Production of high purity 212Pb

Abstract

The present invention relates to assemblies and methods of obtaining a container comprising containing 212Pb on a wall wherein 212Pb is obtained from a 212Pb precursor isotope source. The present invention provides an improved system and method for producing high purity 212Pb that does not require processing, is high in yield, and can safely and efficiently transport the high purity 212Pb to its location of use.

Description

Technical Field

[0001] This invention relates to a single-chamber diffusion generator (assembly), multiple components, and a method for obtaining a container whose walls contain 212 Pb, from 212 Obtained from Pb precursor isotope source 212 This invention provides a method for producing high-purity Pb. 212 An improved system and method for Pb, requiring no pretreatment, with high yield, and capable of safely and efficiently producing high-purity Pb. 212 Pb is transported to its place of use. Background Technology

[0002] The preparation or production of [the product] has been previously described. 212 Pb components, and based on 220 After Rn has diffused from the first chamber (source chamber) to the second chamber (collector chamber), 228 Th is in a chamber with the collection 212 Stearate binding in another chamber of Pb.

[0003] Extract from a container in another system 228 Th / 224 Ra, the pump generates airflow, and 220 Rn / 212 Pb is collected in another container. The system consists of a transport... 220 Rn's "air circuit" and a method for 212 The system consists of Pb flushing and a "fluid loop" collected after flushing. This is a very complex system, unsuitable for transportation and handling, and there is a high possibility of leakage or misuse, for example, in hospitals.

[0004] In another system, a transmitter source is placed in a chamber through which airflow passes and carries... 220 Rn to another collection 220 Rn / 212 The Pb chamber. After a period of time, the carrier gas valve closes, and the collection unit adds liquid through the top valve and collects the liquid through the bottom valve. This system is also relatively complex. Both systems require a significant amount of work from skilled workers, as well as relatively advanced laboratory equipment and operating space.

[0005] In addition, it has been previously introduced that it does not depend on 220 Rn emission and diffusion 212 Pb generator system. In an existing generator system, 224 Ra is combined with ion exchange materials and extracted by acid elution. 212 Pb must be evaporated before it can be used for radioactive labeling. In another existing system,224 Ra solution 212 Pb is used for purification and removal via size exclusion. 224 Ra is then used for tracing. Both methods are effective, but require additional processing time, with the first method taking longer than the second.

[0006] 212 Pb has a half-life of only 10.6 hours. This short half-life makes the radioisotope ideal for medical applications such as cancer treatment, as it acts directly on its target and does not produce long-term side effects due to its long half-life. However, this characteristic also makes it difficult to use in commercial environments involving centralized production and long-distance transportation to end users, because it decays rapidly, reducing yields over time.

[0007] Therefore, the current challenge facing radiation and diffusion systems is transmission distance, due to... 220 Rn decays before reaching the collection container, significantly reducing efficiency over transmission distance. For example, one system reported collecting 2.01 MBq over 3 days. 212 The total yield obtained from Pb was compared with the 7.05 MBq yield obtained from 3 days of operation. 228 Compared to the total yield obtained from the Th source, the yield is less than 30%. Increasing the operating time does not increase the collection volume, and the system is very sensitive to airflow.

[0008] Alpha-emitter therapy is needed for biomedical applications. Lead-212 ( 212 Pb is a β emitter that decays into short-lived offspring that produce α particles, and therefore can be used in vivo as an α emitter generator for α emitter therapy.

[0009] Therefore, the industry needs an improved system and method for producing high-purity [products / materials]. 212 Pb requires no processing, has high yield, and can be produced in high purity. 212 Pb can be safely and efficiently transported to its place of use. Summary of the Invention

[0010] One object of the present invention relates to a method for obtaining a wall containing 212 A method for constructing a container for Pb includes the step of providing a component comprising a first part and a second part, wherein the first part comprises a container and the second part comprises... 212 A Pb precursor isotope source is used to connect the first and second parts, so that... 212 The Pb precursor isotope source does not contact the inner wall of the container and provides a single-chamber container assembly, enabling... 212 Pb precursor isotopes have sufficient time to decay into offspring. 220 Rn、 216Po or 212 Pb, and make 220 Rn、 216 Po and / or 212 Pb has sufficient time to settle onto the inner wall of the single-chamber container assembly, removing or isolating residual Pb in the single-chamber assembly. 212 Pb precursor isotopes, without the need for Pb precursor isotopes, and without making 212 A Pb precursor isotope source is brought into contact with the inner wall of a single-chamber container assembly to obtain a container containing [a specific substance] on its inner wall. 212 Pb and the inner wall of the container is basically free of it. 212 The system can be referred to as a Pb precursor isotope source. 212 Single-chamber diffusion generator for Pb.

[0011] In the following text, precursor isotopes are defined as... 212 Pb includes parent nuclides, grandmother nuclides, great-grandmother nuclides, etc., i.e. 216 Po、 220 Rn、 224 Ra et al.

[0012] Another object of the present invention relates to an assembly comprising a first portion and a second portion, wherein the first portion comprises a container and the second portion comprises... 212 Pb precursor isotope source, wherein the first part and the second part are connected to form such that 212 The Pb precursor isotope source does not come into contact with the inner wall of the container, thus providing a single-chamber container assembly.

[0013] Another object of the present invention relates to a single-chamber container assembly comprising a first portion and a second portion, wherein the first portion comprises a container and the second portion comprises... 212 A Pb precursor isotope source, wherein the first and second portions are connected to make... 212 The Pb precursor isotope source does not come into contact with the inner wall of the container.

[0014] In one or more embodiments of the present invention, the single-chamber container assembly is airtight.

[0015] In one or more embodiments of the present invention 212 Pb precursor isotope source selected from 232 Th、 228 Ra、 228 Ac、 228 Th and / or 224 Ra.

[0016] In one or more embodiments of the present invention 212 Pb precursor isotope source is 232 Th、 228 Ra、 228 Ac、228 Th and 224 A mixture of Ra.

[0017] In one or more embodiments of the present invention 212 Pb precursor isotope source is 228 Th and 224 A mixture of Ra.

[0018] In one or more embodiments of the present invention, 212 Pb precursor isotope source is 224 Ra. In one or more embodiments of the present invention 212 Pb precursor isotope source is 228 Th. Depends on the inward growth state. 212 Pb activity can typically be found in the generator. 224 The activity of Ra precursor varied between 0% and 114%. 212 Pb activity can be 224 At least 90%, for example, at least 80%, for example, at least 70%, for example, at least 60%, for example, at least 50%, for example, at least 40%, for example, at least 30%, for example, at least 20%, for example, at least 10% of the Ra precursor activity.

[0019] In one or more embodiments of the present invention 212 Pb precursor isotope source is 228 Th, according to relative 212 The percentage of radioactivity of Pb is measured to be at least 90%, for example at least 80%, for example at least 70%, for example at least 60%, for example at least 50%, for example at least 40%, for example at least 30%, for example at least 20%, for example at least 10%. 228 Th.

[0020] In one or more embodiments of the present invention 212 Pb precursor isotope source is 224 Ra, which is relative to 212 The percentage of radioactivity of Pb is measured to be at least 90%, for example at least 80%, for example at least 70%, for example at least 60%, for example at least 50%, for example at least 40%, for example at least 30%, for example at least 20%, for example at least 10%. 224 Ra。。。

[0021] In one or more embodiments of the present invention, the total radioactivity in the single-chamber container assembly is 1 kBq-100 GBq.

[0022] In one or more embodiments of the present invention 212 Pb precursor isotope sources are in the form of inorganic or organic salts, such as RaCl2.

[0023] In one or more embodiments of the present invention 212 Pb precursor isotope sources are combined with non-radioactive materials, such as particles or holding materials.

[0024] In one or more embodiments of the present invention 212 The Pb precursor isotope source is in dry form or a liquid solution, such as an aqueous solution or a dispersant.

[0025] In one or more embodiments of the present invention 212 The Pb precursor isotope source is in a liquid solution with an acidic, neutral, or alkaline pH.

[0026] In one or more embodiments of the present invention 212 Pb precursor isotope sources are deposited on strips or spheres made of a material suitable for applying liquid.

[0027] In one or more embodiments of the present invention 212 The Pb precursor isotope source is deposited on strips or spheres, which are made of materials selected from: paper, plastic, metal, ceramics, and natural or synthetic fibers and cellulose.

[0028] In one or more embodiments of the invention, the strip or ball is attached to a second portion, the second portion including means for holding the strip or ball, such as a rod.

[0029] In one or more embodiments of the invention, the second part includes a syringe, or the rod is a syringe.

[0030] In one or more embodiments of the invention, the syringe tip has been pushed past the rubber cap.

[0031] In one or more embodiments of the invention, the second part includes a rod attached to means for opening and closing the container.

[0032] In one or more embodiments of the present invention, the means for opening and closing the container is a cap, lid, or cover.

[0033] In one or more embodiments of the invention, the cap, lid, or cover is made of a material selected from rubber, glass, paper, plastic, metal, ceramic, and natural or synthetic fibers.

[0034] In one or more embodiments of the present invention 212 The Pb precursor isotope source is placed on or inside a sphere, which is suitable for maintaining the source but allowing radon to diffuse.

[0035] In one or more embodiments of the present invention, the container includes212 A permeable barrier that Pb precursor isotope sources cannot pass through.

[0036] In one or more embodiments of the present invention 212 The air-permeable barrier that Pb precursor isotope sources cannot pass through and 212 Pb precursor isotope source contact.

[0037] In one or more embodiments of the present invention, the container does not include 212 A permeable barrier that Pb precursor isotope sources cannot pass through.

[0038] In one or more embodiments of the present invention, the volume of the container is 1 μl to 10 L, for example 1 μl to 1 L, for example 100 μl to 10 ml, for example 100 μl to 100 ml.

[0039] In one or more embodiments of the present invention, according to 212 The relative percentage of Pb radioactivity was measured, and the inner wall of the container was essentially free of Pb. 212 Pb precursor isotope sources are defined as those less than 212 Pb precursor isotope source 224 Ra is 3%, for example, less than 1%, for example, less than 0.5%.

[0040] In one or more embodiments of the invention, the inner wall of the container is coated. The coating may be a salt film on the inner wall or other suitable material.

[0041] In one or more embodiments of the present invention, the inner wall of the container is coated with a compound containing substances that can interact with... 212 Chelating agents that form Pb complexes.

[0042] In one or more embodiments of the invention, the inner wall of the container is coated with a chelating agent, which is TCMC or a variant thereof.

[0043] In one or more embodiments of the present invention, the container contains an aqueous solution or an oil solution. Attached Figure Description

[0044] Figure 1 Showing 232 Th decays into its descendants. The value indicates the decay type (α or β) and also the half-life. These half-lives are important because they determine the decay rate and therefore also determine the decay behavior. 212 Pb production 212 The key to the optimal isotope mixture of Pb precursor isotope sources.

[0045] Figure 2A A diagram showing a single-chamber container assembly with container (A) is displayed. 212Pb precursor isotope source (B) production 220 Rn gas, this 220 Rn gas is released into the single-chamber container assembly, where it decays into... 212 Pb settles onto the inner container wall (C) in the form of deposits. The upper part of the single-chamber container assembly (D) is the second section, which includes... 212 The Pb precursor isotope source, in this case, is a cap / lid with a rod pointing towards the center of the container, thus enabling the... 212 Pb precursor isotope source 220 Rn is released into the container.

[0046] Figure 2B This illustrates a situation where 212 The Pb precursor isotope source (B) has been withdrawn to ensure that no [further details are available]. 220 Rn is released into the airtight seal of the container. 212 The Pb precursor isotope source can also be completely removed from the component.

[0047] Figure 3 The image shows an original version of the generator system based on a 3 ml vial, with the open top cap of the insert membrane pierced by the syringe tip (position secured by tape on the top of the cap), and a lab workbench paper attached to the syringe tip (shown in the left image). 212 (Pb precursor isotope source and container). Use a pipette to... 212 The Pb precursor isotope source is placed on the test strip, and then the cap with the source is carefully attached to the vial (right figure). It is very important to ensure that the source does not come into contact with the vial during assembly and disassembly of the device to avoid cross-contamination.

[0048] Figure 4 With scalable source 212 An example of a Pb single-chamber diffusion generator simplifies the rinsing of the inner surface by incorporating a syringe-permeable zone on a diaphragm-equipped cap. 212 For Pb handling, the syringe can be used to rinse the inner surface without causing cross-contamination of radionuclides when the device is in the closed position.

[0049] Figure 5. The top image shows the image used for... 212 Pb manufactures 100 ml, 50 ml, and 10 ml generator units. The bottom image shows a cap with quartz wool at the center of the inner surface. It can be used... 212 The Pb precursor nuclide solution was placed on silica wool, and then the flask was stored upside down to produce a deposit on the inner surface of the flask. 212 Pb, which is obtained from precursor materials 220 Produced by Rn diffusion. Detailed Implementation

[0050] Given the current need for a simpler and safer system that is smaller and allows for shorter transport distances to handle... 220 Rn and 212 Due to the short half-life of Pb, the inventors have designed a component that places the radon generation source within a collection chamber or container. This invention is flexible and does not require the use of only... 228 Th is not the source, but can use pure 224 Ra or 228 Th or 224 Combinations of Ra as sources, or even their precursor isotopes ( Figure 1 ).

[0051] The components of this invention can be manufactured in a very compact and simple manner, making them suitable for transportable and disposable applications. 212 Pb generator unit. In this document, components, diffusion generators, and systems are used interchangeably. The components or systems can therefore be referred to as those used for… 212 Single-chamber diffusion generator for Pb.

[0052] Therefore, one object of the present invention relates to a method for obtaining a substance containing on the inner wall 212 A method for a container of Pb, the method comprising the step of providing a component including a first part and a second part, wherein the first part includes a container and the second part includes... 212 A Pb precursor isotope source is used to connect the first and second parts, so that... 212 The Pb precursor isotope source does not contact the inner wall of the container and provides a single-chamber container assembly, thereby allowing 212 Pb precursor isotopes have sufficient time to decay into offspring. 220 Rn、 216 Po and / or 212 Pb, and making 220 Rn、 216 Po and / or 212 Pb has sufficient time to settle onto the inner wall of the single-chamber container assembly, removing or isolating residual Pb in the assembly. 212 Pb precursor isotopes, without causing 212 A Pb precursor isotope source is brought into contact with the inner wall of a single-chamber container assembly to obtain a container having a substrate on its inner wall. 212 Pb, and the inner wall of the container is basically free of it. 212 Pb precursor isotopes. Examples of such containers or components are described in the examples of this disclosure and can also be seen in Figures 2-5.

[0053] One aspect of the present invention relates to obtaining 212 A method for obtaining a Pb solution containing Pb on a wall, the method comprising:212 The above-mentioned container of Pb and 212 Pb is collected in solution. 212 Pb can be collected in a solution in a container before formation, or during formation. 212 Pb is then collected using a solution introduced into a container. For example, a syringe can be used for collection.

[0054] Another object of the present invention relates to an assembly comprising a first portion and a second portion, wherein the first portion comprises a container and the second portion comprises... 212 A Pb precursor isotope source is provided, wherein the first and second portions are connected such that the 212Pb precursor isotope source does not contact the inner wall of the container, thus providing a single-chamber container assembly.

[0055] Another object of the present invention relates to a single-chamber container assembly comprising a first portion and a second portion, wherein the first portion comprises a container and the second portion comprises... 212 Pb precursor isotope source, wherein the first part and the second part are connected to form a Pb precursor isotope source. 212 The Pb precursor isotope source does not come into contact with the inner wall of the container.

[0056] A significant advantage of this component (or also defined herein as a container, system, or generator) is its ability to supply even without an active level. 212 The ability of Pb is determined by 212 The short (10.6 hours) half-life of Pb determines this. Using the described system, diffusion generators can be produced in a centralized production facility and shipped to end users. Portable, disposable generators can be manufactured and transported from one end of the world to the other, such as to a hospital. For such disposable devices, it is best to use pure Pb. 224 Ra (excluding) 228 (Th), because it will become inactive in about 40-50 days, avoiding the generation of long-lived radioactive waste. This source of diffusion will follow... 224 Ra is generated stably in a determined manner. 220 Rn / 212 Pb (Table 1 and Figure 1 Due to the nature of isotopic decay, it contains... 212 The container of the Pb precursor isotope source will produce 212 Pb. Deposited 212 The amount of Pb will depend on several factors, including 212 The selection and timing of the Pb precursor isotope source are crucial. Time is an important factor. One object of this invention relates to a method for preparing substantially pure Pb precursor isotopes. 212 A method for obtaining a Pb solution, the method comprising obtaining the components and container described herein, wherein... 212 The Pb precursor isotope source is held in a sealed assembly and container for a given time, i.e.212 The Pb precursor isotope source is isolated or removed without contact, and then collected by adding a suitable material. 212 Pb solution collected on the wall 212 Pb. 212 The Pb precursor isotope source can be retained in the components and containers of this invention for minutes, hours, days, or even years, depending on... 212 Selection of Pb precursor isotope sources and required 212 The amount of Pb. The time frame can be at least one day. The time frame can be at least two days. The time frame can be at least four days. The time frame can be at least one week. The time frame can be at least two weeks. The time frame can be at least one month. The time frame can be at least one year.

[0057] 212 Pb is a member of the thorium family of naturally occurring radioactive isotopes and can be found in substances containing... 232 Th material found (t 1 / 2 =1.4x 10 (10 years). Therefore, it can be selected based on the intended use. 212 Pb precursors. Precursors with longer half-lives can be selected to generate components or systems that will act as... 212 Pb generators are intended for continuous production over extended periods. Alternatively, the use of isotopes with shorter half-lives is envisioned for applications such as hospitals or similar facilities where the generation of long-lived radioactive waste may be problematic. Naturally, mixtures of different precursors will also be relevant, and specific assembly will be required to produce specific quantities over specific time periods. 212 It is also relevant in the case of Pb.

[0058] Therefore, in one or more embodiments of the present invention, 212 Pb precursor isotope source selected from 232 Th、 228 Ra、 228 Ac 、228 Th and / or 224 Ra. Therefore, in the following text, 212 Pb precursor isotopes are defined as 212 Pb includes parent nuclides, grandmother nuclides, great-grandmother nuclides, etc., i.e. 216 Po、 220 Rn、 224 Ra、 228 Th、 228 Ac、 228 Ra、 232 Th.

[0059] The decay of these radioactive isotopes can Figure 1 As seen in the text, this clearly demonstrates the creation of materials with different decay curves.212 The possibility of Pb precursor isotope sources, and that different combinations of precursor isotopes could produce Pb at different rates over different time periods. 212 Pb.

[0060] In one or more embodiments of the present invention 212 Pb precursor isotope source is 232 Th、 228 Ra、 228 Ac, 228Th and 224 A mixture of Ra. In one or more embodiments of the invention. 212 Pb precursor isotope source is 228 Th and 224 A mixture of Ra. The source can also be... 232 Th、 228 Ra、 228 Ac、 228 Th and 224 Each of Ra, but due to decay, will naturally form mixtures over time, because 232 Th will decay into 228 Ra, etc. The key is that it produces a gaseous state. 220 Rn, because it will diffuse from the source, and then... 212 Pb is deposited on the inner wall of the container.

[0061] In one or more embodiments of the present invention 212 Pb precursor isotope source is 228 Th, according to relative 212 The percentage of radioactivity of Pb is measured to be at least 90%, for example at least 80%, for example at least 70%, for example at least 60%, for example at least 50%, for example at least 40%, for example at least 30%, for example at least 20%, for example at least 10%. 228 Th.

[0062] In one or more embodiments of the present invention 212 Pb precursor isotope source is 224 Ra. In one or more embodiments of the present invention 212 Pb precursor isotope source is 228 Th. Depends on the inward growth state. 212 Pb activity is typically found in generators. 224 The activity of Ra precursor varied between 0% and 114%. 212 Pb activity can be 224The activity of the Ra precursor is at least 90%, for example at least 80%, for example at least 70%, for example at least 60%, for example at least 50%, for example at least 40%, for example at least 30%, for example at least 20%, for example at least 10%. 212 Pb activity can be 224 At least 10% of the Ra precursor activity. 212 Pb activity can be 224 At least 10% of the Ra precursor activity. 212 Pb activity can be 224 At least 20% of the Ra precursor activity. 212 Pb activity can be 224 At least 30% of the Ra precursor activity. 212 Pb activity can be 224 At least 40% of the Ra precursor activity. 212 Pb activity can be 224 At least 50% of the Ra precursor activity. 212 Pb activity can be 224 At least 60% of the Ra precursor activity. 212 Pb activity can be 224 At least 70% of the Ra precursor activity. 212 Pb activity can be 224 At least 80% of the Ra precursor activity. 212 Pb activity can be 224 At least 90% of the Ra precursor activity. 212 Pb activity can be 224 At least 100% of the Ra precursor activity. 212 Pb activity can be 224 At least 110% of the Ra precursor activity. 212 Pb activity can reach up to 224 20% of Ra precursor activity. 212 Pb activity can reach up to 224 30% of the Ra precursor activity. 212 Pb activity can reach up to 224 40% of the Ra precursor activity. 212 Pb activity can reach up to 224 50% of the Ra precursor activity. 212 Pb activity can reach up to 224 60% of the Ra precursor activity. 212 Pb activity can reach up to 224 70% of the Ra precursor activity. 212 Pb activity can reach up to 224 80% of the Ra precursor activity. 212 Pb activity can reach up to 224 90% of the Ra precursor activity.212 Pb activity can reach up to 224 100% of Ra precursor activity.

[0063] In one or more embodiments of the present invention 212 Pb precursor isotope source is 224 Ra. In one or more embodiments of the present invention 212 Pb precursor isotope source is 224 Ra, which is relative to 212 The percentage of radioactivity of Pb is measured to be at least 90%, for example at least 80%, for example at least 70%, for example at least 60%, for example at least 50%, for example at least 40%, for example at least 30%, for example at least 20%, for example at least 10%. 224 Ra.

[0064] As 212 Components for the Pb generator unit can be mass-produced in a centralized production facility and shipped to end users for the production of radiopharmaceuticals. It can also be adapted for... 212 The large-scale centralized production of Pb allows for the adjustment of the radioactivity level in a component according to its intended use. In one or more embodiments of the invention, the total radioactivity in a single-chamber container assembly can therefore be 1 kBq – 100 GBq, for example 1 kBq – 10 MBq, for example 100 kBq – 10 MBq, for example 1 MBq – 1 GBq, for example 10 MBq – 10 GBq, for example 1 MBq – 1 GBq, for example 1 GBq – 100 GBq. The total radioactivity in a single-chamber container assembly can be 1 kBq – 100 GBq. The total radioactivity in a single-chamber container assembly can be 1 kBq – 10 MBq. The total radioactivity in a single-chamber container assembly can be 100 kBq – 10 MBq. The total radioactivity in a single-chamber container assembly can be 1 MBq – 1 GBq. The total radioactivity in a single-chamber container assembly can be 10 MBq – 10 GBq. The total radioactivity in a single-chamber container assembly can be 1 MBq – 1 GBq. The total radioactivity in a single-chamber container assembly can range from 1 GBq to 100 GBq.

[0065] In one or more embodiments of the present invention, in a single-chamber container assembly 212The amount of Pb radioactivity can therefore be 1 kBq – 100 GBq, for example 1 kBq – 10 MBq, for example 100 kBq – 10 MBq, for example 1 MBq – 1 GBq, for example 10 MBq – 10 GBq, for example 1 MBq – 1 GBq, for example 1 GBq – 100 GBq. In one or more embodiments of the invention, in a single-chamber container assembly 212 The amount of radioactivity in a Pb precursor isotope source can therefore be 1 kBq – 100 GBq, for example 1 kBq – 10 MBq, for example 100 kBq – 10 MBq, for example 1 MBq – 1 GBq, for example 10 MBq – 10 GBq, for example 1 MBq – 1 GBq, for example 1 GBq – 100 GBq.

[0066] 212 Pb precursor isotope sources can have different forms, sizes, and shapes, depending on the application. Therefore, in one or more embodiments of the invention, 212 Pb precursor isotope sources are in the form of inorganic or organic salts, such as RaCl2. 212 The Pb precursor isotope source can also be in dry form or a liquid solution, such as an aqueous solution or dispersion. In one or more embodiments of the invention, 212 The Pb precursor isotope source is in a liquid solution with an acidic, neutral, or alkaline pH. The pH can be 1-14, for example, pH 1-6, pH 2-6, pH 2-8, pH 4-8, pH 5-7, pH 6-8, pH 7-8, pH 7.2, pH 8-10, pH 8-12, or pH 10-14.

[0067] The solution can be an aqueous solution. It can be a 0.1M HCl aqueous solution. This solution can also be used to dissolve residues on the component walls. 212 Pb.

[0068] Components used as generator systems can be used to prepare for single-patient dosing or for dosing multiple patients, or even for industrial applications. Therefore, the amount of radioisotope can be adjusted depending on the application of the component.

[0069] 212 The Pb precursor isotope source can be placed directly on a rod or on a strip connected to the rod, typically with a very small liquid volume. In one or more embodiments of the invention, 212 The Pb precursor isotope source is deposited on a strip or sphere made of a material suitable for applying a liquid. The amount of this liquid can be from 1 µl to 1 ml, for example from 1 µl to 10 µl, or from 1 µl to 100 µl.

[0070] When the container (which may be a vial) is empty or contains a small amount of liquid at the bottom, it does not come into contact with the source. In one or more embodiments of the invention, the container contains an aqueous solution or an oil solution.

[0071] Importantly, the source will not drip or break in a manner that would cause cross-contamination between the inner surface of the collection unit (container) and the source material, nor will it drip or break in a manner that would allow the source and source support to be removed and / or taken out of the collector without causing cross-contamination through contact.

[0072] In one or more embodiments, the source is surrounded by a mesh or encapsulated in a porous material to reduce the risk of cross-contamination. This encapsulation can be... 212 A permeable barrier that Pb precursor isotope sources cannot pass through.

[0073] Therefore, in one or more embodiments of the present invention, the container may or may not contain 212 A permeable barrier that Pb precursor isotope sources cannot pass through.

[0074] In one or more embodiments of the present invention 212 The Pb precursor isotope source is placed on or inside a sphere, suitable for retaining the source but allowing radon diffusion. The container may include... 212 A permeable barrier that the Pb precursor isotope source cannot pass through, and 212 The air-permeable barrier that the Pb precursor isotope source cannot penetrate allows it to... 212 Pb precursor isotope source contact. In one or more embodiments of the invention, the single-chamber container assembly is hermetically sealed.

[0075] Figure 2 shows an example of a single-chamber container assembly, in which the container (first part) is connected to a lid, and a rod attached to the lid is used for securing it. 212 Pb precursor isotope source (part two) without having to bring the source into contact with the inner wall of the container throughout the process.

[0076] In one or more embodiments of the present invention 212 Pb precursor isotope sources can therefore be bound to non-radioactive materials, such as particles or holding materials. This ensures that the source does not contaminate the container. 212 Pb precursor isotope sources can be deposited on strips, spheres, or rods made of materials selected from paper, plastics, metals, ceramics, and natural or synthetic fibers. The strips or spheres may be attached to, contained in, or included in a second portion, the second portion including means for holding the strips or spheres. Such means may, for example, be a rod.

[0077] In one or more embodiments of the invention, the second portion optionally includes a rod attached to a means for opening and closing the container. The means for opening and closing the container can be a cap, hood, or lid, and can be made of a material selected from rubber, glass, paper, plastic, metal, ceramics, and natural or synthetic fibers, cellulose, ion exchange resins, natural minerals, and polymers. Alternatively, the source is attached to material placed on the cap, which may or may not be adhered to the cap. If the cap is placed at the bottom, the source material can be simply placed inside the cap without contact. 212 The Pb collector section is held in place by gravity. In this case, the generator unit should be stored and processed in place so that the cap with the source is always kept at the bottom.

[0078] Devices for opening and closing containers may include 212 Pb precursor isotope source. 212 Pb precursor isotope sources can be placed in sponges, wool, or other materials capable of [removing / absorbing these materials]. 212 The Pb precursor isotope source is held in the material within the device used to open and close the container. The wool can be quartz wool. Wool can also be mineral wool. Wool can also be glass wool. [The last sentence appears to be incomplete and possibly refers to a different material.] 212 Pb precursor isotope sources are held in devices used to open and close containers. The substances can be joined by glue, double-sided mounting tape, or other means of connection.

[0079] In one or more embodiments of the invention, the second part includes a syringe, or wherein the rod is a syringe. The means for holding may be deposited on a strip or sphere made of a material selected from paper, plastics, metals, ceramics, and natural or synthetic fibers, cellulose, ion exchange resins, natural minerals, and polymers.

[0080] In one or more embodiments of the invention, the syringe tip has been pushed past the rubber cap. Another design is that the second part is a rubber cap, or a permeable and preferably self-sealing diaphragm of another material, with the syringe tip for fixation. 212 The device for attaching a Pb precursor isotope source is attached to the cap or the inner wall of a container. In this case, the user of the assembly will be able to deliver the Pb precursor isotope source from the inner wall of the container by pushing a syringe through the cap. 212 Pb dissolves in an aqueous solution. The resulting... 212 The Pb aqueous solution can then be collected using the same syringe, which creates an option for operation in a GMP environment and direct application to patients. Therefore, in one embodiment, the Pb aqueous solution will... 212The Pb precursor isotope source is extracted into the capsule or similar, allowing for container cleaning, for example, by using a solution transferred via a syringe through a rubber diaphragm, without having to disassemble both units. In another embodiment, the component can be autoclaved, and the solution is a physiologically acceptable composition containing a chelating agent for disease targeting, allowing for reabsorption into the syringe and direct infusion with or without a sterile syringe filter. In one embodiment, the component comprising all subunits is autoclaved and has a syringe-permeable area on the cap, allowing for aseptic extraction from the component. 212 Pb.

[0081] After running for several hours or days, with 212 Components of the Pb precursor isotope source can be used to produce 212 Pb, the method is to recover 212 Pb precursor isotope sources, for example, those with attached... 212 The cap of the Pb precursor isotope source was replaced with a new, non-radioactive cap, and the inner surface was cleaned with a suitable solution to dissolve surface deposits. 212 Pb and its offspring. Due to 212 Pb solutions do not contain long-lived precursor radionuclides, so they can be used directly to label carrier molecules, such as in cancer treatment, without further chemical processing.

[0082] 212 Pb precursor isotope sources can be associated with needles, rods, or strips of material. 212 Pb precursor isotope sources are attached to needles, rods, or strips of material to allow 220 Rn diffusion. The source may or may not contain a support for the radioactive portion and a mesh or ring or similar structure surrounding the source to prevent Rn diffusion during removal from the container. 212 Cross-contamination can occur when using a Pb precursor isotope source. In one embodiment, it can be attached to a nut that can be used to seal a container. 212 The Pb precursor isotope source can be isolated from the container by retracting the source into the cap. This will ensure that during extraction... 212 The Pb decay source does not cross-contaminate the inner walls of the container and also limits the risk of component user contact. Importantly, after a period of decay, 212 Pb precursor isotope source and adsorbed on the inner surface of the vial 212 Pb can be removed from the container. 212 Separation is achieved using a Pb precursor isotope source, for example, by replacing the nut connecting the source via a rod or similar with a standard hermetically sealed nut. Therefore, in a particular embodiment, 212The Pb precursor isotope source is equipped with a retractable radioactive source that retracts into a cap similar to a "click pen system," or retracts back into a cap, similar to a cap used to isolate the source from the inner surface of the generator unit, thus eliminating the need for cap removal and replacement (e.g., Figure 2 and...). Figure 4 Therefore, the second part of the assembly may include a piston that can be in an open and closed position. The second part of the assembly may also include a chamber with a hermetically sealed O-ring. In one or more further embodiments, the assembly includes a hermetically and liquidally sealed cap or valve in the second part.

[0083] The second part of the component may optionally include needles, rods, or strips, which may be provided with spheres of material capable of absorbing radium or thorium, including glass wool, quartz wool, mineral wool, metals, paper, cotton, stearates or other fatty acids, cellulose, natural minerals, polymers, ion exchange resins, or other fibrous materials. The composition of the precursor isotope scaffold should be carefully selected based on the known affinity of radon for various materials. 228 Th and or 224 Ra exhibits good adsorption or adsorption properties for it, and 220 Rn would be suitable for materials with low affinity for it.

[0084] The container can be made of glass (including quartz), polymer, and / or metal, such as a glass vial, having a nut or similar attachment thereto. The container (or component) can be an inverted glass flask, with, for example, a [missing information - likely a cap or similar element] placed at the center inside the cap. 224 Ra or 228 The quartz wool of Th. It can be produced in the following manner. 212 Pb, that is, unscrew the cap from the inverted flask with the source, and then use a dissolving agent. 212 The Pb solution is used to clean the inside of the flask. The container volume can range from 1µl to 10L, for example, 1µl to 1L, 100µl to 10ml, or 100µl to 100ml. The volume size depends on the application, with smaller volumes typically involved in single-use applications and larger volumes involved in industrial batches.

[0085] Minimizing the risk of cross-contamination is important, and components must be designed to ensure that... 212 The Pb precursor isotope source will not come into contact with the inner wall of the container. Therefore, in one or more embodiments of the present invention, the container is substantially free of [pb precursor isotope source] on its inner wall. 212 Pb precursor isotope sources. The definition of "basically non-existent" depends on the components produced. 212 The use of Pb. In one or more embodiments of the invention, "substantially free" is defined as less than 212 Pb precursor isotope source 224 3% of Ra, for example, less than 1%, for example, less than 0.5%, is measured relative to212 The percentage of Pb radioactivity. In one or more embodiments of the invention, "substantially free" refers to the solution originating from the container wall. 212 Pb relative to 224 The purity of Ra. This purity is better than 95%. This purity is better than 98%. This purity is better than 99%. This purity is better than 99.5%. This purity is better than 99.8%.

[0086] The container surrounds but does not touch. 212 Pb precursor isotope source. This should be made of a suitable material, such as glass, plexiglass, metal, ceramic, polymers including polypropylene and polytetrafluoroethylene, or other suitable materials that allow deposition on its inner wall. 220 Rn and / or 212 Pb is permitted during washing with a solution further used for radiolabeling. 212 Pb dissolution. The inner walls of the container can be cleaned with the solution to extract the radionuclide, mainly... 212 Pb and its offspring. It may be present in... 212 Pb exists in the component during production, or in... 212 The Pb precursor isotope source has been removed or extracted before application. In one embodiment, the solution may be transferred and neutralized before being administered to the patient along with an acidic or alkaline solution. In one embodiment, the solution may be water of pharmaceutical purity. The solution volume for a single dose is 1 μL to 1 L, for example, 100 μL to 10 ml may be used, and 1 μL to 10 L or, for multiple doses, a larger solution volume.

[0087] The container may or may not contain a surface film or some liquid on its inner surface to aid in the collection of diffusion products. This surface film may, for example, be a coating. For single-dose units, the size and volume can be from microliters to milliliters; for multiple-dose units, the size and volume can be from microliters to tens of liters or higher. The inner wall of the container may be coated. This coating ensures... 212 Pb settles in an optimal manner. In one or more embodiments of the invention, the inner wall of the container is coated with a compound containing substances that can react with... 212 Chelating agents that complex with Pb. When needed with... 212 In the case of Pb complexation, the inner wall may also be coated with one or more compounds. In one or more embodiments of the present invention, the inner wall of the container is coated with a chelating agent. 212 A chelating agent for Pb. This chelating agent can be TCMC or a variant thereof. The coating can be a salt film on the inner wall or other suitable material.

[0088] In one particular embodiment, the container is washed directly with a reaction solution containing a complexing agent to produce a radiolabeled solution, which, after an appropriate reaction time, can be used directly for therapeutic purposes. In one embodiment, the final product solution is autoclaved and / or aseptically filtered before being administered to the subject in need.

[0089] In one embodiment, the component can be attached to a flushing and filtration circuit, whereby a reservoir of solution is connected and an outlet with a sterile filter and a syringe or vacuum pump is attached to flush the chamber when the source is withdrawn from the chamber, and, for example, using a... 99m The Tc generator collects the rinsing solution in a similar manner.

[0090] Typically, the surface ratio between the precursor scaffold and the collector cavity surface should be optimized to generate as much as possible. 212 Pb is deposited on the surface of the collector cavity. The surface can be smooth or porous, or it can contain structures that increase the surface area relative to the diffusion subunit, container, or component.

[0091] Production can be carried out in cycles of 5 hours, 10 hours, 20 hours, or longer. Afterward, the source can be withdrawn from the chamber back into a tubular support or similar device with an airtight and liquid-sealed cap at the bottom, which closes when the source is fully withdrawn. This allows for the addition of washing fluid, for example via a syringe, or activation of the flushing and collection circuit, similar to... 99m Tc generators are generally operated.

[0092] In one particular embodiment, the single-chamber diffusion unit... 212 The Pb precursor isotope source is placed as a film on the inner surface of the component, and... 212 The Pb collector cell (container) is inserted into the surface covered by the source without contacting these surfaces, i.e., the opposite of the configuration shown in Figure 2.

[0093] In another embodiment, the diffusion generator is temperature-controlled, either by increasing or decreasing the temperature relative to 20°C.

[0094] Uses of this invention include the production of radiopharmaceuticals, medical devices, and / or... 212 A standardized source for Pb. The components of this invention can be used to generate a source for calibration. 212 Pb standard.

[0095] In one or more embodiments of the present invention, the components of the present invention are contained in having 212 The kit contains a Pb precursor isotope source, a solution containing a chelating agent, and a compound for treatment. This compound can be nanoparticles or microparticles. In one embodiment, such a kit would contain... 212Pb precursor isotope sources, solutions for cleaning the inner walls of containers, and solutions or dried forms of carrier compounds, such as chelating agents, micro or nanoparticles.

[0096] surface Table 1. 224 Main radiation characteristics of the Ra series.

[0097] Radioactive nuclides (half-life) α and β (average energy, in MeV) X-ray and gamma energy and % abundance <![CDATA[ 224 Ra (3.6 days)]]> α 5.6 241 keV, 4.1% <![CDATA[ 220 Rn (55.6s)]]> α 6.3 <![CDATA[ 216 Po (145ms)]]> α 6.8 <![CDATA[ 212 Pb (10.6h)]]> β 0.1 75 keV, 10.3%77 keV, 17.1%87 keV, 6.0%90 keV, 1.5%239keV, 43.6%300 keV, 3.3% <![CDATA[ 212 Bi (1 h)]]> <![CDATA[α 6.1 × 0.36 (effective at 2.2 MeV 1 )β 0.7 × 0.64 (effective at 0.4 MeV)]]> 727 keV, 6.7% (4.3% effective) <![CDATA[ 212 Po (299ns)(64%branch)]]> α 8.8 (5.6 effective) <![CDATA[ 208 Tl (3.1min)(36%branch)]]> β 0.6 (effective at 0.2 MeV) 75 keV, 3.4% (1.2% effective); 511 keV, 22.6% (8.1% effective); 583 keV, 85.0% (30.6% effective); 860 keV, 12.5% ​​(4.5% effective); 2615 keV, 99.8% (35.9% effective). 1 Each due to branching 224 The average value of the Ra transform. X-rays or gamma rays that account for only 1% or more of the effective abundance. Each time. 224 Ra atoms decay completely into stable forms through their offspring. 208 When dealing with Pb atoms, the total effective energy is approximately 26.5 MeV for α plus 0.7 MeV for β.

[0098] Table 2. With an initial 100 MBq 212 Pb pure 212 The Pb source was kept sealed and emptied only once. 212 Pb.

[0099] time 24 h 48 h 72 h 96 h <![CDATA[ 212 Pb (MBq) Total]]> 23.1 4.4 0.92 0.192

[0100] Table 3. Based on a source with an initial 100 MBq 224 Ra's lead 212 production process is kept sealed and vented only once. 212 Pb.

[0101] time 24 h 48 h 72 h 96 h <![CDATA[ 212 Pb (MBq) Total]]> 70.3 72.9 63.4 53.1 <![CDATA[70% of the final product is extracted and recycled (MBq 212 Pb)]]> 49.2 51.0 44.4 37.2

[0102] Table 4. Based on a source with an initial 100 MBq 224 Ra's lead-212 production is kept sealed and vented only once every 24 hours. 212 Pb.

[0103] time 24 h 48 h 72 h 96 h <![CDATA[ 212 Pb (MBq) Total]]> 70.3 58.2 48.1 39.8 <![CDATA[70% of the final product is extracted and recovered (MBq 212 Pb)]]> 49.2 40.7 33.7 27.9

[0104] The invention will now be illustrated with accompanying drawings and embodiments. These drawings and embodiments are intended to be illustrative and should not be construed as limiting in any way. Example

[0105] Example 1 - Calculating the relative time points 212 Pb nuclide level Background. The short half-life (10.6 hours) of radionuclides hinders the purification of pure radionuclides. 212 The development and use of Pb in therapeutic radiopharmaceuticals makes it virtually impossible to manufacture products in a centralized manner and ship them to end users.

[0106] If 224 Ra is used as 212 A short-term generator for Pb, then 212 The activity level of Pb can be basically determined based on 224 Ra maintains its properties through a half-life of 3.6 days. This demonstrates the purity... 224 Ra sealed source 212 Changes in Pb levels.

[0107] Methods: A general-purpose activity calculator was used to calculate the activity of pure... 224 Ra source 212 Pb grows inward.

[0108] Results: Table 2 shows the results after production of pure (non-pure) 224 Ra) drug solution and stored in an airtight container at different time points 212 Pb content. It can be seen that pure... 212 The Pb source decayed rapidly, with a loss of over 75% every 24 hours. Table 3 shows the Pb content in a sealed 224Ra source at the same time point. 212 The amount of Pb. It can be seen that... 212 Pb activity remained at a high level (>50%) for at least 96 hours.

[0109] Table 4 shows the data based on multiple "milking" events within 96 hours. 224 A generator for producing Ra precursors 212 The effect of Pb.

[0110] The data also shows that when from pure 224 At the beginning of Ra, a large number of daughter nuclides exist within a relatively short period of time. It is noteworthy that in solution... 212 Pb and 224 The Ra ratio reaches 1 after 36 hours, then gradually increases to around 1.1, remaining constant at 1.1 for the rest of the time until it completely decays. In summary, using... 224 Ra as 212 The source of Pb enables centralized production and transportation of logistics to end users, providing a means of... 224 Extracted from Ra 212 A simple method for Pb.

[0111] Example 2 - Preparation of radionuclides and counting of radioactive samples In the following text, all work involving concentrated radioactive agents, including solvent evaporation, will be conducted in a glove box. 1 M HNO3 was obtained from a commercial supplier. 228The source of Th. Ac resin was obtained from Eichrom Technologies LLC (Lisle, IL, USA) in pre-packaged form.

[0112] Radium-224 is produced by combining it with actinide resins (Eichrom Technologies, LLC). 228 The method involves eluting a column containing actinide resin with 1 M HCl, wherein the resin is immobilized with... 228 The eluent was purified on a second Ac resin column, and then evaporated to dryness using a capped evaporator flask with an inlet and outlet, placed in a heater assembly at approximately 110°C, and the solvent was evaporated under a gentle nitrogen flow. When no solvent remained in the evaporator flask, 0.1M HCl was added to dissolve the residue, typically 200-400 µl. Generally, extraction and purification can be performed using the method described above. 228 More than 70% of the Th source 224 Ra.

[0113] The radioactive sample was counted using a Cobra II Autogamma counter (Packard Instruments, Downer Grove, IL, USA). From... 228 Extracted from Th source 224 During Ra, a CRC-25R dose calibrator (Capintec Inc., Ramsey, NJ, USA) was used.

[0114] Example 3 - Determining before reaching radioactive equilibrium 212 Pb / 224 Ra mixture 212 Net count rate of Pb Three days later, the sample, which was kept airtight for practical purposes, was... 212 Pb and 224 There is a 1.1x "balance" between Ra.

[0115] In an airtight unit, regardless of 212 Whether Pb is in equilibrium or below equilibrium, it can be assumed that equilibrium will be reached in 3 days, because of the excess... 212 Pb decreased by 99%, and 212 Pb from 224 Ra's inward growth is actually complete, not "balanced".

[0116] The Cobra II Autogamma counter with a counting window set to 70-80 keV is mainly given as follows: 212 Pb, and 224The contributions of other radionuclides in the Ra series are small. When the initial... 212 Pb disappeared and 224 R and 212 Once Pb reaches equilibrium (approximately 3 days later), radium-224 must be calculated indirectly. This indirect counting requires storing the sample in a relatively airtight container; otherwise... 220 Rn may escape, thus preventing 212 Pb and 224 A radionuclide balance of 1.1 was achieved between Ra.

[0117] Since sampling and counting may be spaced out over a period of time, adjustments can be made for decay. 212 The net count rate of Pb is used to determine the net count rate at the time of sampling. 212 Pb count rate. By 212 Pb samples can be stored for a week or longer and then remeasured to determine... 224 The amount of Ra contaminants, because the activity is not [affected] after approximately 110 hours of storage. 212 Pb is not derived from Pb, but from a longer-lived precursor isotope.

[0118] Example 4 - For 212 A simplified single-chamber (diffusion chamber generator) assembly produced by Pb (Figure 3).

[0119] A 3 ml V-shaped vial with an open top cap. The open top cap has a syringe tip-permeable membrane. Push the syringe tip through the membrane and secure it at the top with tape to lock the tip in position relative to the open top cap. Place an absorbent paper strip approximately 0.5 x 3 cm on the syringe tip by inserting it into the two holes on the strip. Add 2-40 μL of absorbent paper to the paper strip. 224 Ra solution. Then, carefully place the cap on the V-shaped vial, ensuring the syringe tip and radioactive strip do not touch the inside of the vial. Afterward, allow the assembly to stand for varying periods to allow for... 220 Rn is generated by diffusion from the strip into the space surrounding the strip. 212 Pb. 212 Pb tends to settle on the inner surface of the V-shaped vial. (Based on the method used to...) 224 The volume of liquid applied to the strip by the Ra source may result in some liquid condensation due to the evaporation / condensation of the liquid used. Alternatively, the source can be dried before assembling the unit to prevent solvent from condensing on the inner surface of the V-tube.

[0120] Example 5A: Production 212 Pb, of which 212 The Pb precursor isotope source is adsorbed onto the paper strip.

[0121] Method: Assemble the components,224 Ra was placed Figure 3 Insert the diffusion subunit strip into the V-shaped vial and let it stand for 17.5 hours or longer to produce 220 Rn and 212 Pb production 212 Pb is used to evaluate the radiochemical purity of the product. At the end of the production period, the entire device is measured on a Capintec dosimeter. The product is evaluated by separating the source from the container, sealing the container with a hermetically sealed nut, and immediately measuring in a Capintec dosimeter. A few days later, when all... 212 Pb has decayed, but long-lived precursor nuclides have been detected. 224 Ra 和228 At that time, the purity of the product was determined by measuring the collector subunit again. Result: Highly purified product was collected in the collector subunit. 212 Pb was produced with a relevant yield of 65.6% (range 62.7–69.9%, n=4), and no measurable long-lived precursor nuclides were found (< 0.5%). Conclusion: This assembly allows for efficient production and collection purification in a simple manner. 212 Pb does not require further purification.

[0122] Example 5B: 212 Pb production, in which 212 The Pb precursor isotope source was adsorbed onto a sealing film strip. Experiment 5A was repeated, except that a sealing film strip was used instead of paper strip to carry the precursor isotope source.

[0123] Results: The inner surface of the collector subunit (vial or container) was found to contain... 212 The Pb yield was only 19.3%. In contrast, a device operating in parallel with the same configuration and firing cycle yielded 63.9%. In summary, the yield for absorption and retention... 212 The material of the Pb precursor isotope source will greatly influence 212 Pb yield on collector subunits or containers.

[0124] Example 6: Dissolving from a container using a solution 212 Pb.

[0125] Method: Add 0.3–0.5 ml of 0.1 M HCl to the collection bottle, gently rotate the bottle to bring the inner surface into contact with the liquid, and count in a Capintec dosimeter. Subsequently, transfer the liquid to an Eppendorf tube and measure in a Capintec dosimeter. The extraction rate was 74.0% (range 70.0–76.9%, n=3) when the collector subunit (3 ml V-shaped vial) was washed once with 0.3 ml of 0.1 M HCl. In summary, the amount absorbed onto the container surface...212 Pb is used in the rapid and good yield dissolution of solutions in radiopharmaceutical processing.

[0126] Example 7: Thin-layer chromatography analysis Thin-layer chromatography (TLC) was performed using a chromatographic strip (model #150-772, Biodex Medical Systems Inc, Shirley, NY, USA). A small beaker containing approximately 0.5 ml of 0.9% NaCl was used to hold the test strip with the sample spot. Typically, 1–4 µl of sample was added to the test strip approximately 10% above the bottom of the strip. After the solvent front had moved approximately 20% from the top of the strip, the strip was cut in half, and each half was placed in a 5 ml test tube for counting. In this system, radiolabeled antibodies and free radionuclides do not migrate from the lower half, while radionuclides complexed with EDTA migrate to the upper half. A formulation buffer (FB) consisting of 7.5% human serum albumin in DPBS and 1 mM EDTA, adjusted to approximately pH 7 with NaOH, was mixed with the radioconjugate at a 2:1 ratio for at least 5 minutes, and then applied to the test strip to identify free radionuclides. It has been confirmed that in the presence of free... 212 In the Pb test solution, the radionuclide is completely (> 99%) complexed with EDTA when mixed with FB and will move to the upper part of the TLC test strip.

[0127] Example 8: In solution 212 In situ chelation of Pb.

[0128] Background: The extraction from the container using 0.1 M HCl was evaluated. 212 Labeling characteristics of Pb. Method: Before adding the chelating agent, a mixture of 0.1 M HCl and 5 M ammonium acetate in a ratio of 10:1 was used. 212 Pb was used to maintain the pH range of the reaction between 5 and 6. Reaction times were tested at 37 °C for 15–30 minutes. TLC determined a good yield of 96.6% for every 100 µl of 5 µg PSMA-617 solution. Furthermore, approximately 1.0 mg / mL of TCMC-conjugated Herceptin antibody solution was prepared with purified Pb. 212 Pb labeling was performed in good yield (98.9%). Conclusion: Lead-212 produced using this component readily conjugates with both small and large molecules, indicating its suitability for producing Pb-based... 212 Pb-based radiopharmaceuticals.

[0129] Example 9 - Utilization when the unit remains sealed and is emptied only at one point in time 224 Ra source production 212 Pb The bottom row of Table 3 shows the results when using 100 MBq. 224 Examples of the output of the diffusion generator after the Ra source is inserted into the device and then emptied at various time points. As shown in the figure, the generator provides a relatively stable output. 212 Pb output, up to 96 hours.

[0130] Example 10 - When the device is emptied once a day for four consecutive days, for example if 212 When Pb is used in graded radionuclide therapy, etc., it utilizes... 224 Ra source generation 212 Pb.

[0131] Table 4 shows the output when the component "milks" once every 24 hours. Starting with a 100 MBq source, the total output is 151.5 MBq. 212 Pb. In summary, single-compartment components are suitable for both single-dose and fractionated-dose production.

[0132] Example 11 - Component example with scalable source (Figure 2 and...) Figure 4 ) The materials used can be glass (including quartz), polymers, metals, ceramics, or other materials suitable for drug containers. The rod in Figure 2 ( Figure 4 The piston (in the device) slides within a tube with an O-ring or similar material at the top to ensure an airtight seal. The valve at the bottom of the rod is both airtight and liquid-tight in the closed position of the device.

[0133] In the open position, the source will be exposed inside the container and emitted. 220 Rn and cause 212 Pb is deposited on the inner surface. In the closed position, the source is isolated from the container. Figure 2B The container surface can come into contact with a suitable solution to dissolve. 212 Pb.

[0134] In one embodiment, the cap has a syringe-permeable membrane, and a sterile syringe containing a sterile solution is used for extraction without removing the cap. 212 Pb. If during extraction 212 Pb has previously autoclaved such devices, so the complete procedure can be performed in a sterile / aseptic manner.

[0135] Example 12. Placing the precursor nuclide in 212 On the quartz wool in the Pb single-chamber generator.

[0136] Method: Use as follows Figure 5The flask shown is for reference only. Flask sizes may vary, but 10-100 ml flasks are commonly used. When using the flask as a generator, it can be inverted. Remove the cap and place quartz or glass wool inside the center of the cap. Place radium-224 in the solution on the quartz wool, and attach the flask to the cap, ensuring the quartz wool does not touch the flask. Keep the apparatus leak-proof and store it in an inverted position for a period of time to allow the radium to grow inward. 212 After one to several days, unscrew the lid from the flask while inverting it and carefully remove it from the lid, avoiding contact with the quartz wool. Combine the lid with the active material into another flask and store it inverted for further production. 212 Pb. (The last part appears to be incomplete and possibly contains errors.) 212 Add 0.5–2 ml of 0.1 M HCl solution to the flask, and extract Pb by washing the inner surface of the flask. 212 Pb and 212 Pb collection and use.

[0137] Result: Typically, the produced 212 50-70% of the Pb activity is present in the flask; after careful cleaning, over 90% can be recovered. 212 Pb activity can be collected in the washing solution. The generated... 212 Pb has very high purity. 224 Ra and freshly extracted solution 212 Compared to Pb, the purity is as low as 10. -4 This product is ideal for labeling proteins and small molecules containing chelating agents, with a very high labeling rate, typically above 97%.

[0138] In summary, the data shows that quartz wool is very suitable for housing. 224 The Ra source indicates that quartz / glass / mineral wool, metal wool, etc., are suitable for this purpose. A flask / quartz wool system can also be used in an upright position; quartz wool is also provided, which can be adhered to the capsule, for example, with glue, double-sided mounting tape, etc. In the current example, the flask is used upside down; the quartz wool does not adhere but is held in place by gravity within the lid.

[0139] Example 13. Inverted flask system version of a single-chamber generator.

[0140] For marking 212 Flask-based diffusion generator for Pb.

[0141] Lead-212 produces therapeutically high LET radiation because it decays through short-lived alpha emission progeny, resulting in an average of [missing information - likely a specific radiation level]. 212 Pb decay produces an alpha particle. 212Pb has a half-life of 10.6 hours, which limits its applications and necessitates rapid and safe production and purification procedures. If ready-to-use products are to be produced in a centralized production facility and shipped to end users, the activity level will drop below 25% within a day.

[0142] use 212 Pb has been used in clinical trials of lead-212-based radioimmunoconjugates for peritoneal cancer, among which... 212 Pb from cation exchange column 224 The sample is separated from Ra and eluted in an inorganic acid, which must be redissolved before radiolabeling. This method requires a large workload and suitable facilities and equipment for evaporating inorganic acids, etc., to extract the sample from Ra. 224 Ra generator material processing 212 Pb. developed and tested another based on 224 Ra generator method, 224 Ra is absorbed onto the quartz wool and placed within the central ring of a removable cap (generator cap) in the generator chamber. This chamber consists of an inverted glass bottle supported by the removable cap. 224 Ra-marked quartz wool (Figure 5). When 224 During Ra decay, short-lived 220 Rn is released from the silica wool and leads to long-lived decay products. 212 Pb is absorbed onto the inner surface of the flask. The flask can be removed from the lid without the glass coming into contact with the silica wool. After removing the flask from the generator lid, the inside of the flask can be rinsed with 0.1 M HCl to dissolve the Pb. 212 Pb deposits are thus produced to create high-purity Pb ​​deposits. 212 Pb solution. The generator flask was first operated and rinsed, then radiolabeled with NG001. When the generator is operated correctly (i.e., the source does not contact the wall), the solution... 212 Pb and 224 The purity of Ra is better than 99.8%. The generator can be reused by attaching a new glass bottle to the generator cap, and it is typically stored for 1-2 days to produce fresh results. 212 Pb.

[0143] In summary, this generator method is easier to use and less time-consuming compared to ion-exchange-based generators. The generator can be reused multiple times (although the capacity decreases as radioactive decay depends on the source half-life).

[0144] Example 14: Size of the collection bottle Flask sizes of 10ml, 50ml, and 100ml were tested. Figure 5 (The upper part). 224Ra was added to the quartz wool in the inverted flask lid. Compared to the theoretical yield, the yield on the flask... 212 The percentage of Pb varies between approximately 40% and 60%. Using a larger flask cap to cover the inner surface volume often provides an advantage for achieving higher yields. In summary, flasks of various sizes can be used for generator purposes, but relatively larger flasks and caps appear to improve yield. 212 Pb production is relatively low because of the absorption by the cap and source material.

[0145] Example 15: Material of the source.

[0146] To secure the source material inside the generator, such as in the center of the inner cover, steel wool, glass wool, and quartz wool are used. 224 Ra sources were tested. These materials are porous, fluffy, and diffuseable. 100-150 μL of 0.1 M HCl solution was used. 224 Ra was deposited on the material placed inside the cap of a 100 ml flask. After standing for 2-3 days or longer, the material present in the generator... 224 Compared to Ra, it is 52-64%. 212 Pb will settle on the glass surface, thus allowing all three materials to work, i.e., in conjunction with the generator. 224 Compared to Ra activity, the average value for silica wool across 5 tests was 59.9% (range 52.1-64.4%), glass wool was 54.9%, and steel wool was 64.1%. In conclusion, several different materials can be used to keep the source contained in a single-chamber diffusion generator.

[0147] Example 16: Source.

[0148] Radionuclides 224 Ra and 228 Th is used as the source within the generator. Based on 224 Ra generators are typically reusable for up to several weeks, while those based on 228 Th's device can be reused for several months and provides 212 Pb can be produced simply by replacing the glass flask with an unused flask and cleaning the first flask. 212 Pb solution. Aside from the radionuclide decay in the generator, reuse does not significantly reduce the yield. Cross-contamination from the source to the glass flask is minimal as long as the source is centered inside the cap to avoid contact with the glass flask, and the flask and cap are kept dry. In summary, the single-chamber diffusion apparatus is reusable. 228 Th and 224 Ra source production 212 Pb was used as the source. In four tests, it was found that the source was Pb. 228The average lead-212 activity on the inner glass surface of the Th source was 49.3% (range 40.9%–66.7%).

[0149] Example 17: Preparation including heating: Heating the flask with the source material before attaching it to the lid may be a way to reduce the pressure inside the generator. The flask is heated to 90°C in the heating chamber for at least 15 minutes, and then the flask and lid are tightened together to maintain an airtight seal. The generator unit is then stored at room temperature, causing the internal pressure to decrease. After 1-4 days, the chamber is opened and measurements are taken on the glass flask. 212 Pb activity. Used on quartz wool. 224 The four tests conducted by Ra yielded an average yield of 68.1% (range 60.5%–75.9%), indicating an improvement in yield compared to previous atmospheric pressure flask data (average 59.9%). In conclusion, reducing the chamber pressure may improve the yield using a one-chamber diffusion generator. 212 Pb yield.

[0150] Example 18: Rinse solution 212 Pb yield.

[0151] Extract the precipitate trapped on the inner surface of the glass of a 100 ml flask using 0.1 M HCl standard solution. 212 Pb. Carefully agitate the washing solution and rotate it to cover the inside of the flask for approximately 2 minutes. Then, remove 80% of the volume and measure it, comparing it to the total count in the flask before the washing procedure. Assume that the 80% volume should be divided by 0.8 to determine the total activity in the liquid. Through a similar washing operation, approximately 85% was extracted with 0.6 ml and 93% with 1 ml. Based on 8 tests... 224 The Ra generator extracted an average of 86.1% (range 79.4%–93.4%) from the glass vial. In two tests, based on… 228 The generator extracted an average of 86.5% (range 84.5%–88.5%) of Th from the glass vials. In summary, the Th captured on the glass surface inside the generator can be easily extracted with 0.1 M HCl. 212 Pb.

[0152] Example 19. Radiolabeled reactivity of solution: The molecule NG001 (Stenberg et al 2020), based on the TCMC chelating agent, was used for testing. 212 Pb labeling, generator extraction 212 Pb. Lead-212 in 0.1 M HCl was added to sodium acetate to adjust the pH to approximately 5.5. Subsequently, NG001 was added at a rate of 10–20 μg per mL.

[0153] After reacting at 37°C for 30 minutes using a Thermomixer (Eppendorf, Germany), the sample was removed and subjected to thin-layer chromatography (TLC) by mixing the sample with 1 mM EDTMP in a 1:2 ratio in 7.5% bovine serum albumin solution and allowing it to stand for 5 minutes. Subsequently, 1–5 μL was applied to a chromatographic strip (model #150-772, Biodex) and eluted with 0.9% NaCl solution in a beaker. When the liquid front reached the top of the test strip, it was cut in half, each half placed in a tube and counted separately in a Packard Cobra II gamma counter (Packard Instruments Co Inc, USA). Data showed that after 3 hours, the activity of the lower half typically reached >99%, indicating a near-quantitative yield. Blind testing was performed without NG001, but all other compounds showed less than 3% activity in the lower half of the test strip, indicating good selectivity for the TLC assay. In summary, the extract from the generator flask… 212 Pb exhibits excellent reactivity, indicating its suitability for radiopharmaceuticals.

[0154] Example 20. Radiochemical purity of the extraction solution.

[0155] Lead-212 solution should be stored for 10 days or longer and then recounted for measurement. 224 Ra. (will) 224 Ra activity decay correction back to time 0. 224 Ra and 212 Pb was determined to be an average of 0.045% (range 0.01%-0.13%). In summary, the Pb generated by the generator... 212 Pb has high radiochemical purity relevant to pharmaceutical applications.

Claims

1. A method for generating a radioactive isotope, the method comprising: By sliding the lever from the closed position to the open position, the inner surface of the container is exposed to the precursor isotope source, in which the precursor isotope source is sealed and isolated from the inner surface of the container, and in the open position, the precursor isotope source is exposed to the inner surface of the container. The precursor isotope source is disposed on the rod; Allow sufficient time for the precursor isotope source to decay into one or more progeny isotopes and for the one or more progeny isotopes to be emitted into the container; as well as By sliding the rod from the open position to the closed position, the precursor isotope source is isolated from the container; The precursor isotope source includes those selected from... 232 Th、 228 Ra、 228 Ac、 228 Th and / or 224 Precursor isotopes in the Ra group; and The inner surface of the container is exposed to the precursor isotope source without the precursor isotope source coming into contact with the inner surface.

2. The method of claim 1, wherein exposing the inner surface to the precursor isotope source comprises exposing the inner surface to thorium-228 isotope (… 228 Th) and / or radium-224 isotopes ( 224 Ra), the method also includes allowing the 228 Th decays into the radon-220 isotope ( 220 Rn) and lead-212 isotopes ( 212 At least one of Pb.

3. The method of claim 1, wherein the method further comprises allowing the 228 Th decays into the radon-220 isotope ( 220 Rn), bismuth-212 isotope ( 212 Bi) and lead-212 isotope ( 212 At least one of Pb.

4. The method of claim 1, wherein isolating the precursor isotope source from the container further comprises retrieving the precursor isotope source into a hermetically sealed chamber.

5. The method of claim 4, wherein retrieving the precursor isotope source into the hermetic seal comprises sealing the rod within the tube using an O-ring to form the hermetic seal between the rod and the tube.

6. The method of claim 1, further comprising rotating the container before exposing the inner surface to the precursor isotope.

7. The method of claim 1, wherein allowing sufficient time for the at least one progeny isotope to be emitted from the precursor isotope source into the container comprises allowing the at least one progeny isotope to be emitted from the precursor isotope source into the container through a gas-permeable barrier.

8. The method of claim 1, wherein allowing sufficient time for the at least one progeny isotope to be emitted from the precursor isotope source into the container comprises allowing sufficient time for the at least one progeny isotope to be emitted from the precursor isotope source disposed in a sponge, wool, strip, or sphere into the container, the sponge, wool, strip, or sphere comprising at least one selected from the group consisting of: quartz, glass, minerals, paper, plastics, metals, ceramics, natural fibers, and synthetic fibers.

9. The method of claim 1, wherein allowing sufficient time for the precursor isotope source to decay comprises allowing 5 hours, 10 hours, 20 hours, 24 hours, 48 ​​hours, 72 hours, or 96 hours.

10. The method of claim 1, further comprising altering the orientation of the container before exposing the inner surface to the precursor isotope.

11. The method of claim 1, wherein the precursor isotope source is disposed on the rod by attaching the precursor isotope source to the rod.

12. The method of claim 1, wherein the precursor isotope source is disposed on the rod by attaching the precursor isotope source to the side of the rod.

13. The method of claim 1, wherein the precursor isotope source is disposed on the rod by directly attaching the precursor isotope source to the rod.

14. The method of claim 1, wherein the precursor isotope source is disposed on the rod by depositing a solution containing the precursor isotope onto the rod.

15. The method of claim 1, wherein the precursor isotope source is disposed on the rod by depositing the precursor isotope source on a strip and attaching the strip to the rod.

16. The method of claim 1, wherein the precursor isotope source is disposed on the rod by depositing a solution containing the precursor isotope onto a strip and attaching the strip to the rod.

17. The method of claim 1, further comprising attaching the rod to a cap, lid, or cover for opening and closing the container.

18. A system for generating a radioactive isotope, the system comprising: A precursor isotope source is disposed on a rod configured to slide between an open position and a closed position, wherein in the open position the precursor isotope is exposed to the inner surface of a container to allow the precursor isotope source to decay into one or more progeny isotopes emitted into the container, and in the closed position the precursor isotope source is sealed and isolated from the container to isolate the precursor isotope source from the inner surface, and the rod is slidable to isolate the precursor isotope source when the rod slides from the open position to the closed position; The precursor isotope source includes those selected from... 232 Th、 228 Ra、 228 Ac、 228 Th and / or 224 Precursor isotopes in the group consisting of Ra; and In the open position, the precursor isotope source is exposed to the inner surface without contacting it.

19. The system of claim 18, wherein the precursor isotope source is attached to the outer surface of the rod.

20. The system of claim 18, wherein the precursor isotope source is attached to a side surface of the rod.

21. The system of claim 18, wherein the precursor isotope source is directly attached to the outer surface of the rod.

22. The system of claim 18, wherein the precursor isotope source is deposited on the rod as a solution containing the precursor isotope.

23. The system of claim 18, wherein the precursor isotope source is deposited on a strip, wherein the strip is attached to the rod.

24. The system of claim 18, wherein the precursor isotope source is deposited on the strip as a solution containing the precursor isotope, wherein the strip is attached to the rod.

25. The system of claim 18, comprising a cap, lid, or cover for opening and closing the container, wherein the rod is attached to the cap, lid, or cover.

26. The system of claim 18, wherein the precursor isotope source comprises thorium-228 isotope ( 228 Th) and / or radium-224 isotopes ( 224 Ra), the one or more progeny isotopes including radon-220 isotope ( 220 Rn) and lead-212 isotopes ( 212 At least one of Pb.

27. The system of claim 18, wherein the one or more progeny isotopes comprise radon-220 isotope ( 220 Rn), bismuth-212 isotope ( 212 Bi) and lead-212 isotope ( 212 At least one of Pb.

28. The system according to claim 18, wherein, In the closed position, the rod and the tube in which the rod slides form an airtight seal to isolate the precursor isotope source from the inner surface.

29. The system of claim 28, wherein the rod includes at least one O-ring to form the hermetic seal with the tube in the closed position.

30. The system of claim 28, wherein the rod includes an airtight valve at one end.

31. The system of claim 18, wherein the precursor isotope source is encapsulated in a gas-permeable barrier.

32. The system of claim 18, wherein the precursor isotope source is disposed on a sponge, wool, strip, or sphere, the sponge, wool, strip, or sphere comprising at least one material selected from the following list: quartz, glass, minerals, paper, plastics, metals, ceramics, natural fibers, and synthetic fibers.

33. The system of claim 26, further comprising the container, wherein the inner surface of the container is configured to allow the... 212 Pb is deposited on the inner surface.

34. The system of claim 18, wherein the precursor isotope source is configured to decay and emit one or more progeny isotopes into the container for 5 hours, 10 hours, 20 hours, 24 hours, 48 ​​hours, 72 hours, or 96 hours.

35. A radioactive isotope generator, comprising: A solid precursor isotope source is configured to emit one or more gaseous progeny isotopes, the solid precursor isotope source being disposed on a ceramic material that retains the precursor isotopes; The radioactive isotope generator is configured to expose the collector surface to the one or more gaseous progeny isotopes to deposit one or more solid progeny isotopes on the collector surface. The solid precursor isotope source does not contact the collector surface; The precursor isotopes are selected from 232 Th、 228 Ra、 228 Ac、 228 Th and / or 224 The group consisting of Ra; and The radioactive isotope generator mentioned above is 212 Pb generator.

36. The radioisotope generator according to claim 1, wherein the ceramic material is porous.

37. The radioactive isotope generator according to claim 1, wherein the precursor isotope is absorbed in the ceramic material.

38. The radioactive isotope generator according to claim 1, wherein the precursor isotope is adsorbed in the ceramic material.

39. The radioisotope generator according to claim 1, wherein the precursor isotope is encapsulated in the ceramic material.

40. The radioisotope generator according to claim 1, wherein the precursor isotope comprises thorium-228 isotope ( 228 Th) and / or radium-224 isotopes ( 224 Ra), the one or more gaseous progeny isotopes including radon-220 isotope ( 220 Rn), and the one or more solid progeny isotopes include lead-212 isotope (Rn). 212 Pb).

41. The radioisotope generator of claim 1, wherein the collector surface is the inner surface of a container, and wherein the container has an internal volume at least partially defined by the inner surface, the internal volume being configured to receive the one or more gaseous progeny isotopes.

42. The radioactive isotope generator of claim 41, wherein the solid precursor isotope source is configured to be connected to an opening in the container.

43. The radioisotope generator of claim 41, further comprising the container, wherein the container is configured to be removably connected to the solid precursor isotope source.

44. The radioisotope generator of claim 41, further comprising a chelating agent disposed on the inner surface, the chelating agent being configured to chelate the one or more solid progeny isotopes.

45. The radioisotope generator of claim 44, wherein the chelating agent comprises TCMC.

46. ​​The radioisotope generator according to any one of claims 1 to 45, wherein the radioisotope generator does not include a gas-permeable barrier that is impermeable to the precursor isotope source.

47. The radioisotope generator of claim 41, wherein the container is configured to receive a solvent configured to dissolve the one or more solid progeny isotopes from the inner surface.

48. The radioisotope generator of claim 47, further comprising the solvent disposed in the container, the solvent comprising an aqueous solution.

49. The radioisotope generator of claim 1, wherein the radioisotope generator is configured to switch from a first configuration to a second configuration, wherein in the first configuration the collector surface is not in communication with the solid precursor isotope source fluid, and in the second configuration the collector surface is in communication with the solid precursor isotope source fluid.

50. The radioisotope generator according to any one of claims 1 to 49, wherein the precursor isotope is retained on the ceramic material by a process comprising depositing a solution containing the precursor isotope on the outer surface of the ceramic material, thereby retaining the precursor isotope on the outer surface of the solid precursor isotope source.

51. The radioisotope generator according to claim 50, wherein the ceramic material is a strip, a sphere, or a rod.

52. The radioactive isotope generator according to any one of claims 1 to 51, wherein the total amount of radioactivity in the generator is in the range of 1 GBq to 100 GBq.

53. The radioactive isotope generator according to any one of claims 1 to 51, wherein the total amount of radioactivity in the generator is in the range of 10 MBq to 10 GBq.

54. A method of generation 212 Pb's method, the method comprising: Allows one or more gaseous progeny isotopes to be emitted from a solid precursor isotope source, said solid precursor isotope source comprising a ceramic material that retains the precursor isotopes; The precursor isotopes are selected from 232 Th、 228 Ra、 228 Ac、 228 Th and / or 224 Groups composed of Ra; and Expose the collector surface to the one or more gaseous progeny isotopes to deposit one or more solid progeny isotopes on the collector surface; The solid precursor isotope source does not contact the collector surface.

55. The method of claim 54, further comprising converting the radioisotope generator from a first configuration to a second configuration such that the collector surface is exposed to the one or more gaseous progeny isotopes, or that the collector surface is isolated from the one or more gaseous progeny isotopes.

56. The method of claim 54, further comprising removing the collector surface from the solid isotope source.

57. The method of claim 54, wherein the ceramic material is porous.

58. The method of claim 54, wherein the precursor isotope is adsorbed in the ceramic material.

59. The method of claim 54, wherein the precursor isotope is absorbed into the ceramic material.

60. The method of claim 54, wherein the precursor isotope is encapsulated in the ceramic material.

61. The method of claim 54, wherein the precursor isotope comprises thorium-228 isotope ( 228 Th) and / or radium-224 isotopes ( 224 Ra), the one or more gaseous progeny isotopes including radon-220 isotope ( 220 Rn), the one or more gaseous progeny isotopes are configured to decay into one or more solid isotopes, the one or more solid progeny isotopes including lead-212 isotopes (Rn). 212 Pb).

62. The method of claim 54, wherein the collector surface is the inner surface of a container, the method further comprising receiving the one or more gaseous progeny isotopes in an internal volume of the container, the internal volume being at least partially defined by the inner surface.

63. The method of claim 62, further comprising removably connecting the solid precursor isotope source to an opening in the container.

64. The method of claim 62, further comprising allowing the one or more solid progeny isotopes to deposit on the inner surface of the container.

65. The method of claim 64, further comprising using a chelating agent disposed on the inner surface to chelate the one or more solid progeny isotopes.

66. The method of claim 65, wherein the chelating agent comprises TCMC.

67. The method of claim 62, further comprising receiving a solvent in the container and dissolving the one or more solid progeny isotopes from the inner surface in the solvent, wherein the solvent comprises an aqueous solution.

68. The method of claim 54, wherein exposing the collector surface to the one or more gaseous progeny isotopes comprises converting the radioisotope generator from a first configuration to a second configuration, wherein in the first configuration the collector surface is not in communication with the solid precursor isotope source fluid, and in the second configuration the collector surface is in communication with the solid precursor isotope source fluid.

69. The method of claim 54, further comprising using the one or more solid progeny isotopes to form a radiopharmaceutical.

70. The method according to any one of claims 54 to 69, wherein the precursor isotope is retained on the ceramic material by a process comprising depositing a solution containing the precursor isotope on the outer surface of the ceramic material, thereby retaining the precursor isotope on the outer surface of the solid precursor isotope source.

71. The method of claim 70, wherein the ceramic material is a strip, a ball, or a rod.

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