Estimated Isotopic Compositions of Yb in Enriched 176 Yb for Producing 177 Lu with High Radionuclide Purity by 176 Yb ( d , x ) 177

Oarai Research Center, Chiyoda Technol Corporation, Oarai, Ibaraki 311-1313, Japan Quantum Beam Science Research Directorate, National Institutes for Quantum Science and Technology, Tokai, Ibaraki 319-1106, Japan Nuclear Science and Engineering Center, Japan Atomic Energy Agency, Tokai, Ibaraki 319-1195, Japan Advanced Science Research Center, Japan Atomic Energy Agency, Tokai, Ibaraki 319-1195, Japan Radiation Sources Production Section, Chiyoda Technol Corporation, Tokai, Ibaraki 319-1195, Japan Cyclotron and Radioisotope Center, Tohoku University, Sendai 980-8578, Japan


Introduction
Early non-invasive diagnosis and targeted radionuclide therapy (TRT) have been playing an important role in treating patients with a variety of cancers using radionuclide therapy radiopharmaceuticals labelled with various kinds of medical radionuclides. 1) Radionuclides that emit low-energy γ-rays and=or annihilation γ-rays are used for diagnosis, and that emit charged particles (Auger electron, À -ray, alpha particle) are employed for TRT. 2,3) In treating cancers, a low-dose imaging procedure is performed to obtain necessary pretherapy information on biodistribution and dosimetry in patients, followed by making higher dose targeted molecular therapy in the same patients. This approach of merging therapeutic and diagnosis (imaging) treatments is now called the theranostics approach, 4) the concept of which is very important to make a personalized medicine treatment for a specific patient. In fact, 90 Y, a pure À -ray emitter with an average À -ray energy (E av ) of 934 keV, is used with the γray emitting 111 In to treat large solid tumors, 5) and a variety of low-to-medium energy À -ray emitting radionuclides are being developed aimed at treating small tumors.
Recently, considerable interest has arisen in 177 Lu with a half-life (T 1=2 ) of 6.65 d owing to successful treatments for patients with a certain type of neuroendocrine tumors using 177 Lu-labelled radiopharmaceuticals. 6) 177 Lu emits À -rays (E av ¼ 134 keV) and low-energy 113 (I ¼ 6:6%) and 208 (I ¼ 11%) keV γ-rays. 7) Percentages in brackets indicate the absolute γ-ray emission probability (I ). Recent studies with the use of two (tandem) therapeutic radionuclides, such as 90 Y= 177 Lu-radiopharmaceuticals in combination, provide an overall survival longer than that with a single radioisotope, 90 Y-radiopharmaceutical. 8) A tandem pair of 67 Cu= 177 Luradiopharmaceuticals used for treating mice with tumors also demonstrates a significant survival improvement compared with delivery as a single fraction of 67 Cu-or 177 Luradiopharmaceuticals. 9) These results provide important aspects of 177 Lu utilized for treating a wide variety of cancers. 177 Lu is currently produced in reactors either by the 176 Lu(n,γ) 177 Lu reaction or by the 176 Ybðn,Þ 177 Yb ! 177 Lu reaction. 10,11) In order to encourage widespread use of 177 Lu for therapeutic applications, the production route of 177 Lu in accelerators has also been studied using proton, 12) deuteron, [13][14][15][16] α-particle 17) and electron 18) beams. The results of these studies demonstrate that the 176 Yb(d,x) 177 Lu reaction has the largest cross section at a deuteron energy (E) of about 12 MeV. Hence, hereafter we consider the productions of 177 Lu using deuteron beams because this study aims at a large-scale production of 177 Lu with high specific activity. The specific activity of a radionuclide is one of parameters used to describe a radiopharmaceutical that is defined as an activity per quantity of atoms of a particular radioisotope (usually given in units of Bq=g). It is an important criterion for the efficacy of targeted therapeutic radiopharmaceuticals, especially for receptor or antigen targeting agents; this is because the mass levels of peptides or antibodies that can be used to develop labelled radiopharmaceuticals for therapy are limited due to finite receptor or antigen binding sites. Therefore, for medical use one has to produce radionuclides with high specific activity. Here, it is noted that the specific activity of 177 Lu that is produced by charge-exchange reactions on 176 Yb samples, such as the 176 Yb(d,x) 177 Lu reaction and also the 176 Yb(n,γ) 177 Yb( À ) 177 Lu reaction, is expected to be high. This is because carrier-free 177 Lu (i.e., all atoms in a sample contain only one specific isotope of the element) can be obtained from deuteron or neutron-irradiated Yb samples by employing chemical separation methods. 11) In fact, a specific activity of carrier-free 177 Lu with 4070 GBq=mg is expected to be produced by the 176 Yb(n,γ) 177 -Yb( À ) 177 Lu reaction. 3) Here, it should be mentioned two things. Firstly, impurity radionuclides of Lu present in 177 Lu that affect the specific activity of 177 Lu cannot be chemically separated from 177 Lu, which requires us to use enriched 176 Yb samples for producing 177 Lu having high radionuclide purity. Secondly, enriched 176 Yb samples generally contain a small amount of Yb isotopes other than 176 Yb, such as the second and third heaviest Yb isotopes, 174 Yb and 173 Yb. In such cases long-lived radionuclides of 174m Lu (T 1=2 ¼ 142 d) and 174g Lu (T 1=2 ¼ 3:31 y) would be produced not only by the 176 Yb(d,4n) reaction, but also via the 174 Yb(d,2n) and 173 Yb(d,n) reactions, [13][14][15][16] 176 Yb samples are precisely known, the yields of (impurity) 174g Lu and 174m Lu can be accurately calculated. Namely, when a variety of Lu radionuclides are produced by the 176 Yb(d,x)Lu reaction, if the excitation functions of individual reactions that produce the Lu radionuclides are precisely known, the isotopic compositions of Yb in enriched 176 Yb samples required to produce 177 Lu with high radionuclide purity can be estimated. In this study, the excitation functions will be derived by referring to previously measured excitation functions of the nat Yb(d,x)Lu reaction in the deuteron energy range of 2 to 40 MeV. [13][14][15][16] However, a problem remains in the previous data; the latest results of the excitation functions of 172 Lu, 173 Lu, 174g+m Lu, 176m Lu, and 177 Lu by Khandaker et al. differ from the older ones in some deuteron energy range. 16) Hence, we first measured integral yields of Lu radionuclides by the nat Yb(d,x)Lu reaction to test the validity of the latest results; the test can be performed by comparing the measured integral yields with integral yields that are estimated using the latest results. Note that theoretical studies of the excitation functions of the deuteron-induced reactions on nat Yb were also performed with nuclear model codes, such as ALICE-IPPE, EMPIRE-II, and TALYS TALYS-1.4. Theoretical results are roughly in agreement with the measured excitation functions at E ¼ 2{40 MeV, but the absolute values of the cross sections differ from each other. 16) To the best of our knowledge, such a study for estimating the relation between the radionuclide purity of 177 Lu and the isotopic compositions of Yb present in enriched 176 Yb samples has not yet been conducted.
The paper comprises five sections. We report on the measurement of integral yields of Lu radionuclides by the nat Yb(d,x)Lu reaction in Sect. 2. In Sect. 3 we describe a method to determine the aforementioned individual excitation functions, and compare the integral yields estimated using both the measured excitation functions and individual excitation functions with the measured integral yields of Lu radionuclides. We report on the estimated results of the radionuclide purity of 177 Lu produced by the 176 Yb(d,x) 177 Lu reaction with various kinds of isotopic composition of Yb isotopes present in enriched 176 Yb samples in Sect. 4, and summarize this study in Sect. 5.

Measurements
We measured the integral yields of Lu radionuclides produced by the nat Yb(d,x)Lu reaction to compare them with those estimated by using the latest measured excitation functions of the reaction. 16) The Lu radionuclides were generated by irradiating a metallic nat Yb sample for 10 min with a 0.338 µA, 25 MeV deuteron beams that was provided from the azimuthally variable field (AVF) cyclotron at Cyclotron and Radioisotope Center (CYRIC), Tohoku University, in Japan. 19) We used 25 MeV deuteron beams in order to obtain a large integral yield of 177 Lu by referring to the latest result of the excitation function of the 176 Yb(d,x) 177 Lu reaction, measured by using nat Yb samples. 16) The nat Yb sample of 1.831 g mass with a thickness of 6 mm that was enough to stop 25 MeV deuterons in the sample was used. A tantalum slit with a diameter of 10 mm was placed before the nat Yb sample. Note that the isotopic composition of nat Yb is 0.1% for 168 Yb, 3.0% for 170 Yb, 14.1% for 171 Yb, 21.7% for 172 Yb, 16.1% for 173 Yb, 32.0% for 174 Yb, and 13.0% for 176 Yb. 20) Shortly after the end of irradiation (EOI) and 37 days after the EOI, we took γ-ray spectra of the irradiated nat Yb sample with high-purity Ge (HPGe) detectors to obtain the yields of short-lived and long-lived Lu radionuclides, respectively. Isotope assignments of observed γ-rays were made on the basis of their energies and decay curves. In the former measurement the yield of Lu radionuclides with a short halflife, such as 176m Lu (T 1=2 ¼ 3:66 h), 170 Lu (T 1=2 ¼ 2:0 d), and 169 Lu (T 1=2 ¼ 34:1 h), were obtained by measuring γ-rays that were emitted from the irradiated ingot nat Yb sample. Here, the self-absorption correction for the γ-rays following the decays of 176m Lu (T 1=2 ¼ 3:66 h), 170 Lu (T 1=2 ¼ 2:0 d), and 169 Lu in the ingot nat Yb sample was made, as follows. We first determined an average depth, d, which is given as the distance of the position of the average radioactivity of the irradiated nat Yb sample from the sample surface, and then calculated the attenuation of a γ-ray with an energy of E emitted from the sample by using a photon cross-sectional database provided by the National Institute of Standards and Technology. 21) Here, because the γ-ray self-absorption factor strongly depends on the γ-ray energy, we used a number of γ-rays of well-known relative intensity such as 78.7, 181.5, 203.4, 377.5, 528.3, 810.1, 900.7, and 1093.6 keV γ-rays from the decay of 172 Lu (T 1=2 ¼ 6:70 d). 16) We accurately determined d to be 0.34 mm by comparing the γ-ray intensities corrected for the detection efficiency and γ-ray self-absorption with the intensities given in Ref. 16. The calculated yields of 172 Lu using observed γ-ray yields, absolute γ-ray emission probability of γ-rays from the decay of 172 Lu (I ), γ-ray detection efficiency of a HPGe detector and calculated self-absorption correction factors that are given in Table I agree each other within an uncertainty of 7%, except for the case of 181.5 keV.
In the latter measurement a solution sample that was obtained by dissolving an irradiated ingot nat Yb sample in hydrochloric acid was used to determine the yields of Lu radionuclides with a reduced systematic uncertainty for the self-absorption correction of observed γ-rays. A solution sample of 1 ml was contained in a polyethylene bottle with a diameter of 10 mm. Hence, for example, the attenuation coefficient for the 208 keV γ-ray (from the decay of 177 Lu) is small, 0.01. A typical γ-ray spectrum taken using the solution sample is shown in Fig. 1. The efficiencies of the HPGe detectors were obtained using a 152 Eu standard γ-ray source.
The integral yields of observed Lu radionuclides were obtained by analyzing the intensities of the following characteristic γ-rays of Lu radionuclides: 177 Lu (T 1=2  16) The total uncertainty of the measured yield was estimated to be 12% by taking a quadratic sum of the uncertainty of the γ-ray intensities (∼3%) and the overall systematic uncertainty of the intensity distribution of the deuteron beam size (∼10%), the absolute activity of 152 Eu (3%), the γ-ray detection efficiency (∼5%), and the γ-ray emission probability (∼2%). The integral yield of 177 Lu was determined by analyzing the 208.4 keV γ-ray line in the latter measurement because the γ-ray line was found to be contaminated by the 207.7 keV γ-ray line of 169 Lu in the former measurement. Measured integral yields of 177g Lu, 177g Lu, 177g Lu, 177g Lu, and 177g Lu radionuclides at the EOI were obtained by using the data taken 37 days after the EOI, and those of 176m Lu, 170g Lu, and 169g Lu radionuclides at the EOI were derived by making the γ-ray self-absorption corrections for the data taken shortly after the EOI; they are given in Table II.

Method to Determine an Excitation Function of an Individual Reaction
We derived the aforementioned excitation functions of individual reactions using the latest results that were studied by the nat Yb(d,x)Lu reaction. 16) With these derived excitation functions together with measured excitation functions of Lu radionuclides 16) we calculated integral yields of Lu radionuclides, which can be compared with the integral yields measured in this study. The comparison tests the validity of the derived excitation functions of individual reactions and the measured excitation functions.
Firstly, we note that a single Lu radionuclide, B Lu, with a mass number of B is produced via several deuteron-induced reactions on Yb isotopes present in nat Yb; this is shown by the nat Yb(d,x)Lu reaction study using deuteron beams of up to 40 MeV. Next, we consider an integral yield of B Lu, Y , which is produced from A Yb with a mass number of A via a reaction channel, ðA; BÞ of A Yb(d,x) B Lu, it is given by Eq. (1): Table I. Absolute γ-ray emission probability of γ-rays (I ) from the decay of 172 Lu (%), self-absorption correction factors of these γ-rays, measured and calculated yields of 172 Lu using the observed γ-ray yields.
γ-ray emission probability (%) Here, 2 B Lu means summation over all individual reaction channels α contributing to produce the radionuclide B Lu. Y( B Lu) will be compared with the aforementioned measured integral yield of B Lu, after we derive ðE d Þ of the excitation function of the individual reaction channel, α.
In the following discussion, the Q-value of the individual reaction channel, α, plays an important role, and therefore we give all the Q-values of relevant reaction channels for producing B Lu by the A Yb(d,x) B Lu reaction at 2 E 40 MeV in Table III 177 Lu reactions were obtained by fitting these measured excitation functions with a function that is given by Eq. (3) as the sum of a Gauss function at energies below E<E sw and a reciprocal function at above E>E sw : Here, E stands for the incident deuteron energy, and E sw is the switching energy to connect the two functional types; a i and b j (i ¼ 1, 2, and 3, j ¼ 1 and 2) are the parameters of the aforementioned functions. Two functions are smoothly connected by considering the continuity of the first derivative at E sw . Note that a 1 and a 2 are the height of the Gaussian's peak and the energy of the center of the peak, and a 3 is related to the full width at half maximum of the peak, respectively, and b 1 and b 2 are arbitrary constants that are  related to a normalization factor of the reciprocal function and the energy of the center of the peak. Here, it is worth mentioning that the excitation function of the 176 Yb(d,2n) 176m Lu reaction was measured at a deuteron energy higher than the peak energy; that allowed us to determine the values of a 2 and b 2 by least-squares fits; their values are close to each other, 12.0 and 10.9, respectively. However, when excitation functions of the nat Yb(d,x) B Lu reaction have not yet been measured at deuteron energies higher than the peak cross section, values for a 2 and b 2 cannot be determined by least-squares fits. Therefore, in such a case two values were assumed to be identical to each other because they are related to the peak energy of the cross sections, as aforementioned. If excitation functions of the nat Yb(d,x) B Lu reaction are given to be composed of two reaction channels, such as the (d,2n) and (d,4n) reactions, the difference between the value for a 2 (or b 2 ) of the (d,2n) reaction and the value for a 2 (or b 2 ) of the (d,4n) reaction was assumed to be the same as the difference of the  Fig. 2. Here, although the excitation function of the 176 Yb(d,n) 177 Lu reaction has not yet been measured at a deuteron energy above 24 MeV, the peak energy, denoted by E max , at which the cross section becomes maximal, was derived by fitting the measured cross sections with Eq. (3), resulting in E max ¼ 24 MeV. This peak energy is about 12 MeV higher than that of the 176 Ybðd,pÞ 177 Yb ! 177 Lu reaction despite that the Q-value of the 176 Yb(d,n) 177 Lu reaction is only 0.6 MeV higher than that of the 176 Yb(d,p) 177 Yb reaction. The large difference between the peak energies was discussed by Hermanne et al. by considering the Coulomb barrier between Yb and the deuteron, which is about 13 MeV. 15) The peak energy of the (d,n) channel, therefore, is expected to be obtained by simply adding the Coulomb barrier energy of 13 to 12 MeV, the peak energy of the (d,p) reaction channel, and the result is consistent to the present estimation of E max ¼ 24 MeV. Here, it should be noted that the (d,n) channel has a peak structure, because when the deuteron energy is as high as about 25 MeV, the (d,3n) reaction channel with a Q-value of −9.40 MeV, leading to the stable 175 Lu isotope, becomes dominant over the (d,n) reaction channel. Hence, the cross section of the (d,n) channel decreases with increasing the deuteron energy, resulting in the peak structure for the (d,n) reaction channel. The excitation function of the 176 Yb(d,n) 177 Lu reaction above E>25 MeV remains to be measured for testing the estimated shape. In this study, we obtained the three parameters a i (i ¼ 1, 2, and 3) in Eq. (3) for the 176 Yb(d,n) 177 Lu reaction by the fitting procedure, and then determined b 1 and E sw so as to smoothly connect the two fitting functions, assuming that a 2 and b 2 are equal.
Similarly, the measured excitation function of the 176 Yb(d,2n) 176m Lu reaction was fitted with Eq. (3), as shown in Fig. 3. Note that the deuteron energy, E max , of the reaction is about 11.7 MeV, which is 8.6 MeV higher than the Q-value of −3.1 MeV. Hence, we used Eq. (3) to fit all of the data in the following discussions.

Excitation function for cumulative productions of Lu radionuclides by the nat Yb(d,x)Lu reaction
We discuss an excitation function for cumulative productions of B Lu by the nat Yb(d,x) B Lu reaction. 174g Lu (T 1=2 ¼ 3:31 y) is cumulatively produced by the 173 Yb(d,n), 174 Yb(d,2n), and 176 Yb(d,4n) reactions, and an isomeric decay of the isomeric state at 171 keV (T 1=2 ¼ 142 d). [13][14][15][16] In fact, in the measured excitation function of the nat Yb(d,x) 174g+m Lu reaction shown in the left panel of Fig. 4 (filled circle), we can clearly see the two peaks at about 14 and 26 MeV contributing 174g+m Lu yields that result from two different nuclear reactions. These reactions are 174 Yb(d,2n) 174g+m Lu and 176 Yb(d,4n) 174g+m Lu from the Qvalues of their reactions, as listed in Table III. The measured excitation function of the nat Yb(d,x) 174g+m Lu reaction was fitted using Eq. (3), as shown in the left panel of Fig. 4 (solid line), by considering the isotopic compositions of Yb in the nat Yb sample. The peak deuteron energy, E max , of the nat Yb(d,x) 174g+m Lu reaction is about 14 and 9.6 MeV higher than the threshold energy of the 174 Yb(d,2n) 174g Lu reaction, suggesting that the maximum cross section is dominated by this reaction. As for the second peak at about 24 MeV, we note that the measured cross section of the nat Yb(d,x) 174g+m Lu reaction at E ! 20 MeV goes up with increasing deuteron energy, and conclude that the peak is most likely to be due to the 176 Yb(d,4n) 174g+m Lu reaction. In addition, the 173 Yb(d,n) 174g+m Lu reaction might also contribute to the measured yield of 174g+m Lu, similarly to the case of the 176 Yb(d,n) 177 Lu reaction. Here, because the excitation function of the 173 Yb(d,n) 174g+m Lu reaction as well as E max has not yet been measured at E ¼ 2{40 MeV, they were assumed to be the same as those of the 176 Yb(d,n) 177 Lu reaction. We determined the fitting parameters including a 2 Similarly, the measured excitation functions of the nat Yb(d,x) 172g+m Lu, nat Yb(d,x) 171g+m Lu, nat Yb(d,x) 170g+m Lu, and nat Yb(d,x) 169g+m Lu reactions were also fitted using Eq. (3), as shown in Fig. 6. Here, 169g+m Lu is considered to be mainly produced by the 170 Yb(d,3n) 169g+m Lu reaction by noting the isotopic compositions for 168 Yb and 170 Yb are 0.1 and 3.0%, respectively.
Through the least-squares fit of the measured excitation functions of a variety of Lu radionuclides produced by the nat Yb(d,x)Lu reaction using Eq. (3), we obtained values of all parameters (a 1 , a 2 , a 3 , b 1 , b 2 , and E sw ) as listed in Table IV. Namely, we obtained excitation functions of individual reactions to calculate production yields of Lu radionuclides using enriched 176 Yb samples having a variety of isotopic compositions of Yb.

Comparison of the measured and calculated integral
yields of Lu radionuclides We tested the validity of the excitation functions of the individual reactions that were derived in the previous section, as follows. We first calculated the integral yields of Lu radionuclides at the EOI that will be generated by irradiating a nat Yb sample with 25 MeV deuteron beams, and compared them with the measured integral yields. The calculations were undertaken using the aforementioned excitation functions of individual reactions, the isotopic compositions of nat Yb, and the deuteron-fluences in the nat Yb sample, fðEÞ. The fluences, fðEÞ, were obtained by performing a particle transport  simulation using the PHITS code while taking into account the geometry of the experimental setup, discussed in Sect. 2. The intensity of the deuteron beam irradiated on the nat Yb sample as well as the deuteron beam irradiation time was the same as that of the present measurement. Here, we summed over all reaction channels that contributed to produce a radionuclide B Lu, as given by Eq. (2).
The calculated integral yields of Lu radionuclides are in good agreement mostly with the measured yields within the experimental uncertainties, as shown in Table V. Here, the total systematic uncertainties in the calculation were evaluated to be 14% by considering errors associated with the total uncertainty of the data (12.8%) by Khandaker et al. 16) and parameters (5%) that were used in the fit. The total uncertainty of the measured yield was estimated to be 12%, as aforementioned. The agreement clearly suggests that the fitted approach for the individual reactions presented in the last section can be used to estimate the yields of Lu radionuclides, i.e., the radionuclide purity of 177 Lu, which will be produced by irradiating an enriched 176 Yb sample  having a variety of isotopic compositions of Yb. Consequently, we can estimate the radionuclide purity of 177 Lu as a function of the deuteron energy. Note that the yield of 174m Lu was not obtained because low energy γ-rays, such as 44 and 67 keV γ-rays, were not clearly identified in this study, and the yield of 177m Lu (T 1=2 ¼ 160:4 d) derived by analyzing the 367.4 keV γ-ray line (I ¼ 52:4%) of 177m Lu is less than 1=100 of that of 177 Lu.

Isotopic compositions of Yb in enriched 176
Yb samples and radionuclide purity of 177 Lu On the basis of the reasonable agreement between the calculated integral yields of Lu radionuclides and the measured ones, we estimated the yields of Lu radionuclides that will be produced by irradiating enriched 176 Yb samples having three sets of the isotopic compositions of Yb (discussed below) with deuteron beams. Here, the excitation functions of individual reactions given in Table IV  In order to obtain 177 Lu with high radionuclide purity we discuss the origins of each impurity of the Lu radionuclide and its deuteron energy dependence in the following. Firstly, the present results demonstrate that a significant amount of 177 Lu with a radionuclide impurity of less than a few% can be produced by irradiating commercially available enriched 176

Summary
We developed a method for estimating the isotopic compositions of enriched 176 Yb samples required to produce a carrier-free 177 Lu with high radionuclide purity by the 176 Yb(d,x) 177 Lu reaction. Here, we derived the excitation function of individual reactions for producing a radionuclide of B Lu, such as 169 Lu, 170 Lu, 171 Lu, 172 Lu, 173 Lu, 174g Lu, 174m Lu, 176m Lu, and 177 Lu, using the latest measured excitation functions of the nat Yb(d,x)Lu reactions. Note that we demonstrated that our measured integral yields of a variety of Lu radionuclides produced by the nat Yb(d,x)Lu reaction agree with the calculated integral yields of Lu radionuclides using the derived excitation functions. Our results demonstrate that the estimated radionuclide purity of 177 Lu for the 99.90 and 97.60% enriched 176 Yb samples at 2.5 days after the EOI is >98 and >99%atE ¼ 20 and 15 MeV. We also evaluated an integral yield of the carrier-free 177 Lu that is obtained by irradiating a 176 Yb sample of 0.25 mm thickness with a 100 µA, 25 MeV deuteron beams for 24 h. The yield is calculated to be 28 GBq using the measure yield of 177 Lu, 8:61 Â 10 4 Bq as given in Table II, that was obtained by irradiating the thick nat Yb sample (the abundance of 176 Yb is 13.0%) with 0.338 µA deuteron beams for 10 min. This yield is compared with a typical carrier-free 177 Lu activity of about 8 GBq; that is produced in a reactor with a typical thermal neutron flux of 1:0 Â 10 14 n=cm 2 =sec for a neutron irradiation time of 24 h using an enriched 176 Yb sample of 100 mg. 24) Here, we note a typical dose of therapeutic radiation of 177 Lu-radiopharmaceuticals that is delivered to tumor cells. Lu-177 dotatate (Lutathera ® ) was approved by the U.S. Food and Drug Administration (FDA) in 2018 (in the EU approved by the European Medicines Agency in 2017) for the treatment of neuroendocrine tumors that occur in the gastrointestinal tract, such as stomach, small and large intestine, pancreas and appendix, and lungs. The recommended dosage of 177 Lu-dotatate by the FDA is 7.4 GBq=patient every 8 weeks four intravenous infusions. 22) Therefore, the present yield of 28 GBq=day encourages us to produce 177 Lu by the 176 Yb(d,x) 177 Lu reaction using enriched 176 Yb samples. The production method of 177 Lu by the 176 Yb(d,x) 177 Lu reaction will play an important role in promoting the widespread use of 177 Lu for a variety of therapeutic applications. In addition, the present method would play an important role in determining the isotopic compositions of enriched samples for producing medical radionuclides with high radionuclide purity from measured excitation functions of nuclear reactions of natural samples in accelerators.