Solid target system for the production of high purity radionuclide compositions

Abstract

The present disclosure relates to a novel solid target system that uses a medical cyclotron to produce novel high purity radionuclide compositions, which are suitable for radionuclide and chemical purity for use in radiopharmaceutical applications, such as targeted radionuclide therapy in diagnostic imaging and nuclear medicine.

Description

[Background technology]

[0001] The present disclosure relates to a solid target system that uses a medical cyclotron to produce high purity radionuclide compositions, which are suitable for radionuclide and chemical purity for use in radiopharmaceutical applications, such as diagnostic imaging and therapeutic use in nuclear medicine.

[0002] Radionuclides primarily used worldwide in diagnostic imaging procedures in the fields of oncology, neurology, and cardiology are currently produced by medical cyclotron accelerators and nuclear reactors. In cyclotron production, a target coin (or simply "target coin") bearing a target metal is bombarded with subatomic particles, thereby converting the target metal into the desired radionuclide via a nuclear reaction. The increasing number of cyclotrons of different energies installed worldwide has had a profound impact on the production of traditional and emerging radionuclides for medical applications (see, e.g., Synowiecki MA, et al. Production of Novel Diagnostic Radionuclides in Small Medical Cyclotrons. EJNMMI Radiopharm. Chem. 2018;3:1-25).

[0003] In particular, a major advantage of using medical cyclotrons is the possibility to produce desired medical radionuclides on-site and on-demand. Technological advances in cyclotron-based production have recently encouraged the use of novel radionuclides (mainly radiometals) in medical applications to implement so-called personalized medicine approaches. In particular, the strength of this approach relies on the possibility of selecting patients who will respond positively to targeted treatment by performing preliminary imaging with the same radiopharmaceutical using various radionuclides (therapeutic approach) (Boschi A., Martini P., Costa V., Pagnoni A., Uccelli L. Interdisciplinary Tasks in the Cyclotron Production of Radiometals for Medical Applications. The Case of 47Sc as Example. Molecules. 2019;24:444; Srivastava SCA Bridge Not Too Far: Personalized Medicine with the Use of Theragnostic Radiopharmaceuticals. J. Postgrad. Med. Educ. Res. 2013;47:31-46; Qaim SM Medical Radionuclide Production. De Gruyter; Berlin, Germany: 2019).

[0004] The availability of novel, radioactive, and highly pure medical radionuclides is essential for the development of personalized nuclear medicine. A variety of copper radionuclides are used in nuclear medicine, offering versatile options for radionuclide imaging (e.g., radiotracers) and therapy.

[0005] 60 Cu, 61 Cu, 62 Cu, 64 Cu and 67 Copper radionuclides, including Cu, offer a versatile option for applications in imaging and therapy.60 Cu(t 1 / 2 =23.4 minutes), 61 Cu(t 1 / 2 =3.32h) and 62 Cu(t 1 / 2 = 9.76 min) is the electron capture and β + It decays by emission to form Cu-pyruvaldehyde bis(N 4 It has been used to prepare contrast agents such as Cu-methyl thiosemicarbazone (PTSM) and Cu-ethylglyoxal bis(thiosemicarbazone) ETS. 67 Cu(t 1 / 2 =62.01h) is β - It decays exclusively upon release and has been used to label monoclonal antibodies and antibody fragments for radioimmunotherapy. 64 Cu has an intermediate half-life of 12.7 h and a characteristic decay lifetime profile (β + :18%, β - : 38% and electron capture: 44%, making it useful for radiolabeling nanoparticles, antibodies, antibody fragments, peptides, and small molecules for Positron Emission Tomography (PET) imaging and radionuclide therapy. 64 Cu radiopharmaceuticals are 64 Cu or its β-emitting isotope substitute 67 Quantitative PET imaging can be used to calculate radiation dosimetry before targeted radiotherapy with Cu. 64 Cu has been incorporated into many labeled bioconjugates based on antibodies, peptides and small molecules that target specific receptors or antigens, especially in oncology applications.

[0006] Relatively recently, 61 Cu(t1 / 2=3.33h, 61%β + , Emax=1.216MeV) is 60 Cu and 62Due to its longer half-life (3.33 h) compared to Cu, it is considered a good choice for imaging at later time points in processes with slower kinetics and for achieving higher tumor-to-background signal ratios in the detection of small metastases. 61 Cu is 68 Copper-60 and copper-61 are positron-emitting radionuclides that exhibit decay characteristics comparable to Ga, but with the advantage of lower maximum positron energy (Emax = 1.216 MeV vs. Emax = 1.899 MeV) and a substantially more practical half-life (3.33 h vs. 68 min). (McCarthy, D.W. et al. High-purity production and potential applications of copper-60 and copper-61. Nucl. Med. Biol. 1999, 26, 351-358). The intermediate half-life and favorable decay characteristics allow for better image quality and potentially lower radiation doses to the patient.

[0007] The cost and complexity of producing high-quality Cu radioisotopes in quantities sufficient for medical applications present a major challenge to their wider adoption as radiopharmaceuticals. Ensuring the availability of suitable target materials is essential to providing high-quality cyclotron-produced radioisotopes in the quantities needed for medical purposes.

[0008] High apparent molar activity is often required when using Cu radionuclides to generate radiopharmaceuticals, e.g., radiolabeled bioconjugates using bifunctional chelators. To this end, contamination of radiopharmaceutical compositions with non-radioactive trace metals (i.e., "cold metals") must be reduced. For example, the presence of non-radioactive carrier copper must be reduced because it competes with the desired radionuclide for chelation, thereby inhibiting radiolabeling, reducing yield, and, for example, reducing the apparent molar activity of the radiopharmaceutical. Another concern is that metal targets used to prepare radionuclides (e.g., enriched Ni to make radioactive copper) often contain other trace metal impurities, including iron and zinc. Metal contaminants in radiopharmaceutical compositions also arise from solutions and equipment used in various manufacturing processes. Radionuclide impurities must also be reduced. One source of such impurities, for example, comes from isotopically enriched Ni targets, which often contain nickel isotopic impurities that can give rise to undesirable Cu isotopic impurities upon bombardment.

[0009] Therefore, when preparing radionuclides for radiopharmaceutical use, there is a need to reduce both radiochemical and radionuclide contaminants that adversely affect the labeling and apparent molar activity of the final radiopharmaceutical. Summary of the Invention

[0010] The present disclosure, among other things, reduces the amount of expensive isotopically enriched Ni target metal, resulting in more cost-effective production of radioactive copper, and reduces the amount of radionuclide impurities, especially 60 Co), non-radioactive Cu and other trace metal contaminants, and increase the radiochemical purity, radionuclide purity, chemical purity and apparent molar activity of the resulting radionuclide compositions, which are suitable for use in medical applications, such as the production of radioactive tracers for medical imaging and cancer treatment. 6x This paper describes the construction and evaluation of a Cu) generation system.

[0011] A first aspect of the present disclosure provides a novel target material for bombardment by subatomic particles, for example for use in producing radionuclides on a medical cyclotron, the target material including a backing composed of Nb having a purity of at least 98.8%. In certain embodiments, various impurities in the Nb backing are limited to, for example, 40 ppm or less Fe, 60 ppm or less Ti, 19 ppm or less Zn, 5 ppm or less Cu, 8 ppm or less Sn, 5 ppm or less Ni, and 5 ppm or less Al. In further embodiments, the backing has a backing surface that is free or substantially free of oxides, particularly metal oxides.

[0012] A second aspect of the present disclosure provides a target material as described in the first aspect of the present disclosure above, which also includes an electroplated coating of a target metal adhered to a backing surface. In certain embodiments, certain impurities in the target are limited to, for example, 0.0005 ppm Cd or less, 0.005 ppm Co or less, 0.005 ppm Pb or less, 0.08 ppm Cu or less, and 0.15 ppm Fe or less.

[0013] In certain embodiments, the target metal is Ni or Zn at its naturally occurring isotopic abundance ("native" Ni or Zn), or enriched to various levels of isotopic abundance.

[0014] A third aspect of the present disclosure is a method for preparing a target material comprising an electroplated target metal adhered to a backing surface, the backing comprising a corrosion-resistant material, the method comprising electroplating the target metal onto the backing surface from a plating solution, the plating solution having a pH of 9.5 to 10.7. In certain embodiments, the backing comprises Nb, Ag, Pt, Au, Al, or W, and more particularly Nb.

[0015] A fourth aspect of the present disclosure provides a method for preparing a target material as described above in the second aspect of the present disclosure, the method comprising electroplating a target metal from a plating solution onto a backing surface to form a target coating. In certain embodiments, the pH of the plating solution is 9.5 to 10.7. In further embodiments, there is provided a target material prepared according to the methods provided herein.

[0016] In embodiments of the third and fourth aspects, the method further includes one or more of the following elements: polishing the backing surface prior to electroplating, wherein the plating solution includes nitrate ions, the electroplating occurs at a current of 120-300 μA, the electroplating occurs for 3 hours or less, the target metal starting source used to prepare the plating solution is at least 99.9% pure, preparing the plating solution includes ammonium ions, the electroplating occurs in an electrolytic cell with a stationary anode, and the plating solution is characterized by the reduction of certain impurities to certain threshold levels, such as 0.1 ppm or less Cu, 10 ppm or less Fe, 0.1 ppm or less Ga, Lu, Pb, Y, 0.3 ppm or less Co, 1 ppm or less Cd, Cr, Al, Mn, Mo, Sn, Ti, and V, and 1000 ppm or less Group 1 (alkali metals) and Group 2 (alkaline earth metals) elements.

[0017] A fifth aspect of the present disclosure provides a high purity radionuclide composition, the composition comprising a radionuclide and having a radionuclide purity of 95% or greater at the end of synthesis of the radionuclide (EoB+90 min), wherein the radionuclide is a Cu radionuclide, and / or the presence of certain radionuclide impurities is 0.1 Bq / g or less. 110m Ag, 0.1Bq / g or less 108m Ag and below 0.1Bq / g 109 In certain embodiments, the high purity radionuclide composition may be, for example, 61 In certain embodiments, the radionuclide is in the form of an aqueous chloride salt solution, such as [Cu]CuCl. 61 Cu,64 Cu or 68 and Ga. In certain embodiments, the high-purity radionuclide composition is characterized by a radionuclide chemical purity of 99.0% or greater. In further embodiments, certain chemical impurities are limited to certain amounts, such as 2 mg / L or less of Fe, stable Cu isotopes are 1 mg / L or less, 2 mg / L or less of Zn(II), 0.01 mg / L or less of Sn(IV), 0.01 mg / L or less of Ti(IV), 2 mg / L or less of Al(III), 1 mg / L or less of As, 1 mg / L or less of Ni, and any one of Cr, Cd, Co, and Y is 0.1 mg / mL or less. In certain embodiments, the high-purity radionuclide composition is characterized by one or more of a radioactivity concentration of 0.25-25 GBq at calibration (EoB + 8 hours), an apparent molar activity of 10-100 MBq at calibration, and a radioactivity of greater than 500 MBq at the end of synthesis (EoB + 90 minutes).

[0018] In a sixth aspect of the present disclosure, there is provided a method of making a high purity radionuclide composition as described in the fifth aspect of the present disclosure above, the method comprising irradiating a target metal of a target material as described in the second aspect of the present disclosure above in a particle accelerator to produce irradiated target material, and isolating the high purity radionuclide composition. In certain embodiments, the method comprises the following elements: purifying a chloride radionuclide solution to reduce chemical impurities, and the irradiation time is at most two half-lives long of the radionuclide, such as one half-life.

[0019] In certain embodiments of the sixth aspect, the target metal is natural Ni, 60 Ni, 61 Ni, and the radionuclide of the high purity radionuclide composition is reacted with the following reaction: nat Ni(d,n) 61 Cu and 60 Ni(d,n) 61 Cu 61 In certain embodiments, the target metal is 61 Ni, a radionuclide, undergoes the following reaction: 61 Ni(p,n)61 Generated according to Cu 61 In certain embodiments, the target metal is: 64 Zn, a radionuclide, undergoes the following reaction: 64 Zn(p,α) 61 Generated according to Cu 61 In certain embodiments, the target metal is: 60 Ni, a radionuclide, undergoes the following reaction: 60 Ni(p,n) 60 Generated according to Cu 60 In certain embodiments, the target metal is: 62 Ni, a radionuclide, undergoes the following reaction: 62 Ni(p,n) 62 Generated according to Cu 62 In certain embodiments, the target metal is: 64 Ni, a radionuclide, undergoes the following reaction: 64 Ni(p,n) 64 Generated according to Cu 64 In certain embodiments, the target metal is: 68 Zn, a radionuclide, undergoes the following reaction: 68 Zn(p,αn) 64 Generated according to Cu 64 Cu. In further embodiments, the target metal is naturally occurring or at least 95%, at least 97%, or at least 99% enriched in the identified isotope. [Brief explanation of the drawings]

[0020] These and other features, aspects, and advantages of the present disclosure will become better understood with regard to the following description, appended claims, and accompanying drawings.

[0021] [Figure 1] Panels A-C show the improved surface porosity and pore distribution uniformity produced by electrodeposition at increasing pH: pH 9.3 (Panel A), pH 10.0 (Panel B), and pH 10.2 (Panel C).

[0022] [Figure 2] Panels A-C show, at increasing magnification, a homogenous nickel coating with durable adhesion to the niobium target material upon completion of electroplating, as assessed using a DINOLite digital microscope: Panel A at 20x magnification, Panel B at 50x magnification, and Panel C at 250x magnification.

[0023] [Figure 3] 1 shows a sample of target material provided in accordance with the present disclosure, with nickel deposited in the center of a niobium backing.

[0024] [Figure 4] Figure 1 shows an analysis of the 61Cu purity of a [61Cu]CuCl solution obtained by irradiation of natNi on a Nb backing with a deuterium beam at 8.4 MeV at 50 μA for 3 hours. The curve corresponds to the decrease in % purity of 61Cu over time, and the bars correspond to becquerels of radioactive cobalt over time.

[0025] [Figure 5] Figure 1 shows an analysis of the 61Cu purity of a [61Cu]CuCl solution obtained by irradiation of 60Ni on a Nb backing with a deuterium beam at 8.4 MeV at 50 μA for 3 hours. The curve corresponds to the decrease in % purity of 61Cu over time, and the bars correspond to becquerels of radioactive cobalt over time.

[0026] [Figure 6]The figures show the radioactivity concentrations of impurities detected in [61Cu]CuCl2 solutions produced according to various methods. The extracted target material (Ag, natNi) data was generated by irradiation of a commercially available natNi target on an Ag backing. The (Nb, natNi) and (Nb, Ni-61) data were generated based on irradiation of Ni targets (natural and isotopically enriched in 61Ni, respectively) electroplated according to the present disclosure on a high-purity Nb backing. The radioactivity concentrations were assessed by gamma spectrometry and reported in Bq / g. The data show that silver and cobalt isotopes are significantly depleted in [61Cu]CuCl2 solutions produced by irradiation of Ni targets electroplated according to the present disclosure on a high-purity Nb backing.

[0027] [Figure 7] The data show a significant reduction in the total radionuclide impurities present in [61Cu]CuCl2 solutions produced according to various methods. The extracted target material (Ag, natural Ni (natNi)) data was generated based on the irradiation of a commercially available natNi (natural Ni) target on an Ag backing. The (Nb, natural Ni (natNi)) and (Nb, Ni-61) data were generated based on the irradiation of Ni targets (natural and isotopically enriched in 61Ni, respectively) electroplated according to the present disclosure on a high-purity Nb backing. Radionuclide impurities were determined by gamma spectrometry and reported in Bq / g (total radionuclide impurities). The presented data particularly highlight the overall impurity reduction in [61Cu]CuCl2 solutions when produced according to the present disclosure.

[0028] [Figure 8]The data show the sustained high radionuclide purity of the [61Cu]CuCl2 solution produced in accordance with the present disclosure compared to a commercially available natNi (natural Ni) target on an Ag backing (extracted target material (Ag, natural Ni (natNi))). The (Nb, natural Ni (natNi)) and (Nb,Ni-61) target materials were prepared by electrodeposition in accordance with the present disclosure on a high-purity Nb backing. Data were generated using gamma spectrometry and reported in Bq / g, providing the combined radionuclide purity at t=0 h and t=12 h. The presented data highlight the superior quality of the [61Cu]CuCl2 solution when produced by irradiation of a Ni target electroplated in accordance with the present disclosure on a high-purity Nb backing, where the purity after 12 h is still well above the purity limit set by the Pharmacopoeia for similar radionuclides for medical applications.

[0029] [Figure 9] 1 shows the chemical impurities of [61Cu]CuCl2 solution as measured by ICP-MS when produced by natNi (native Ni) vs. 61Ni collisions when produced by irradiation of a Ni target electroplated according to the present disclosure onto a high purity Nb backing. DETAILED DESCRIPTION OF THE INVENTION

[0030] 4.1 Target Coin One aspect of the present disclosure is the provision of novel target materials comprising metal targets for bombardment by subatomic particles to produce radionuclide compositions. In certain embodiments, the provided target materials are specifically designed for use in low-energy biomedical cyclotrons. In certain embodiments, the provided target materials are designed for use in biomedical cyclotrons.

[0031] 4.1.1. Backing In certain embodiments, the target material of the present disclosure includes a backing. The backing has a mass and, in certain embodiments, at least one backing surface onto which the target metal is deposited. As used herein, the term "backing surface" refers to one side of the backing that is or will be in contact with the target metal. In certain embodiments, the target metal is adhered to the backing, for example, by electrodeposition. To describe this another way, the target metal may be adhered to the backing in the form of, for example, an electroplated coating or layer, but this material will be referred to herein simply as the "target" or "target metal." After the target metal is adhered to the backing, the target material is obtained.

[0032] In certain embodiments of the present disclosure, the backing comprises a chemically inert material such as Nb, Ag, Pt, Au, Al, or W, particularly Nb. In certain embodiments of the present disclosure, the backing consists of a chemically inert material such as Nb, Ag, Pt, Au, Al, or W, particularly Nb.

[0033] In certain embodiments, the backing is a Nb or Ag backing. In certain embodiments, the backing is an Ag backing. In certain embodiments, the backing is a Nb backing. In certain embodiments, the backing is a Pt backing. In certain embodiments, the backing is an Au backing. In certain embodiments, the backing is an Al backing. In certain embodiments, the backing is a W backing.

[0034] In certain embodiments, the backing is not an Ag backing. In certain embodiments, the backing is not a Pt backing. In certain embodiments, the backing is not an Au backing. In certain embodiments, the backing is not an Al backing. In certain embodiments, the backing is not a W backing.

[0035] In certain embodiments, the backing does not include Ag. In certain embodiments, the backing does not include Pt. In certain embodiments, the backing does not include Au. In certain embodiments, the backing does not include Al. In certain embodiments, the backing does not include W.

[0036] 4.1.1.1 High purity Nb In certain embodiments of the present disclosure, the backing is a high-purity Nb backing. In certain embodiments, the purity of Nb is 98.8% or more. In certain embodiments, the purity of Nb is 99.8% or more. In certain embodiments, the purity of Nb is 99 to 99.9%. In certain embodiments, the purity of Nb is 99 to 99.99%. In certain embodiments, the purity of Nb is 99 to 99.999% or more.

[0037] In certain embodiments, the purity of the Nb backing is 98.850% or greater, 98.900% or greater, 98.950% or greater, 990% or greater, 99.050% or greater, 99.100% or greater, 99.150% or greater, 99.200% or greater, 99.250% or greater, 99.300% or greater, 99.350% or greater, 99.400% or greater, 99.450% or greater, 99.500% or greater, 99.510% or greater, 99.520% or greater, 99.530% or greater, 99.540% or greater, 99.550% or greater, 99.560% or greater, 99.570% or greater, 99.580% or greater, 99.590% or greater Above, 99.600% or more, 99.610% or more, 99.620% or more, 99.630% or more, 99.640% or more, 99.650% or more, 99.660% or more, 99.670% or more, 99.680% or more, 99.690% or more, 99.700% or more, 99.710% or more, 99.720% or more, 99.730% or more, 99.740% or more, 99.750% or more, 99.760% or more, 99.770% or more, 99.780% or more, 99.790% or more, 99.800% or more, 99.810% or more, 99.820% or more, 99.830% or more, 99.840% or higher, 99.850% or higher, 99.853% or higher, 99.856% or higher, 99.859% or higher, 99.862% or higher, 99.865% or higher, 99.868% or higher, 99.871% or higher, 99.874% or higher, 99.877% or higher, 99.880% or higher, 99.883% or higher, 99.886% or higher, 99.889% or higher, 99.892% or higher, 99.895% or higher, 99.898% or higher, 99.901% or higher, 99.904% or higher, 99.907% or higher, 99.910% or higher, 99.913% or higher, 99.916% or higher, 99.919% or higher, 99.92 2% or more, 99.925% or more, 99.928% or more, 99.931% or more, 99.934% or more, 99.937% or more, 99.940% or more, 99.943% or more, 99.946% or more, 99.949% or more, 99.952% or more, 99.955% or more, 99.958% or more, 99.961% or more, 99.964% or more, 99.967% or more, 99.970% or more, 99.973% or more, 99.976% or more, 99.979% or more, 99.982% or more, 99.985% or more, 99.988% or more, 99.991% or more, 99.994% or more or 99.997% or greater. In a specific embodiment, the purity of the Nb backing is 99.810%.

[0038] In certain embodiments, the Nb backing is characterized by limiting the amount of certain impurities as described below.

[0039] In certain embodiments of Nb backings, the amount of Fe in the backing is 30 ppm or less. In certain embodiments, the amount of Fe in the backing is 27 ppm or less, 28 ppm or less, 29 ppm or less, 30 ppm or less, 31 ppm or less, 32 ppm or less, 33 ppm or less, 34 ppm or less, 35 ppm or less, 36 ppm or less, 37 ppm or less, 38 ppm or less, 39 ppm or less, 40 ppm or less, 41 ppm or less, 42 ppm or less, 43 ppm or less, 44 ppm or less, 45 ppm or less, 46 ppm or less, 47 ppm or less, 48 ​​ppm or less, 49 ppm or less, or 50 ppm or less.

[0040] In certain embodiments of Nb backings, the amount of Ti in the backing is 60 ppm or less, for example, 10 ppm or less of Ti. In certain embodiments, the amount of Ti in the backing is 5 ppm or less, 6 ppm or less, 7 ppm or less, 8 ppm or less, 9 ppm or less, 10 ppm or less, 11 ppm or less, 12 ppm or less, 13 ppm or less, 14 ppm or less, 15 ppm or less, 16 ppm or less, 17 ppm or less, 18 ppm or less, 19 ppm or less, 20 ppm or less, 21 ppm or less, 22 ppm or less, 23 ppm or less, 24 ppm or less, 25 ppm or less, 26 ppm or less, 27 ppm or less, 28 ppm or less, 29 ppm or less, 30 ppm or less, 31 ppm or less, 32 ppm or less, 33 ppm or less, 34 ppm or less, 35 ppm or less, 36 ppm or less, 37 ppm or less, 38 ppm or less, 39 ppm or less, 40 ppm or less, 41 ppm or less, 42 ppm or less, 43 ppm or less, 44 ppm or less, 45 ppm or less, 46 ppm or less, 47 ppm or less, 48 ​​ppm or less, 49 ppm or less, 50 ppm or less, 51 ppm or less, 52 ppm or less, 53 ppm or less, 54 ppm or less, 55 ppm or less, 56 ppm or less, 57 ppm or less, 58 ppm or less, 59 ppm or less, 60 ppm or less, 61 ppm or less, 62 ppm or less, 63 ppm or less, 64 ppm or less, 65 ppm or less, 66 ppm or less, 67 ppm or less, 68 ppm or less, 69 ppm or less, 70 ppm or less, 71 9 ppm or less, 40 ppm or less, 41 ppm or less, 42 ppm or less, 43 ppm or less, 44 ppm or less, 45 ppm or less, 46 ppm or less, 47 ppm or less, 48 ​​ppm or less, 49 ppm or less, 50 ppm or less, 51 ppm or less, 52 ppm or less, 53 ppm or less, 54 ppm or less, 55 ppm or less, 56 ppm or less, 57 ppm or less, 58 ppm or less, 59 ppm or less, 60 ppm or less, 61 ppm or less, 62 ppm or less, 63 ppm or less, 64 ppm or less, 65 ppm or less, 66 ppm or less, 67 ppm or less, 68 ppm or less, 69 ppm or less, 70 ppm or less, 71 ppm or less, 72 ppm or less, 73 ppm or less, or 74 ppm or less.

[0041] In certain embodiments of Nb backings, the amount of Zn in the backing is 19 ppm or less, for example 10 ppm or less of Zn. In certain embodiments, the amount of Fe in the backing is 5 ppm or less, 6 ppm or less, 7 ppm or less, 8 ppm or less, 9 ppm or less, 10 ppm or less, 11 ppm or less, 12 ppm or less, 13 ppm or less, 14 ppm or less, 15 ppm or less, 16 ppm or less, 17 ppm or less, 18 ppm or less, 19 ppm or less, 20 ppm or less, 21 ppm or less, 22 ppm or less, 23 ppm or less, 24 ppm or less, 25 ppm or less, 26 ppm or less, 27 ppm or less, 28 ppm or less, 29 ppm or less, or 30 ppm or less.

[0042] In certain embodiments of Nb backings, the amount of Cu in the backing is 5 ppm or less, for example 3 ppm or less of Cu. In certain embodiments, the amount of Cu in the backing is 0.5 ppm or less, 1 ppm or less, 1.5 ppm or less, 2 ppm or less, 2.5 ppm or less, 3 ppm or less, 3.5 ppm or less, 4 ppm or less, 4.5 ppm or less, 5 ppm or less, 5.5 ppm or less, 6 ppm or less, 6.5 ppm or less, 7 ppm or less, 7.5 ppm or less, or 8 ppm or less.

[0043] In certain embodiments of Nb backings, the amount of Sn in the backing is 5 ppm or less, or 0.5 ppm or less, 1 ppm or less, 1.5 ppm or less, 2 ppm or less, 2.5 ppm or less, 3 ppm or less, 3.5 ppm or less, 4 ppm or less, 4.5 ppm or less, 5 ppm or less, 5.5 ppm or less, 6 ppm or less, 6.5 ppm or less, 7 ppm or less, 7.5 ppm or less, 8 ppm or less, 8.5 ppm or less, 9 ppm or less, 9.5 ppm or less, 10 ppm or less, 10.5 ppm or less, 11 ppm or less, 11.5 ppm or less, 12 ppm or less, 12.5 ppm or less, or 13 ppm or less.

[0044] In certain embodiments of Nb backings, the amount of Ni in the backing is 5 ppm or less, for example, less than 1 ppm Ni. In certain embodiments, the amount of Ni in the backing is 0.2 ppm or less, 0.4 ppm or less, 0.6 ppm or less, 0.8 ppm or less, 1 ppm or less, 1.2 ppm or less, 1.4 ppm or less, 1.6 ppm or less, 1.8 ppm or less, 2 ppm or less, 2.5 ppm or less, 3 ppm or less, 3.5 ppm or less, 4 ppm or less, 4.5 ppm or less, 5 ppm or less, 5.5 ppm or less, 6 ppm or less, 6.5 ppm or less, 7 ppm or less, 7.5 ppm or less, or 8 ppm or less.

[0045] In certain embodiments of Nb backings, the amount of Al in the backing is 5 ppm or less, or 0.2 ppm or less, 0.4 ppm or less, 0.6 ppm or less, 0.8 ppm or less, 1 ppm or less, 1.2 ppm or less, 1.4 ppm or less, 1.6 ppm or less, 1.8 ppm or less, 2 ppm or less, 2.5 ppm or less, 3 ppm or less, 3.5 ppm or less, 4 ppm or less, 4.5 ppm or less, 5 ppm or less, 5.5 ppm or less, 6 ppm or less, 6.5 ppm or less, 7 ppm or less, 7.5 ppm or less, 8 ppm or less, 8.5 ppm or less, 9 ppm or less, 9.5 ppm or less, or 10 ppm or less.

[0046] In certain embodiments of a Nb backing, the amount of Fe in the backing is 50 ppm or less (e.g., 30 ppm or less), the amount of Ti in the backing is 60 ppm or less (e.g., 10 ppm or less), the amount of Zn in the backing is 19 ppm or less (e.g., 10 ppm or less), the amount of Cu in the backing is 5 ppm or less (e.g., 3 ppm or less), the amount of Sn in the backing is 13 ppm or less (e.g., 5 ppm or less), the amount of Ni in the backing is 5 ppm or less (e.g., less than 1 ppm), and / or the amount of Al in the backing is 5 ppm or less (e.g., 1 ppm), or any combination of the above.

[0047] In certain embodiments, the Nb backing is 99.8% pure and contains up to 24 ppm C, up to 1 ppm H, up to 2 ppm Mo, up to 4 ppm Ni, up to 1 ppm Si, up to 2 ppm Ti, up to 3 ppm Zr, up to 1 ppm Fe, up to 2 ppm Hf, up to 14 ppm N, up to 56 ppm O, up to 785 ppm Ta, and up to 4 ppm W. In certain embodiments, the Nb backing is 99.9% pure and contains up to 10 ppm B, up to 5 ppm Ni, up to 100 ppm O, up to 100 ppm Si, up to 10 ppm Zr, up to 500 ppm Ta, up to 10 ppm H, up to 100 ppm W, up to 25 ppm C, up to 20 ppm Ni, up to 30 ppm Fe, up to 5 ppm Cu, up to 10 ppm Mo, and up to 10 ppm Ti.

[0048] 4.1.1.2 Backing dimensions The backings described herein may be any two-dimensional shape with any thickness suitable for their intended use, without limitation. In certain embodiments, the backing is a circle, an oval, or a geometric shape having 3 to 10 sides, for example, a quadrilateral such as a rectangle, square, trapezoid, or parallelogram, a triangle, a composite of multiple geometric shapes, or a natural shape with irregular sides.

[0049] In certain embodiments, the backing has a circular cross-section (i.e., a disk shape). In further such embodiments, the backing has a diameter of 35 to 15 mm, e.g., 28 mm or 22 mm. Unless otherwise specified, the tolerance on the diameter is ±0.1 mm.

[0050] In certain embodiments, the backing has a thickness of 0.50 to 3 mm or 1 to 2 mm. In certain embodiments, the backing has a thickness of 0.75 to 2.25 mm, 0.88 to 2.13 mm, 1 to 2 mm, 1.13 to 1.88 mm, 1.25 to 1.75 mm, or 1.38 to 1.63 mm. In certain embodiments, the backing has a thickness of 0.5 mm, 0.63 mm, 0.75 mm, 0.88 mm, 1 mm, 1.13 mm, 1.25 mm, 1.38 mm, 1.5 mm, 1.63 mm, 1.75 mm, 1.88 mm, 2 mm, 2.13 mm, 2.25 mm, 2.38 mm, 2.5 mm, 2.63 mm, 2.75 mm, 2.88 mm, or 3 mm.

[0051] In certain embodiments, the backing has a thickness of 1 mm to 2.5 mm, hi certain embodiments, the backing has a thickness of 1.5 mm.

[0052] Unless otherwise stated, the tolerance on backing thickness values ​​reported herein is ±0.05 mm.

[0053] In certain embodiments, the backing includes a central disc-shaped groove. In further embodiments, the disc-shaped groove has a diameter of 10 mm and a depth of about 0.6 mm.

[0054] In certain embodiments, the surface of the backing material has a roughness (Ra) of 1.6 μm (micrometers). In certain embodiments, the surface of the backing material has an Ra of 1.5 μm. In certain embodiments, the surface of the backing material has an Ra of 1.4 μm. In certain embodiments, the surface of the backing material has an Ra of 1.3 μm. In certain embodiments, the surface of the backing material has an Ra of 1.2 μm. In certain embodiments, the surface of the backing material has an Ra of 1.1 μm. In certain embodiments, the surface of the backing material has an Ra of 1 μm. In certain embodiments, the surface of the backing material has an Ra of 0.9 μm. In certain embodiments, the surface of the backing material has an Ra of 0.8 μm. In certain embodiments, the surface of the backing material has an Ra of 0.7 μm. In certain embodiments, the surface of the backing material has an Ra of 0.6 μm. In certain embodiments, the surface of the backing material has an Ra of 0.5 μm. In certain embodiments, the surface of the backing material has an Ra of 0.4 μm. In certain embodiments, the surface of the backing material has an Ra of 0.3 μm. In certain embodiments, the surface of the backing material has an Ra of 0.2 μm. In certain embodiments, the surface of the backing material has an Ra of 0.1 μm.

[0055] Variations in the dimensions of the backing provided herein without tolerance values ​​are in accordance with ISO 2768 1:1989 General tolerances - Part 1: Tolerances for linear and angular dimensions without individual tolerance designations.

[0056] 4.1.1.3 Backing Surface In certain embodiments, the backing, particularly the backing surface to which the target metal adheres, is free of oxides, as assessed, for example, by visual inspection. The presence of oxides is typically evident as discoloration that obscures the natural luster or color of the raw metal backing. In certain of these embodiments, any observed oxides are removed, for example, by polishing. Without being bound by theory, treatment of the backing surface using a polishing method can further improve the purity of the radionuclide product and / or ensure sufficient adhesion of the target coating, thereby ensuring the integrity of the target metal during target material movement and particle bombardment.

[0057] In certain embodiments, the backing comprises Nb, and the backing surface is free or substantially free of oxides, particularly metal oxides. In certain embodiments, the Nb backing is new or unused, e.g., manufactured and stored to avoid exposure to oxidizing physical conditions. In certain embodiments, the backing is rolled from a metal foil having a thickness greater than the desired backing thickness, thereby imparting surface roughness.

[0058] In certain embodiments, the Nb backing surface is somewhat oxidized, as observed, for example, by the presence of a natural sheen or color discoloration on the raw metal surface. In related embodiments, the oxidation is removed by physical abrasion, for example, as described herein.

[0059] 4.1.2. Target Metal In certain embodiments, the target metal is a material that can be irradiated (e.g., bombarded with protons or deuterium) to thereby produce the radionuclide compositions of the present disclosure. In certain embodiments, the impurities in the target metal are limited to certain levels described herein.

[0060] In certain embodiments, the target metal is electrodeposited, pressed, sintered, press-bonded, melted, or physically deposited (by vapor or atomic deposition) onto a backing that acts as a stable support during the irradiation process. In certain embodiments, the target metal is in the form of a foil. In certain embodiments, the foil is a sheet or roll.

[0061] In certain embodiments, the electrodeposited target metal forms a target coating. In certain embodiments, the target coating covers only a portion of the backing surface, e.g., the center of the backing surface, but not the entire perimeter of the backing surface. In certain embodiments, the target coating is prepared by electroplating the target metal from a plating solution, e.g., as described herein. In certain embodiments, the target coating is prepared by electroplating the target metal from a plating solution onto the backing surface.

[0062] In certain embodiments, the deposited target is a smooth, homogeneous deposit with no observable cracks or craters and a uniform thickness (with less than 25%, 20%, 15%, 12%, 10%, or 5% variation, particularly less than 15% variation).

[0063] In certain embodiments, the maximum thickness of the target coating is 0.07 mm, 0.075 mm, 0.08 mm, 0.085 mm, 0.09 mm, 0.095 mm, 0.1 mm, 0.105 mm, 0.11 mm, 0.115 mm, 0.12 mm, 0.125 mm, 0.13 mm, or 0.135 mm. In certain embodiments, the maximum thickness of the target coating is 0.1 mm.

[0064] In certain embodiments, the minimum thickness of the target coating is 0.1 mm, 0.105 mm, 0.11 mm, 0.115 mm, 0.12 mm, 0.125 mm, 0.13 mm, 0.135 mm, 0.14 mm, 0.145 mm, 0.15 mm, 0.155 mm, 0.160 mm, 0.165 mm, 0.17 mm, 0.175 mm, or 0.18 mm. In certain embodiments, the minimum thickness of the target coating is 0.14 mm.

[0065] Unless otherwise specified, the tolerance on thickness measurements is ±0.005 mm.

[0066] In certain embodiments, the amount of target metal deposited on the backing is 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 55 mg, 60 mg, 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, 90 mg, 95 mg, 100 mg, 105 mg, 110 mg, 115 mg, 120 mg, 125 mg, 130 mg, 135 mg, 140 mg, 145 mg, 150 mg, 155 mg, 160 mg, 165 mg, 170 mg, 175 mg, 180 mg, 185 mg, 190 mg, 195 mg, 200 mg, 205 mg, 210 mg, 215 mg, 220 mg, 225 mg, 230 mg, 235 mg, or 240 mg.

[0067] In certain embodiments, the amount of target metal deposited on the backing is 20 mg, 21 mg, 22 mg, 23 mg, 24 mg, 25 mg, 26 mg, 27 mg, 28 mg, 29 mg, 30 mg, 31 mg, 32 mg, 33 mg, 34 mg, 35 mg, 36 mg, 37 mg, 38 mg, 39 mg, 40 mg, 41 mg, 42 mg, 43 mg, 44 mg, 45 mg, 46 mg, 47 mg g, 48mg, 49mg, 50mg, 51mg, 52mg, 53mg, 54mg, 55mg, 56mg, 57mg, 58mg, 59mg, 60mg, 61mg, 62mg, 63mg, 64mg, 65mg, 66mg, 67mg, 68mg, 69mg, 70mg, 71mg, 72mg, 73mg, 74mg, 75mg, 76mg, 77mg, 78mg, 79mg or 80mg.

[0068] Unless otherwise indicated, the tolerance for mass measurements is ±0.5 mg.

[0069] 4.1.2.1.1 Nickel In certain embodiments, the target metal is Ni. In certain embodiments, the target metal is natural Ni. Naturally occurring nickel is composed of five stable isotopes. 58 Ni is the most abundant isotope (68.077% natural abundance). The four less abundant (i.e., least abundant) stable isotopes and their corresponding natural abundances are: 60 Ni (26.223%), 61 Ni (1.140%), 62 Ni (3.635%) and 64 Ni (0.926%).

[0070] In certain embodiments, the target metal is Ni, and the natural abundance of the minor isotopes in Ni is 、60 Ni, 61 Ni, 62 Ni and 64 It is isotopically enriched in selected minor isotopes of Ni.

[0071] In a particular embodiment, the target metal is Ni that is isotopically enriched in the minority isotope to 95% or more.

[0072] In certain embodiments, the target metal is 95% to 99.99% 60 In certain embodiments, the target metal is enriched in Ni from 96% to 99.99%. 60 In certain embodiments, the target metal is enriched in Ni by 97% to 99.99%. 60 In certain embodiments, the target metal is enriched in Ni by 98% to 99.99%. 60 In certain embodiments, the target metal is enriched in Ni by 99% to 99.99%. 60 It is Ni that is concentrated in Ni.

[0073] In certain embodiments, the target metal is 95% to 99.99% 61 In certain embodiments, the target metal is enriched in Ni by 95% to 99.99%. 61 In certain embodiments, the target metal is enriched in Ni from 96% to 99.99%. 61 In certain embodiments, the target metal is enriched in Ni by 97% to 99.99%. 61 In certain embodiments, the target metal is enriched in Ni by 98% to 99.99%. 61 In certain embodiments, the target metal is enriched in Ni by 99% to 99.99%. 61 It is Ni that is concentrated in Ni.

[0074] In certain embodiments, the target metal is 95% to 99.99% 62 In certain embodiments, the target metal is enriched in Ni from 96% to 99.99%. 62 In certain embodiments, the target metal is enriched in Ni by 97% to 99.99%. 62 In certain embodiments, the target metal is enriched in Ni by 98% to 99.99%. 62 In certain embodiments, the target metal is enriched in Ni by 99% to 99.99%. 62 It is Ni that is concentrated in Ni.

[0075] In certain embodiments, the target metal is 95% to 99.99% 64 In certain embodiments, the target metal is enriched in Ni from 96% to 99.99%. 64 In certain embodiments, the target metal is enriched in Ni by 97% to 99.99%. 64 In certain embodiments, the target metal is enriched in Ni by 98% to 99.99%. 64In certain embodiments, the target metal is enriched in Ni by 99% to 99.99%. 64 In certain embodiments, the target metal is enriched in Ni. 64 In certain embodiments, the target metal is enriched in Ni. 64 In certain embodiments, the target metal is enriched in Ni by up to 97%. 64 In certain embodiments, the target metal is enriched in Ni. 64 In certain embodiments, the target metal is enriched in Ni. 64 It is Ni that is concentrated in Ni.

[0076] In certain embodiments, the target metal is Ni that is isotopically enriched in the minority isotope to 97% or more. 60 In certain embodiments, the target metal is enriched in Ni by 98% to 99.99%. 60 In certain embodiments, the target metal is enriched in Ni by 99% to 99.99%. 60 In certain embodiments, the target metal is enriched in Ni by 97% to 99.99%. 61 In certain embodiments, the target metal is enriched in Ni by 98% to 99.99%. 61 In certain embodiments, the target metal is enriched in Ni by 99% to 99.99%. 61 In certain embodiments, the target metal is enriched in Ni by 97% to 99.99%. 62 In certain embodiments, the target metal is enriched in Ni by 98% to 99.99%. 62 In certain embodiments, the target metal is enriched in Ni by 99% to 99.99%. 62In certain embodiments, the target metal is enriched in Ni by 97% to 99.99%. 64 In certain embodiments, the target metal is enriched in Ni by 98% to 99.99%. 64 In certain embodiments, the target metal is enriched in Ni by 99% to 99.99%. 64 In certain embodiments, the target metal is enriched in Ni by up to 97%±1%. 62 It is Ni that is concentrated in Ni.

[0077] In certain embodiments, the target metal is Ni that is isotopically enriched in the minority isotope by 99% or more. 60 In certain embodiments, the target metal is enriched in Ni by 99% to 99.99%. 61 In certain embodiments, the target metal is enriched in Ni by 99% to 99.99%. 62 In certain embodiments, the target metal is enriched in Ni by 99% to 99.99%. 64 In certain embodiments, the target metal is enriched in Ni by up to 99% ± 0.5%. 60 In certain embodiments, the target metal is enriched in Ni by up to 99% ± 0.5%. 61 It is Ni that is concentrated in Ni.

[0078] Unless otherwise stated, the tolerance associated with a given concentration value is ±0.1%.

[0079] 4.1.2.1.2 Zinc In certain embodiments, the target metal is Zn. In certain embodiments, the target metal is Zn. 68 It is isotopically enriched in Zn. Natural Zn is 64It is composed of five stable isotopes, with Zn being the most abundant isotope (49.17% natural abundance). In addition to these natural abundances, minor isotopes are 66 Zn (27.73%), 67 Zn (4.04%), 68 Zn (18.45%) and 70 Zn (0.61%).

[0080] In certain embodiments, the target metal is, for example, 95% or more, for example, 95% to 99.99%. 68 In certain embodiments, the target metal is Zn, and is isotopically enriched in Zn to 99% or greater. 68 It is isotopically enriched in Zn.

[0081] 4.1.2.2 Target Coating Purity In the disclosed aspects, the target coating, i.e., the material electrochemically deposited on the backing surface, is highly pure. In certain embodiments, nuclear bombardment of the proposed high-purity target coating provides a higher purity radionuclide composition than would be achieved if a lower-purity target coating were used. In certain embodiments, the target coating contains one or more of: 0.0005 ppm or less Cd, 0.005 ppm or less Co, 0.005 ppm or less Pb, 0.08 ppm or less Cu, and 0.15 ppm or less Fe.

[0082] In certain embodiments, the target metal is natural Ni having a chemical purity of 95% to 99.99%, such as 96% to 99.99%, 97% to 99.99%, 98% to 99.99%, or 99% to 99.99%.

[0083] In certain embodiments, the target metal is natural Ni having a chemical purity of 95% or greater, 96% or greater, 97% or greater, 98% or greater, or 99% or greater.

[0084] In certain embodiments, the target metal has a chemical purity of 95% to 99.99%, such as 96% to 99.99%, 97% to 99.99%, 98% to 99.99%, or 99% to 99.99%. 60 It's Ni.

[0085] In certain embodiments, the target metal has a chemical purity of 95% to 99.99%, such as 96% to 99.99%, 97% to 99.99%, 98% to 99.99%, or 99% to 99.99%. 61 It is Ni enriched in Ni.

[0086] In certain embodiments, the target metal has a chemical purity of 95% to 99.99%, such as 96% to 99.99%, 97% to 99.99%, 98% to 99.99%, or 99% to 99.99%. 62 It is Ni that is concentrated in Ni.

[0087] In certain embodiments, the target metal has a chemical purity of 95% to 99.99%, such as 96% to 99.99%, 97% to 99.99%, 98% to 99.99%, or 99% to 99.99%. 64 Ni is concentrated in Ni.

[0088] 4.1.3 Target Coating Dimensions The dimensions of the target coatings of the present disclosure are not particularly limited. The dimensions can be adjusted, for example, according to the intended use of the target material. In certain embodiments, the surface area, mass, and thickness of the target coating are selected to accommodate various types of irradiation processes. In certain embodiments, the surface area (e.g., based on the diameter of a circular target material), mass, and / or thickness of the target coating are selected to optimize the radioactivity yield and / or radionuclide purity of the generated radionuclide composition, for example, based on knowledge of the beam characteristics and reaction cross-section provided by a particular cyclotron.

[0089] 4.1.3.1 Target Coating Thickness In certain embodiments, the target coating has a thickness of 5 to 250 μm, e.g., 5 to 200 μm, 5 to 180 μm, 5 to 170 μm, 5 to 160 μm, 5 to 150 μm, 5 to 140 μm, 5 to 130 μm, 5 to 120 μm, 5 to 110 μm, 20 to 150 μm, 50 to 150 μm, 75 to 150 μm, 90 to 150 μm, 50 to 130 μm, or 70 to 100 μm.

[0090] In certain embodiments, the target coating has a thickness of 40-250 μm, e.g., 50-250 μm, 60-250 μm, 70-250 μm, 80-250 μm, 90-250 μm, 100-250 μm, 110-250 μm, 120-250 μm, 130-250 μm, 140-250 μm, 150-250 μm, 160-250 μm, 170-250 μm, 180-250 μm, 190-250 μm, 200-250 μm, 220-250 μm, 50- The thickness may be 220 μm, 50 to 200 μm, 50 to 180 μm, 50 to 160 μm, 50 to 150 μm, 50 to 140 μm, 50 to 130 μm, 50 to 120 μm, 50 to 110 μm, 50 to 100 μm, 50 to 90 μm, 50 to 80 μm, 50 to 70 μm, 100 μm, 125 μm, 150 μm, 175 μm, 200 μm, 225 μm or 250 μm.

[0091] 4.1.3.2 Target Coating Mass In certain embodiments, the target coating has a mass of 40 mg or more. In certain embodiments, the target coating has a mass of 45 mg or more. In certain embodiments, the target coating has a mass of 50 mg or more. In certain embodiments, the target coating has a mass of 60 mg or more. In certain embodiments, the target coating has a mass of 30-200 mg, 30-180 mg, 30-160 mg, 30-140 mg, 30-120 mg, 30-100 mg, 30-90 mg, 30-75 mg, 40-160 mg, 40-130 mg, 40-110 mg, 45-100 mg, 60-100 mg, or 70-90 mg. In certain embodiments, the target coating has a mass of 75-85 mg, 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, or 90 mg. Unless otherwise stated, the tolerance on the mass values ​​provided is ±3 mg.

[0092] In certain embodiments, electroplating is performed in an electrolytic cell with a fixed anode. In these embodiments, a thicker target coating metal deposition occurs in the center of the backing. This thicker target coating material occurs where the cyclotron beam is most intense, providing a larger effective surface area and volume for direct impingement. This, in turn, improves activation efficiency and substantially increases the dissolution rate of the irradiated target coating. In certain embodiments, the target coating has a variation in target coating thickness across the coating surface of less than about 25%, about 20%, about 15%, about 12%, about 10%, or about 5%. In certain embodiments, the variation is 15% or less. In certain embodiments, the variation is 10% or less. For example, in certain embodiments, the coating thickness is 15% greater in the center compared to the thickness at the edge of the coating.

[0093] In certain embodiments, the target coating is 5-30% thicker in the center compared to the average thickness of the surrounding coating, including, for example, 5%, 7%, 10%, or 12%-15%, 17%, 20%, 25% or 30% thicker, including 5-15%, 5-20%, 10-15%, 10-17%, 10-20%, 10-25%, 12-15%, 12-17%, 15-20% or 12-25%, and especially 10-15% thicker in the center compared to the average thickness of the surrounding coating.

[0094] In certain embodiments, the target coating is generally circular in shape and has a diameter of 3 cm or less, e.g., 2.5 cm to about 0.75 cm. In certain embodiments, 95% of the target coating mass is within a radius of 2.5 cm, 2.0 cm, 1.5 cm, 1.2 cm, or 1 cm. In certain embodiments, the radius may vary by 10%, 7%, 5%, 3%, 2%, or 1%.

[0095] 4.2 Target diameter In certain embodiments, the target coating is electrodeposited onto the surface of a circular backing having a diameter of 1 cm. In certain embodiments, the diameter is between 5 mm and 1 cm, e.g., between 5 mm and 500 mm, between 5 mm and 250 mm, between 5 mm and 100 mm, between 10 mm and 50 mm, between 10 mm and 25 mm, or between 8 mm and 15 mm. In certain embodiments, the target coating is circular and has a diameter of 10 mm or 13 mm ± 1 mm.

[0096] 4.2.1.1 Durability of target coating In certain embodiments, the target coating material remains intact on the surface of the target material after being transported to and from the cyclotron, such as by a pneumatic target material movement system. An advantage of the target material of the present invention is that the electroplated target coating is durable enough to remain adhered to the backing under the conditions of direct airflow and rapid mechanical motion experienced during target material movement.

[0097] In certain embodiments, the target coating remains adhered to the backing during pneumatic transfer to and from the cyclotron. Such pneumatic systems are typically supplied by a compressed air connection at 6-7 bar and a minimum of 360 SLPM flow. Such systems are "push-push," so compressed air is typically blown onto both the front and back sides of the target material, depending on the direction of transfer. In certain embodiments, the target coating remains adhered to the backing even after the target material suddenly stops once it reaches the target station or hot cell.

[0098] In certain embodiments, suitable tests to indicate the durability of the target coating include the following: visual inspection, gently tapping / dapping on a blank countertop to check for loosening of the target coating granules, gently rubbing an acid-cleaned Teflon® spatula against the deposited target coating to check for loosening of the target coating particles, and / or placing on a piece of Scotch® tape and gently pressing it against the target coating, whereby the total plating mass loss for all tests combined should be negligible (e.g., less than 2 w / w%).

[0099] If access to a cyclotron is available, it is recommended that the target material be moved back and forth multiple times to ensure stability of the target coating (i.e., no mass loss). Such testing may be performed with or without a degrader in place (e.g., a thin sheet of 500 μm Al with dimensions at least as large as or larger than the target coating).

[0100] 4.3 Target material preparation method In a further aspect of the present disclosure, a method is provided for preparing a target material comprising a target metal according to the present disclosure as described herein, the method including electroplating the dissolved target metal onto a backing surface from a plating solution, wherein the pH of the plating solution is between 9.5 and 10.7.

[0101] 4.3.1 Obtaining / preparing the backing In certain embodiments, the backing is composed of a corrosion-resistant material. In certain embodiments, the backing comprises Nb, Ag, Pt, Au, Al, or W. In certain embodiments, the backing comprises Nb or Ag. In certain embodiments, the backing consists of Nb.

[0102] In certain embodiments, the backing comprises high purity Nb as described herein, eg, for use in preparing high purity radionuclide compositions.

[0103] In further embodiments of these methods, the method further comprises polishing the backing surface. The method of polishing is not particularly limited and includes any type of mechanical polishing. In certain embodiments, the entire area of ​​the backing surface to be electroplated is polished to ensure adhesion of the target coating and / or to remove any oxides or tarnish that may inhibit electroplating. In certain embodiments, polishing is performed using an oscillating tumbler. In certain embodiments, polishing is performed using a corundum grinding wheel. In certain embodiments, polishing is performed using a grinding wheel with a grinding speed of about 650-550 mm. 2 This is done using a Bosh Impact 12 hand grinder (pink corundum abrasive grit, size 60) at 50 rpm for a period of approximately 45-60 seconds to cover a surface area of ​​1000 mm.

[0104] 4.3.2 Preparation of plating solution One aspect of the present disclosure is that by utilizing a basic solution in the plating solution, a higher anode-cathode potential can be achieved, shortening the plating time, for example, to less than 3 hours, compared to commercially available 24-hour plating. In addition, the presence of ammonia in the plating solution results in a reduced hydrogen generation rate, and the structure of the target metal coating, e.g., Ni or Zn plating layer, results in a more homogeneous and uniform crystalline structure or uniform micropores. Without being bound by any particular theory, this is believed to be due to the chemical properties of NH3 and the ability to accept hydrogen atoms and produce NH4 + This may be due to the tendency of the

[0105] In certain embodiments, 40-100 mg of target metal (e.g., nat Ni, 60 Ni or 61 A mass of Ni) is electroplated onto the backing surface used in a single impact session. In certain embodiments, a mass of 50-100 mg of target metal is electroplated onto the backing surface used in a single impact session, e.g. 61 Cu or 68 Ga, especially 61 Obtain the radioactive nuclide of Cu.

[0106] In one aspect of the present disclosure, a plating solution having a basic pH is provided. In certain embodiments, the pH of the plating solution is 9 to 11, e.g., 9.5 to 10.7 or 10 to 10.4. In certain embodiments, the pH of the plating solution is 9.5 to 10.7. In certain embodiments, the pH of the plating solution is 10 to 10.4. Unless otherwise indicated, the tolerance of any pH value of the plating solution is ±0.1.

[0107] In certain embodiments, preparing the plating solution includes dissolving a target metal starting material, such as a metal powder, in nitric acid.

[0108] In certain embodiments, electroplating the target metal is with a plating solution, and the plating solution includes nitrate ions. In certain embodiments, the plating solution includes or is prepared using an aqueous HNO solution. In certain embodiments, the plating solution does not include sulfate ions.

[0109] In certain embodiments, the method further comprises preparing a plating solution.

[0110] In certain embodiments, preparing the plating solution includes dissolving a target metal starting material. In certain embodiments, the plating solution is prepared by combining the target metal with a molar excess of HNO. In certain embodiments, the HNO is in the form of 65% nitric acid (aqueous) and is added to the plating solution in excess of 40 grams of HNO per gram of target metal (e.g., 40 g HNO:1 g Ni).

[0111] In certain embodiments, 20 to 200 mg of target metal (e.g., nat Ni, 60 Ni or 61 A mass of Ni) is dissolved in the plating solution. In certain embodiments, a mass of 50 to 100 mg of target metal is dissolved in the plating solution. In certain embodiments, the mass of target metal dissolved in the plating solution is 20 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 55 mg, 60 mg, 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, 90 mg, 95 mg, 100 mg, 105 mg, 110 mg, 115 mg, 120 mg, 125 mg, 130 mg, 135 mg, 140 mg, 145 mg, 150 mg, 155 mg, 160 mg, 165 mg, 170 mg, 175 mg, 180 mg, 185 mg, 190 mg, 195 mg, or 200 mg. In certain embodiments, a mass of 50 mg of target metal is dissolved in the plating solution. In a specific embodiment, a mass of 100 mg of target metal is dissolved in the plating solution. Unless otherwise specified, the target mass has a tolerance of ±3 mg.

[0112] In certain embodiments, preparing the plating solution includes preparing a buffer solution by combining ammonium chloride and ammonium hydroxide in water. In certain embodiments, the plating solution is an ammonium buffer solution. In certain embodiments, the plating solution is or includes ammonium ions. In certain embodiments, the pH of the buffer solution is 9.2 to 9.40, e.g., 9.28 to 9.30. In certain embodiments, the pH of the buffer solution is about 9.3 at room temperature.

[0113] In certain embodiments, preparing the plating solution includes adding a buffer solution to the plating solution including ammonium ions. In certain embodiments, the plating solution is prepared by contacting a metal salt with a buffer solution. In certain embodiments, the plating solution is prepared by contacting a metal nitrate with a buffer solution. In certain embodiments, the plating solution is prepared by contacting nickel nitrate with a buffer solution. In certain embodiments, the plating solution includes a metal salt dissolved in a buffer solution. In certain embodiments, the plating solution includes a nickel salt dissolved in a buffer solution. In certain embodiments, the plating solution includes dissolved metal ions. In certain embodiments, the plating solution includes dissolved metal ions for electrodeposition. In certain embodiments, the plating solution includes ammonium ions and a dissolved metal for electrodeposition. In certain embodiments, the plating solution includes nickel ions. In certain of these embodiments, the plating solution includes a dissolved target metal.

[0114] In certain embodiments, the plating solution comprises: nat Ni and / or 60 In certain embodiments, the plating solution comprises: nat In certain embodiments, the plating solution comprises: 60 In certain embodiments, the plating solution comprises: 61 Contains Ni or its salts.

[0115] In certain embodiments, the plating solution has a pH of 8.5 to 11. In certain embodiments, the plating solution has a pH of 8 to 10.8. In certain embodiments, the pH is 8.10 to 10.6, 8.2 to 10.5, 8.3 to 10.4, 8.5 to 10.3, 8.6 to 10.25, 8.7 to 10.2, 8.5 to 10.15, 8.5 to 10.1, 8.5 to 10, 8.5 to 9.9, 8.5 to 9.80, 8.5 to 9.6, 8.5 to 9.50, 8.5 to 9.4, 8.5 to 9.3, 8.5 to 9.2, 8.5 to 9.1, or 8.5 to 9. In certain embodiments, the pH of the plating solution is 9, 9.50, 10, 10.05, 10.10, 10.15, 10.20, 10.25, 10.30, 10.35, 10.40, 10.50, 10.60 or 10.70, 9, 10, 10.05, 10.10, 10.15, 10.20, 10.25, 10.30, 10.35 or 10.40.

[0116] In certain embodiments, the step of preparing the plating solution further comprises adjusting the pH of the plating solution, e.g., after adding a buffer, by adding an effective amount of NH4OH to obtain a particular pH value for the plating solution.

[0117] In a further embodiment, adjusting the pH of the plating solution comprises adding further NH4OH, for example dropwise, to the plating solution until the desired pH is reached.

[0118] 4.3.3 Purity of Electroplating Solution One aspect of the present disclosure provides a high-purity plating solution for use in producing high-purity radionuclide compositions. Some sources of trace metals are the target metal starting material itself, particularly enriched nickel, and the reagents and equipment used. Iron is common and requires careful consideration for reduction from the environment in which the plating solution is prepared. Reagents are selected to reduce impurities.

[0119] In certain embodiments of the provided methods, the target metal is selected from those described herein. In certain embodiments, the target metal used to prepare the plating solution (i.e., the target metal source material) is in the form of a metal salt, oxide, or elemental metal. In certain of these embodiments, the metal oxide or metal (e.g., rods, granules, powder) is at least 98% pure based on trace metal analysis. In certain embodiments, the target metal source material is at least 99.9% pure based on trace metal analysis. In certain embodiments, the target metal source material is at least 99.99% pure based on trace metal analysis. In certain embodiments, the target metal source material contains 150 ppm or less of total trace metal impurities.

[0120] In certain embodiments, the method of preparing a target material further includes purifying the plating solution prior to the electroplating step. In certain embodiments, purifying the plating solution follows known methods for reducing dissolved Cu, Zn, Fe, Co, Sn, Ti, and / or Al from the plating solution. In certain embodiments, purifying follows known methods for reducing Cu, Zn, Fe, Sn, Ti, and / or Al from the plating solution. In certain embodiments, purifying follows known methods for reducing Cu, Zn, and / or Fe from the plating solution. In certain embodiments, purifying follows known methods for reducing Cu from the solution.

[0121] In certain embodiments, the plating solution contains less than or equal to 0.1 ppm Cu, less than or equal to 0.2 ppm Cu, less than or equal to 0.3 ppm Cu, less than or equal to 0.4 ppm Cu, less than or equal to 0.5 ppm Cu, less than or equal to 0.6 ppm Cu, less than or equal to 0.7 ppm Cu, less than or equal to 0.8 ppm Cu, less than or equal to 0.9 ppm Cu, less than or equal to 10 ppm Cu, less than or equal to 10.1 ppm Cu, less than or equal to 10.2 ppm Cu, less than or equal to 10.3 ppm Cu, less than or equal to 10.4 ppm Cu, The plating solution may contain 0.1 ppm or less Cu, 10.5 ppm or less Cu, 10.6 ppm or less Cu, 10.7 ppm or less Cu, 10.8 ppm or less Cu, 10.9 ppm or less Cu, 11 ppm or less Cu, 12 ppm or less Cu, 13 ppm or less Cu, 14 ppm or less Cu, 15 ppm or less Cu, 16 ppm or less Cu, 17 ppm or less Cu, 18 ppm or less Cu, 19 ppm or less Cu, or 20 ppm or less Cu. In certain embodiments, the plating solution contains 0.1 ppm or less Cu. In certain embodiments, the plating solution contains 0.2 ppm or less Cu. In certain embodiments, the plating solution contains 0.3 ppm or less Cu. In certain embodiments, the plating solution contains 0.4 ppm or less Cu. In certain embodiments, the plating solution contains 0.5 ppm or less Cu. In certain embodiments, the plating solution contains 0.6 ppm or less Cu. In certain embodiments, the plating solution contains 0.7 ppm or less of Cu. In certain embodiments, the plating solution contains 0.1 ppm or less of Cu.

[0122] In certain embodiments of the provided methods, the plating solution contains 10 ppm or less Fe. In certain embodiments, the plating solution contains 1 ppm or less Fe, 5 ppm or less Fe, 10 ppm or less Fe, 15 ppm or less Fe, 20 ppm or less Fe, 25 ppm or less Fe, 30 ppm or less Fe, 32 ppm or less Fe, or 35 ppm or less Fe. In certain embodiments, the plating solution contains 1 ppm or less Fe. In certain embodiments, the plating solution contains 5 ppm or less Fe. In certain embodiments, the plating solution contains 10 ppm or less Fe. In certain embodiments, the plating solution contains 15 ppm or less Fe. In certain embodiments, the plating solution contains 20 ppm or less Fe. In certain embodiments, the plating solution contains 25 ppm or less Fe. In certain embodiments, the plating solution contains 30 ppm or less Fe. In certain embodiments, the plating solution contains 32 ppm or less Fe. In certain embodiments, the plating solution contains 35 ppm or less Fe.

[0123] In certain embodiments of the provided methods, the following specific elements are limited to the provided threshold values. That is, in certain embodiments, the plating solution contains the following: Ga, Lu, Pb and / or Y are each 0.1 ppm or less; Zn and / or Co are each 0.3 ppm or less; Cd, Cr, Al, Mn, Mo, Sn, Ti and / or V are each 1 ppm or less; Group 1 and / or Group 2 elements are individually not more than 1000 ppm.

[0124] In certain embodiments, the highest grade reagents must be used to avoid trace metal contamination of the target coating, as more than one tenth of a microgram per 100 mg of target metal (i.e., 1 ppm of target metal) is significant contamination that can render the target material unusable for the purification of high-purity radionuclides. In the case of radioactive copper production, adding more than 0.1 ppm of cryogenic Cu is unacceptable because it reduces the purity of the prepared radionuclide composition.

[0125] In certain embodiments of the provided method of preparing a plating solution, the maximum level of impurities (referenced to the trace metal analysis of the supplied starting material) that can be added to the target metal starting material by the process is: ·Copper (Cu) 0.1ppm or less, High affinity metals (Ga, Lu, Pb, Y) are individually 0.1 ppm or less, Zinc and cobalt (Zn, Co) are each 0.3 ppm or less. Transition metals and other metals (Cd, Cr, Al, Mn, Mo, Sn, Ti, V, etc.) are individually 1 ppm or less. Iron (Fe) 10 ppm or less, and · Group 1 and Group 2 elements (K, Ba, Mg, Be, etc.) are each 1000 ppm or less.

[0126] In certain embodiments of the provided methods of preparing a plating solution, only small amounts of impurities are added to the solution. In these embodiments, the process reduces the trace metal content of the target metal starting material (e.g., nat The maximum level of impurities added to the Ni isotopes is: ·Silver (Ag): 0.2ppm or less, Cobalt (Co): 0.5 ppm or less Chromium (Cr): 0.2 ppm or less ·Copper (Cu): 0.3ppm or less, Iron (Fe): 32 ppm or less Potassium (K): 0.2 ppm or less Magnesium (Mg): 0.1 ppm or less Manganese (Mn): 0.1 ppm or less Sodium (Na): 3.2 ppm or less, and Titanium (Ti): Limited to 0.1 ppm or less.

[0127] In certain embodiments of the provided methods of preparing a plating solution, the process produces a target metal (e.g., nat Zn and XX The maximum level of impurities (Zn isotopes) allowed in starting materials (see trace metal analysis of supplied starting materials) is: High affinity metals (Ga, Lu, Pb, Y) are individually 0.1 ppm or less, Zinc and cobalt (Zn, Co) are each 0.3 ppm or less. Transition metals and other metals (Cd, Cr, Al, Mn, Mo, Sn, Ti, V, etc.) are individually 1 ppm or less. Iron (Fe) 10 ppm or less, and ·One or more of the following: Group 1 and Group 2 elements (K, Ba, Mg, Be, etc.) are each 1000 ppm or less.

[0128] 4.3.4 Electroplating In certain embodiments, electroplating is performed at a current of 100 to 380 μA. In certain embodiments, electroplating is performed at a current of 100 to 360 μA, 100 to 340 μA, 100 to 320 μA, 100 to 300 μA, 100 to 280 μA, 100 to 260 μA, 100 to 240 μA, 100 to 220 μA, 100 to 210 μA, 100 to 200 μA, 100 to 180 μA, 100 to 170 μA, 100 to 160 μA, 120 to 380 μA, 140 to 380 μA, 160 to 380 μA, 170 to 380 μA, 180 to 390 μA, 190 to 210 μA, 200 to 220 μA, 210 to 240 μA, 220 to 230 μA, 230 to 250 μA, 240 to 260 μA, 250 to 280 μA, 260 to 280 μA, 270 to 290 μA, 280 to 300 μA, 290 to 310 μA, 310 to 320 μA, 320 to 330 μA, 340 to 350 μA, 350 to 360 μA, 360 to 370 μA, 370 to 380 μA, 380 to 390 μA, 390 to 400 μA, 390 to 410 μA, 390 to 420 μA, 390 to Electroplating is performed at a current of 80 μA, 180-380 μA, 200-380 μA, 220-380 μA, 240-380 μA, 260-380 μA, 280-380 μA, 300-380 μA, 320-380 μA, 120-350 μA, 120-320 μA, 120-300 μA, 120-280 μA, 120-260 μA, 120-240 μA, 120-220 μA, or 120-200 μA. In certain embodiments, electroplating is performed at a current of 120-180 μA, 130-170 μA, 140-170 μA, or 150-170 μA. In certain embodiments, electroplating is performed at a current of 155-165 μA. In certain embodiments, electroplating is performed at a current of 140 μA, 145 μA, 150 μA, 155 μA, 160 μA, 165 μA, 170 μA, 175 μA, or 180 μA. In certain embodiments, electroplating is performed at a current of 140 μA. In certain embodiments, electroplating is performed at a current of 145 μA. In certain embodiments, electroplating is performed at a current of 150 μA. In certain embodiments, electroplating is performed at a current of 155 μA. In certain embodiments, electroplating is performed at a current of 160 μA. In certain embodiments, electroplating is performed at a current of 165 μA. In certain embodiments, electroplating is performed at a current of 170 μA. In certain embodiments, electroplating is performed at a current of 175 μA. In certain embodiments, electroplating is performed at a current of 180 μA. Unless otherwise specified, the tolerance on any provided current value is ±0.3.

[0129] In certain embodiments, electroplating is performed at a voltage of 2.5 to 6.5 V. In certain embodiments, electroplating is performed at a voltage of 3.5 to 6 V. In certain embodiments, electroplating is performed at 3.25, 3.50, 3.75, 4.0, 4.25, 4.50, 4.75, 5.0, 5.25, 5.50, 5.75, or 6 V, or within a range defined by any two of these values. For example, electroplating is performed at a voltage of 4.25 to 5.25 V or 4.5 to 5.5 V. In certain embodiments, electroplating is performed at a voltage of 5.5 V. Unless otherwise indicated, the tolerance on any provided voltage value is ±0.2 V.

[0130] In certain embodiments, electroplating is carried out at a temperature of 15-30° C. In certain embodiments, electroplating is carried out at a temperature of 20-25° C. Unless otherwise indicated, the tolerance on any provided temperature value is ±0.5° C.

[0131] In certain embodiments, electroplating is performed in a cycle time of 5 hours or less. In certain embodiments, electroplating is performed in a cycle time of 4 hours or less. In certain embodiments, electroplating is performed in a cycle time of 3 hours or less. In certain embodiments, electroplating is performed in a cycle time of 2 hours or less. In certain embodiments, electroplating is performed in a cycle time of 90 minutes or less. In these embodiments, the cycle may include plating a single target material, two targets, or three or more targets in a batch process.

[0132] In certain embodiments, electroplating is performed under one or more conditions selected from a voltage of 3.5 to 5.5 V, a temperature of 20 to 25° C., and a cycle time of 3 hours or less. In certain embodiments, electroplating is performed under two or more conditions selected from a voltage of 3.5 to 5.5 V, a temperature of 20 to 25° C., and a cycle time of 3 hours or less. In certain embodiments, electroplating is performed under all three conditions selected from a voltage of 3.5 to 5.5 V, a temperature of 20 to 25° C., and a cycle time of 3 hours or less.

[0133] In particular embodiments, electroplating is carried out using a plating solution volume of 30 mL, 25 mL, 20 mL, 15 mL, 12 mL, 10 mL, 7 mL or 5 mL or less, particularly 10 mL or less.

[0134] In certain embodiments, electroplating is performed in an electrolytic cell containing a stationary anode. In certain embodiments, the anode is selected from a graphite anode and a platinum anode. In certain embodiments, the anode is 99.999% trace metal free by weight. In certain embodiments, the anode is a platinum anode. In certain embodiments, the platinum anode is in the form of a wire or foil.

[0135] 4.4 Methods for Producing High-Purity Radionuclide Compositions One aspect of the disclosure provided herein is a method of making a high-purity radionuclide composition, the method comprising irradiating a target metal of a target material in a particle accelerator in accordance with the present disclosure to produce an irradiated target coating, and isolating the produced high-purity radionuclide composition.

[0136] In certain embodiments, the target material comprises a high purity Nb backing as described herein. In further embodiments, the target material comprises a target coating as described herein.

[0137] Copper radionuclides x Cu (e.g., 60 Cu, 61 Cu, 62 Cu or 64 The manufacturing process for preparing Cu) is outlined below: (1) Natural or highly enriched nickel isotopes as the target metal, present as a target coating bonded to a high-purity Nb backing ( nat Ni, 60 Ni, 61 Ni, 62 Ni or 64 Ni) or highly enriched zinc isotopes ( 64 Zn or 68Zn) ↓ (2) Target coating irradiation using protons or deuterium by particle accelerators such as cyclotrons ↓ (3) Irradiated target coating using an acidic medium such as 10 M HCl ( x Cu / Ni or x Dissolution of Cu / Zn-containing target material ↓ (4) Ion exchange resin and purification unit from Ni or Zn starting material x Purification of Cu ↓ (5) For characterization and use in labeling or distribution x Cu]CuCl2 transfer

[0138] In certain embodiments of the method for producing a high purity radionuclide, the isolating comprises: x and dissolving the irradiated target coating in an aqueous HCl solution to obtain a chloride radionuclide solution, such as an aqueous solution of Cu]CuCl. In certain of these embodiments, the aqueous HCl solution is a 10 M HCl solution.

[0139] 4.4.1 Collision 60 Cu, 61 Cu, 62 Cu and 64 High purity compositions containing positron-emitting isotopes of copper, such as Cu, suitable for medical applications, e.g., by diagnostic imaging or positron emission tomography (PET) scans, are produced by deuterium or proton bombardment of target materials (e.g., high purity Nb backings with target coatings containing stable nickel or zinc isotopes) prepared according to the present disclosure through a particle accelerator. Certain embodiments of nuclear reactions and corresponding feasible production routes using a small hospital cyclotron are listed in Table 1 below: [Table 1]

[0140] In various of these embodiments, the radionuclide is a Cu radionuclide. In certain embodiments, the radionuclide is 61 In certain embodiments, the radionuclide is nat Ni(d,n) 61 Cu. In certain embodiments, the radionuclide is 60 Ni(d,n) 61 Cu. In certain embodiments, the radionuclide is 61 Ni(p,n) 61 Prepared according to Cu.

[0141] In certain embodiments, the radionuclide is 64 In certain embodiments, the radionuclide is 64 Ni(p,n) 64 Prepared according to Cu.

[0142] In certain embodiments, the radionuclide is 67 In certain embodiments, the radionuclide is 68 Zn(p,2p) 67 Cu or 70 Zn(p,α) 67 Prepared according to Cu.

[0143] 4.4.1.1 Collision time In certain embodiments of the method for producing a high purity radionuclide, irradiation is carried out for one half-life of the radionuclide. In certain of these embodiments, irradiation is for 60 to 220 minutes. In certain embodiments, irradiation is for 30 to 200 minutes. In certain embodiments, irradiation is for 50 to 180 minutes. In certain embodiments, irradiation is for 60 to 180 minutes. In certain embodiments, irradiation is for 80 to 180 minutes. In certain embodiments, irradiation is for 90 to 180 minutes. In certain embodiments, irradiation is for 100 to 180 minutes. In certain embodiments, irradiation is for 110 to 180 minutes. In certain embodiments, irradiation is for 120 to 180 minutes. In certain embodiments, irradiation is for 30 to 160 minutes. In certain embodiments, irradiation is for 30 to 140 minutes. In certain embodiments, irradiation is for 30 to 120 minutes. In certain embodiments, irradiation is for 30 to 110 minutes. In certain embodiments, the irradiation is for 30 to 100 minutes. In certain embodiments, the irradiation is for 30 to 90 minutes. In certain embodiments, the irradiation is for 30 to 80 minutes. In certain embodiments, the irradiation is for 30 to 70 minutes. In certain embodiments, the irradiation is for 30 to 60 minutes. In certain embodiments, the irradiation is for 30 minutes, 45 minutes, 60 minutes, 75 minutes, 90 minutes, 105 minutes, 120 minutes, 135 minutes, 150 minutes, or 165 minutes. In certain embodiments, the irradiation is for 30 minutes. In certain embodiments, the irradiation is for 45 minutes. In certain embodiments, the irradiation is for 60 minutes. In certain embodiments, the irradiation is for 30 minutes. In certain embodiments, the irradiation is for 75 minutes. In certain embodiments, the irradiation is for 90 minutes. In certain embodiments, the irradiation is for 105 minutes. In certain embodiments, the irradiation is for 120 minutes. In certain embodiments, the irradiation is for 135 minutes. In certain embodiments, the irradiation is for 150 minutes. In certain embodiments, the irradiation is for 165 minutes. In certain embodiments, the irradiation is for 200 minutes. In certain embodiments, the irradiation is for 220 minutes.

[0144] 4.4.1.2 Colliding particles In certain embodiments of the method for producing high purity radionuclides, the irradiation comprises colliding the target metal with protons, deuterium, or alpha particles. In certain embodiments, the impinging beam is selected from protons, deuterium, alpha particles, and photons. In certain embodiments, the impinging beam is selected from protons, deuterium, electrons, and photons. In certain embodiments, the impinging beam is selected from protons and deuterium. In certain embodiments, the impinging beam is selected from protons and deuterium. In certain embodiments, the impinging beam comprises deuterium. In certain embodiments, the impinging beam comprises protons. In certain embodiments, the impinging beam comprises alpha particles. In certain embodiments, the impinging beam comprises photons.

[0145] 4.4.1.3 Deuterium collision energy In certain embodiments of the method for producing high purity radionuclides, the target metal is bombarded with deuterium having a beam energy of 9 MeV or less, 3-9 MeV or less, or 8-9 MeV or less. In certain embodiments, the beam energy is 1-10 MeV, 3-9 MeV, 5-9 MeV, 6-9 MeV, 7-9 MeV, 8-9 MeV, 8.1 MeV, 8.2 MeV, 8.3 MeV, 8.4 MeV, 8.5 MeV, 8.6 MeV, 8.7 MeV, 8.8 MeV, or 8.9 MeV.

[0146] 4.4.1.4 Deuterium collision current In certain embodiments for producing high purity radionuclides, the target metal is bombarded with deuterium using a beam current of 100 μA or less, e.g., 10-100 μA, 10-60 μA, 10-50 μA, 20-60 μA, 30-60 μA, 40-60 μA, 20-50 μA, 30-50 μA, 35-50 μA, 40-60 μA, 40-55 μA, 40-50 μA, or 40-45 μA.

[0147] In certain of these embodiments, the target metal is nat Ni, 60 Ni or 61 In these embodiments, the high purity radionuclide composition comprises: 61 Contains Cu.

[0148] In a particular embodiment of the method for producing high purity radionuclides, the target metal is bombarded with deuterium having one or both of a beam energy of 9 MeV or less and / or a beam current of 100 μA or less.

[0149] 4.4.1.5 Proton collision energy In certain embodiments, the target metal is bombarded with protons having a beam energy of 7 to 20 MeV, e.g., 7 to 18 MeV, 7 to 16 MeV, 7 to 14 MeV, 7 to 12 MeV, 7 to 10 MeV, 8 to 18 MeV, 9 to 18 MeV, 10 to 18 MeV, 11 to 18 MeV, 12 to 18 MeV, 13 to 18 MeV, 8 to 16 MeV, 9 to 15 MeV, 10 to 14 MeV, 11 to 14 MeV, 12 to 14 MeV, 13 to 14 MeV, 13.1 MeV, 13.2 MeV, 13.3 MeV, 13.4 MeV, 13.5 MeV, 13.6 MeV, 13.7 MeV, 13.8 MeV, or 13.9 MeV.

[0150] 4.4.1.6 Proton impact current In certain embodiments, the target metal is bombarded with protons having a beam current of 10-150 μA, e.g., 10-140 μA, 10-130 μA, 10-120 μA, 10-110 μA, 10-100 μA, 10-90 μA, 10-80 μA, 20-150 μA, 30-150 μA, 50-150 μA, 60-150 μA, 70-150 μA, 80-150 μA, 90-150 μA, 100-150 μA, 110-150 μA, 75 μA, 80 μA, 85 μA, 90 μA, or 100 μA.

[0151] In certain of these embodiments, the target metal is 61 Contains Ni, and radionuclides 61 In certain of these embodiments, the target metal is a Cu radionuclide. 60 Contains Ni, and radionuclides 60 In certain of these embodiments, the target metal is a Cu radionuclide. 64 Contains Ni, and radionuclides 64In certain of these embodiments, the target metal is a Cu radionuclide. 64 Contains Zn, and radionuclides 61 In certain of these embodiments, the target metal is a Cu radionuclide. 68 Contains Zn, and radionuclides 64 It is a Cu radionuclide.

[0152] In certain embodiments, the radionuclide is nat Ni(d,n) 61 Prepared according to Cu.

[0153] In certain embodiments, the radionuclide is 60 Ni(d,n) 61 Prepared according to Cu.

[0154] In certain embodiments, the radionuclide is 61 Ni(p,n) 61 Prepared according to Cu.

[0155] In certain embodiments, the radionuclide is 64 Zn(p,α) 61 Prepared according to Cu.

[0156] In certain embodiments, the radionuclide is 64 In certain embodiments, the radionuclide is, for example, Cu, on a particle accelerator such as a medical cyclotron. 64 Ni(p,n) 64 Prepared according to Cu.

[0157] In certain embodiments, the radionuclide is 68 Zn(p,αn) 64 Prepared according to Cu.

[0158] 4.4.2 Purification In certain embodiments, high purity radionuclides (e.g., xSeparation and purification of [Cu]CuCl (aqueous solution) is achieved using a cassette-based FASTlab platform. In certain embodiments, TBP (tributyl phosphate) resin, e.g., (1 mL) (50-100 μm particle size, pre-packed, Triske®), is used. In certain embodiments, a weakly basic resin, e.g., (tertiary amine, TK201) (2 mL) (50-100 μm particle size, pre-packed, Triske®), is used. In certain embodiments, the resin is pre-conditioned with HO (7 mL) and HCl (10 M, 7 mL). In certain embodiments, cassette reagent vials were prepared using concentrated HCl (Optima grade, Fisher Scientific), NaCl (ACS, Fisher Scientific), and / or milli-Q water (Millipore system, 18 MΩ-cm resistivity), e.g., 6 M HCl (2 × 4.2 mL), 5 M NaCl in 0.05 M HCl (4.2 mL). In certain embodiments, the obtained 61 Cu was purified using two subsequent ion exchange resins in a FASTlab synthesis unit. In a specific embodiment, the acid-adjusted lysis solution (approximately 7 mL) was loaded onto both columns in series and directed towards the "Ni collection fraction." In a specific embodiment, the TBP resin was loaded onto the Fe 3+ It is implemented as a guard column because it quantitatively retains ions, but Cu 2+ and Co 2+ The complex is quantitatively retained on the tertiary amine (TK201) resin. In certain embodiments, to maximize Ni recovery for future recycle, both columns are used and washed with 6 M HCl (4 mL). In certain embodiments, the TK201 column is washed with, for example, 4.5 M HCl (5.5 mL), and most of the cobalt salts are eluted into the waste stream. In certain embodiments, the TK201 column is washed with HCl, for example, 5 M NaCl in 0.05 M (4 mL), to reduce residual acid on the resin and further remove any remaining cobalt salts. In certain embodiments, the TK201 column is washed with HCl, for example, 0.05 M HCl (3 mL), and [ 61 Cu]CuCl2 was quantitatively eluted.

[0159] 4.5. Radionuclide Compositions In a further aspect of the present disclosure, radionuclide compositions, such as 61 In various embodiments, the radionuclide composition is produced by bombardment of a target metal with subatomic particles that have been irradiated with protons, deuterium, electrons, or alpha particles, particularly protons or deuterium.

[0160] In certain embodiments, the radionuclide composition is in the form of an aqueous solution, e.g., 61 In certain embodiments, the radioactive composition is dissolved in an HCl solution.

[0161] In various embodiments, the radionuclide composition is in the form of a lyophilized halide salt. In various embodiments, the radionuclide composition is in the form of a lyophilized chloride salt.

[0162] 4.5.1. Radionuclide Purity The term "radionuclide purity" refers to the ratio of radionuclides expressed as a percentage of the total radioactivity of the radionuclides containing the composition. As reported herein, unless otherwise specified, radionuclide purity is determined by high-resolution gamma spectroscopy (e.g., using a high-purity germanium (HPGe) detector) on samples after completion, e.g., over 8 hours or over 3 weeks, and then extrapolated (e.g., using the TENDLE 2019 database using procedures known in the art) and reported herein as the value at the completion of synthesis of the radionuclide (EoB+2 hours).

[0163] Radionuclide purity at "end of synthesis" or "EoS" refers to the measurement at the time the final radionuclide composition is obtained, e.g., after dissolution and any purification. Unless otherwise specified, EoS is EoB + 90 minutes.

[0164] Various methods for purifying produced copper radioisotopes are known to those skilled in the art, see, for example, INTERNATIONAL ATOMIC ENERGY AGENCY, Production of Emerging Radionuclides towards Theranostic Applications: Copper-61, Scandium-43 and -44, and Yttrium-86, IAEA-TECDOC-1955, IAEA, Vienna (2021) and references cited therein. 61 Cu or 64 Cu-related trialkyl phosphate and ion exchange based purification schemes are generally applicable, such as any of the Cu purification methods.

[0165] In various embodiments, the radionuclide composition has a radionuclide purity of 95.0% or greater at the end of synthesis (EoB+90 min). In certain embodiments, the high purity composition comprises: 6x Cu radionuclides, e.g. 61 Cu, 64 Cu or 67 In certain embodiments, the high purity composition is for use, e.g., as a diagnostic agent. 64 In other embodiments, the high purity composition is for use, e.g., as a therapeutic agent. 67 In certain embodiments, the high purity composition comprises Cu. For example, the high purity composition is for use in radiolabeling radiotracers for medical applications such as diagnostic imaging. 61 Contains Cu.

[0166] In various embodiments, the high purity composition is 61 It contains Cu and has a radionuclide purity of 97.0% or more at the end of synthesis.

[0167] In certain embodiments, 61 Cu, 64 Cu or 67 Cu, especially 61 Radionuclide compositions, e.g., high purity radionuclides, containing Cu, meet the following purity requirements: 0.1Bq / g or less 110mAg, 0.1Bq / g or less 108m Ag, and 0.1Bq / g or less 109 Characterized by one or more of Cd.

[0168] Considering the radioactive cobalt impurity, 64 The Ni(p,α) reaction is 61 Co(t 1 / 2 =1.649h) and other radioactive cobalt impurities (e.g., 55 Co) arise primarily from other (A≠64) minor Ni isotopes in the isotopically enriched starting material, except that 61 In the context of Cu, among other reactions on other Ni isotopes, the main 61 Ni(p,α) and 60 The Ni(d,α) reaction is 61 Compared to Cu, the values ​​are 0.05% and 0.11%, respectively. 58 Long-lived Co relative activity producing 58 Co(t 1 / 2 = 70.86d). Therefore, efficient purification of radionuclide compositions from radioactive cobalt by-products requires: 61 In the context of Cu purification, it may prove even more important. 61 When considering the QC of Cu, Section 2.6 of IAEA Radioisotopes and Radiopharmaceuticals Reports No. 1 [INTERNATIONAL ATOMIC ENERGY AGENCY, Cyclotron produced radionuclides: Emerging positron emitters for medical applications: 64 Cu and 124 I, Radioisotopes and Radiopharmaceuticals Reports 1, IAEA, Vienna (2016) 63, the entire contents of which are incorporated herein by reference] 64 More details on Cu radionuclide purity and apparent molar activity are presented.

[0169] In certain embodiments, the high purity radionuclide composition is made from natural nickel or 60 via deuterium irradiation of Ni, or 61 Produced via proton irradiation of Ni, the composition is as follows: 1500Bq / g or less 56 Co, 100Bq / g or less 57 Co, 15,000Bq / g or less 58 Co, and 15Bq / g or less 60 Co.

[0170] In certain embodiments, the high purity radionuclide composition is made from natural nickel or 60 via deuterium irradiation of Ni, or 61 Produced via proton irradiation of Ni, the composition is as follows: 1500Bq / g or less 56 Co, 100Bq / g or less 57 Co, 15,000Bq / g or less 58 Co, and 15Bq / g or less 60 Co, and / or Less than: 1 Bq / g or less 110m Ag, 1Bq / g or less 108m Ag, and 1Bq / g or less 109 Cd.

[0171] In certain embodiments, the high purity radionuclide composition is made from natural nickel or 60 via deuterium irradiation of Ni, or 61 Generated via proton irradiation of Ni, the radionuclide is not a Cu radionuclide, and has the following composition: 0.1Bq / g or less 110m Ag, 0.1Bq / g or less 108m Ag, and 0.1Bq / g or less109 Contains one or more of the following: Cd

[0172] 4.5.2.Chemical Purity As used herein, the term "chemical purity" is understood to refer to the mole percent of a specified or desired radionuclide relative to all metals in a sample. The radionuclide compositions prepared by the methods disclosed herein exhibit high chemical purity, which facilitates the production of radiopharmaceuticals with high radiochemical purity.

[0173] Radiochemical purity, as understood herein, is the ratio or percent of radioactivity from the desired radionuclide in the radiopharmaceutical relative to the total radioactivity of the sample containing the radiopharmaceutical. Non-radioactive isotopes of metals ("cold" metals) do not contribute to the total radioactivity of the sample, but they may compete with the desired radionuclide for inclusion in the radiopharmaceutical, e.g., by competing for chelation sites in the radiopharmaceutical.

[0174] In certain embodiments, the radionuclide compositions described herein have a chemical purity of 99.0 mole % or greater. In certain embodiments, the radionuclide compositions are prepared according to the methods provided herein.

[0175] In certain embodiments, the radionuclide composition is an aqueous solution, Fe less than 2 mg / L, The total is less than 1 mg / L 69 Cu and 65 Cu, Zn below 2 mg / L; Sn less than 0.01 mg / L, Ti below 0.01 mg / L, Al below 2 mg / L, As below 1 mg / L, characterized by one or more of the following: Ni less than or equal to 1 mg / L; Any one of Cr, Cd, Co, and Y is 0.1 mg / mL or less.

[0176] In certain embodiments, the radionuclide composition is an aqueous solution and is characterized by containing 2 mg / L or less of Fe. In some embodiments, the radionuclide composition is an aqueous solution characterized by containing 2 mg / L or less, 1.9 mg / L or less, 1.8 mg / L or less, 1.7 mg / L or less, 1.6 mg / L or less, 1.5 mg / L or less, 1.4 mg / L or less, 1.3 mg / L or less, 1.2 mg / L or less, 1.1 mg / L or less, 1 mg / L or less, 0.9 mg / L or less, 0.8 mg / L or less, 0.7 mg / L or less, 0.6 mg / L or less, 0.5 mg / L or less, 0.4 mg / L or less, 0.3 mg / L or less, 0.2 mg / L or less, or 0.1 mg / L or less of Fe.

[0177] In certain embodiments, the radionuclide composition is an aqueous solution and has a concentration of 1 mg / L or less. 69 Cu and 65 In certain embodiments, the radionuclide composition is an aqueous solution and is characterized by a total of 1 mg / L or less, 1 mg / L or less, 0.9 mg / L or less, 0.8 mg / L or less, 0.7 mg / L or less, 0.6 mg / L or less, 0.5 mg / L or less, 0.4 mg / L or less, 0.3 mg / L or less, 0.2 mg / L or less, 0.1 mg / L or less, 0.09 mg / L or less, 0.08 mg / L or less, 0.07 mg / L or less, 0.06 mg / L or less, 0.05 mg / L or less, 0.04 mg / L or less, 0.03 mg / L or less, 0.02 mg / L or less, or 0.01 mg / L or less 69 Cu and 65 Characterized by the sum of Cu.

[0178] In certain embodiments, the radionuclide composition is an aqueous solution and is characterized by comprising 1 mg / L or less, 1 mg / L or less, 0.9 mg / L or less, 0.8 mg / L or less, 0.7 mg / L or less, 0.6 mg / L or less, 0.5 mg / L or less, 0.4 mg / L or less, 0.3 mg / L or less, 0.2 mg / L or less, 0.1 mg / L or less, 0.09 mg / L or less, 0.08 mg / L or less, 0.07 mg / L or less, 0.06 mg / L or less, 0.05 mg / L or less, 0.04 mg / L or less, 0.03 mg / L or less, 0.02 mg / L or less, or 0.01 mg / L or less of Ni.

[0179] In certain embodiments, the radionuclide composition is an aqueous solution and is characterized by containing no more than 2 mg / L, no more than 1.9 mg / L, no more than 1.8 mg / L, no more than 1.7 mg / L, no more than 1.6 mg / L, no more than 1.5 mg / L, no more than 1.4 mg / L, no more than 1.3 mg / L, no more than 1.2 mg / L, no more than 1.1 mg / L, no more than 1 mg / L, no more than 0.9 mg / L, no more than 0.8 mg / L, no more than 0.7 mg / L, no more than 0.6 mg / L, no more than 0.5 mg / L, no more than 0.4 mg / L, no more than 0.3 mg / L, no more than 0.2 mg / L, or no more than 0.1 mg / L of Zn.

[0180] In certain embodiments, the radionuclide composition is an aqueous solution and is characterized by containing less than or equal to 0.1 mg / L, less than or equal to 0.09 mg / L, less than or equal to 0.08 mg / L, less than or equal to 0.07 mg / L, less than or equal to 0.06 mg / L, less than or equal to 0.05 mg / L, less than or equal to 0.04 mg / L, less than or equal to 0.03 mg / L, less than or equal to 0.02 mg / L, less than or equal to 0.01 mg / L, less than or equal to 0.009 mg / L, less than or equal to 0.008 mg / L, less than or equal to 0.007 mg / L, less than or equal to 0.006 mg / L, less than or equal to 0.005 mg / L, less than or equal to 0.004 mg / L, less than or equal to 0.003 mg / L, less than or equal to 0.002 mg / L, or less than or equal to 0.001 mg / L of Sn.

[0181] In certain embodiments, the radionuclide composition is an aqueous solution and is characterized by containing less than or equal to 0.1 mg / L, less than or equal to 0.09 mg / L, less than or equal to 0.08 mg / L, less than or equal to 0.07 mg / L, less than or equal to 0.06 mg / L, less than or equal to 0.05 mg / L, less than or equal to 0.04 mg / L, less than or equal to 0.03 mg / L, less than or equal to 0.02 mg / L, less than or equal to 0.01 mg / L, less than or equal to 0.009 mg / L, less than or equal to 0.008 mg / L, less than or equal to 0.007 mg / L, less than or equal to 0.006 mg / L, less than or equal to 0.005 mg / L, less than or equal to 0.004 mg / L, less than or equal to 0.003 mg / L, less than or equal to 0.002 mg / L, or less than or equal to 0.001 mg / L of Ti.

[0182] In certain embodiments, the radionuclide composition is an aqueous solution and is characterized by containing less than or equal to 2 mg / L, less than or equal to 1.9 mg / L, less than or equal to 1.8 mg / L, less than or equal to 1.7 mg / L, less than or equal to 1.6 mg / L, less than or equal to 1.5 mg / L, less than or equal to 1.4 mg / L, less than or equal to 1.3 mg / L, less than or equal to 1.2 mg / L, less than or equal to 1.1 mg / L, less than or equal to 1 mg / L, less than or equal to 0.9 mg / L, less than or equal to 0.8 mg / L, less than or equal to 0.7 mg / L, less than or equal to 0.6 mg / L, less than or equal to 0.5 mg / L, less than or equal to 0.4 mg / L, less than or equal to 0.3 mg / L, less than or equal to 0.2 mg / L, or less than or equal to 0.1 mg / L of Al.

[0183] In certain embodiments, the radionuclide composition is an aqueous solution and has a concentration of 1 mg / L or less, 0.9 mg / L or less, 0.8 mg / L or less, 0.7 mg / L or less, 0.6 mg / L or less, 0.5 mg / L or less, 0.4 mg / L or less, 0.3 mg / L or less, 0.2 mg / L or less, 0.1 mg / L or less, 0.09 mg / L or less, 0.08 mg / L or less, 0.07 mg / L or less, 0.06 mg / L or less, 0.05 mg / L or less 0.006mg / L or less, 0.005mg / L or less, 0.004mg / L or less, 0.003mg / L or less, 0.02mg / L or less, 0.01mg / L or less, 0.009mg / L or less, 0.008mg / L or less, 0.007mg / L or less, 0.006mg / L or less, 0.005mg / L or less, 0.004mg / L or less, 0.003mg / L or less, 0.002mg / L or less, or 0.001mg / L or less of As.

[0184] In certain embodiments, the radionuclide composition is an aqueous solution and is characterized by containing less than or equal to 0.1 mg / L, less than or equal to 0.09 mg / L, less than or equal to 0.08 mg / L, less than or equal to 0.07 mg / L, less than or equal to 0.06 mg / L, less than or equal to 0.05 mg / L, less than or equal to 0.04 mg / L, less than or equal to 0.03 mg / L, less than or equal to 0.02 mg / L, less than or equal to 0.01 mg / L, less than or equal to 0.009 mg / L, less than or equal to 0.008 mg / L, less than or equal to 0.007 mg / L, less than or equal to 0.006 mg / L, less than or equal to 0.005 mg / L, less than or equal to 0.004 mg / L, less than or equal to 0.003 mg / L, less than or equal to 0.002 mg / L, or less than or equal to 0.001 mg / L of Cr.

[0185] In certain embodiments, the radionuclide composition is an aqueous solution and is characterized by containing less than or equal to 0.1 mg / L, less than or equal to 0.09 mg / L, less than or equal to 0.08 mg / L, less than or equal to 0.07 mg / L, less than or equal to 0.06 mg / L, less than or equal to 0.05 mg / L, less than or equal to 0.04 mg / L, less than or equal to 0.03 mg / L, less than or equal to 0.02 mg / L, less than or equal to 0.01 mg / L, less than or equal to 0.009 mg / L, less than or equal to 0.008 mg / L, less than or equal to 0.007 mg / L, less than or equal to 0.006 mg / L, less than or equal to 0.005 mg / L, less than or equal to 0.004 mg / L, less than or equal to 0.003 mg / L, less than or equal to 0.002 mg / L, or less than or equal to 0.001 mg / L of Cd.

[0186] In certain embodiments, the radionuclide composition is an aqueous solution and is characterized by containing less than or equal to 0.1 mg / L, less than or equal to 0.09 mg / L, less than or equal to 0.08 mg / L, less than or equal to 0.07 mg / L, less than or equal to 0.06 mg / L, less than or equal to 0.05 mg / L, less than or equal to 0.04 mg / L, less than or equal to 0.03 mg / L, less than or equal to 0.02 mg / L, less than or equal to 0.01 mg / L, less than or equal to 0.009 mg / L, less than or equal to 0.008 mg / L, less than or equal to 0.007 mg / L, less than or equal to 0.006 mg / L, less than or equal to 0.005 mg / L, less than or equal to 0.004 mg / L, less than or equal to 0.003 mg / L, less than or equal to 0.002 mg / L, or less than or equal to 0.001 mg / L of Co.

[0187] In certain embodiments, the radionuclide composition is an aqueous solution and is characterized by comprising no more than 0.1 mg / L, no more than 0.09 mg / L, no more than 0.08 mg / L, no more than 0.07 mg / L, no more than 0.06 mg / L, no more than 0.05 mg / L, no more than 0.04 mg / L, no more than 0.03 mg / L, no more than 0.02 mg / L, no more than 0.01 mg / L, no more than 0.009 mg / L, no more than 0.008 mg / L, no more than 0.007 mg / L, no more than 0.006 mg / L, no more than 0.005 mg / L, no more than 0.004 mg / L, no more than 0.003 mg / L, no more than 0.002 mg / L, or no more than 0.001 mg / L of Y.

[0188] In certain embodiments, trace metal analysis is performed by ICP-MS, for example, over a period of more than 3 weeks.

[0189] In certain embodiments, the total impurities in the radionuclide composition is 15 μg / GBq or less.

[0190] In certain embodiments, the radionuclide composition is characterized by 1.5 μg / GBq or less of Cu, eg, 1.0 μg / GBq or less or 0.5 μg / GBq or less.

[0191] In certain embodiments, the radionuclide composition is characterized by Al of 3.0 μg / GBq or less, eg, 2.5 μg / GBq or less or 2 μg / GBq or less.

[0192] In certain embodiments, the radionuclide composition is characterized by Co of 2 μg / GBq or less, eg, 1.5 μg / GBq or less or 1 μg / GBq or less.

[0193] In certain embodiments, the radionuclide composition is characterized by Fe of 4 μg / GBq or less, eg, 3.5 μg / GBq or less or 3 μg / GBq or less.

[0194] In certain embodiments, the radionuclide composition is characterized by 3 μg / GBq or less of Pb, eg, 2.5 μg / GBq or less or 2 μg / GBq or less.

[0195] In certain embodiments, the radionuclide composition is characterized by 3 μg / GBq or less of Ni, eg, 2.50 μg / GBq or less or 2 μg / GBq or less.

[0196] In certain embodiments, the radionuclide composition is characterized by 2 μg / GBq or less of Zn, eg, 1.5 μg / GBq or less or 1 μg / GBq or less.

[0197] 4.5.3 Copper isotopes 60 Cu, 61 Cu, 62 Cu, 64 Cu or 67 High purity radioactive copper compositions containing Cu are produced by deuterium, proton, electron, or alpha particle bombardment of target material prepared as described herein. In certain embodiments, the target material comprises a high purity Nb backing, a target metal (e.g., nickel isotopes or mixtures thereof, or zinc isotopes, or mixtures thereof) via a particle accelerator such as a cyclotron as described herein.

[0198] In certain embodiments, the high purity copper radionuclide composition is obtained according to any one of the target metals, isotopic enrichment levels and incident beam energies set forth in Table 1 below, and the irradiation is performed in a cyclotron (e.g., a medical cyclotron).

[0199] 4.6 [ 61 Characterization of Cu]CuCl2 solutions The radionuclide solutions provided by the methods and materials described herein can be characterized according to various properties and attributes. In some embodiments, for example, radioactivity concentration can be determined by a dose calibrator, pH value can be determined by pH paper, radiochemical purity can be determined by radio thin layer chromatography, radionuclide purity and / or identity can be determined by gamma spectrometry, and chemical purity can be determined by inductively coupled plasma mass spectrometry (ICP-MS). Among the non-limiting characterization profiles of the radionuclide and radiochemical compositions of the present disclosure are high purity [ 61 Cu]CuCl2 can be measured according to some of the following characteristics:

[0200] 4.6.1 Appearance In certain embodiments, the radioactive copper salts provided herein (e.g., [ 61 In certain embodiments, compositions comprising radioactive copper salt solutions (e.g., [Cu]CuCl2) are characterized by a color or a mixture of colors. 61 In certain embodiments, an aqueous solution of a radioactive copper salt (e.g., [Cu]CuCl2) is blue. 61 In certain embodiments, an aqueous solution of a radioactive copper salt (e.g., [Cu]CuCl) is green in color. 61 In certain embodiments, an aqueous solution of a radioactive copper salt (e.g., [Cu]CuCl2) is turquoise in color. 61 Cu]CuCl2) is colorless.

[0201] 4.6.2 Radioactivity In certain embodiments, the radionuclide compositions as described herein are further characterized by one or more of a radioactivity concentration of 0.01-23.33 GBq at calibration, a molar activity of 10-580 MBq at calibration, and a radioactivity at end of synthesis greater than 500 MBq. One embodiment is further characterized by one or more of a radioactivity concentration of greater than 25 GBq at calibration, a molar activity of 10-580 MBq at calibration, and a radioactivity at end of synthesis greater than 150 MBq, as described herein.

[0202] In certain embodiments, the radionuclide composition has at least 500 MBq, at least 490 MBq, at least 480 MBq, at least 470 MBq, at least 460 MBq, at least 450 MBq, at least 440 MBq, at least 430 MBq, at least 420 MBq, at least 410 MBq, at least 400 MBq, at least 390 MBq, at least 380 MBq, at least 370 MBq, at least 360 MBq, at least 350 MBq, at least 340 MBq, at least 330 MBq, at least 320 MBq, at least 310 MBq, at least 300 MBq, at least 290 MBq, at least 280 MBq, at least 2 70MBq or more, 260MBq or more, 250MBq or more, 240MBq or more, 230MBq or more, 220MBq or more, 210MBq or more, 200MBq or more, 190MBq or more, 180MBq or more, 170MBq or more, 160MBq or more, 150MBq or more, 140MBq or more, 130MBq or more, 120MBq or more, 110MBq or more, 100MBq or more, 90MBq or more, 80MBq or more, 70MBq or more, 60MBq or more, 50MBq or more, 40MBq or more, 30MBq or more, 20MBq or more or 10MBq or more 61 Cu]CuCl2 radioactivity.

[0203] In certain embodiments, the radionuclide composition has a concentration of greater than 500 MBq at the end of synthesis. 61 Cu]CuCl2 radioactivity.

[0204] In certain embodiments, the radionuclide composition has a concentration of greater than 150 MBq at the end of synthesis. 61 Cu]CuCl2 radioactivity.

[0205] 4.6.2.1 Radioactivity concentration In certain embodiments, the [ 61 Compositions containing CuCl2 include 50-400MBq / mL, 55-395MBq / mL, 60-390MBq / mL, 65-385MBq / mL, 70-380MBq / mL, 75-375MBq / mL, 80-370MBq / mL, 85-365MBq / mL, 90-360MBq / mL, 95-355MBq / mL, 100-350MBq / mL, 105-345MBq / mL, 110-340MBq / mL, 115-335MBq / mL, 120-330MBq / mL, 125-325MBq / mL, 130-320MBq / mL, and 135-315MBq / mL. , 140-310MBq / mL, 145-305MBq / mL, 150-300MBq / mL, 155-295MBq / mL, 160-290MBq / mL, 165-285MBq / mL, 170-280MBq / mL, 175-275MBq / mL, 180-270MBq / mL, 185-265MBq / mL, 190-260MBq / mL, 195-255MBq / mL, 200-250MBq / mL, 205-245MBq / mL, 210-240MBq / mL, 215-235MBq / mL or 220-230MBq / mL.

[0206] In certain embodiments, as provided herein, 61[Cu]CuCl2, the composition may be 400MBq / mL or more, 395MBq / mL or more, 390MBq / mL or more, 385MBq / mL or more, 380MBq / mL or more, 375MBq / mL or more, 370MBq / mL or more, 365MBq / mL or more, 360MBq / mL or more, 355MBq / mL or more, 350MBq / mL or more, 345MBq / mL or more, 340MBq / mL or more, 335MBq / mL or more, 330MBq / mL or more, 325MBq / mL or more, 320MBq / mL or more, 315MBq / mL or more, 325MBq / mL or more, 320MBq / mL or more, 335MBq / mL or more, 330 ... Bq / mL or more, 310 MBq / mL or more, 305 MBq / mL or more, 300 MBq / mL or more, 295 MBq / mL or more, 290 MBq / mL or more, 285 MBq / mL or more, 280 MBq / mL or more, 275 MBq / mL or more, 270 MBq / m L or more, 265MBq / mL or more, 260MBq / mL or more, 255MBq / mL or more, 250MBq / mL or more, 245MBq / mL or more, 240MBq / mL or more, 235MBq / mL or more, 230MBq / mL or more, 225MBq / mL or more, 2 20MBq / mL or more, 215MBq / mL or more, 210MBq / mL or more, 205MBq / mL or more, 200MBq / mL or more, 195MBq / mL or more, 190MBq / mL or more, 185MBq / mL or more, 180MBq / mL or more, 175MB q / mL or more, 170 MBq / mL or more, 165 MBq / mL or more, 160 MBq / mL or more, 155 MBq / mL or more, 150 MBq / mL or more, 145 MBq / mL or more, 140 MBq / mL or more, 135 MBq / mL or more, 130 MBq / mL and characterized by a radioactivity concentration of ≥ 125MBq / mL, ≥ 120MBq / mL, ≥ 115MBq / mL, ≥ 110MBq / mL, ≥ 105MBq / mL, ≥ 100MBq / mL, ≥ 95MBq / mL, ≥ 90MBq / mL, ≥ 85MBq / mL, ≥ 80MBq / mL, ≥ 75MBq / mL, ≥ 70MBq / mL, ≥ 65MBq / mL, ≥ 60MBq / mL, ≥ 55MBq / mL, ≥ 50MBq / mL, ≥ 45MBq / mL, or ≥ 40MBq / mL.

[0207] In certain embodiments, the radionuclide composition at the time of calibration has a concentration of 30 MBq / mL or more, 29 MBq / mL or more, 28 MBq / mL or more, 27 MBq / mL or more, 26 MBq / mL or more, 25 MBq / mL or more, 24 MBq / mL or more, 23 MBq / mL or more, 22 MBq / mL or more, 21 MBq / mL or more, 20 MBq / mL or more, 19 MBq / mL or more, 18 MBq / mL or more, 17 MBq / mL or more, 16 MBq / mL or more, 15 MBq / mL or more, 14 MBq / mL or more, 13 MBq / mL or more, 12 MBq / mL or more, 11 MBq / mL or more, 10 MBq / mL or more, 9 MBq / mL or more, 8 MBq / mL or more, 7 MBq / mL or more, 6 MBq / mL or more, 5 MBq / mL or more, 4 MBq / mL or more, 3 MBq / mL or more, 2 MBq / mL or more, or 1 MBq / mL or more 61 Cu]CuCl2 contains radioactive concentration.

[0208] In certain embodiments, the radionuclide composition has a radionuclide concentration of 0.01 to 25 GBq / mL at calibration. 61 Cu]CuCl2 radioactivity concentration.

[0209] In certain embodiments, the radionuclide composition, upon calibration, has a concentration of 0.01-30 GBq / mL, 0.50-29.50 GBq / mL, 1-29 GBq / mL, 1.50-28.50 GBq / mL, 2-28 GBq / mL, 2.50-27.50 GBq / mL, 3-27 GBq / mL, 3.50-26.50 GBq / mL, 4-26 GBq / mL, 4.50-25.50 GBq / mL, 5-25 GBq / mL, 5.50-24.50 GBq / mL, 6-24 GBq / mL, 6.50-23.50 GBq / mL, 7-23 GBq / mL, q / mL, 7.50~22.50GBq / mL, 8~22GBq / mL, 8.50~21.50GBq / mL, 9~21GBq / mL, 9.50~20.50GBq / mL, 10~20GBq / mL, 10.50~19.50GBq / mL, 11~19GB [ 61Cu]CuCl2 radioactivity concentration.

[0210] In certain embodiments, the radionuclide composition, at the time of calibration, has a concentration of 0.01-3 GBq / mL, 0.05-2.95 GBq / mL, 0.10-2.90 GBq / mL, 0.15-2.85 GBq / mL, 0.20-2.80 GBq / mL, 0.25-2.75 GBq / mL, 0.30-2.70 GBq / mL, 0.35-2.65 GBq / mL, 0.40-2.60 GBq / mL, 0.45-2.55 GBq / mL, 0.50-2.50 GBq / mL, 0.55-2.45 GBq / mL, 0.60-2.40 GBq / mL, 0.65-2.35 GBq / mL, 0.7 0~2.30GBq / mL, 0.75~2.25GBq / mL, 0.80~2.20GBq / mL, 0.85~2.15GBq / mL, 0.90~2.10GBq / mL, 0.95~2.05GBq / mL, 1~2GBq / mL, 1.05~1.95GBq / mL, 1.10~ [ 61 Cu]CuCl2 radioactivity concentration.

[0211] 0.25~0.50 GBq / mL, 0.50~0.50GBq / mL, 0.50~0.50GBq / mL, 0.50~0.50 GBq / mL. 1GBq / mL、1~1.25GBq / mL、1.25~1.50GBq / mL、1.50~1.75GBq / mL、1.75~2GBq / mL、2~2.25GBq / mL、2.25~2.50GBq / mL、2.50~2.75GBq / mL、2.75~3GBq / mL、 3~3.25GBq / mL、3.25~3.50GBq / mL、3.50~3.75GBq / mL、3.75~4GBq / mL、4~4. 25GBq / mL、4.25~4.50GBq / mL、4.50~4.75GBq / mL、4.75~5GBq / mL、5~5.25GB q / mL、5.25~5.50GBq / mL、5.50~5.75GBq / mL、5.75~6GBq / mL、6~6.25GBq / mL 、6.25~6.50GBq / mL、6.50~6.75GBq / mL、6.75~7GBq / mL、7~7.25GBq / mL、7.2 5~7.50GBq / mL、7.50~7.75GBq / mL、7.75~8GBq / mL、8~8.25GBq / mL、8.25~8.5 0GBq / mL、8.50~8.75GBq / mL、8.75~9GBq / mL、9~9.25GBq / mL、9.25~9.50GBq / mL、9.50~9.75GBq / mL、9.75~10GBq / mL、10~10.25GBq / mL、10.25~10.50GB q / mL、10.50~10.75GBq / mL、10.75~11GBq / mL、11~11.25GBq / mL、11.25~11. 50GBq / mL、11.50~11.75GBq / mL、11.75~12GBq / mL、12~12.25GBq / mL、12.25~ 12.50GBq / mL、12.50~12.75GBq / mL、12.75~13GBq / mL、13~13.25GBq / mL、13 .25~13.50GBq / mL、13.50~13.75GBq / mL、13.75~14GBq / mL、14~14.25GBq / m L、14.25~14.50GBq / mL、14.50~14.75GBq / mL、14.75~15GBq / mL、15~15.25G Bq / mL、15.25~15.50GBq / mL、15.50~15.75GBq / mL、15.75~16GBq / mL、16~16.25 GBq / mL, 16.25 - 16.50 GBq / mL, 16.50 - 16.75 GBq / mL, 16.75 - 17 GBq / mL, 17 - 17.25 GBq / mL, 17.25 - 17.50 GBq / mL, 17.50 - 17.75 GBq / mL, 17.75 - 18 GBq / mL, 18 - 18.25 GBq / mL, 18.25 - 18.50 GBq / mL, 18.50 - 18.75 GBq / mL, 18.75 - 19 GBq / mL, 19 - 19.25 GBq / mL, 19.25 - 19.50 GBq / mL, 19.50 - 19.75 GBq / mL, 19.75 - 20 GBq / mL, 20 - 20.25 GBq / mL, 20.25 - 20.50 GBq / mL, 20.50 - 20.75 GBq / mL, 20.75 - 21 GBq / mL, 21 - 21.25 GBq / mL, 21.25 - 21.50 GBq / mL, 21.50 - 21.75 GBq / mL, 21.75 - 22 GBq / mL, 22 - 22.25 GBq / mL, 22.25 - 22.5 GBq / mL, 22.5 - 22.75 GBq / mL, 22.75 - 23 GBq / mL, 23 - 23.25 GBq / mL, 23.25 - 23.50 GBq / mL, 23.50 - 23.75 GBq / mL, 23.75 - 24 GBq / mL, 24 - 24.25 GBq / mL, 24.25 - 24.50 GBq / mL, 24.50 - 24.75 GBq / mL or 24.75 - 25 GBq / mL of 61 contains the radioactivity concentration of [Cu]CuCl2.

[0212] 4.6.2.2 Molar Activity In certain embodiments, the compositions described herein comprise a 10-600 MBq / nmol, 25-600 GBq / nmol, 50-600 GBq / nmol, 75-600 GBq / nmol, 100-600 GBq / nmol, 125-600 GBq / nmol, 150-600 GBq / nmol, 175-600 GBq / nmol, 200-600 GBq / nmol, 225-600 GBq / nmol, 250-600 GBq / nmol, 275-600 GBq / nmol, 300-3500 GBq / nmol, 350-3500 GBq / nmol, 360-3700 GBq / nmol, 375-3800 GBq / nmol, 380-3900 GBq / nmol, 390-4000 GBq / nmol, 400-4000 GBq / nmol, 410-4100 GBq / nmol, 420-4200 GBq / nmol, 430-4300 GBq / nmol, 440-4400 GBq / nmol, 450-4500 GBq / nmol, 460-4700 GBq / nmol, 475-4800 GBq / nmol, 480-4900 GBq / nmol, 490-4900 GBq / nmol, 500-5000 GBq / nmol, 510-5200 GBq / nmol, 520-5300 GBq / nmol, 540-5500 GBq / nmol, 550-5600 GBq / nmol, 560-5700 GBq / nmol, 580-59 0GBq / nmol, 300-600GBq / nmol, 325-600GBq / nmol, 350-600GBq / nmol, 375-600GBq / nmol, 400-600GBq / nmol, 425-600GBq / nmol, 450-600GBq / nmol, 475-600GBq / nmol, 500-600GBq / nmol, 525-600GBq / nmol, 550-600GBq / nmol or 575-600GBq / nmol 61 Cu]CuCl2 is characterized by its molar activity concentration.

[0213] In certain embodiments, the compositions described herein comprise a 10-25 GBq / nmol, 10-50 GBq / nmol, 10-75 GBq / nmol, 10-100 GBq / nmol, 10-125 GBq / nmol, 10-150 GBq / nmol, 10-175 GBq / nmol, 10-200 GBq / nmol, 10-225 GBq / nmol, 10-250 GBq / nmol, 10-275 GBq / nmol, 10-300 GBq / nmol, 10-325 GBq / nmol, 10-350 GBq / nmol, 10-375 GBq / nmol, 10-400 GBq / nmol, 10-425 GBq / nmol, 10-450 GBq / nmol, 10-500 GBq / nmol, 10-525 GBq / nmol, 10-540 GBq / nmol, 10-560 GBq / nmol, 10-580 GBq / nmol, 10-590 GBq / nmol, 10-600 GBq / nmol, 10-610 GBq / nmol, 10-625 GBq / nmol, 10-630 GBq / nmol, 10-640 GBq / nmol, 10-650 GBq / nmol, 10-660 GBq / nmol, 10-670 GBq / nmol, 10-680 GBq / nmol, 10-690 GBq / nmol, 10-700 GBq / nmol, 10-710 GBq / nmol, 10-725 GBq / nmol, 10-750 GBq / nmol, 10-750 GBq / 0~450GBq / nmol, 10~475GBq / nmol, 10~500GBq / nmol, 10~525GBq / nmol, 10~550GBq / nmol, 10~575GBq / nmol, 25~600GBq / nmol, 50~575GBq / nmol, 75~550GBq / nmol, 100~52 [ 61 Cu]CuCl2 is characterized by its molar activity concentration.

[0214] In certain embodiments, the compositions described herein comprise a concentration of 10-150 MBq / nmol, 20-150 MBq / nmol, 30-150 MBq / nmol, 40-150 MBq / nmol, 50-150 MBq / nmol, 60-150 MBq / nmol, 70-150 MBq / nmol, 80-150 MBq / nmol, 90-150 MBq / nmol, 100-150 MBq / nmol, 110-150 MBq / nmol, 120-150 MBq / nmol, 130-150 MBq / nmol, 140-150 MBq / nmol, 10-140 MBq / nmol, 10-130 MBq / nmol nmol, 10~120MBq / nmol, 10~110MBq / nmol, 10~100MBq / nmol, 10~90MBq / nmol, 10~80MBq / nmol, 10~70MBq / nmol, 10~60MBq / nmol, 10~50MBq / nmol, 10~40MBq / nmol [ 61 Cu]CuCl2 is characterized by its molar activity concentration.

[0215] In certain embodiments, the radionuclide composition has a [ 61 Cu]CuCl2 molar activity concentration.

[0216] pH In certain embodiments, the [ 61The compositions containing Cu]CuCl2 are: 0.11, 0.12, 0.13, 0.14, 0.15, 0.16, 0.17, 0.18, 0.19, 0.2, 0.21, 0.22, 0.23, 0.24, 0.25, 0.26, 0.27, 0.28, 0.29, 0.3, 0.31, 0.32, 0.33, 0.34, 0.35, 0.36, 0.37, 0.38, 0.39, 0.4, 0.41, 0.42, 0.43, 0.44, 0.45, 0.46, 0.47, 0.48, 0.49, 0.5, 0.51, 0.52, 0.53, 0.54, 0.55, 0.56, 0.57, 0.58, 0.59, 0.6, 0.61, 0.62, 0.63, 0.64, 0.65, 0.66, 0.67, 0.68, 0.69, 0.7, 0.71, 0.72, 0.73, 0.74, 0.75, 0.76, 0.77, 0.78, 0.79, 0.8, 0.81, 0.82, 0.83, 0.84, 0.85, 0.86, 0.87, 0.88, 0.89, 0. 9, 0.91, 0.92, 0.93, 0.94, 0.95, 0.96, 0.97, 0.98, 0.99, 1, 1.01, 1.02, 1.03, 1.04, 1.05, 1.06, 1.07, 1.08, 1.09, 1.1, 1.11, 1.12, 1.13, 1.14, 1.15, 1.16, 1.17, 1.18, 1.19, 1.2, 1.21, 1.22, 1.23, 1.24, 1.25, 1.26, 1.27, 1.28, 1.29, 1.30, 1.31, 1.32, 1.33, 1.34, 1.35, 1.36, 1.37, 1.38, 1.39, 1.40, 1.41, 1.42, 1.43, 1.44, 1.45, 1.46, 1.47, 1.48, 1.49, 1.50, 1.51, 1.52, 1.53, 1.54, 1.55, 1.56, 1.57, 1.58, 1.59, 1.60, 1.61, 1.62, 1.63, 1.64, 1.65, 1.66, 1.67, 1.68, 1.69, 1.70, 1.71, 1.72, 1.73, 1.74, 1.75, 1. 1.51, 1.52, 1.53, 1.54, 1.55, 1.56, 1.57, 1.58, 1.59, 1.6, 1.61, 1.62, 1.63, 1.64, 1.65, 1.66, 1.67, 1.68, 1.69 or 1.7.

[0217] In certain embodiments, 61 The pH of the CuCl solution is 1 to 1.6. In certain embodiments, the pH is 1.05 to 1.55, 1.10 to 1.45, 1.15 to 1.35, or 1.20 to 1.25.

[0218] In certain embodiments, 61 The pH of the CuCl2 solution was 0.11–1.7, 0.12–1.69, 0.13–1.68, 0.14–1.67, 0.15–1.66, 0.16–1.65, 0.17–1.64, 0.18–1.63, 0.19–1.62, 0.2–1.61, 0.21–1.6, 0.22–1.59, 0.23–1.58, 0.24–1.57, 0.25–1.56, 0.26–1.55, 0.27–1.54, 0.28–1.55, 0.29–1.56, 0.30–1.57, 0.31–1.58, 0.32–1.59, 0.33–1.59, 0.34–1.59, 0.35–1.56, 0.36–1.55, 0.37–1.56, 0.38–1.57, 0.39–1.58, 0.40–1.59, 0.41–1.59, 0.42–1.59, 0.43–1.59, 0.44–1.59, 0.45–1.59, 0.46–1.59, 0.47–1.59, 0.48–1.59, 0.49–1.59, 0.50–1.50, 0.51–1.52, 0.52–1.53, 0.53–1.54, 0.54–1.55, 0.55–1.56, 0.56–1.57 8~1.53, 0.29~1.52, 0.3~1.51, 0.31~1.5, 0.32~1.49, 0.33~1.48, 0.34~1.47, 0.35~1.46, 0.36~1.45, 0.37~1.44, 0.38~1.43, 0.39~1.42, 0.4~1.41, 0.41~1.4, 0.42~1.39, 0.43~1.38, 0.44~1.37, 0.45~1.36, 0.46~1.35, 0.4 7~1.34, 0.48~1.33, 0.49~1.32, 0.5~1.31, 0.51~1.3, 0.52~1.29, 0.53~1.28, 0.54~1.27, 0.55~1.26, 0.56~1.25, 0.57~1.24, 0.58~1.23, 0.59~1.22, 0.6~1.21, 0.61~1.2, 0.62~1.19, 0.63~1.18, 0.64~1.17, 0.65~1.16, 0. 66 to 1.15, 0.67 to 1.14, 0.68 to 1.13, 0.69 to 1.12, 0.7 to 1.11, 0.71 to 1.1, 0.72 to 1.09, 0.73 to 1.08, 0.74 to 1.07, 0.75 to 1.06, 0.76 to 1.05, 0.77 to 1.04, 0.78 to 1.03, 0.79 to 1.02, 0.8 to 1.01, 0.81 to 1, 0.82 to 0.99, 0.83 to 0.98 or 0.84 to 0.97.

[0219] 4.6.4. Radionuclide Purity In certain embodiments, the [ 61

[0023] The composition comprising CuCl2 is 99.99% or more, 99.98% or more, 99.97% or more, 99.96% or more, 99.95% or more, 99.94% or more, 99.93% or more, 99.92% or more, 99.91% or more, 99.90% or more, 99.89% or more, 99.88% or more, 99.87% or more, 99.86% or more, 99.85% or more, 99.84% or more, 99.83% or more, 99.82% or more, 99.81% or more, 99.80% or more, 99.79% or more, 99.78% or more, 99.77% or more, 99.76% or more, 99.75% or more, 99.74% or more, 99.73% or more, 99.72% or more, 99.71% or more, 99.70% or more, 99.69% or more, 99.68% or more, 99.67% or more, 99.66% or more, 99.65% or more, 99.64% or more, 99.63% or more, 99.62% or more, 99.61% or more, 99.60% or more , 99.59% or more, 99.58% or more, 99.57% or more, 99.56% or more, 99.55% or more, 99.54% or more, 99.53% or more, 99.52% or more, 99.51% or more, 99.50% or more, 99.49% or more, 99.48% or more, 99.47% or more, 99.46% or more Above, 99.45% or higher, 99.44% or higher, 99.43% or higher, 99.42% or higher, 99.41% or higher, 99.40% or higher, 99.39% or higher, 99.38% or higher, 99.37% or higher, 99.36% or higher, 99.35% or higher, 99.34% or higher, 99.33% or higher, 99.32% or higher, 99.31% or higher, 99.30% or higher, 99.29% or higher, 99.28% or higher, 99.27% ​​or higher, 99.26% or higher, 99.25% or higher, 99.24% or higher, 99.23% or higher, 99.22% or higher, 99.21% or higher, 99.20% or higher, 99.19% or higher, 99.18 % or higher, 99.17% or higher, 99.16% or higher, 99.15% or higher, 99.14% or higher, 99.13% or higher, 99.12% or higher, 99.11% or higher, 99.10% or higher, 99.09% or higher, 99.08% or higher, 99.07% or higher, 99.06% or higher, 99.05% or higher, 99.04% or higher, 99.03% or higher, 99.02% or higher, 99.01% or higher, 99.00% or higher, 98.99% or higher, 98.98% or higher, 98.97% or higher, 98.96% or higher, 98.95% or higher, 98.94% or higher, 98.93% or higher, 98.92% or higher, 98.91% or higher, 98.90% or more, 98.89% or more, 98.88% or more, 98.87% or more, 98.86% or more, 98.85% or more, 98.84% or more, 98.83% or more, 98.82% or more, 98.81% or more, 98.80% or more, 98.79% or more, 98.78% or more, 98.77% or more, 98.76% or more, 98.75% or more, 98.74% or more, 98.73% or more, 98.72% or more, 98.71% or more, 98.70% or more, 98.69% or more, 98.68% or more, 98.67% or more, 98.66% or more, 98.65% or more, 98.64% or more, 98.63% or more, 98.62% or more, 98.61% or more, 98.60% or more, 98.59% or more, 98.58% or more, 98.57% or more, 98.56% or more, 98.55% or more, 98.54% or more, 98.53% or more, 98.52% or more, 98.51% or more, 98.50% or more, 98.49% or more , 98.48% or more, 98.47% or more, 98.46% or more, 98.45% or more, 98.44% or more, 98.43% or more, 98.42% or more, 98.41% or more, 98.40% or more, 98.39% or more, 98.38% or more, 98.37% or more, 98.36% or more, 98.35% or more Above, 98.34% or above, 98.33% or above, 98.32% or above, 98.31% or above, 98.30% or above, 98.29% or above, 98.28% or above, 98.27% or above, 98.26% or above, 98.25% or above, 98.24% or above, 98.23% or above, 98.22% or above, 98.21% or above, 98.20% or above, 98.19% or above, 98.18% or above, 98.17% or above, 98.16% or above, 98.15% or above, 98.14% or above, 98.13% or above, 98.12% or above, 98.11% or above, 98.10% or above, 98.09% or above, 98.08% or above, 98.07 % or more, 98.06% or more, 98.05% or more, 98.04% or more, 98.03% or more, 98.02% or more, 98.01% or more, 98.00% or more, 97.99% or more, 97.98% or more, 97.97% or more, 97.96% or more, 97.95% or more, 97.94% or more, 97.93% or more, 97.92% or more, 97.91% or more, 97.90% or more, 97.89% or more, 97.88% or more, 97.87% or more, 97.86% or more, 97.85% or more, 97.84% or more, 97.83% or more, 97.82% or more, 97.81% or more, 97.80% or more, 97.79% or higher, 97.78% or higher, 97.77% or higher, 97.76% or higher, 97.75% or higher, 97.74% or higher, 97.73% or higher, 97.72% or higher, 97.71% or higher, 97.70% or higher, 97.69% or higher, 97.68% or higher, 97.67% or higher, 97.66% or higher, 97.65% or higher, 97.64% or higher, 97.63% or higher, 97.62% or higher, 97.61% or higher, 97.60% or higher, 97.59% or more, 97.58% or more, 97.57% or more, 97.56% or more, 97.55% or more, 97.54% or more, 97.53% or more, 97.52% or more, 97.51% or more, 97.50% or more, 97.49% or more, 97.48% or more, 97.47% or more, 97.46% or more, 97.45% or more, 97.44% or more, 97.43% or more, 97.42% or more, 97.41% or more, 97.40% or more, 97.39% or more, 9 7.38% or higher, 97.37% or higher, 97.36% or higher, 97.35% or higher, 97.34% or higher, 97.33% or higher, 97.32% or higher, 97.31% or higher, 97.30% or higher, 97.29% or higher, 97.28% or higher, 97.27% or higher, 97.26% or higher, 97.25% or higher, 97.24% or higher, 97.23% or higher, 97.22% or higher, 97.21% or higher, 97.20% or higher, 97.19% or higher, 97.1 Characterized by a radionuclide purity of 8% or greater, 97.17% or greater, 97.16% or greater, 97.15% or greater, 97.14% or greater, 97.13% or greater, 97.12% or greater, 97.11% or greater, 97.10% or greater, 97.09% or greater, 97.08% or greater, 97.07% or greater, 97.06% or greater, 97.05% or greater, 97.04% or greater, 97.03% or greater, 97.02% or greater, 97.01% or greater, or 97% or greater.

[0220] 4.6.5. Long-lived radionuclide impurities In certain embodiments of the methods for producing high-purity radionuclides provided herein that include isolating a desired radionuclide, the method further includes purifying the radionuclide salt solution to reduce the amount of chemical impurities. In certain of these embodiments, the purifying includes anion / cation exchange chromatography. In certain embodiments, the purifying includes alkyl phosphate resin chromatography. In certain embodiments, the purifying includes weak cation exchange chromatography. In certain embodiments, the purifying includes reducing the specific activity (e.g., Bq / g) of a particular radionuclide below a certain threshold.

[0221] 4.6.5.1 Cobalt isotopes 56 Co, 57 Co, 58 Co and 60 Co In certain embodiments, the [ 61 Compositions containing Cu]CuCl2 are 1500 Bq / g or less, 1450 Bq / g or less, 1400 Bq / g or less, 1350 Bq / g or less, 1300 Bq / g or less, 1250 Bq / g or less, 1200 Bq / g or less, 1150 Bq / g or less, 1100 Bq / g or less, 1050 Bq / g or less, 1000 Bq / g or less, 950 Bq / g or less, 900 Bq / g or less, 850 Bq / g or less g or less, 800Bq / g or less, 750Bq / g or less, 700Bq / g or less, 650Bq / g or less, 600Bq / g or less, 550Bq / g or less, 500Bq / g or less, 450Bq / g or less, 400Bq / g or less, 350Bq / g or less, 300Bq / g or less, 250Bq / g or less, 200Bq / g or less, 150Bq / g or less, 100Bq / g or less or 50Bq / g or less 56 Characterized by Co specific activity.

[0222] In certain embodiments, the [ 61Compositions containing Cu]CuCl2 are 100Bq / g or less, 95Bq / g or less, 90Bq / g or less, 85Bq / g or less, 80Bq / g or less, 75Bq / g or less, 70Bq / g or less, 65Bq / g or less, 60Bq / g or less, 55Bq / g or less, 50Bq / g or less, 45Bq / g or less, 40Bq / g or less, 35Bq / g or less, 30Bq / g or less, 25Bq / g or less, 2 0Bq / g or less, 15Bq / g or less, 10Bq / g or less, 5Bq / g or less, 4.6Bq / g or less, 4.5Bq / g or less, 4.4Bq / g or less, 4.3Bq / g or less, 4.2Bq / g Below, 4.1Bq / g or less, 4Bq / g or less, 3.9Bq / g or less, 3.8Bq / g or less, 3.7Bq / g or less, 3.6Bq / g or less, 3.5Bq / g or less, 3.4Bq / g or less, 3.3Bq / g or less, 3.2Bq / g or less, 3.1Bq / g or less, 3Bq / g or less, 2.9Bq / g or less, 2.8Bq / g or less, 2.7Bq / g or less, 2.6Bq / g or less, 2.5 Bq / g or less, 2.4Bq / g or less, 2.3Bq / g or less, 2.2Bq / g or less, 2.1Bq / g or less, 2Bq / g or less, 1.9Bq / g or less, 1.8Bq / g or less, 1.7Bq / g or less, 1.6Bq / g or less, 1.5Bq / g or less, 1.4Bq / g or less, 1.3Bq / g or less, 1.2Bq / g or less, 1.1Bq / g or less, 1Bq / g or less, 0.9Bq / g or less, 0.8Bq / g or less, 0.7Bq / g or less, 0.6Bq / g or less, 0.5Bq / g or less, 0.4Bq / g or less, 0.3Bq / g or less, 0.2Bq / g or less or 0.1Bq / g or less 57 Characterized by Co specific activity.

[0223] In certain embodiments, the [ 61Compositions containing Cu]CuCl2 are 1500 Bq / g or less, 1450 Bq / g or less, 1400 Bq / g or less, 1350 Bq / g or less, 1300 Bq / g or less, 1250 Bq / g or less, 1200 Bq / g or less, 1150 Bq / g or less, 1100 Bq / g or less, 1050 Bq / g or less, 1000 Bq / g or less, 950 Bq / g or less, 900 Bq / g or less, 850 Bq / g or less, 800 Bq / g or less, 750 Bq / g or less, 700 Bq / g or less, 650 Bq / g or less, 600 Bq / g or less, 575 Bq / g or less, 550Bq / g or less, 525Bq / g or less, 500Bq / g or less, 475Bq / g or less, 450Bq / g or less, 425Bq / g or less, 400Bq / g or less, 375Bq / g or less, 350Bq / g or less, 325Bq / g or less, 300Bq / g or less, 275Bq / g or less, 250Bq / g or less, 225Bq / g or less, 200Bq / g or less, 175Bq / g or less, 150Bq / g or less, 125Bq / g or less, 100Bq / g or less, 75Bq / g or less, 50Bq / g or less or 25Bq / g or less 58 Characterized by Co specific activity.

[0224] In certain embodiments, the [ 61 Compositions containing Cu]CuCl2 are 15 Bq / g or less, 14 Bq / g or less, 13 Bq / g or less, 12 Bq / g or less, 11 Bq / g or less, 10 Bq / g or less, 9 Bq / g or less, 8 Bq / g or less, 7 Bq / g or less, 6 Bq / g or less, 5 Bq / g or less, 4 Bq / g or less, 3 Bq / g or less, 2.9 Bq / g or less, 2.8 Bq / g or less, 2.7 Bq / g or less, 2.6 Bq / g or less, 2.5 Bq / g or less, 2.4 Bq / g or less, 2.3 Bq / g or less, 2.2 Bq / g or less, 2.1Bq / g or less, 2Bq / g or less, 1.9Bq / g or less, 1.8Bq / g or less, 1.7Bq / g or less, 1.6Bq / g or less, 1.5Bq / g or less, 1.4Bq / g or less, 1.3Bq / g or less, 1.2Bq / g or less, 1.1Bq / g or less, 1Bq / g or less, 0.9Bq / g or less, 0.8Bq / g or less, 0.7Bq / g or less, 0.6Bq / g or less, 0.5Bq / g or less, 0.4Bq / g or less, 0.3Bq / g or less, 0.2Bq / g or less, or 0.1Bq / g or less 60 Characterized by Co specific activity.

[0225] In certain embodiments, the [ 61 Compositions containing Cu]CuCl2 are 2 Bq / g or less, 1.9 Bq / g or less, 1.8 Bq / g or less, 1.7 Bq / g or less, 1.6 Bq / g or less, 1.5 Bq / g or less, 1.4 Bq / g or less, 1.3 Bq / g or less, 1.2 Bq / g or less, 1.1 Bq / g or less, 1 Bq / g or less, 0.9 Bq / g or less, 0.8 Bq / g or less, 0.7 Bq / g or less, 0.6 Bq / g or less, 0.5 Bq / g or less, 0.4 Bq / g or less, 0.3 Bq / g or less, 0.2 Bq / g or less, 0.1 Bq / g or less 108m Characterized by Ag specific activity.

[0226] In certain embodiments, the [ 61 Compositions containing Cu]CuCl2 are 5Bq / g or less, 4.9Bq / g or less, 4.8Bq / g or less, 4.7Bq / g or less, 4.6Bq / g or less, 4.5Bq / g or less, 4.4Bq / g or less, 4.3Bq / g or less, 4.2Bq / g or less, 4.1Bq / g or less, 4Bq / g or less, 3.9Bq / g or less, 3.8Bq / g or less, 3.7Bq / g or less, 3.6Bq / g or less, 3.5Bq / g or less, 3.4Bq / g or less, 3.3Bq / g or less, 3.2Bq / g or less, 3.1Bq / g or less, 3Bq / g or less, 2.9Bq / g or less, 2.8Bq / g or less, 2.7Bq / g or less, 2.6 Bq / g or less, 2.5Bq / g or less, 2.4Bq / g or less, 2.3Bq / g or less, 2.2Bq / g or less, 2.1Bq / g or less, 2Bq / g or less, 1.9Bq / g or less, 1.8Bq / g or less, 1.7Bq / g or less, 1.6Bq / g or less, 1.5Bq / g or less, 1.4Bq / g or less, 1.3Bq / g or less, 1.2Bq / g or less, 1.1Bq / g or less, 1Bq / g or less, 0.9Bq / g or less, 0.8Bq / g or less, 0.7Bq / g or less, 0.6Bq / g or less, 0.5Bq / g or less, 0.4Bq / g or less, 0.3Bq / g or less, 0.2Bq / g or less or 0.1Bq / g or less 110m Characterized by Ag specific activity.

[0227] In certain embodiments, the [ 61Compositions containing Cu]CuCl2 are 15 Bq / g or less, 14 Bq / g or less, 13 Bq / g or less, 12 Bq / g or less, 11 Bq / g or less, 10 Bq / g or less, 9 Bq / g or less, 8 Bq / g or less, 7 Bq / g or less, 6 Bq / g or less, 5 Bq / g or less, 4 Bq / g or less, 3 Bq / g or less, 2 Bq / g or less, or 1 Bq / g or less 109 Characterized by Cd specific activity.

[0228] 4.6.6 Radiochemical Identity In certain embodiments, 61 The presence and / or quality of Cu is characterized by γ-photons. 61 Cu is characterized by a γ-photon with an energy peak of 511±20 keV. 61 Cu is characterized by γ-photons with energy peaks of 511±20 keV and 283 keV±20 KeV. 61 Cu is characterized by γ-photons with energy peaks of 511±20 keV, 283 keV±20 keV, and 656 keV±20 keV. 61 Cu is characterized by γ-photons with energy peaks of 511±20 keV (final total peak at 1022 keV±20 keV), 283 keV±20 keV and 656 keV±20 keV.

[0229] 4.6.7 Chemical purity In certain embodiments, 61 Cu may be characterized by other chemical impurities. In certain embodiments, the non-radioactive (low temperature) element is [ 61 In certain embodiments, low temperature elements are present and quantified by ICP-MS (inductively coupled plasma mass spectrometry). 61 Cu is a transformation product provided by the methods disclosed herein. In some embodiments, the target metal (e.g., nat Ni, 60 Ni or 61Ni) variants are available at various levels of radiochemical purity. 61 Provide Cu.

[0230] 4.6.7.1 Aluminum In certain embodiments, the [ 61 The composition comprising Cu]CuCl2 is characterized by containing aluminum (e.g., non-radioactive) in an amount of 2 ng / MBq or less, 1.9 ng / MBq or less, 1.8 ng / MBq or less, 1.7 ng / MBq or less, 1.6 ng / MBq or less, 1.5 ng / MBq or less, 1.4 ng / MBq or less, 1.3 ng / MBq or less, 1.2 ng / MBq or less, 1.1 ng / MBq or less, 1 ng / MBq or less, 0.9 ng / MBq or less, 0.8 ng / MBq or less, 0.7 ng / MBq or less, 0.6 ng / MBq or less, 0.5 ng / MBq or less, 0.4 ng / MBq or less, 0.3 ng / MBq or less, 0.2 ng / MBq or less, or 0.1 ng / MBq or less.

[0231] 4.6.7.2 Cobalt In certain embodiments, the [ 61 The composition comprising Cu]CuCl2 is characterized by including cobalt (e.g., non-radioactive) in an amount of 2 ng / MBq or less, 1.9 ng / MBq or less, 1.8 ng / MBq or less, 1.7 ng / MBq or less, 1.6 ng / MBq or less, 1.5 ng / MBq or less, 1.4 ng / MBq or less, 1.3 ng / MBq or less, 1.2 ng / MBq or less, 1.1 ng / MBq or less, 1 ng / MBq or less, 0.9 ng / MBq or less, 0.8 ng / MBq or less, 0.7 ng / MBq or less, 0.6 ng / MBq or less, 0.5 ng / MBq or less, 0.4 ng / MBq or less, 0.3 ng / MBq or less, 0.2 ng / MBq or less, or 0.1 ng / MBq or less.

[0232] 4.6.7.3 Copper In certain embodiments, the [ 61The composition comprising Cu]CuCl2 is characterized by containing copper (e.g., non-radioactive) in an amount of 2 ng / MBq or less, 1.9 ng / MBq or less, 1.8 ng / MBq or less, 1.7 ng / MBq or less, 1.6 ng / MBq or less, 1.5 ng / MBq or less, 1.4 ng / MBq or less, 1.3 ng / MBq or less, 1.2 ng / MBq or less, 1.1 ng / MBq or less, 1 ng / MBq or less, 0.9 ng / MBq or less, 0.8 ng / MBq or less, 0.7 ng / MBq or less, 0.6 ng / MBq or less, 0.5 ng / MBq or less, 0.4 ng / MBq or less, 0.3 ng / MBq or less, 0.2 ng / MBq or less, or 0.1 ng / MBq or less.

[0233] 4.6.7.4 Iron In certain embodiments, the [ 61 [Cu]CuCl2, the composition containing CuCl2 is 3ng / MBq or less, 2.9ng / MBq or less, 2.8ng / MBq or less, 2.7ng / MBq or less, 2.6ng / MBq or less, 2.5ng / MBq or less, 2.4ng / MBq or less, 2.3ng / MBq or less, 2.2ng / MBq or less, 2.1ng / MBq or less, 2ng / MBq or less, 1.9ng / MBq or less, 1.8ng / MBq or less, 1.7ng / MBq or less, 1.6ng / MBq or less, 1.5ng / MBq The iron may be characterized by containing iron (e.g., non-radioactive) in an amount of less than or equal to 1.4 ng / MBq, less than or equal to 1.3 ng / MBq, less than or equal to 1.2 ng / MBq, less than or equal to 1.1 ng / MBq, less than or equal to 1 ng / MBq, less than or equal to 0.9 ng / MBq, less than or equal to 0.8 ng / MBq, less than or equal to 0.7 ng / MBq, less than or equal to 0.6 ng / MBq, less than or equal to 0.5 ng / MBq, less than or equal to 0.4 ng / MBq, less than or equal to 0.3 ng / MBq, less than or equal to 0.2 ng / MBq, or less than or equal to 0.1 ng / MBq.

[0234] 4.6.7.5 Lead In certain embodiments, the [ 61The composition comprising Cu]CuCl2 is characterized by containing lead (e.g., non-radioactive) in an amount of 2 ng / MBq or less, 1.9 ng / MBq or less, 1.8 ng / MBq or less, 1.7 ng / MBq or less, 1.6 ng / MBq or less, 1.5 ng / MBq or less, 1.4 ng / MBq or less, 1.3 ng / MBq or less, 1.2 ng / MBq or less, 1.1 ng / MBq or less, 1 ng / MBq or less, 0.9 ng / MBq or less, 0.8 ng / MBq or less, 0.7 ng / MBq or less, 0.6 ng / MBq or less, 0.5 ng / MBq or less, 0.4 ng / MBq or less, 0.3 ng / MBq or less, 0.2 ng / MBq or less, or 0.1 ng / MBq or less.

[0235] 4.6.7.6 Nickel In certain embodiments, the [ 61 The compositions containing Cu]CuCl2 are 4.5ng / MBq or less, 4.4ng / MBq or less, 4.3ng / MBq or less, 4.2ng / MBq or less, 4.1ng / MBq or less, 4ng / MBq or less, 3.9ng / MBq or less, 3.8ng / MBq or less, 3.7ng / MBq or less, 3.6ng / MBq or less, 3.5ng / MBq or less, 3.4ng / MBq or less, 3.3ng / MBq or less, 3.2ng / MBq or less, 3.1ng / MBq or less, 3ng / MBq or less, 2.9ng / MBq or less, 2.8ng / MBq or less, 2.7ng / MBq or less, 2.6ng / MBq or less, 2.5ng / MBq or less, 2.4ng / MBq or less, 2.3ng / MBq or less. and characterized by containing nickel (e.g., non-radioactive) in an amount of 2 ng / MBq or less, 2.1 ng / MBq or less, 2 ng / MBq or less, 1.9 ng / MBq or less, 1.8 ng / MBq or less, 1.7 ng / MBq or less, 1.6 ng / MBq or less, 1.5 ng / MBq or less, 1.4 ng / MBq or less, 1.3 ng / MBq or less, 1.2 ng / MBq or less, 1.1 ng / MBq or less, 1 ng / MBq or less, 0.9 ng / MBq or less, 0.8 ng / MBq or less, 0.7 ng / MBq or less, 0.6 ng / MBq or less, 0.5 ng / MBq or less, 0.4 ng / MBq or less, 0.3 ng / MBq or less, 0.2 ng / MBq or less, or 0.1 ng / MBq or less.

[0236] 4.6.7.7 Zinc In certain embodiments, the [ 61 The composition comprising Cu]CuCl2 is characterized by containing zinc (e.g., non-radioactive) in an amount of 2 ng / MBq or less, 1.9 ng / MBq or less, 1.8 ng / MBq or less, 1.7 ng / MBq or less, 1.6 ng / MBq or less, 1.5 ng / MBq or less, 1.4 ng / MBq or less, 1.3 ng / MBq or less, 1.2 ng / MBq or less, 1.1 ng / MBq or less, 1 ng / MBq or less, 0.9 ng / MBq or less, 0.8 ng / MBq or less, 0.7 ng / MBq or less, 0.6 ng / MBq or less, 0.5 ng / MBq or less, 0.4 ng / MBq or less, 0.3 ng / MBq or less, 0.2 ng / MBq or less, or 0.1 ng / MBq or less. 4.7. Enumerated Embodiments 1. A target material for bombardment by subatomic particles, the target material comprising: a backing including a backing surface, the backing comprising: A target material containing Nb, the Nb having a purity of 98.8% or more. 2. The target material according to the embodiment, wherein Nb has a purity of 99 to 99.999% or more, a purity of 99.8% or more, and preferably a purity of 99.99% or more. 3.Nb is the following: Fe below 40 ppm, Ti below 60 ppm, Zn below 19 ppm, Cu below 5 ppm, Sn below 8 ppm, Less than 5 ppm Ni, and 3. The target material of embodiment 1 or 2, characterized by one or more of: 5 ppm Al or less. 4.Nb is the following: Fe below 30 ppm, Ti below 10 ppm, Zn less than 10 ppm, Cu below 3 ppm, Sn less than 5 ppm, and 3. The target material of embodiment 2, characterized by one or more of: less than 1 ppm Ni. 5.Nb is the following: Fe below 30 ppm, Ti below 2 ppm, Zn less than 10 ppm, Cu below 5 ppm, Sn less than 5 ppm, and 3. The target material of embodiment 2, characterized by less than 1 ppm Ni. 6. The target material of any one of embodiments 1 to 5, wherein the backing has a thickness of 1 to 1.5 mm. 7. Further comprising a target coating; the target coating comprises a target metal; The target material according to any one of the first to sixth embodiments. 8. The target material of embodiment 7, wherein the target coating is characterized by one or more of the following: ≦0.005 ppm Cd, ≦0.0005 ppm Co, ≦0.005 ppm Pb, ≦0.08 ppm Cu, and ≦0.15 ppm Fe. 9. The target material of embodiment 7 or 8, wherein the target coating has a thickness of 5 to 150 μm, 60 to 125 μm, or 70 to 100 μm. 10. The target material according to any one of embodiments 6 to 9, wherein the target coating has a mass of 30 mg or more, 40 to 100 mg, 45 to 80 mg, 40 to 70 mg, for example, 70 mg ± 3 mg or 50 mg ± 3 mg. 11. A target material according to any one of embodiments 6 to 10, wherein the thickness of the target coating varies by no more than 15%, or no more than 10%, e.g., the target coating is 15% thicker in the center compared to the average thickness of the coating around the periphery of the target coating. 12. The target material according to any one of embodiments 6 to 11, wherein the target coating is a circular shape having a diameter of 1.5 cm or less. 13. The target material according to any one of embodiments 6 to 12, wherein the target metal is Ni. 14. The target material of embodiment 13, wherein the target metal is native Ni or Ni of a naturally occurring isotopic composition. 15. The target metal is isotopically enriched with minor isotopes of Ni relative to native Ni, and the minor isotopes are 60 Ni, 61 Ni, 62 Ni and 64 Ni, for example 60 Ni or 61 14. The target material of embodiment 13, wherein the target material is Ni. 16. The target material of embodiment 15, wherein the target metal is isotopically enriched in the minority isotope to 95% or more, 96% or more, 97% or more, 98% or more, 99% or more. 17. Minor isotopes are 64 16. The target material of embodiment 15, wherein the target material is Ni. 18. The target material of embodiment 15, wherein the target metal is isotopically enriched in the minority isotope to 97% or more. 19. Minor isotopes are 62 17. The target material of embodiment 16, wherein the target material is Ni. 20. The target material of embodiment 15, wherein the target metal is isotopically enriched in the minority isotope to 99% or more. 21. Minor isotopes are: 60 16. The target material of embodiment 15, wherein the target material is Ni. 22. Minor isotopes are: 61 16. The target material of embodiment 15, wherein the target material is Ni. 23. The target material according to any one of embodiments 6 to 12, wherein the target metal is Zn. 24. The target metal is natural Zn. 68 24. The target material of embodiment 23, which is isotopically enriched in Zn. 25. Target metal is up to 95% or more 68 25. The target material of embodiment 24, which is isotopically enriched in Zn. 26. Target metal is up to 99% or more 6825. The target material of embodiment 24, which is isotopically enriched in Zn. 27. A method for preparing a target material for bombardment by subatomic particles, comprising: The target material is a backing including a backing surface; a target coating adhered to the backing surface, the target coating comprising a target metal; The method is: electroplating a target metal from a plating solution onto a backing surface; The plating solution contains cations of the target metal, and the pH of the plating solution is 9.5 to 10.7; This method prepares a target material. 28. The method of embodiment 27, wherein the backing comprises Nb, Ag, Pt, Au, Al, or W. 29. The method of embodiment 28, wherein the backing comprises Nb or Ag. 30. The method of embodiment 29, wherein the backing comprises Nb. 31. A method, comprising: electroplating a target metal from a plating solution onto a backing surface; The plating solution contains cations of the target metal; 31. The method for preparing a target material according to any one of embodiments 27 to 30, whereby a target material is prepared. 32. The method is 32. The method of any one of embodiments 31, further comprising polishing the backing surface before electroplating. 33. The method of embodiment 32, wherein the polishing is performed using a vibratory tumbler. 34. The method of embodiment 32, wherein the polishing is carried out using a corundum grinding wheel. 35. The method of any one of embodiments 27-31, wherein the pH of the plating solution is 9.5 to 10.7. 36. The method of embodiment 35, wherein the pH of the plating solution is 10 to 10.4. 37. The method of any one of embodiments 27-39, wherein the plating solution comprises nitrate ions. 38. The method of embodiment 37, wherein the plating solution is HNO3. 39. The method of any one of embodiments 27 to 38, wherein the electroplating is carried out at a current of 120 to 180 μA. 40. Electroplating is Voltage 3.5~5.5V, Temperature of 20-25℃ and 40. The method of any one of embodiments 27-39, wherein the method is carried out under one or more conditions selected from a cycle time of 5 hours or less. 41. The method of embodiment 40, wherein electroplating is performed at a voltage of 4.25 to 5.25 V. 42. The method of embodiment 40, wherein the voltage is 4.5 to 5.5 V. 43. The method of embodiment 40, wherein the voltage is 5.5 V. 44. The method of any one of embodiments 27-43, wherein the volume of the plating solution is 10 mL or less. 45. The method of any one of embodiments 27-44, wherein electroplating is carried out for 3 hours or less. 46. ​​The method of any one of embodiments 27-45, further comprising preparing a plating solution. 47. The method of embodiment 46, wherein the plating solution is prepared by combining the target metal with a molar excess of HNO3. 48. The method of embodiment 47, wherein the HNO3 is in the form of 65% nitric acid in water. 49. The method of embodiment 48, wherein HNO3 is added to the plating solution at greater than 40 grams of HNO3 per gram of target metal. 50. The method of any one of embodiments 47-49, wherein the target metal is in the form of a metal powder that is at least 98% pure. 51. The method of embodiment 50, wherein the metal powder is at least 99.9% pure. 52. The method of any one of embodiments 46-51, wherein preparing the plating solution further comprises adjusting the pH of the plating solution by adding an effective amount of NH4OH. 53. The method of any one of embodiments 27-52, further comprising adding a buffer to the plating solution before electroplating. 54. The method of embodiment 53, wherein the buffer comprises NH4Cl and NH4OH. 55. The method of embodiment 53 or 54, wherein the pH of the buffer is 8.30 to 9.30. 56. The method of embodiment 55, wherein the pH of the buffer is 9.35 to 9.25. 57. The method of any one of embodiments 27 to 56, wherein the electroplating is carried out in an electrolytic cell containing a stationary anode. 58. The method of embodiment 57, wherein the anode is selected from a graphite anode and a platinum anode. 59. The method of embodiment 58, wherein the anode is 99.999% trace metal free. 60. The method of embodiment 58 or 59, wherein the anode is a platinum anode. 61. The method of embodiment 60, wherein the platinum anode is in the form of a wire or foil. 62. The method of any one of embodiments 27-61, wherein the plating solution contains 10 ppm or less of Fe. 63. The plating solution is: Ga, Lu, Pb, Y below 0.1 ppm Zn, Co, less than 0.3 ppm Cd, Cr, Al, Mn, Mo, Sn, Ti and V, less than 1 ppm; 1000 ppm or less of one or more of Group 1 and Group 2 elements. 64. The method of any one of embodiments 27-63, wherein the target metal is Ni. 65. The method of embodiment 64, wherein the target metal is native Ni. 66. The target metal is isotopically enriched with minor isotopes of Ni relative to native Ni, and the minor isotopes are 60 Ni,62 Ni, 61 Ni and 64 65. The method of embodiment 64, wherein the hydroxybenzoate is selected from Ni. 67. The method of embodiment 66, wherein the target metal is isotopically enriched in the minority isotope to 95% or more. 68. The method of any one of embodiments 64-67, wherein the method further comprises purifying the plating solution to remove copper prior to electroplating. 69. The method of embodiment 68, wherein the plating solution contains 0.1 ppm or less of Cu. 70. The method of any one of embodiments 27-63, wherein the target metal is Zn. 71. The target metal is natural Zn. 68 71. The method of embodiment 70, wherein the Zn is isotopically enriched in Zn. 72. Target metal is up to 95% or more 68 72. The method of embodiment 71, wherein the Zn is isotopically enriched in Zn. 73. The plating solution is Ga, Lu, Pb, Y below 0.1 ppm Co below 0.3 ppm, Cd, Cr, Al, Mn, Mo, Sn, Ti and V, less than 1 ppm; 73. The method of embodiment 70 or 72, characterized by having one or more of the following elements in the recited ranges: Group 1 and Group 2 elements, not exceeding 1000 ppm. 74. A target material prepared according to the method of any one of embodiments 27 to 73. 75. A high purity radionuclide composition, the composition comprising a radionuclide and having a radionuclide purity of 95.0% or greater at the end of synthesis of the radionuclide; the radionuclide is a Cu radionuclide, and / or The composition comprises: 0.1Bq / g or less 110m Ag, 0.1Bq / g or less 108m Ag, and 0.1Bq / g or less 109 A high purity radionuclide composition containing one or more of Cd. 76. The composition according to embodiment 75, wherein the composition is an aqueous solution and comprises a radionuclide in the form of a radionuclide cation. 77. The composition of embodiment 76, wherein the aqueous solution further comprises chloride anions. 78. The composition of embodiment 77, wherein the chloride anion is present in molar excess of the radionuclide cation. 79. The composition of any one of embodiments 75-78, wherein the radionuclide is a Cu radionuclide. 80. Radionuclides are: 61 80. The composition of embodiment 79, wherein Cu. 81. Radionuclides are: 68 The composition of embodiment 79, wherein Ga. 82. The composition comprises: 0.1Bq / g or less 110m Ag, 0.1Bq / g or less 108m Ag, and 0.1Bq / g or less 109 82. The composition of any one of embodiments 75-81, comprising one or more of: Cd. 83. The composition comprises: 1500Bq / g or less 56 Co, 100Bq / g or less 57 Co, 15,000Bq / g or less 58 Co, and 15Bq / g or less 60 82. The composition of any one of embodiments 75-81, comprising one or more of: 84. The composition comprises: 1500Bq / g or less 56 Co, 100Bq / g or less 57 Co, 15,000Bq / g or less 58 Co, and 15Bq / g or less 60 Co, and / or below: 1Bq / g or less 110m Ag, 1Bq / g or less 108m Ag, and 1Bq / g or less 109 84. The composition of embodiment 83, wherein the composition comprises two or more of: Cd. 85. The radionuclide is not a Cu radionuclide and the composition is: 0.1Bq / g or less 110m Ag, 0.1Bq / g or less 108m Ag, and 0.1Bq / g or less 109 79. The composition of any one of embodiments 75-78, comprising one or more of the following: Cd. 86. The composition of any one of embodiments 75-85, having a chemical purity for the radionuclide of 86.99 mole % or greater. 87. The composition is an aqueous solution, Fe less than 2 mg / L, The total is less than 1 mg / L 69 Cu and 65 Cu, Zn below 2 mg / L; Sn less than 0.01 mg / L, Ti below 0.01 mg / L, Al below 2 mg / L, As below 1 mg / L, Contains one or more of the following: Ni at 1 mg / L or less; The composition of embodiment 85, wherein any one of Cr, Cd, Co, and Y is 0.1 mg / mL or less. 88. The composition of embodiment 87, wherein the composition comprises 2 mg / L or less of Fe. 89. The composition of embodiment 87, wherein the composition comprises 1 mg / L or less of Cu. 90. The composition of embodiment 87, wherein the composition comprises 1 mg / L or less of Ni. 91. Radioactivity concentration of 0.25 to 25 GBq / mL at calibration (EoB + 8 hours), Molar activity of 10-100MBq / nmol at calibration (EoB+8 hours) and Radioactivity exceeding 500MBq at the end of synthesis (EoB+90 min), 91. The composition of any one of embodiments 75 to 90, characterized by one or more of: 92. A method for making a high purity radionuclide composition comprising a radionuclide, the method comprising: irradiating a target metal of the target material of any one of embodiments 7 to 26 or embodiment 74 in a particle accelerator to produce an irradiated target material; and isolating the high purity radionuclide composition. 93. The method according to embodiment 92, wherein the high purity radionuclide composition is that of any one of embodiments 75-86. 94. To isolate 93. The method of embodiment 92 or 92, comprising dissolving the irradiated target material in an aqueous HCl solution to obtain a chloride radionuclide solution. 95. The method of embodiment 94, wherein the aqueous HCl solution is a greater than 5M HCl solution. 96. To isolate 96. The method of embodiment 94 or 95, further comprising purifying the chloride radionuclide solution to reduce chemical impurities. 97. The method of any one of embodiments 92-96, wherein the irradiating is carried out for one half-life of the radionuclide. 98. The method of embodiment 97, wherein the irradiation is carried out for 60 to 120 minutes. 99. Irradiation is 99. The method of any one of embodiments 92-98, comprising bombarding the target metal with protons, deuterium, or alpha particles. 100. The method of embodiment 99, wherein the target metal is bombarded with deuterium. 101. The method of embodiment 99, wherein the deuterium has a beam energy of 9 MeV or less and / or a beam current of 60 μA or less. 102. The method of embodiment 101, wherein the deuterium has a beam energy of 3 to 9 MeV. 103. The method of embodiment 101, wherein the deuterium has a beam current of 10 to 60 μA. 104. The target metal is natural Ni,60 Ni or 61 Contains Ni, and the radionuclide is 61 Cu, 61 Cu reacts with the following: nat Ni(d,n) 61 Cu, 61 Ni(p,n) 61 Cu, or 60 Ni(d,n) 61 104. The method according to any one of embodiments 100 to 103, wherein the compound is produced according to one of the following: 105. The method of embodiment 99, wherein the target metal is bombarded with protons. 106. The method of embodiment 105, wherein the protons have a beam energy of 18 MeV or less and / or a beam current of 120 μA or less. 107. The method of embodiment 106, wherein the protons have a beam energy of 6 to 18 MeV. 108. The method of embodiment 106, wherein the protons have a beam current of 10 to 120 μA. 109. The target metal is 61 Contains Ni, and the radionuclide is 61 Cu, 61 Cu reacts with the following: 61 Ni(p,n) 61 109. The method of any one of embodiments 104-108, wherein the method is produced according to Cu. 110. The target metal is 64 Contains Zn, and radionuclides include 61 Cu, 61 Cu reacts with the following: 64 Zn(p,α) 61 109. The method of any one of embodiments 104-108, wherein the method is produced according to Cu. 111. The target metal is 60 Contains Ni, and the radionuclide is 60 Cu, 60 Cu reacts in the following way: 60 Ni(p,n) 60 109. The method of any one of embodiments 104-108, wherein the method is produced according to Cu. 112. The target metal is 62Contains Ni, and the radionuclide is 62 Cu, 62 Cu reacts in the following way: 62 Ni(p,n) 62 109. The method of any one of embodiments 104-108, wherein the method is produced according to Cu. 113. The target metal is 64 Contains Ni, and the radionuclide is 64 Cu, 64 Cu reacts in the following way: 64 Ni(p,n) 64 109. The method of any one of embodiments 104-108, wherein the method is produced according to Cu. 114. The target metal is 68 Contains Zn, and radionuclides include 64 Cu, 64 Cu reacts in the following way: 68 Zn(p,αn) 64 109. The method of any one of embodiments 104-108, wherein the method is produced according to Cu. 115. 60 Cu, 61 Cu, 62 Cu or 64 1. A method for producing Cu, the method comprising irradiating a target material with subatomic particles, the target material comprising a niobium backing and a target backing, the target coating comprising: nat Ni, 60 Ni, 61 Ni, 62 Ni, 64 Ni or 68 Zn, and the subatomic particles are selected from protons, deuterium, neutrons, electrons, and alpha particles.

[0237] 5. Example 5.1 Summary of experimental results Aspects of the present disclosure relate to a rapid electroplating method in a basic medium to produce target materials for use in particle accelerator-based radionuclide production. Examples of materials that can be irradiated using the provided method relate to isotopes of nickel and zinc electroplated onto a niobium backing material, which is typically relatively inert.

[0238] Aspects of the present disclosure include aqueous chloride forms (e.g., [ 61

[0003] The present disclosure provides a technology that enables the production of high-purity radionuclides using a target metal (e.g., a natural or enriched nickel or zinc isotope) in a particle accelerator, such as a medical cyclotron, to produce an irradiated target coating, i.e., a radionuclide. The purity of the target metal and target material backing is one aspect that enables the production of high-quality radionuclide compositions, with respect to radionuclide and chemical purity. The present disclosure provides a process that uses superior quality target metals and backings that are relatively low cost and available in large quantities for industrial radionuclide production, allowing the production of target materials that are manufactured in significantly less time than currently used methods.

[0239] Aspects of the target material preparation method of the present disclosure provide significant improvements over current target material plating methods currently found in the literature. For example, embodiments of the method of the present disclosure rely on nitric acid to dissolve the target metal source material for electroplating, as opposed to known electroplating methods utilized in the literature, which require hydrochloric and sulfuric acids. This literature uses additional chemical components used during the preparation of the plating solution, such as cyanide or bromide, which act as buffers that pose health hazards to operators during the chemical process and are not suitable for use in radiopharmaceuticals. A production method is provided that does not rely on such components, thereby being able to offset these risk factors.

[0240] Additionally, embodiments of the present disclosure incorporate the concept of an electrolytic bath or plating solution (e.g., prepared by dissolving the target metal in nitric acid followed by a buffer based on ammonium chloride / hydroxide solution) having a significantly higher pH (e.g., 9.9-10.8) that unexpectedly overcomes the challenges of producing high-quality, highly adhesive, electroplated target metals and enables target material production within a much shorter period of time. The disclosed reliance on a basic plating solution is significantly different from typical protocols that rely on acidic or weakly basic solutions to plate target coatings for target material production. IAEA Radioisotopes and Radiopharmaceuticals Reports No. 1 (INTERNATIONAL ATOMIC ENERGY AGENCY, Cyclotron produced radionuclides: Emerging positron emitters for medical applications: 64 Below is a table taken from Cu and 124I, Radioisotopes and Radiopharmaceuticals Reports 1, IAEA, Vienna (2016) 63 - "IAEA Report"), which shows the electroplating conditions for nickel electroplating procedures. [Table 2]

[0241] The higher pH of the disclosed method, achieved through the addition of NH4OH, shifts the anode-cathode to a higher potential, reduces the rate of H2 evolution on the cathode, and reduces the cycle time required for the plating procedure, e.g., from 24 hours to less than 3 hours for complete plating of 100 mg of target metal, while producing a higher quality coating with a more homogeneous and uniform porous structure. See Figure 1 (Panels A-C).

[0242] In contrast, weakly basic solutions are predominantly found in the literature, as shown in Table 2 above.

[0243] The reliance on H2SO4 is also consistently noted, as evidenced by the presence of sulfate counterions in all basic examples shown in IAEA Table 3. As a first issue, weakly basic solutions were used throughout all experiments, compared to the more alkaline pH used in the techniques described herein. This indicates that current market suppliers are unaware of, or unable to, realize the benefits of increasing the ammonium content in plating solutions. This disclosure is the first to report the benefits of increasing ammonia concentrations and using highly basic pHs in plating solutions. These benefits appear to be related to the observation that hydrogen evolution is significantly reduced due to a more uniform porosity in the crystalline structure of nickel plated on the backing material. Without being bound by theory, this is believed to be due to the protons combining with NH4 + This can be attributed to the characteristic chemical state of NH3 and its tendency to form

[0244] Furthermore, the weakly basic pH levels utilized in the prior art methods referenced in Table 2 above limit the optimum voltage that can be reached during the electroplating process due to the low NH content, which affects the achievable anode-cathode potential. In comparison, the present method describes a more alkaline plating solution that can tolerate a high anode-cathode potential, resulting in a relatively elevated optimum voltage. As a result, the electroplating duration can be reduced from an average of 24 hours to less than 3 hours while achieving a similar plating mass.

[0245] Prior to the present disclosure, the benefits associated with Nb were not anticipated, in part because it was believed that Nb would result in poor adhesion. Indeed, the implementation of a niobium backing is clearly not preferred (see, for example, Table 3 below, reproduced from an IAEA report). Prior art methods rely on producing irradiation targets based on silver, gold, or platinum as the target backing material, requiring weaker acids to dissolve the target metal for plating. However, these materials cannot withstand the acidic properties of strong acids such as HNO because they begin to dissolve on contact. Niobium, on the other hand, is highly resistant to acids at room temperature, allowing the use of more aggressive acids such as HNO. Embodiments of the disclosed method allow the use of HNO (nitric acid), which produces Ni(NO) , instead of the more commonly used HSO (sulfuric acid), which produces NiSO . Contrary to conventional wisdom, the present disclosure reveals that good adhesion between a Ni target coating and a Nb backing is possible, achieving many unexpected benefits. For example, the strong acidic properties of nitric acid allow the feedstock to be dissolved more quickly and to a higher concentration than with sulfuric acid, avoiding the loss of more expensive isotopically enriched material and thereby making the use of enriched targets more economically viable. [Table 3]

[0246] Furthermore, the predominance of NiSO4 in the IAEA report (and related report review) suggests that the nickel plating solution used was purchased from a supplier as nickel sulfate. This raises the possibility of contaminants or impurities in the plating solution, as this factor depends on source-derived parameters and the chemical supplier. This difference between 99.9% and 99.99% purity plays a major role in the radionuclide, radiochemical, and chemical purity achieved by radiopharmaceuticals incorporating radionuclides, where the presence of low-temperature copper, zinc, iron, or cadmium is problematic. Furthermore, the feasibility of prepurifying raw materials is not believed to be feasible. All procurement of chemicals and processes related to the electroplating process in embodiments of the disclosed method is carried out under controlled conditions using pure reagents and inert, non-metallic materials. This significantly reduces the possibility of contamination from trace metals or other undesirable chemicals detected during the purification process. The use of metallic tools and accessories in contact with the solution and raw materials was limited throughout the entire process. Even under less than ideal temperature and air quality conditions, the disclosed procedures ensure the production of high quality target material.

[0247] Table 3, above, on page 8 of the IAEA report, identifies viable backing materials for use with cyclotron-generated radioisotopes for medical purposes. This indicates that the advantages of Nb are not understood. This is accompanied by documented data showing poor electroplating quality due to poor adhesion. In contrast, the poor adhesion previously observed when using Nb backings was not observed when applying the electroplating method provided herein. The electrochemical plating process differs from the plasma coating process. Plasma coating alters the grain structure of the backing material through a heat treatment process, thereby causing changes in the grain structure and resulting in high bonding of the plating material to the backing material. However, these changes prevent effective dissolution in acidic solutions. In certain embodiments, niobium's inert properties and ability to withstand acid at room temperature can be used for radioisotope production by modifying the surface structure, for example, by polishing the backing material, as disclosed herein.

[0248] Applying this consensus to the production of radionuclides and plating solutions in controlled environments (such as those specified in the sections above) yields different results in terms of purification and dissolution. The data in Figures 6, 7, and 8 show the results of Nb backing at 8.4 MeV, 60 μA for 60 minutes. nat Deuterium irradiation of Ni target coating (niobium natural nickel (nat-Ni)) and Nb backing at 13 MeV, 40 μA for 40 min 61 Obtained from proton irradiation of a Ni target (niobium Ni-61) 61 The results are compiled from gamma spectrometry and observation of radionuclide impurities measured in Cu]CuCl2 solution. 61 A comparison of impurities in Cu]CuCl2 solutions was performed according to the provided method using a commercially available natural Ni (natNi) target (extracted target material).

[0249] As can be seen, irradiation of Nb backed target material prepared in accordance with the present disclosure is superior to conventional irradiation of silver on a niobium backing. nat 89.3% reduction in radionuclide impurities compared to Ni, on a niobium backing 61 Ni versus conventional silver backing nat 94% reduction in radionuclide impurities compared to Ni, and 100% reduction in radionuclide impurities on the niobium backing when considering the sum of all impurities. 61 Against Ni nat It demonstrates a 45.9% reduction in radionuclide impurities when compared to Ni.

[0250] The factors listed affect the radionuclide and chemical purity of the radionuclide, which in turn affects the purity of the radiopharmaceuticals prepared from the radionuclide, as described in more detail below:

[0251] 5.1.1 Chemical purity Trace metals and low-temperature copper 61 They compete with Cu to bind to chelators (e.g., NODAGA) in the following order: low-temperature Cu(II) (i.e., stable isotopes) > Zn(II) > Fe(III) > Sn(IV) > Ti(IV) > Al(III). Competition between these trace metals and low-temperature copper significantly reduces the yield of radiolabeling of the tracer and the purity of the radiochemical. See Innovative Complexation Strategies for the Introduction of Short-lived PET Isotopes into Radiopharmaceuticals (p105). Common sources of trace metals are the raw nickel metal powder itself, especially isotopically enriched nickel, and any metals in the equipment used, such as reagents and iron. Purification processes (ion exchange columns) allow for low-temperature (especially with regard to stable isotopes) 69 Cu and 65 Removes most of the trace metals except for Cu, which are desirable 61Since it is the same element as Cu, it passes through to the product fraction. One way to prevent contamination of the low temperature copper and the associated loss of chemical purity is to pass a dissolved nickel source (stable isotope) through the process and separate the low temperature copper from the nickel before plating (see Figure 9 for ICP-MS analysis), and Table 4 shows the results for the low temperature copper on a niobium backing. nat Ni or 61 By collision of either Ni [ 61 The chemical purity of Cu]CuCl2 and the resulting impurity profile are shown. [Table 4]

[0252] 5.1.2 Radionuclidic Purity Radionuclide purity is important in radiopharmacy because any radionuclide impurities can cause uncertainty in the radiation dose received by the patient and potentially degrade the quality of any imaging procedures performed. For example, the presence of significant levels of other radionuclides can alter biodistribution. Radionuclide samples contain some contaminants resulting from the manufacturing process or the decay of the primary radioisotope. Radionuclide impurities can arise as a result of the manufacturing process. For example, for cyclotron-produced nuclides, contaminants can be present due to impurities in the target or due to the energy of the reaction. Impurities in the target coating transform into many trace elements, increasing the impurity profile after bombardment. To control the impact of these contaminants on the radiation dose received by the patient, limits are placed on the maximum allowable level of contamination. These limits are established by government agencies, e.g., Pharmacopoeia monographs, and vary depending on the physical decay characteristics of the radionuclides and similar contaminants involved. Radionuclide purity measurements can be performed with high resolution using gamma spectroscopy on appropriate samples after bombardment. The activity of the long-lived isotopes is then extrapolated back to EoB or EoS, or even completion. The high activity released from long-lived radionuclide impurities significantly increases the cost and complexity of managing the disposal of all consumables that come into contact with the nuclide composition.

[0253] Natural nickel and 60 Deuterium irradiation of Ni and 61 Through proton irradiation of Ni, a long-lived isotope of cobalt 56 Co, 57 Co, 58 Co and 60 Co is produced. 110m Ag, 108m Ag and 109 Other long-lived radionuclides, such as Cd, are produced through irradiation of commonly used silver backing materials, which are dissolved along with the starting material during the purification process. Due to their long half-lives, the proportion of these radionuclides is 61 Compared to Cu, it increases with time, especiallynat Subsequent use of Ni as a starting material reduces the radionuclide purity of the product. Although most of the cobalt isotopes can be separated in the purification process, 110m Ag, 108m Ag and 109 Cd will eventually 61 The nickel solution is further used for recycling the Cu fraction and irradiated target coating. Long-lived radionuclides are problematic when considering the radiation burden to the patient and the accumulation of radioactive waste. Third-party target material manufacturers have not disclosed any contamination from non-niobium target material backings (e.g., silver). Methods for making and using niobium-containing target materials, as provided by this disclosure, offer advantages, for example, in terms of the radionuclide and chemical purity of samples produced after subatomic particle bombardment, isolation, and purification. 61 Cu product and 61 A detailed comparison with Cu is provided below.

[0254] Considering these factors, niobium backing materials are chosen due to their inertness to acids at room and elevated temperatures. This property allows the niobium backing material to withstand the acidic media used during the dissolution and purification process. This allows for higher radionuclide and chemical purity to be achieved in the aqueous radiometal solution, ultimately resulting in the desired 61 Radiopharmaceuticals prepared from Cu isotopes are highly pure. Although plating methods for niobium exist, this element has not been used to produce radionuclides due to poor adhesion of plated Ni materials. Ni (or 68 Regarding the generation of Ga 68The Zn (Ni) is required to be sufficiently adherent to the target material to withstand the heat load during irradiation (1200 W), pneumatic shuttle acceleration at 5 bar to 7 bar, and sudden stops at the head. However, the plated Ni (or Zn) must be sufficiently soluble during the melting and refining process. Attempts have been made to plasma coat niobium backings to plate nickel (Ni). However, this process resulted in Ni loss from the niobium backing and incomplete dissolution. The heat treatment process associated with plasma coating alters the grain structure of the niobium backing material, creating a strong bond between the plated nickel and the niobium. This strong bond makes it difficult for the nickel to completely dissolve, resulting in loss. The plasma coating process itself results in very high losses in the target coating, making its use unfeasible, especially for highly enriched target metals, which are very expensive. The main reference for this overview is the IAEA document on radionuclide production in cyclotrons, IAEA RADIOISOTOPES AND RADIOPHARMACEUTICALS, REPORTS, No. 1. (INTERNATIONAL ATOMIC ENERGY AGENCY VIENNA, 2016). Furthermore, a monetary evaluation of the acquisition costs of niobium used as a backing material indicates a 40% reduction in costs compared to commonly used backing materials such as gold, silver and platinum, with costs ranging from 80 to 120 euros per backing (single target material).

[0255] In parallel, elements related to the radiochemical purity of the labeling process can be controlled by producing the plating solution under controlled conditions as described herein. For example, by sourcing the plating solution from a raw base material such as nickel, the possibility of contamination is now independent of external sources and suppliers. Materials and equipment used in these cases include inert glass beakers and Falcon tubes (guaranteed free of any undesirable substances), Trace Select purified water, pure reagents (trace metal grade), inert target material adapters, and electrolytic cells (on the electroplating unit). Through this, trace metal contamination can be minimized or avoided altogether. This difference between 99.9% purity and 99.99% purity plays a role in the chemical purity of the resulting radionuclide and, therefore, the radiochemical purity of the radiopharmaceutical prepared from the radionuclide; in this case, the presence of low-temperature Cu, Zn, Fe, Sn, Ti, or Al, or any salts thereof, can affect the purity of the desired radionuclide ( 61 This is problematic because it competes with ZnO (Cu) for binding to the chelating agent in the tracer.

[0256] The robustness of the plating is tested through drop and scratch tests to ensure that the electrodeposited substrate on the backing can withstand the mechanical impacts of the shuttle system and demonstrate increased durability potential under the cyclotron beam.

[0257] In a specific embodiment, the target material is irradiated using an ARTMS on a GE PET trace cyclotron or a GE shuttle system with 8.4 MeV deuterium in the range of 40 μA to 45 μA for an average duration of 120 minutes, or with 13.2 MeV deuterium at 40 μA to 45 μA.

[0258] In a specific embodiment, the target material is irradiated using 8.4 MeV deuterium at a range of 40 μA to 45 μA for an average duration of 120 minutes, or 13 MeV protons at 10 μA to 100 μA using the ARTMS on the GE PET Trace Cyclotron or the GE Shuttle System.

[0259] Dissolution of Ni from the niobium backing is achieved through the use of a dissolution system in 10M HCl. 61 The Cu was then purified using two subsequent ion exchange resins in the FASTlab synthesis unit. The process time for these purifications can reach up to 60 minutes.

[0260] The obtained plating material [ 61 The average radioactivity of the CuCl solutions is 1.7-4.5 GBq. This radioactivity is measured using dose calibrators or by radionuclide purity with a calibrated gamma spectrometer, for example at PSI in Switzerland.

[0261] Gamma spectrometry measurements were performed to identify any radionuclide impurities, especially long-lived radionuclides. These results demonstrate that the niobium backing material is significantly lower than the silver backing material when using the methods disclosed herein. nat Ni and 61 The results show a reduction of 89.3% and 94% for Ni impurities. ICP-MS measurements are performed on the product by low-temperature dissolution by Labor Veritas, Switzerland, to monitor the elemental impurities present in the product according to ICH-Q3D. All detected impurities are within the adjusted ICH-Q3D concentration range (ICH-Q3D guideline, page 25).

[0262] Highly concentrated 61 Ni plating can also be achieved by proton irradiation (typically 10 μA to 100 μA, 20 minutes to 2 hours, and 61 For higher yields and industrial production using 13 MeV protons over up to one half-life of Cu, the same plating parameters as above are possible.

[0263] Following automated transport of the irradiated target material from the cyclotron to the hot cell docking station, the capsule was transferred to the QIS dissolution unit using tongs. The deformed target metal was dissolved from the niobium backing using 7 M HCl:30% H2O2 (Ultrace Analysis, Merck) (4 mL) in a 1:1 ratio. The acid-hydroxide mixture was circulated to immerse the target material and target metal surface at approximately 60 °C at 2 mL / min for approximately 23 minutes to dissolve all irradiated elements. When the target metal was completely dissolved, the acid solution containing the dissolved metal was removed, and the QIS system was flushed with 10 M HCl (3 mL). The combined acid solution was then fed to the FASTlab purification unit.

[0264] 5.2 Example 1: Preparation of target material for deuterium / proton collisions 5.2.1 Example 1.1 Preparation of plating solution 5.2.1.1 Preparation of buffer solutions Ammonium chloride (4.6 g, Aldrich: 326372, Trace Select) was weighed into a clean (metal-free) Falcon tube (50 mL) and a pre-washed magnetic stir bar was added. If any salt adhered to the walls of the Falcon tube, 6 mL of Trace Select water (Honeywell 95305) was added in one aliquot to flush the walls of the Falcon tube. 1 mL of 28% ammonium hydroxide (Sigma 338818) was added eight times using a 1000 μL pipette with the appropriate pipette tip. The lid of the Falcon tube was then closed, and the Falcon tube was then vortexed (1–2 min) (immersion in an ultrasonic bath for 1–2 min was a viable alternative) and shaken until all salt was dissolved. The Falcon tube can also be warmed (e.g., by rolling between hands) to improve solubility. The temperature (e.g., approximately 23°C, preferably 23–25°C) can be adjusted. After complete dissolution of the salt, the pH acceptance criteria of 9.28-9.62 should be verified by measuring the pH of the solution at room temperature, e.g., with an electrolytic pH meter. The Falcon tube was closed with parafilm and stored at room temperature. Any solid salt formers were redissolved before use.

[0265] 5.2.1.2 Preparation of nickel nitrate plating solution A 50 mL glass beaker was washed with nitric acid (Trace Select) followed by water (Trace Select). In a fume hood, the beaker was dried by placing it on a heating plate set at 150 °C. 210 mg of natural (isotope distribution) nickel (powder, Sigma-Aldrich, less than 50 μm, 99.7% trace metals standard, essentially free of any impurities except iron) was added to the beaker. A copper impurity level (reaching less than 0.3 ppm) was weighed into the beaker, and 4 mL of 65% nitric acid was added using a pipette. The beaker was placed back on the powered heating plate, and the stirring was set to 300 rpm. Ensure that the fume hood ventilation is functioning properly (NO2 generation). During dissolution, the solution color turned green. The solution was reduced to a volume of approximately 600 μL by evaporation, removed from the heating plate, and allowed to cool to room temperature. The remaining solution was transferred to a 50 mL metal-free Falcon tube. The glass beaker was rinsed with 2.8 mL of Trace Select water in 0.8 mL, 1 mL, and 1 mL steps, each step transferred to a Falcon tube before adding the next wash fraction. Buffer solution (4 mL), 11 mL of Trace Select water, and 3 mL of ammonium hydroxide 28% (Sigma 338818) were added to the Falcon tube. The pH of the solution was measured and adjusted to the required pH by adding ammonium hydroxide 28% (Aldrich 338818) using a sterile B-Braun syringe.

[0266] 5.2.1.3 60 Ni and 61 Examples of suitable starting materials for preparing Ni electroplating solutions Below is 60 Ni and 61 An exemplary lot of Ni (certificate provided by Isoflex, USA, March 2018). [Table 5] [Table 6] [Table 7]

[0267] The sample of natural nickel from Sigma-Aldrich was essentially free of any impurities except for iron. The amount of copper impurity was less than 0.3 ppm. See the Certificate of Analysis in Example 2. Further suitable sources of natural Ni include: Nickel powder less than 50μm, 99.7% trace metal standard Nickel rod, diameter 6.35mm, =99.99% trace metal standard Nickel foil, 0.5mm thick, 99.98% trace metals 5.2.1.4 Preparation of zinc nitrate plating solution.

[0268] A 50 mL glass beaker was washed with nitric acid (Trace Select) followed by water (Trace Select). In a fume hood, the beaker was dried by placing it on a heating plate set to 150 °C. 210 mg of natural (isotope-distributed) zinc (zinc powder, Sigma-Aldrich, less than 10 μm, greater than 98%) was weighed into the beaker, and 4 mL of 65% nitric acid was added using a pipette. The beaker was placed back on the powered heating plate, and the stirring was set to 300 rpm. Ensure that the fume hood ventilation is functioning properly (NO2 generation). During dissolution, the solution color turned green. The solution was reduced to a volume of approximately 600 μL by evaporation, removed from the heating plate, and allowed to cool to room temperature. The remaining solution was transferred to a 50 mL metal-free Falcon tube. The glass beaker was rinsed with 2.8 mL of Trace Select water in 0.8 mL, 1 mL, and 1 mL steps, each step transferred to a Falcon tube before adding the next wash fraction. 4 mL of buffer (prepared in section 5.2.1.1), 11 mL of Trace Select water, and 3 mL of ammonium hydroxide 28% (Sigma 338818) were added to the Falcon tube. The pH of the solution was measured and adjusted to the required pH by adding ammonium hydroxide 28% (Aldrich 338818) using a sterile B-Braun syringe.

[0269] Optional polishing of the backing surface In certain embodiments, if the target coating does not adhere adequately to the backing surface, the Nb backing surface may be surface treated prior to the electroplating process to improve the adhesion of the target coating. It has been found that if the backing surface is treated with polishing prior to electroplating, the adhesion results approach ideal. Without being bound by theory, one consideration is that oxides form on the surface of the niobium backing, either during manufacturing, storage, or prior use, and the presence of the oxides prevents the target metal, such as Ni or Zn, from adhering to the Nb backing. Another consideration is that the oxide removal process may provide nucleation sites on the Nb backing surface that allow for adhesion by target metal deposition.

[0270] Implementing specific surface pretreatments, such as removing the oxide layer on the receiving backing, ensured that adequate adhesion to the target coating was achieved.

[0271] In a particular embodiment, the niobium backing can be surface treated using a Bosch Impact 12 hand grinder at 50 rpm for a duration of approximately 45-60 seconds (pink corundum abrasive grit, size 60) and ethanol.

[0272] Electroplating of backing surface A niobium backing disk (28 mm x 1 mm) was obtained from high-purity Nb as described herein, washed with ethanol (high purity), and inserted into a Comecer V21204 electroplating unit. A platinum wire anode was positioned approximately 1 mm to 3 mm away from the target surface and adjusted with a polymer spacer. The target mass was determined to be 5.25 grams. The niobium backing (22 mm x 1 mm, weighing 3.3 g) was used. The plating solution was placed in an electrolytic chamber and attached to the device. The voltage was set to 4.5 V. After 5 minutes of stabilization, the measured current was 180 μA. The pump duty cycle was set to 45%. The plating solution changed from blue to transparent, and a slow decrease in current to 160 μA was observed over a 120-minute period. The plating process was stopped. The target was removed from the electrolytic cell and its weight was measured. The target material was also subjected to microscopic evaluation as shown in Figures 2 and 3 using a DINOLite digital microscope to observe the crystalline structure and surface homogeneity. The target material (Figure 33) was stored in a metal-free Falcon tube under a nitrogen atmosphere.

[0273] 5.2.1.5 Electroplating Results After electroplating was completed, the target material was subjected to microscopic evaluation using a DINOLite digital microscope to observe the crystalline structure and surface homogeneity. As can be seen in Figure 2 (Panels A-C), a homogeneous target coating with persistent adhesion was obtained.

[0274] 5.3 Example 2 High Purity [ 61 General guidelines for the production of Cu]Cl2 The objective of this example is to determine whether natural nickel and / or enriched 60 Deuterium irradiation of Ni to copper-61( 61 The goal of this effort was to enable the bulk production of Cu. 61 There was no benchmark specification for Cu. However, the inventors 60 After Ni irradiation, or nat After scaling accordingly for Ni exposure, [ 61The target performance, target geometry / material use, irradiation parameters, and chemical processing methods were optimized to produce [Cu]CuCl2. Although there were no clear pharmacopoeial specifications for radioactive copper, the test QC method was based on the (extracted [ 61 After initial irradiation and yield measurements, the commercial viability of [Cu]CuCl2 will be demonstrated. This will include evaluation of radionuclide purity and apparent molar activity. 61 To confirm the formation of Cu]CuCl2 (USZ, GE, SN), the final yield parameters were determined from each other.

[0275] This example shows two different types of targets: natural nickel ( nat Ni) target and highly enriched nickel-60( 60 Ni) targets, both of which were suitable for deuterium bombardment, except that nat Ni is available at low cost and with high purity, 60 Ni remains expensive, and efficient standards are needed. If even higher yields are desired, efforts to prepare target coatings are focused on proton-based 61 Ni(p,N) 61 It can be directly converted to Cu pathway, but concentrated 61 Considering the cost of Ni (approximately 25 USD / mg), such an approach imposes the need for recycling of the target metal.

[0276] The following list of guidelines allows for the production of high purity [Nb] from Nb target material using electroplated Zn or Ni (either isotopically enriched) coatings as provided herein. 61 Cu]CuCl2, 61 All types of targets can be used in the production of Cu. Specific details are also provided for deuterium and proton irradiation, respectively. Following this protocol, all [ 61 Cu]Cl composition was produced. [Table 8-1] [Table 8-2] [Table 8-3] [Table 8-4] [Table 8-5] [Table 8-6] [Table 8-7]

[0277] 5.4 Example 3 61 Purification and characterization of Cu]CuCl2 and waste streams The irradiated target coating was dissolved in a total volume of 7 mL of 6 M HCl with the addition of 30% hydrogen peroxide via a dissolution chamber.

[0278] Separation and purification were achieved using a FASTlab platform based on cassettes using TBP (tributyl phosphate) resin (1 mL) (particle size 50-100 μm, pre-packed, Triske) followed by weakly basic (tertiary amine, TK201) resin (2 mL) (particle size 50-100 μm, pre-packed, Triske). Each of these was pre-conditioned with HO (7 mL) and HCl (10 M, 7 mL). Cassette reagent vials were prepared using concentrated HCl (Optima grade, Fisher Scientific), NaCl (ACS, Fisher Scientific), and / or milli-Q water (Millipore system, 18 MΩ-cm resistivity), e.g., 6 M HCl (2 × 4.2 mL), 5 M NaCl in 0.05 M HCl (4.2 mL). Subsequent61 Cu was then purified using two subsequent ion exchange resins in the FASTlab synthesis unit as follows. 1) The acid-adjusted dissolution solution (approximately 7 mL) was loaded onto both columns in series and directed toward the "Ni collection fraction." The TBP resin was used to 3+ It is implemented as a guard column because it quantitatively retains ions, but Cu 2+ and Co 2+ The complex is quantitatively retained on a tertiary amine (TK201) resin. 2) To maximize Ni recovery for future recycle, both columns are washed with 6 M HCl (4 mL). 3) The TK201 column was washed with 4.5 M HCl (5.5 mL) to elute most of the cobalt salts. 4) The TK201 column is washed with HCl, 5M NaCl in 0.05M HCl (4 mL) to reduce residual acid on the resin and to further remove any residual cobalt salts. 5) Wash the TK201 column with 0.05 M HCl (3 mL) and 61 Cu]CuCl2 was quantitatively eluted.

[0279] The obtained plating material [ 61 The average radioactivity of the CuCl solutions is 1-4.5 GBq. This radioactivity was measured using a dose calibrator manufactured by Comecer or by its radionuclide purity by gamma spectrometry at PSI, Switzerland.

[0280] Gamma spectrometry measurements were performed to identify any radionuclide impurities, especially long-lived radionuclides. These results demonstrate that the niobium backing material is significantly lower than the silver backing material when using the methods disclosed herein. nat Ni and 61The impurities for Ni show a reduction of 89.3% and 94%. ICP-MS measurements were performed on the product by low-temperature dissolution by Labor Veritas, Switzerland, to monitor the elemental impurities present in the product according to ICH-Q3D. All detected impurities were within the adjusted ICH-Q3D concentration range (ICH-Q3D guideline, page 25).

[0281] Highly concentrated 61 Ni plating can also be achieved by proton irradiation (typically 80 μA to 100 μA, 1 hour to 2 hours, and 61 For higher yields and industrial production using 13 MeV protons over up to one half-life of Cu, the same plating parameters as above are possible. 5.5 Example 4: Using Nb backing target material, nat Ni(d,n) 61 Cu and 60 Ni(d,n) 61 Prepared from Cu 61 Purity and radioactivity evaluation of Cu]CuCl2 composition

[0282] This example shows a target material containing a natural nickel target coating and a target metal enriched with 60 Ni-containing target materials, i.e., nat Ni(d,n) 61 Cu and 60 Ni(d,n) 61 Cobalt radioisotopes generated by deuterium irradiation using Cu with a Nb backing, produced using Ni electrodeposited target material of the present disclosure. 61 Information on the radioactivity of Cu is presented. The irradiated material was dissolved and purified as described in Example 3.

[0283] The obtained and purified 61 Cu]Cu product and natural Ni / Nb target material and 60 The waste generated during the purification of the products of deuterium irradiation of Ni / Nb target materials was treated and analyzed by gamma spectrometry and is presented below.

[0284] The yield calculations for the thick target coating based on TENDL-2019 are for the natural Ni / Nb target material and the enriched Ni / Nb target material, respectively. 60 The isotopic abundance of the Ni / Nb target material is used.

[0285] 5.5.1 Radioactive cobalt content Table 8 shows nat The activity of the cobalt radioisotope in the different fractions after FASTlab purification is included as an average of three measurements (n = 3 irradiations) using Ni / Nb target material. The activity was extrapolated to a 3 h and 50 μA beam at EoB (end of collision) + 2 h. 61 The radioactivity of [Cu]CuCl2 was experimentally determined and found to be approximately 80% of the TENDL-2019-based estimate.

[0286] generated by irradiation with deuterium at 8.4 MeV, 80% efficiency, and 50 μA for 3 hours 61 Cu activity (EoB+2h): 3052MBq. 61 See also Figure 4 for the change in cobalt radioisotopes over time, with corresponding changes in Cu purity. [Table 9]

[0287] Table 9 shows the target metals enriched to 99% 60 Contains the calculated activity of the cobalt radioisotope obtained using Ni. Activity was extrapolated to a beam of 3 h and 50 μA at EoB (end of collision) + 2 h. Therefore, 61 The radioactivity of Cu was calculated.

[0288] Produced by deuterium irradiation at 8.4 MeV, 80% efficiency, and 50 μA for 3 hours 61 Radioactivity of Cu (EoB+2h): 11.552MBq. Changes in cobalt radioisotopes over time and 61See also Figure 5 for the corresponding change in Cu purity. [Table 10]

[0289] 5.5.2 Radioactivity and Chemical Purity Based on a combination of theoretical calculations and experimental results, nat Deuterium irradiation of Ni / Nb targets produced [ 61 Cu]CuCl2 purity, concentrated 60 Deuterium irradiation of Ni / Nb target materials 61 Cu]CuCl2.

[0290] Table 10 shows the extrapolated radioactivity of radioactive cobalt and the target metal for 50 μA, 3 h deuterium irradiation after FASTlab purification. nat Generated by Ni 61 Cu]CuCl2 solution 61 Cu purity was given. [Table 11]

[0291] Assuming a product expiration date of 8 hours after EoB, less than 0.03% of non-Cu radioisotopes ( 56 Co and 58 Co) remains in the copper fraction. This value is based on the cyclotron-generated data found in the Pharmacopoeia. 68 This was lower than the limit allowed for Ga (*0.1% at termination for non-Ga radioisotopes).

[0292] nat Derived from Ni irradiation 64 Cu (approximately 5% content at end) is the major impurity and is found to be 61 Cu reduces the radioisotopic purity of the product (shown as the gray curve in Figure 4).

[0293] In Table 11:60 Ni / Nb target material 61 Analysis of Cu radioactivity and purity and after FASTlab purification. 61 Cu]CuCl2 solution and the extrapolated radioactive cobalt activity 61 Indicates Cu purity. [Table 12]

[0294] Assuming a product expiration date of 8 hours after EoB, less than 0.01% of non-Cu radioisotopes ( 56 Co and 58 Co) remained in the Cu fraction. This value was consistent with the cyclotron-generated values ​​found in the pharmacopoeias. 68 This was 10 times lower than that tolerated for Ga (0.1% at termination for non-Ga radioisotopes).

[0295] Less than 0.02% 64 Cu remained in the copper fraction at expiration time 8 hours after EoB, 68 The results were 100 times lower than the specifications required for Ga (2% Ga radioisotope 68 Ga was tolerated).

[0296] 5.5.3 [Produced from Ni / Nb target material] 61 Purity of Cu]CuCl2: Comparison with commercially available radionuclides Table 12 compares the regulatory specifications for purity of commercially available radionuclides for natNi / Nb and enriched 60 High purity [ 61 Cu]CuCl2 after purification by FASTlab. [Table 13]

[0297] The first notable comparison is the proton irradiation 68Cyclotron production of Ga also produces long-lived radionuclides (see, for example, Applied Radiation and Isotopes, 65(10), 1101-1107, IAEA-TECDOC-1863 Gallium-68 Cyclotron Production), especially 66 Zn(p,pn) 65 Zn decay 65 Zn (half-life = 244 days) is produced. 68 Approximately 0.365% of Zn in the starting target metal 66 For Zn, about 770 Bq 65 Zn is produced from a 50 μA, 3 h beam with an energy of 13 MeV in a thick target coating (TENDL-2019 based calculations). 66 Using natural Zn with an abundance of 27.7% in Zn, 58 kBq 65 Zn is produced in a single 3-hour beam run at 50 μA, so the isotopic purity of the target metal, Zn, is very important.

[0298] [ 61 Similar to the formation of Cu]CuCl2, proton irradiation [ 64 Cyclotron production of Cu]CuCl2 also involves the long-lived cobalt radionuclide, i.e. 55 Co, 57 Co, 58 Co and 60 Co (see, for example, Nuclear Medicine & Biology, Vol. 24, pp. 35-43, 1997; Applied Radiation and Isotopes 68 (2010) 5-13). By operating with a depleted beam below 13 MeV, ( 64 Ni(p,na) 60 Co) 60 Co was reduced to 1 Bq per 3 h run at 50 μA. For beam energies below 13 MeV, 58 Ni(p,a) reaction 55 Formed from Co 55 Co remains the major impurity (half-life = 17.53 hours).57 170Bq of Co, mostly 60 Ni(p,a) 57 Co was formed at about 170 Bq under these conditions.

[0299] Note: These estimates are: 0.00376% 58 Ni, 0.00298% 60 Ni, 0.0058% 61 Ni, 0.135% 62 Ni, 99.858% 64 Like Ni, TENDL-2019 cross section data and enrichment 64 It was calculated from the thick target coating yield using the isotopic abundance of Ni.

[0300] 5.6 Example 5: Enrichment of Nb as target metal on backing target material 61 Ni 61 Cu is high purity 61 via a cyclotron equipped with a solid target system that irradiates a high-purity niobium target material plated with Ni (purity 99.42%). 61 The beam was generated by proton bombardment of a Ni-electroplated Nb backing target. The proton beam current used was up to 100 μA, with a beam energy of 13 MeV. An aluminum beam degluter was used.

[0301] The solid target irradiated material was dissolved in a total volume of 7 mL of 6 M HCl with 30% H2O2 added via a heated dissolution chamber. 61Cu was purified from metal and radiometal impurities via a GE Healthcare FASTlab2 module through a tributyl phosphate cartridge and a tertiary amine-based weak ion exchange resin containing a long-chain alcohol. The product was eluted in 3 mL of 0.05 M HCl in an ISO Class 5 environment through a Millex 4 mm Durapore PVDF 0.22 μm sterile filter into a sterile evacuated vial. Vials were handled with care using appropriate shielding and may be stored at room temperature until use using appropriate shielding for transport and handling. [Table 14]

[0302] As shown in Table 14 and Figure 6, 61 Cu is a radionuclide impurity, 110m Ag(t 1 / 2 439) and 109 In addition to Cd, especially high levels 56 Co, 60 Cu and 58 Contains Co. Commercially available [ 61 Cu]CuCl2 is a radionuclide impurity, 110m Ag and 109 In addition to Cd, especially high levels 56 Co and 58 Co. Removal of Ag and Cd isotopes from Cu-61 products by replacing silver with niobium as the backing material. 56 There was a 9-fold reduction in Co isotopes and a less than 2000-fold reduction in Ni-61 (requiring less shielding of the radioactive waste). A 50% reduction in long-lived cobalt isotopes (early final disposal of the purified waste) was also observed. From the following data, it can be seen that the [ 61 The radionuclide purity of [Cu]CuCl2 was shown to be superior to previously known methods and products. High levels of long-lived Co, Ag, and Cd radionuclides were found to reduce radiation burden for patients and the risk of complications during radiopharmaceutical manufacture and radiolabeling. 61There is a radioactive waste problem with consumables that come into contact with the Cu]CuCl2 product.

[0303] The presence of long-lived impurities creates complications in contaminant handling and waste management. These data demonstrate that the provided compositions significantly reduce the radiation burden to patients and also significantly reduce the cost and complexity of waste management. 61 All materials / consumables that come into contact with the CuCl solution must be disposed of in accordance with local government regulations. Waste disposal costs increase proportionally with the radioactivity and half-life of any radionuclide impurities present. [Table 15]

[0304] [Table 16]

[0305] 5.6.1 Endotoxin determination by Limulus amebocyte lysate (LAL test) Bacterial endotoxin was determined by LAL testing using the Charles River Endosafe™ PTS system.

[0306] [ 61 During dispensing of the [Cu]CuCl2 solution, 1 mL aliquots were dispensed for quality control testing. Testing was performed in an unclassified quality control laboratory. The solution was 61 Cu]CuCl2, 0.05 M HCl (aq). [Table 17]

[0307] [ 61 The CuCl solution (pH 1.3) was diluted prior to analysis using LAL reagent water and buffer to reach a pH value in the range of 6 to 7.6. To adjust the pH, TRIS buffer was added to [ 61Cu]CuCl2 solution.

[0308] The dilutions were then analyzed to determine the 61 Cu]CuCl2 in endotoxin-free dilution tubes as follows: dilution factor (1:75), [ 61 Mix the following reagents: Cu[CuCl] sample (10 μL), TRIS buffer (40 μL), and water (700 μL). Mix for approximately 30 seconds.

[0309] 5.6.2 Conclusion Generated after deuterium irradiation [ 61 The experimental activity of [Cu]CuCl2 was approximately 80% of the theoretical yield as calculated from TENDL-2019 cross section data.

[0310] [ 61 The main long-lived nuclides in the radioactive waste fraction from the cyclotron production of Cu]CuCl2 are 56 Co, 57 Co, 58 Co and 60 Co is a radioactive cobalt species. After 4 years, 56 Co, 57 Co and 58 Co decays below the Swiss clearance limit (LL) 60 Only Co remains. *Clearance limit (LL) means the value corresponding to the specific activity level of material at which handling of this material is no longer subject to mandatory authorization or corresponding control.

[0311] [ 61 Cu]CuCl2 99% enriched to improve product yield and purity 60 Ni or 61 Ni-containing target materials can be used. 61 The extrapolated purity of Cu is 64 It is higher because Cu is not formed as a radioisotopic impurity. 56 Co and 60 The Co content is reduced by 100 times. 57 The amount of Co is four times as much,58 The amount of Co is doubled, but the former is less radioactive ( 56 Co / 58 Co before decaying below LL), the latter ( 56 Co and 60 There will be an increase in the LL of 1 Bq / g (vs. 0.1 Bq / g for Co). Overall, the handling of Co waste will remain similar (immediate disposal vs. long-term storage after 4 years), but 60 The amount of Co is calculated by replacing natural Ni. 60 A 100-fold reduction can be achieved using Ni.

[0312] 5.7 Example 6 High purity Ga-68( 68 How to prepare Ga 68 The planned processes related to irradiation and purification for Ga production are listed below.

[0313] Exemplary Procedure for Zinc Electroplating: High Concentration (e.g., 99% or More) 68 Zn plating was performed using proton irradiation (typically 80 μA-100 μA, 13.5 MeV protons for 1-2 hours) with the same plating parameters as above for higher yields and industrial production.

[0314] On the Nb target material 68 Zn target metal was irradiated with 13.5 MeV protons on a cyclotron in the range of 10-100 μA for an average of 120 min.

[0315] Niobium backing 68 Dissolution of Zn is carried out via the ARTMS system in 10 M HCl. 68 The [Ga]GaCl was then purified using two subsequent ion exchange resins in the FASTlab synthesis unit. The average processing time for these purifications is approximately 30-60 min.

[0316] The plating material is dissolved 100% to obtain 68The mean radioactivity of [Ga]GaCl was measured and the decay-corrected yield was calculated. The measurement tools used were a dose calibrator from COMECER or its radionuclide purity by gamma spectrometry at PSI, Switzerland.

[0317] Gamma spectrometry measurements were performed to record any radionuclide impurities, especially long-lived radionuclides. At the same time, ICP-MS measurements were performed on the product by low-temperature dissolution by Labor Veritas, Switzerland, to monitor the elemental impurities present in the product according to ICH-Q3D regulations.

[0318] 6. Equivalents and Incorporation by Reference While aspects of the present disclosure have been particularly shown and described with reference to certain specific embodiments and various alternative embodiments, those skilled in the art will recognize that various changes in form and detail can be made therein without departing from the spirit and scope of the present disclosure.

[0319] All references, issued patents, and patent applications cited within the body of this specification are hereby incorporated by reference in their entirety for all purposes. In particular, U.S. Provisional Patent Application No. 63 / 409,684, filed September 23, 2022, is hereby incorporated by reference in its entirety.

Claims

1. 1. A target material for bombardment by subatomic particles, comprising: A target material comprising a backing, the backing being made of Nb, the Nb having a purity of 98.8% or more.

2. 2. The target material according to claim 1, wherein the Nb has a purity of 99% or more, 99.8% or more, preferably 99.99% or more.

3. The Nb is: Fe not exceeding 40 ppm, Ti not exceeding 60 ppm, Zn not exceeding 19 ppm, Cu not exceeding 5 ppm, Sn less than or equal to 8 ppm, less than 5 ppm Ni, and 3. The target material of claim 1 or 2, characterized by one or more of the following: 5 ppm or less Al.

4. The Nb is: Fe not exceeding 30 ppm, Ti not exceeding 10 ppm, Zn not exceeding 10 ppm, Cu less than or equal to 3 ppm, 5 ppm or less of Sn, and 3. The target material of claim 2, characterized by one or more of: less than 1 ppm Ni.

5. The Nb is: Fe not exceeding 30 ppm, Ti not exceeding 2 ppm, Zn not exceeding 10 ppm, Cu not exceeding 5 ppm, 5 ppm or less of Sn, and 3. The target material of claim 2, characterized by less than 1 ppm Ni.

6. A target material according to any preceding claim, wherein the backing has a thickness of 0.5 to 3 mm, for example 1.5 mm ± 0.3 mm.

7. further comprising a target coating; the target comprises a target metal; The target material according to any one of claims 1 to 6.

8. 8. The target material of claim 7, wherein the target coating is characterized by one or more of the following: ≦0.0005 ppm Cd, ≦0.005 ppm Co, ≦0.005 ppm Pb, ≦0.08 ppm Cu, and ≦0.15 ppm Fe.

9. 9. The target material according to claim 7 or 8, wherein the target coating has a thickness of 0.05 to 20 mm.

10. A target material according to any one of claims 6 to 9, wherein the target coating has a mass of 30 to 200 mg, for example 70 to 100 mg.

11. 8. The target material of claim 7, wherein the mass of the target coating is 70 mg ± 3 mg.

12. 8. The target material of claim 7, wherein the mass of the target coating is 50 mg ± 3 mg.

13. 13. A target material according to any one of claims 6 to 12, wherein the thickness of the target coating has a variation of no more than 15%, or no more than 10%, across the surface of the target material, for example the target coating is 15% thicker in the centre when compared to the average thickness of the coating around the periphery of the target coating.

14. The target material according to any one of claims 6 to 13, wherein the target coating is circular in shape with a diameter of 1.5 cm or less.

15. The target material according to any one of claims 6 to 14, wherein the target metal is Ni.

16. 16. The target material of claim 15, wherein the target metal is Ni of naturally occurring isotopic composition.

17. Ni is isotopically enriched with a minor isotope of Ni relative to natural Ni, and the minor isotope is ６０ Ni, ６１ Ni, ６２ Ni and ６４ Ni, for example ６０ Ni or ６１ 16. The target material of claim 15, wherein the target material is Ni.

18. 18. The target material of any one of claims 6 to 17, wherein the target metal is isotopically enriched in the minority isotope to 95% or more, 96% or more, 97% or more, 98% or more, or 99% or more.

19. The minority isotope is ６４ 18. The target material of claim 17, which is Ni.

20. 20. The target material of claim 19, wherein said target metal is isotopically enriched in said minority isotope to greater than 97%.

21. The minority isotope is ６２ 18. The target material of claim 17, which is Ni.

22. 22. The target material of claim 21, wherein said target metal is isotopically enriched in said minority isotope to greater than 99%.

23. The minority isotope is ６０ 18. The target material of claim 17, which is Ni.

24. The minority isotope is ６１ 18. The target material of claim 17, which is Ni.

25. The target material according to any one of claims 6 to 14, wherein the target metal is Zn.

26. The target metal is ６８ 26. The target material of claim 25, which is isotopically enriched in Zn.

27. The target metal is 95% or more ６８ 27. The target material of claim 26, which is isotopically enriched in Zn.

28. The target metal is 99% or more ６８ 27. The target material of claim 26, which is isotopically enriched in Zn.

29. 1. A method for preparing a target material for bombardment by subatomic particles, comprising: The target material is Backing and a target coating adhered to the backing surface, the target coating comprising a target metal; The method comprises: electroplating the target metal onto the backing surface from a plating solution; The method wherein the pH of the plating solution is 9.5 to 10.

7.

30. 30. The method of claim 29, wherein the backing is selected from Nb, Ag, Pt, Au, Al and W backings.

31. 31. The method of claim 30, wherein the backing is selected from Nb and Ag backings.

32. 32. The method of claim 31, wherein the backing is a Nb backing.

33. A method for preparing a target material according to any one of claims 29 to 32, said method comprising: electroplating the target metal onto the backing surface from a plating solution.

34. The method comprises:

32. The method of claim 31, further comprising polishing the backing surface before the electroplating.

35. The method of any one of claims 27 to 31, wherein the pH of the plating solution is from 9.5 to 10.

7.

36. 36. The method of claim 35, wherein the pH of the plating solution is between 10 and 10.

4.

37. 40. The method of any one of claims 27 to 39, wherein the plating solution comprises nitrate ions.

38. The plating solution is HNO ３ 38. The method of claim 37, comprising:

39. The method according to any one of claims 27 to 38, wherein the electroplating is carried out at a current of 120 to 180 μA.

40. The electroplating Voltage of 3.5 to 5.5V, a temperature of 20-25°C, and 40. The method of any one of claims 27 to 39, carried out under one or more conditions selected from a cycle time of 5 hours or less.

41. 41. The method of claim 40, wherein the electroplating is performed at a voltage of 4.25 to 5.25V.

42. 41. The method of claim 40, wherein the voltage is between 4.5 and 5.5 V.

43. 41. The method of claim 40, wherein the voltage is 5.5V.

44. 44. The method of any one of claims 27 to 43, wherein the volume of the plating solution is 10 mL or less.

45. 45. The method of any one of claims 27 to 44, wherein the electroplating is carried out for a period of not more than 3 hours.

46. The method of any one of claims 27 to 45, further comprising preparing the plating solution.

47. The plating solution comprises the target metal and a molar excess of HNO ３ 47. The method of claim 46, wherein the compound is prepared by combining

48. The HNO ３ 48. The method of claim 47, wherein is in the form of 65% nitric acid in water.

49. The HNO ３ However, more than 40 grams of HNO per gram of target metal ３ 49. The method of claim 48, wherein the plating solution is added at

50. A method according to any one of claims 47 to 49, wherein the target metal is in the form of a metal powder that is at least 98% pure.

51. 51. The method of claim 50, wherein the metal powder is at least 99.9% pure.

52. The preparing of the plating solution comprises adding an effective amount of NH ４ 52. The method of any one of claims 46 to 51, further comprising adjusting the pH of the plating solution by adding OH.

53. 53. The method of any one of claims 27 to 52, further comprising adding a buffer to the plating solution before the electroplating.

54. The buffer solution is NH ４ Cl and NH ４ 54. The method of claim 53, comprising OH.

55. 55. The method of claim 53 or 54, wherein the pH of the buffer is between 8.30 and 9.

30.

56. 56. The method of claim 55, wherein the pH of the buffer is between 9.35 and 9.

25.

57. A method according to any one of claims 27 to 56, wherein the electroplating is carried out in an electrolytic cell containing a stationary anode.

58. 58. The method of claim 57, wherein the anode is selected from a graphite anode and a platinum anode.

59. 60. The method of claim 58, wherein the anode is 99.999% trace metal free.

60. 60. The method of claim 58 or 59, wherein the anode is a platinum anode.

61. 61. The method of claim 60, wherein the platinum anode is in the form of a wire or foil.

62. 62. The method of any one of claims 27 to 61, wherein the plating solution comprises 10 ppm or less of Fe.

63. The plating solution comprises: Ga, Lu, Pb, Y at 0.1 ppm or less Zn, Co, less than 0.3 ppm Cd, Cr, Al, Mn, Mo, Sn, Ti, and V at 1 ppm or less; 63. The method of claim 62, comprising one or more of: up to 1000 ppm of Group 1 and Group 2 elements.

64. The method of any one of claims 27 to 63, wherein the target metal is Ni.

65. 65. The method of claim 64, wherein the target metal is native Ni.

66. The target metal is isotopically enriched with a minor isotope of Ni relative to natural Ni, and the minor isotope is ６０ Ni, ６２ Ni, ６１ Ni and ６４ 65. The method of claim 64, wherein the metal is selected from Ni.

67. 67. The method of claim 66, wherein said target metal is isotopically enriched in said minority isotope to 95% or greater.

68. 68. The method of any one of claims 64 to 67, wherein the method further comprises purifying the plating solution to remove copper prior to the electroplating.

69. 69. The method of claim 68, wherein the plating solution contains 0.1 ppm or less of Cu.

70. The method of any one of claims 27 to 63, wherein the target metal is Zn.

71. The target metal is ６８ 71. The method of claim 70, wherein the Zn is isotopically enriched.

72. The target metal is up to 95% or more ６８ 72. The method of claim 71, wherein the Zn is isotopically enriched.

73. The plating solution Ga, Lu, Pb, Y at 0.1 ppm or less Co at most 0.3 ppm, Cd, Cr, Al, Mn, Mo, Sn, Ti, and V at 1 ppm or less; 73. The method of claim 70 or 72, characterized by having one or more of the following elements in the ranges described: Group 1 and Group 2 elements, less than or equal to 1000 ppm.

74. A target material prepared according to the method of any one of claims 27 to 73.

75. A high purity radionuclide composition, said composition comprising a radionuclide and having a radionuclide purity of 95.0% or greater for said radionuclide at the end of synthesis; the radionuclide is a Cu radionuclide, and / or The composition comprises: 0.1 Bq / g or less １１０ｍ Ag, 0.1 Bq / g or less １０８ｍ Ag, and 0.1 Bq / g or less １０９ A high purity radionuclide composition comprising one or more of: Cd.

76. 76. The composition of claim 75, wherein the composition is an aqueous solution and comprises the radionuclide in the form of a radionuclide cation.

77. 77. The composition of claim 76, wherein the aqueous solution further comprises chloride anions.

78. 78. The composition of claim 77, wherein the chloride anion is present in molar excess of the radionuclide cation.

79. 79. The composition of any one of claims 75 to 78, wherein the radionuclide is a Cu radionuclide.

80. The radionuclide is ６１ 80. The composition of claim 79, wherein the metal is Cu.

81. The radionuclide is ６８ 80. The composition of claim 79, wherein the compound is Ga.

82. The composition comprises: 0.1 Bq / g or less １１０ｍ Ag, 0.1 Bq / g or less １０８ｍ Ag, and 0.1 Bq / g or less １０９ 82. The composition of any one of claims 75 to 81, comprising one or more of: Cd.

83. The composition comprises: 1500 Bq / g or less ５６ Co, 100 Bq / g or less ５７ Co, 15,000 Bq / g or less ５８ Co, and 15Bq / g or less ６０ 82. The composition of any one of claims 75 to 81, comprising one or more of:

84. The composition comprises: 1500 Bq / g or less ５６ Co, 100 Bq / g or less ５７ Co, 15,000 Bq / g or less ５８ Co, 15Bq / g or less ６０ Co, and / or below: 1 Bq / g or less １１０ｍ Ag, 1 Bq / g or less １０８ｍ Ag, and 1 Bq / g or less １０９ 84. The composition of claim 83, having two or more of: Cd.

85. and wherein the radionuclide is not a Cu radionuclide and the composition is selected from the group consisting of: 0.1 Bq / g or less １１０ｍ Ag, 0.1 Bq / g or less １０８ｍ Ag, and 0.1 Bq / g or less １０９ 79. The composition of any one of claims 75 to 78, comprising one or more of: Cd.

86. 86. The composition of any one of claims 75 to 85, having a chemical purity for said radionuclide of 99 mole % or greater.

87. The composition is an aqueous solution, Fe less than 2 mg / L, The total is less than 1 mg / L ６９ Cu and ６５ Cu, Zn less than 2 mg / L; Sn less than or equal to 0.01 mg / L; Ti less than or equal to 0.01 mg / L, Al less than 2 mg / L; As less than 1 mg / L; 1 mg / L or less of Ni; 86. The composition of claim 85, wherein any one of Cr, Cd, Co, and Y is 0.1 mg / mL or less.

88. 88. The composition of claim 87, wherein the composition comprises 2 mg / L or less of Fe.

89. 88. The composition of claim 87, wherein the composition comprises 1 mg / L or less of Cu.

90. 88. The composition of claim 87, wherein the composition comprises 1 mg / L or less of Ni.

91. Radioactivity concentration of 0.25 to 25 GBq / mL at the time of calibration; a molar activity of 10-100 MBq / nmol at the time of calibration, and Radioactivity greater than 500 MBq at the end of synthesis (EoB+2 hours), 91. The composition according to any one of claims 75 to 90, characterized by one or more of the following:

92. 1. A method for making a high purity radionuclide composition comprising a radionuclide, said method comprising: irradiating a target metal of the target material of any one of claims 7 to 26 or claim 74 in a particle accelerator to produce an irradiated target coating; and isolating said high purity radionuclide composition.

93. 93. The method of claim 92, wherein the high purity radionuclide composition is according to any one of claims 75 to 86.

94. The isolating step comprises:

93. The method of claim 92, comprising dissolving the irradiated target coating in an aqueous HCl solution to obtain a chloride radionuclide solution.

95. 95. The method of claim 94, wherein the aqueous HCl solution is greater than 5M HCl solution.

96. The isolating step comprises:

96. The method of claim 94 or 95, further comprising purifying the chloride radionuclide solution to reduce chemical impurities.

97. 97. The method of any one of claims 92 to 96, wherein said irradiating is carried out for one half-life of said radionuclide.

98. 98. The method of claim 97, wherein the irradiation is for 60 to 120 minutes.

99. The irradiating step comprises:

99. The method of any one of claims 92 to 98, comprising bombarding the target coating with protons, deuterium or alpha particles.

100. 100. The method of claim 99, wherein the target metal is bombarded with deuterium.

101. 100. The method of claim 99, wherein the deuterium has a beam energy of 9 MeV or less and / or a beam current of 60 μA or less.

102. 102. The method of claim 101, wherein the deuterium has a beam energy of 3 to 9 MeV.

103. 102. The method of claim 101, wherein the deuterium has a beam current of 10 to 60 μA.

104. The target metal is natural Ni, or ６０ Ni, and the radionuclide is ６１ Cu, ６１ Cu reacts with the following reaction: ｎａｔ Ni(d,n) ６１ Cu and ６０ Ni(d,n) ６１ The method according to any one of claims 100 to 103, wherein the metal is produced according to one of the following: Cu.

105. 100. The method of claim 99, wherein the target metal is bombarded with protons.

106. 106. The method of claim 105, wherein the protons have a beam energy of 18 MeV or less and / or a beam current of 120 μA or less.

107. 107. The method of claim 106, wherein the protons have a beam energy of 6 to 18 MeV.

108. 107. The method of claim 106, wherein the protons have a beam current of 10 to 120 μA.

109. The target metal is ６１ Ni, and the radionuclide ６１ Cu and the following reaction: ６１ Ni(p,n) ６１ Cu ６１ Cu]CuCl ２ The method according to any one of claims 104 to 108, wherein

110. The target metal is ６４ Contains Zn and radioactive nuclides ６１ Cu, ６１ Cu reacts with the following reaction: ６４ Zn(p, α) ６１ The method according to any one of claims 104 to 108, wherein the method is produced according to Cu.

111. The target metal is ６０ Ni, and the radionuclide is ６０ Cu, ６０ Cu reacts with the following reaction: ６０ Ni(p,n) ６０ The method according to any one of claims 104 to 108, wherein the method is produced according to Cu.

112. The target metal is ６２ Ni, and the radionuclide is ６２ Cu, ６２ Cu reacts with the following reaction: ６２ Ni(p,n) ６２ The method according to any one of claims 104 to 108, wherein the method is produced according to Cu.

113. The target metal is ６４ Ni, and the radionuclide is ６４ Cu, ６４ Cu reacts with the following reaction: ６４ Ni(p,n) ６４ The method according to any one of claims 104 to 108, wherein the method is produced according to Cu.

114. The target metal is ６８ Zn, and the radionuclide is ６４ Cu, ６４ Cu reacts with the following reaction: ６８ Zn(p, αn) ６４ The method according to any one of claims 104 to 108, wherein the method is produced according to Cu.

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