ Co atoms, ⁸⁰ Br atoms, ¹²¹ Sn atoms, ¹²¹ Those atoms, ¹²⁷ Sn atoms, ¹²⁷ Those atoms, ¹²⁹ Those atoms, ¹³⁷ Ce atoms, ¹⁷⁷ Lu atoms, ¹⁸⁶ Re atoms, ¹⁹² Ir atoms, ¹⁹⁸ Au atoms, ²²⁴ Ra atoms, ²²⁸ Ra atoms and ²⁴² Am atoms, preferably ¹⁷⁷ Lu atoms. 6. The method according to p. 1 or 2, further comprising a step separating the first atoms to form second atoms, preferably by chemical separation, in which the second atoms are separated into a fluid such as gas, liquid and supercritical fluid, or a combination thereof. 7. The method according to p. 6, in which the fluid is preferably water and contains one or more dissolved substances, such as salts, acids, bases, adjuvants, saccharides and stabilizers. 8. A generator of long-lived, with high specific activity and / or carrier-free radioisotopes, the radioisotope generator comprising: target atoms, the target atoms being selected from the group consisting of ⁴⁴ Ca atoms, ⁴⁵ Sc atoms, ⁵⁹ Co atoms, ^58m Co atoms, ⁷⁹ Br atoms, ⁸⁰ Se atoms, ⁸¹ Br atoms, ¹²⁰ Sn atoms, ¹²⁰ Those atoms, ¹²¹ Sb atoms , ¹²² Sn atoms, ¹²² Those atoms, ¹²⁶ Those atoms, ¹²⁷ I atoms, ^127m Sn atoms, ¹²⁸ Those atoms, ¹³⁰ Those atoms, ¹³² Xe atoms, ¹³⁶ Ce atoms, ¹³⁸ Ce atoms, ¹³⁸ La atoms, ¹³⁹ La atoms, ¹⁷⁶ Lu atoms, ¹⁷⁷ Hf atoms, ¹⁸⁵ Re atoms, ¹⁸⁶ W atoms, ¹⁸⁶ Os atoms, ¹⁸⁷ Re atoms, ¹⁹¹ Ir atoms, ¹⁹² Os atoms, ¹⁹² Pt atoms, ¹⁹³ Ir atoms, ¹⁹⁷ Au atoms, ¹⁹⁸ Pt atoms, ¹⁹⁸ Hg atoms , ²²⁹ Ra atoms, ²³² Th atoms, ²³⁵ U atoms and ²⁴¹ Am atoms, and (i) the radioactive first atoms (maternal) of the first element having a first half-life, the first atoms being in a metastable state, (ii) second atoms (daughter) of the first element, which are radioactive and having a second half-life, the second atoms being in a second state, such as a ground state, moreover, the second atom is a radioactive daughter atom of the first atom (parent), and the radioactive daughter atom is formed by emission of gamma radiation with high internal conversion, such as E2, E3, E4, E5, M2, M3, M4, M5, or a combination thereof, and obtained by the method according to any one of paragraphs. 1-7, wherein the first atoms are preferably selected from the group consisting of: 44mSc atoms, 80mBr atoms, 121mSn atoms, 121mTe atoms, 127mTe atoms, ^137m Ce atoms, 177mLu atoms, 186mRe atoms, 192mIr atoms, 198mAu atoms and 242mAm atoms. 9. A product containing a generator of long-lived, with high specific activity and / or carrier-free radioisotopes according to claim 8. 10. The product of claim 9, wherein the radioisotope generator located on the surface and / or is in a liquid and / or is in the matrix, and / or is in a chemical compound and / or is in the complex and / or combinations thereof. 11. The product according to claim 10, in which the radioisotope generator is on a chemically inert surface, such as the inner surface of the tubular structure, the surface of the particle is dissolved in a liquid, is in a 3D and / or 2D matrix, such as a zeolite, is in a chemical a compound, such as an organometallic compound, is in a complex, such as a complex with one or more organic molecules, is in a complex with one or more inorganic molecules, and combinations thereof. 12. The product according to p. 11, containing a tube (1), the tube comprising an inner surface formed by a chemically inert substance such as glass, Teflon, a suitable polymer, silicon, a metal such as copper, tantalum, titanium, a metal alloy, or a combination thereof, an inlet (2) for supplying fluid to the tube, an inlet (3) for draining fluid from the tube, optionally a protective sheath (6) around the tube to prevent radiation from affecting the environment, such as a protective sheath containing lead, and generator of long-lived, with high specific activity or carrier-free radioisotopes inside this tube. 13. A single portion of radioactive atoms, such as ¹⁷⁷ Lu atoms, obtained by the method according to any one of paragraphs. 1-7 or provided by the product according to any one of paragraphs. 9-12 or generator according to claim 8. 14. A kit containing the product according to any one of paragraphs. 10-12 and / or a single serving according to claim 13. 15. The product according to any one of paragraphs. 9-12 and / or a single portion according to claim 13 for the preparation of a medicinal product, for example, for use in radiation therapy or imaging, for example, in peptide receptor radiation therapy, for diagnosis or treatment.

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