Introduction

Nuclear medicine is a special radioisotope carrier that uses radiation to provide diagnostic information regarding the function of a person's specific organs or to treat them ^[1]. Since the discovery of the diagnostic and treatment abilities of nuclear medicine in the last century, a wide variety of medical radioisotopes have been studied and developed to enhance the treatment of cancer and other diseases. Currently, over 40 million nuclear medicine procedures are performed annually, and the demand for radioisotopes has increased by up to 5% ^[1]. For example, diagnostic radioisotopes such as technetium-99 (^99mTc) and therapeutic radioisotopes like actinium-225 (²²⁵Ac) are increasingly being utilized in the field of radiopharmaceuticals, with corresponding minimum activities for pharmaceutical purposes of 40 and 0.1 mCi, respectively. The production of radioisotopes has gained significant prominence in the development of the national economy and healthcare because of their extensive applications in nuclear technology, particularly in nuclear medicine. In China, the Medium- and Long-Term Development Plan for Medical Isotopes (2021–2035) was officially issued by eight ministries and commissions in June 2021 to study the production and application of medical radioisotopes as a national strategy. Compared to the international need, the objective of this plan is to accomplish the key technological development of medical isotopes including ⁹⁹Mo, ⁶⁸Ge/⁶⁸Ga, ^123,124I, ^64,67Cu, ⁸⁹Zr, ¹⁰³Pd, ¹¹¹In, and ²²⁵Ac, as well as to master core competencies in irradiation structure design, optimization of irradiation parameters, post-processing of targets, and recovery of essential raw materials. This is of great significance for improving the capacity of radioisotope-related industries and ensuring the implementation of the Healthy China strategy, which covers public health services, environmental management, the Chinese medical industry, and food and drug safety^[2].

Radioisotopes can be generated through the irradiation of stable isotope targets in nuclear reactors or particle accelerators ^[3-9]. As an effective supplement to isotope production using reactors, irradiation with an accelerator provides a new pathway for generating neutron-deficient nuclides and developing innovative medical radioisotopes. Using high-intensity proton or gamma-ray beam facilities, appropriate targets can be exposed to the particle irradiation and undergo proton- or photon-nuclear reaction to produce new radioisotopes such as ^99mTc and ²²⁵Ac^{[9, 10]}. More than 3000 low-energy medical cyclotrons are being used worldwide for the production of traditional medical radioisotopes, such as ¹⁸F. However, only a few proton accelerators with energies greater than 100 MeV have been used for radioisotope production. To produce specific radioisotopes with high chemical purity according to pharmacopoeia limits, several dedicated facilities for radioisotope research have been constructed at high-energy particle accelerator centers globally. For example, in Switzerland, the 1.4-GeV CERN-MEDICIS (MEDical Isotopes Collected from ISolde) facility delivered its first radioactive ion beam at CERN in December 2017 to support the research and development of nuclear medicine using non-conventional radioisotopes, such as ^149,152,155Tb, ¹⁵³Sm, ^165,167Tm, ¹⁶⁹Er, ¹⁷⁵Yb, and ²²⁵Ac ^[9]. In Canada, the Isotope Separator and Accelerator (ISAC) facility at TRIUMF is a powerful source for producing research quantities of promising therapeutic radioisotopes for feasibility studies ^[11]. In China, a 100-MeV compact cyclotron, CYCIAE-100, has been designed and constructed at CIAE (China Institute of Atomic Energy) to be used as a driver for the BRIF (Beijing Radioactive Ion-beam Facility)^{[12, 13]}, which is highly suitable for the radioisotopes production due to its high beam current up to 520 µA.

China Spallation Neutron Source (CSNS) is a proton-driven complex that provides multidisciplinary platforms for scientific research and applications^[14-16]. In CSNS phase I (CSNS-I), a tungsten coated tantalum (W-Ta) spallation target was bombarded with a 1.6 GeV proton beam with an accelerator power of 100 kW and a repetition rate of 25 Hz. Presently, an important upgrade of the facility, namely CSNS phase II (CSNS-II), which will increase the power of protons to 500 kW, is ongoing. In parallel, a design study for beam quality improvement and an upgrade in proton beam intensity and energy is also being performed. A 300-MeV proton beam can be extracted from the end of the H^- Linear accelerator at CSNS-II to carry out irradiation experiments. This beamline can provide a power of at least 100 kW for radioisotope production, providing a competitive advantage among similar international facilities. This study aimed to analyze the feasibility of medical radioisotope production using proton beams at the CSNS.

The remainder of this paper is organized as follows. Section 2 provides a detailed description of proton beams at the CSNS. Section 3 describes the simulation method and the irradiation of target materials for medical isotope production. The in-target production yields of typical medical isotopes are presented in Sect. 4. Finally, the conclusions are presented in Sect. 5.

Medium proton beams at CSNS

The CSNS facility consists of an H^- Linear accelerator (LINAC), a proton rapid cycling synchrotron (RCS), a target station, and several neutron experimental spectrometers ^[17-19]. A proton beam with medium energy can be extracted from the end of the LINAC, which is suitable for applications in proton irradiation, particularly in medical radioisotope production. The basic parameters of the proton beamlines at the CSNS are summarized in Table 1, and the details are described in the following subsections.

Associated Proton Beam Experiment Platform (APEP) beamline is the first proton irradiation facility to utilize naturally stripped protons extracted from the H^- LINAC at the CSNS. The accelerated H^- ion beams interacted with the residual gas in the vacuum tube, among which a small number of the H^- ions were stripped into protons and transported to the end of the LINAC. The physical design of the APEP beamline, including the proton transport, beam collimation, and radiation shielding, can be found in Ref. [20].

Figure 1 shows the schematic drawing of the APEP beamline, whose actual length is approximately 14.5 m. Two experimental irradiation points, namely the vacuum test point (VTP) and the air test point (ATP), are located on the beamline at flight path lengths of approximately 9.3 and 10 m from the extraction position, respectively. A wedge degrader, which allows a continuous change in the thickness, was used to continuously adjust the proton energy within the range of 10–80 MeV. To satisfy different experimental requirements, a cascading collimation system consisting of three graphite collimators was employed to control the spot sizes, which resulted in beam spot sizes ranging from 10 mm × 10 mm to 50 mm × 50 mm at the irradiation points.

Fig. 1Full-screen View

(Color online) Layout of the APEP

By utilizing a degrader to adjust the proton energy, a series of irradiation experiments on medical isotopes of interest, such as ^123,125I, ¹⁰³Pd, ^99mTc, ⁸²Sr, ⁶⁸Ge, ⁶⁴Cu, and ⁶²Zn, can be performed at both the vacuum and air test points with a proper target material. These isotopes are extensively used in the medical field with a relatively high production cross-section at low proton energies, which is ideal for carrying out verification experiments under the present experimental conditions provided by the APEP.

Tables 2 and 3 list the medical isotopes with potential for APEP production and research. For the 80-MeV (CSNS-I) and 300-MeV (CSNS-II) APEP beamlines, the recommended medical isotopes and corresponding reaction channels are provided, as well as suitable medical applications. The medical isotopes produced by APEP are not limited to those listed in the tables. These isotopes are widely used in medical applications^{[1, 11, 13, 21]}. In general, the 80-MeV APEP can meet the requirements of production experiments for most medical isotopes and the proof-of-principle of some innovative alpha isotopes (see Table 2). With the help of appropriate gamma spectroscopy, two types of experiments can be carried out at 80-MeV APEP at present: (1) quantitative analysis of the end of bombardment (EOB) activity in the irradiated targets; (2) proton-induced reaction cross-section measurement based on the activation analysis technique. The EOB activity of the specific isotope is deduced by using the characteristic γ-ray count of the decay products, while the proton-induced reaction cross section can be calculated by the EOB activity and the incident proton intensity. The latter is generally measured by placing appropriate monitoring targets in a proton beam that receives irradiation simultaneously with the experimental target. The CSNS-I APEP line started operation in 2021, and its application in user experiments has also begun. Recently, an irradiation experiment of ¹⁰⁰Mo target was performed at the APEP, and an experimental yield of ^99mTc conforming to the theoretical calculation was obtained. Based on APEP, a 2-h irradiation of a multi-layer ¹⁰⁰Mo target can produce approximately 60 MBq of ^99mTc and 18 MBq of ⁹⁹Mo sufficient for pre-clinical studies. Further details can be found in Ref.[22].

After the upgrade of CSNS-II, which will be complete in 2028, the maximum proton energy of the APEP line is expected to reach 300 MeV with a proton beam current of approximately 333.3 µA (see in Table 1), significantly extending the variety of isotopes which can be produced. To fully utilize the proton energy, isotopes of interest are expected to be generated by spallation (p, x) reactions at the 300-MeV APEP. High-energy protons can produce isotopes with a wide range of masses, providing an opportunity to study rare radioisotopes. Considering the cross section of the production reaction and the impurity content, appropriate target materials are essential for the generation of nuclides with different mass numbers. Table 3 lists the potential medical isotopes produced by the 300-MeV proton beam. Irradiation of thorium or tantalum target with 300-MeV protons can produce a series of products, including some crucial alpha-emitter isotopes and lanthanide isotopes, which are ideal isotopes for medical applications.

Simulation

Analysis of recommended radioisotopes for production at CSNS-II

Radiologic diagnosis and therapy utilize various types of radioactive emissions to image or kill cancer cells, including gamma (γ), alpha (α), beta (β- and β+), and Auger electron. Diagnostic procedures using radioisotopes are now routine, and the gamma- and positron-emitting radionuclides are extensively used in diagnosis (e.g., ^99mTc (γ-emitter) and ¹⁸F (β⁺-emitter))[22, 28]. Alpha emitter radioisotopes such as ²²⁵Ac, ²²³Ra, and ²¹¹At are becoming more interested in targeted α therapy [29-31]. β- radioisotopes have been applied in clinical practice, including ⁹⁰Y and ¹⁷⁷Lu [32, 33]. Auger electron-emitting radioisotopes such as ¹⁶⁵Er and ⁶⁷Ga are also being considered for targeted therapy[11, 34].

In this section, the recommended radioisotopes for research and production at the CSNS are discussed. Analysis of all potential irradiation targets and corresponding isotopes that could be produced at the CSNS is beyond the scope of this study. We focus on several medical radioisotopes with significant applications that are either promising or extensively used in the medical field. The types of radioisotopes that can be produced by the 300-MeV proton beam of CSNS-II are of great concern to us because of the high proton intensity and production capacity.

4.1

Alpha-emitting radioisotopes

Targeted Alpha Therapy (TAT) is one of the most promising tumor therapies for the future, and the development of radiopharmaceuticals emitting alpha ions is an active field of academic and commercial research worldwide[35]. Alpha radiation can kill cancer cells that are resistant to treatment with beta- or gamma irradiation as well as chemotherapeutic drugs. Additionally, alpha radiation has a shorter range in tissue than beta or gamma radiation, which reduces the risk of damaging surrounding healthy tissue. Generally, the range of α- particles in tissue is 50-100 μm, and they have high linear energy transfer (LET) with a mean energy deposition of 100 keV/μm, which provides a more specific tumor cell killing ability without damage to the surrounding normal tissues than β^—particles[36]. Only a few alpha-emitting radioisotopes can be suitable for the TAT therapy, including ²²⁵Ac, ²²³Ra, ^212,213Bi, and ²¹¹At. These candidate radioisotopes with suitable half-lives have favorable properties for cancer therapy, as detailed in the following subsections.

4.1.1

²²⁵Ac/²¹³Bi

Actinium-225 (²²⁵Ac) has become increasingly prominent owning to its suitable half-life (T_1/2 = 9.9 d) and short range in tissues. The long half-life of ²²⁵Ac allows slow decay during production and delivery. The alpha particles released by ²²⁵Ac have a high LET and a short range of about 50-90 µm in biological tissue, which are conducive to killing tumor cells effectively and minimizing damage to normal tissues. However, the application of ²²⁵Ac-radiopharmaceutical still faces significant challenges, including limited isotope supply and difficulty in chemical separation. Four main different routes are proposed to produce ²²⁵Ac: (1) decay from the ²²⁹Th sources; (2) (p, 2n) reaction of ²²⁶Ra with the proton energy above about 16 MeV; (3) (p, x) reaction of ²³²Th (²³⁸U) via high-energy protons; (4) (γ, n) reaction of ²²⁶Ra produces ²²⁵Ra, which subsequently decays to ²²⁵Ac. More details can be found in the literature [10, 35, 37]. At CSNS, the last route is recommended to perform the experiment of the ²²⁵Ac production due to the high proton energy and the adept ²³²Th target-making technique of the researchers. Based on our previous experience, ²³²Th targets can be prepared using either cold- or hot- pressing with ²³²Th metal powder, depending on the required thickness [38, 39]. By comparing the existing cross-sectional data of ²³²Th (p, x) reaction at different energies [40], we found that the 300-MeV proton beam is very suitable for the production of ²²⁵Ac. Figure 2 shows the generation and decay schemes for ²²⁵Ac and ²¹³Bi. ²²⁵Ac is produced through proton-induced spallation of ²³²Th, followed by the decay of 3 α-particles to ²¹³Bi, which is another important medical alpha-emitting radionuclide.

Fig. 2Full-screen View

Generation and decay scheme of ²²⁵Ac to ²¹³Bi

To evaluate the in-target production rate, the reaction process between 300-MeV protons and ²³²Th was simulated using the FLUKA code, with the geometric model described in Sect. 3.2. The beam intensity was set to 333.3 µA based on the design parameters of CSNS-II. The thickness of ²³²Th target was evaluated using the SRIM code [41] to ensure full deposition of proton energy in the target, which was used as an input for FLUKA. The irradiation time was set to 6 d, which was determined by the operational status of the CSNS. Several important parameters, including the weekly production activity of ²²⁵Ac, the evolution of activity over time, and the radionuclidic impurities of ²²⁵Ac, are discussed.

The activity evolution of the main isotopes of ²²⁵Ac in the irradiated thorium target with a 10 cm thickness is shown in Fig. 3. The activity of ²²⁵Ac increased to approximately 57 Ci after a 6-d irradiation with no off time, which indicates that CSNS-II APEP is capable of producing 1710 Ci ²²⁵Ac per year during 30 weeks of annual operation time with dedicated irradiation. Figure 3(a) shows that the impurity ratio of ²²⁷Ac increased with irradiation time. The ²²⁷Ac/²²⁵Ac ratio was 0.146% after 6 d of irradiation and increased to 0.216% after continuous irradiation for 20 d. After irradiation for a certain period (6 d), the irradiation target was removed in a timely manner and subjected to chemical separation. Based on the results in Fig. 3(b), it can be observed that the ratio of ²²⁵Ac activity to the total activity reaches its peak when the cooling time is approximately 10–20 d, which can be used to estimate the optimal cooling time in practical production.

Fig. 3Full-screen View

(Color online) ²²⁵Ac activity evolution with irradiation time (a) and cooling time (b) in the irradiated thorium target (thickness = 10 cm), accompanying with the activity evolution of major impurities. The dashed lines represent the ratios of ²²⁷Ac/²²⁵Ac (a) and ²²⁵Ac/ total (b) activity, with the corresponding values on the right axes. Note that (b) corresponds to an irradiation time of 6 d.

From Fig. 2, one can see that the short-lived daughter nuclide, ²¹³Bi (T_1/2 = 46 min), is obtained by the emission of three α-particles from ²²⁵Ac and subsequently undergoes alpha-decay and beta-decay to produce ²⁰⁹Tl (2%) and ²¹³Po (98%), respectively, with an α energy of about 8.4 MeV and a short tissue range of about 85 µm. ²¹³Bi is a promising alpha-emitting radioisotope for application in TAT and can be conveniently produced using a ²²⁵Ac-²¹³Bi generator with high specific activity. Detailed descriptions of ²¹³Bi are provided in [36, 42, 43]. The information depicted in Figure 4 reveals that the production yield of ²¹³Bi is nearly equivalent to that of ²²⁵Ac, primarily because of the notably longer half-life of ²²⁵Ac in that of ²¹³Bi. The simulation results showed that the CSNS could provide a substantial amount of ²²⁵Ac and ²¹³Bi for drug research and clinical studies.

Fig. 4Full-screen View

Evolution of ²¹³Bi activity with irradiation time (a) and cooling time (b) in the irradiated thorium target (thickness = 10 cm), accompanying with the activity evolution of ²²⁵Ac. Note that (b) corresponds to an irradiation time of 6 d

4.1.2

²²³Ra

²²³Ra (T_1/2 = 11.4 d) is considered one of the most promising alpha-emitting radioisotopes based on its decay characteristics. The long half-life of ²²³Ra allows ample time for transportation, drug preparation, and injection into patients. As a bone-seeking radiopharmaceutical, Xofigo (²²³RaCl₂) has been used in the clinical treatment of skeletal metastases from breast and prostate cancers [44-46], and is the first TAT radiopharmaceutical worldwide.

In CSNS-II, the production of ²²³Ra is also expected by employing ²³²Th as the target nucleus. As shown in Fig. 5, the spallation reaction produced by the protons on thorium can directly produce ²²³Ra, and the ²²³Ra can also be formed by the decay of ²²⁷Th and ²²⁷Ac which are simultaneously produced by the spallation reactions. Subsequently, ²²³Ra decays into a stable lead through a series of short-lived daughter radionuclides, emitting four alpha particles. In the decay chain of ²²³Ra, 94% of the total decay energy is released by alpha particles[44]，indicating that cancer cells can be effectively killed.

Fig. 5Full-screen View

Generation and decay scheme of ²²³Ra

²²³Ra can also be generated from ²²⁷Ac/²²⁷Th and purified using Ac-resin, which immobilizes both ²²⁷Ac and ²²⁷Th, as previously described [44]. Figure 6 illustrates the variation in radioactive activity with irradiation and cooling times for the three nuclides. As shown in Fig. 6, the EOB activity corresponding to one week of irradiation was approximately 14.5 Ci. However, with an increase in the cooling time, ²²⁷Ac and ²²⁷Th produced by the spallation reaction continued to decay to ²²³Ra, resulting in an increase in ²²³Ra production. After cooling for approximately 20 d, ²²³Ra reached a maximum activity of approximately 24 Ci and maintained a relatively high yield for a long time, which provided sufficient time for chemical separation.

Fig. 6Full-screen View

(Color online) Evolution of ²²³Ra activity with irradiation time (a) and cooling time (b) in the irradiated thorium target (thickness = 10 cm), accompanying with the activity evolution of ²²⁷Ac and ²²⁷Th. Note that (b) corresponds to an irradiation time of 6 d.

4.1.3

²¹¹At

²¹¹At also has attracted significant attention as a therapeutic α-particle emitter for its promising potential in treating microscopic diseases, such as micrometastases and monocellular malignancies [47, 48]. Typically, ²¹¹At (T_1/2 = 7.2 h) is more suitable for production by alpha accelerators based on the ²⁰⁹Bi (α, 2n) reaction with a cross section value of ~1 b at E_α = 29 MeV[31]. However, this restricts the production of ²¹¹At owning to the limited number of alpha accelerators available worldwide.

Recently, researchers have discovered that the use of high-energy protons to bombard Th or U targets to produce ²¹¹Rn (T_1/2 = 14.6 h), the mother isotope of ²¹¹At, is an attractive pathway for producing ²¹¹At [31]. A ²¹¹Rn/²¹¹At generator system is recommended for producing ²¹¹At. As shown in Fig. 7, at CSNS-II, ²¹¹At and ²¹¹Rn can be generated through proton irradiation of thorium. Simultaneously, ²¹¹At is produced via the electron capture (EC) decay of ²¹¹Rn with a probability of approximately 73%. Subsequently, ²¹¹At decays into ²⁰⁷Bi and ²¹¹Po through the α decay (42%) and EC decay (58%), respectively.

Fig. 7Full-screen View

Generation and decay scheme of ²¹¹At

The activity evolutions of ²¹¹At and ²¹¹Rn were calculated, and the results are shown in Fig. 8. The irradiation of thorium target for 6 d with a proton beam intensity of 333.3 µA can produce a maximum of approximately 163.5 Ci of ²¹¹At. However, because of the short half-life of ²¹¹At, the activity reaches the maximum value quickly, which means that prolonged irradiation does not effectively increase the yield (Fig. 8 (a)), and frequent irradiation can improve the production yield.

Fig. 8Full-screen View

Evolution of ²¹¹At activity with irradiation time (a) and cooling time (b) in the irradiated thorium target (thickness = 10 cm), accompanying with the activity evolution of ²¹¹Rn. Note that (b) corresponds to an irradiation time of 6 d

Other alpha-emitting isotopes, such as ²¹²Pb and ²¹²Bi, which are potential candidates for TAT, may not be optimally produced by proton accelerator irradiation. However, we discovered that a considerable in-target yield of these isotopes could also be obtained using thorium as the irradiation target at CSNS-II, which is adequate for proof-of-principle studies and pre-clinical drug research. The weekly production yields of these isotopes and the aforementioned categories are listed in Table 5. Currently, two main methods are used for separating alpha-emitting isotopes based on thorium targets. Taking the separation of ²²⁵Ac as an example, a three-step procedure including liquid-liquid and solid-phase extraction chromatography can result in a recovery rate of over 85% for ²²⁵Ac [49]. A two-step method using 1 M oxalic acid at pH 2 to remove the bulk thorium mass can yield ²²⁵Ac with a recovery yield of over 98%, which is suitable for radiolabeling or generator applications [50, 51]. In addition, alpha-emitting radioisotopes can be separated using an on-line isotope separation method according to their mass-to-charge ratio. Based on the existing experiences of CERN MEDICIS (2.0 GeV, 6.7 uA) [9] and TRIUMF ISAC (500 MeV, 100 uA)[11], CSNS APEP (300 MeV, 333.3 uA) has the potential to provide sufficient yields for clinical experiments by the on-line isotope separation method. In summary, the 300 MeV proton beam at CSNS-II is very suitable for the production of alpha-emitting isotopes and provides an excellent experimental platform for isotope production.

Table 5Full-screen View

In-target production yield of alpha-emitter radioisotopes at CSNS-II

Medical Isotope	Energy of α （MeV）	Production pathway	Theoretical yield (Ci/week, 100 kW)	Daughter isotopes
211At	5.9	Accelerator irradiation	163.5	211Po、207Bi
212Bi	6.1	Accelerator irradiation	103.0	212Po、208Tl
212Pb	6.1	Accelerator irradiation	89.5	212Bi、212Po、208Tl
213Bi	5.8	Accelerator irradiation	58.5	213Po、209Tl、209Pb
225Ac	5.8	Accelerator irradiation	57.0	221Fr、217At、213Bi、213Po、209Tl、209Pb
223Ra	5.7	Accelerator irradiation	14.5	219Rn、215Po、211Pb、211Bi、211Po、207Tl

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4.2

Neutron-deficient lanthanide isotopes

The following advantages make lanthanide radionuclides highly favorable：(1) lanthanide isotopes can emit different types of particles and possess all radiation characteristics suitable for radiotherapy and diagnosis; (2) different lanthanide isotopes have similar chemical properties that provide unique advantages for the molecular labeling of tracer molecules. Neutron-rich lanthanide nuclides, such as ¹⁴¹Ce, ¹⁴³Pr, and ¹⁵³Sm, are typically produced by bombarding ²³⁸U with high-energy protons. Neutron-deficient lanthanide isotopes, such as ¹⁶⁹Yb, ¹⁶⁷Tm, ¹⁴⁹Tb, and ¹⁵²Tb, can be produced by bombarding a tantalum target.

In this study, the evolution of various neutron-deficient lanthanide radioisotopes suitable for production on CSNS-II was evaluated using the FLUKA code, with ¹⁸¹Ta used as the target material. The tantalum target was bombarded by a 300 MeV proton beam with a power of 100 kW and an irradiation time of 6 d. To obtain the maximum in-target production yield, the thickness of the Ta target (8 cm) was maintained such that the proton energy was completely deposited on the target.

Figure 9 shows the variation trends of some lanthanide isotopes over time, and the specific weekly yields are summarized in Table 6. Several isotopes listed in the table have already been used in clinical therapy, and others are undergoing pre-clinical research but show promising application prospects. Lanthanide isotopes release different types of particles during radiotherapy or diagnosis. For example, ¹⁷⁷Lu has been used for beta therapy, ¹⁴⁹Tb for alpha therapy, and ¹⁵²Tb for PET. ¹⁶⁵Er is a promising candidate for Auger electron therapy, and ¹⁶⁹Yb is commonly used for SPECT.

Fig. 9Full-screen View

(Color online) Evolution of the activity of lanthanide isotopes with irradiation time in the irradiated tantalum target (thickness = 8 cm)

Table 6Full-screen View

In-target production yield of neutron-deficient lanthanide isotopes at CSNS-II

Medical isotopes	Theoretical yield (100 kW, Ci/week)	Decay modes	Daughter isotopes
166Yb	343.0	EC	166Tm、166Er
165Er	277.0	EC	165Ho
167Tm	188.0	EC	167Er
161Ho	78.5	EC	161Dy、157Gd
169Yb	74.5	EC	169Tm
152Tb	3.9	EC、β+	152Gd、148Eu、148Sm、144Nd、140Ce、144Pm
177Lu	2.8	β-	177Hf
155Tb	2.4	EC	155Gd
149Tb	0.9	EC、β+	149Gd、145Eu、149Eu、149Sm、145Sm、145Pm、145Nd、141Pr
149Gd	0.5	EC、β+	149Eu、149Sm、145Sm、145Pm、145Nd、141Pr

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As shown in Table 6, a wide range of lanthanide isotopes can be obtained by reacting protons with tantalum; however, some of these can be produced in higher yields using other irradiation targets and reaction channels. Hence, our preference was to utilize the CSNS for the centralized production of one or a few medical radioisotopes, such as the previously mentioned ²²⁵Ac. For other isotopes, we are committed to providing adequate quantities for verification rather than for large-scale production.

Conclusion

In this study, the feasibility of isotope production using a CSNS proton beam was evaluated. Using the FLUKA code, the types and yields of medical isotopes produced by the proton beam at the CSNS were analyzed. The results show that the CSNS APEP facility can provide a unique opportunity for the production of a wide range of medical radioisotopes, especially alpha-emitting radioisotopes. By utilizing specific target materials, APEP can generate sufficient quantities of the desired radioisotopes for researchers to carry out proof-of-principle experiments and even for commercial applications. ²²⁵Ac and ²²³Ra will become the key alpha-emitter medical radioisotopes studied at the CSNS owning to their urgent demand in the domestic market; therefore, the production and separation of these two isotopes will be the main focus of our next work. In the future, we would like to explore the possibility of using online methods to separate the residual nuclei. With future upgrades of the CSNS APEP facility, there are supplementary possibilities for expanding the variety of radioisotopes suitable for medical applications.