The natBr(p,x)73,75Se nuclear processes: a convenient route for the production of radioselenium tracers relevant to amino acid labelling

A possible route for the production of no-carrier-added (n.c.a.) ⁷³Se (T_1/2=7.1 h) and ⁷⁵Se (120 d) is introduced. d,l-2-Amino-4-([⁷³Se]methyl-seleno) butanoic acid (d,l-[⁷³Se]selenomethionine) with an overall radiochemical yield of >40% could be prepared via a 3-step polymer-supported synthesis after successful separation of ⁷³Se from KBr targets. Excitation functions for the ^natBr(p,x) ^72,73,75Se processes were measured from threshold up to 100 MeV utilizing pellets of pressed KBr. Targets were irradiated at the NAC cyclotron with proton beams having primary energies of 40.4, 66.8 and 100.9 MeV. The calculated ⁷³Se yield (EOB) for 1 h irradiation in 1 μA of beam at the optimum proton energy range of 62→42 MeV is 81.4 MBq (2.2 mCi), and the calculated ⁷⁵Se yield (EOB) for the overall range 62 MeV→threshold for the same irradiation conditions is 0.97 MBq (0.026 mCi).     

Excitation functions of (p, 2n) and (p,pn) reactions and differential and integral yields of 123I in proton induced nuclear reactions on highly enriched 124Xe

Excitation functions were measured for (p, 2n) and (p, pn) reactions on 99.9% enriched ¹²⁴Xe from threshold up to 44 MeV. The (p, 2n) reaction is much stronger than the (p, pn) channel; above 36 MeV, however, the two processes have almost equal cross sections. Differential yields of ¹²³I were measured experimentally as a function of proton energy and were also calculated from the excitation functions. Our experimental and theoretical yield data are consistent within 15%, but are lower by a factor of 2 than the literature experimental values. Our studies show that the optimum energy range for the production of ¹²³I is E_p = 29 → 23 MeV. The theoretically expected thick target yield of ¹²³I at 6.6 h after EOB is 11.2 mCi/μAh, and is in agreement with the high-current experimental production yields.     

Chemical processing for production of no-carrier-added selenium-73 from germanium and arsenic targets and synthesis of l-2-amino-4-([73Se]methylseleno) butyric acid (l-[73Se]selenomethionine)

The Ge(⁴He, xn) and ⁷⁵As(p, 3n) reactions were compared as the best potential routes for routine production of selenium-73 (⁷³Se) for medical applications. With 26 MeV α particles, available with compact cyclotrons, the first reaction required an enriched ⁷⁰Ge target of sodium metagermanate to give a production yield of 1 mCi/μAh (0.037 GBq/μAh) in a 105 mg/cm² target. With 55 MeV protons the As(p, 3n) reaction on natural arsenic yielded 20 mCi/μAh (0.74 GBq/μAh) in a 685 mg/cm² target. A simple method was developed and optimized for both targets in order to isolate and purify the no-carrier-added selenium in the elemental form with a radiochemical yield greater than 75% in less than 90 min. An automated radiochemical processing unit has been designed for the routine production of 100–150 mCi (3.7–5.5 GBq) batches of carrier-free ⁷³Se ready for radiopharmaceutical labeling. 30 mCi (1.11 GBq) (EOS) of l-2-amino-4-([⁷³Se]methylseleno) butyric acid (l-[⁷³Se]selenomethionine) ready for injection with a specific activity of 5 Ci/mmol (185 GBq/mmol) (EOS) were obtained through a fast chemical synthesis. Radiation absorbed dose estimates for l-[⁷³Se]selenomethionine have been determined. A value of 0.70 rem/mCi (0.19 mSv/MBq) administered was calculated for the risk from irradiation in man. The first human PET investigation with [⁷³Se]selenomethionine showed a very good delineation between liver and pancreas.     

Production of 38K via the 35Cl(α, n)- process at a compact cyclotron

Excitation functions were measured by the stacked-foil technique for the reactions ³⁵Cl(α, n)³⁸K and ³⁵Cl(α, αn) ^34mCl up to E_α = 26 MeV. Thin foils of poly(1,1-dichloroethene) sandwiched between thin Al foils were used as targets for cross section measurements. The chlorine content of the polymer foil was determined via neutron activation analysis. Cross section data and calculated thick target yields of ³⁸K and ^34mCl show that the optimum energy range for the production of ³⁸K is E_α = 22.5→7 MeV; the thick target yield of ³⁸K amounts to 5.5 mCi/μA·15 min and the level of ^34mCl is < 0.2%. Thick target yields were also measured experimentally under high current production conditions using NaCl as target material; the result (1.8 mCi ³⁸K/μA·15 min) agrees with the published data. ³⁸K is produced in 10 mCi quantities for applications in humans. Results of quality control are given.     

Production of 38K via the 38Ar(p,n)-process at a small cyclotron

The excitation function of the ³⁸Ar(p, n)³⁸K reaction was measured from threshold up to 18 MeV by the activation technique using isotopically enriched ³⁸Ar as target gas. Differential and integral yields of ³⁸K were calculated. The optimum energy range for production was found to be E_p = 16 → 12 MeV, the ³⁸K yield at saturation amounting to 21 mCi (777 MBq)/μA. Experimental thick target yields of ³⁸K were determined under high current production conditions using ^natAr and enriched ³⁸Ar as target gases. The ³⁸Ar(p, n)³⁸K process is ideally suited for production of ³⁸K at a small cyclotron.     

Excitation functions of high-energy 3He- and alpha-particle induced nuclear reactions on natural krypton with special reference to the production of 82Sr

Excitation functions were measured for ^natKr(³He, xn)^82,83,85Sr and ^natKr(³He, pxn)^83,84,86Rb reactions over the energy range 20–92 MeV, and for ^natKr(α, xn)^82,83,85Sr and ^natKr(α, pxn)^83,84,86Rb processes from 20 to 120 MeV. Thick target yields of ^82,83,85Sr were calculated. At a given incident energy, the ³He-particle induced process gives a higher ⁸²Sr-yield than the α-particle process. For E_3He = 90→20 MeV the expected ⁸²Sr-yield is 35 μCi (1290 kBq)/μAh and the ⁸⁵Sr/⁸²Sr ratio is 0.35. For E_α = 120→20 MeV the calculated yield of ⁸²Sr amounts to 52 μCi (1920 kBq)/μAh and the ⁸⁵Sr/⁸²Sr ratio is 1.24.     

Excitation functions of proton induced nuclear reactions on natural tellurium and enriched 123Te: Production of 123I via the 123Te(p,n)123I-process at a low-energy cyclotron

Excitation functions were measured by the stacked-foil technique for (p, xn) reactions up to E_p = 20 MeV on natural tellurium and enriched ¹²³Te. Thick target yields were calculated for the formation of ¹²¹I, ¹²³I, ¹²⁴I, ¹²⁶I, ¹²⁸I and ¹³⁰I from natural tellurium, and ¹²²I and ¹²³I from enriched ¹²³Te. The optimum energy range for the production of ¹²³I via the ¹²³Te(p, n)¹²³I reaction is E_p = 14.5 → 11.0 MeV, and the theoretical thick target yield 4 mCi/μAh. The levels of the three major impurities ¹²⁴I, ¹²⁶I and ¹³⁰I are directly dependent on the ¹²⁴Te, ¹²⁶Te and ¹³⁰Te contents, respectively, in enriched ¹²³Te. The levels of impurities determined experimentally under high-current production conditions agree with those calculated from the cross section data. A comparison of the three direct methods of ¹²³I-production, viz. ¹²⁴Te(p, 2n)¹²³I, ¹²³Te(p, n)¹²³I and ¹²²Te(d, n)¹²³I, under optimum conditions for each reaction, is given. The yield and impurity-level data suggest that the ¹²³Te(p, n)¹²³I reaction has a great potential for production in a low-energy cyclotron, if highly enriched ¹²³Te (>91%) is used.     

Excitation functions and yields for 111In production using 113, 114,natCd(p,xn)111In reactions with 65 MeV protons

Excitation function for the ¹¹³Cd(p,3n)¹¹¹In and ¹¹⁴Cd(p,4n)¹¹¹In reactions were measured by the stacked-foil technique in the energy range from 63 to 3 MeV. The results were compared with theoretical calculations based on the hydrid model using the well developed computer code ALICE. For the same energy range, the effective cross-sections were determined for the ^natCd(p,xn)¹¹¹In reactions. At the initial proton energy of 63 MeV for production of ¹¹¹In from ¹¹³Cd, ¹¹⁴Cd and ^natCd the cumulative yields were found as 16.7, 15.7 and 10.4 mCi/μ Ah respectively. The contamination of the undesired nuclide ^114mIn was determined. The no carrier added (NCA) ¹¹¹In was separated from the cadmium cyclotron-target by a procedure based on ion exchange chemistry. The radionuclidic purity of the final radioindium was determined.     

Production and purification of 89Zr,a potential PET antibody label

The production of ⁸⁹Zr via the (p, n) reaction on ⁸⁹Y using 11 MeV protons was studied. Thick target yields at saturation were measured to be 100 ± 10 mCi/μA while thin target (57 mg/cm²; 11 MeV > E_p > 10 MeV) yields were found to be 43 ± 4 mCi/μA. ⁸⁹Zr was separated from the Y target by extraction into 0.03 M dibutyl phosphate in dibutyl ether. Back-extraction into 4 M HF followed by anion exchange column chromatographic purification results in high purity no carrier added ⁸⁹Zr with radiochemical yield of 84% ± 4%. Yttrium contamination is estimated to be less than the picogram level. ⁸⁹Zr-linked to proteins via DTPA may be useful as a PET antibody label.     

Excitation functions for the formation of some radioisotopes of rubidium in proton induced nuclear reactions on natKr, 82Kr and 83Kr with special reference to the production of 81Rb(81mKr) generator radionuclide

Excitation functions were measured using the “stacked gas cell” technique for the formation of ⁸¹Rb, ^82mRb, ⁸³Rb and ⁸⁴Rb in proton induced nuclear reactions on natural krypton and isotopically enriched ⁸²Kr and ⁸³Kr over the proton energy range of 5–30 MeV. From the experimental data for various enrichments of ⁸²Kr, ⁸³Kr, ⁸⁴Kr and ⁸⁶Kr in target gases, absolute cross-sections were deduced for the reactions ⁸²Kr(p,2n)⁸¹Rb, ⁸³Kr(p,3n)⁸¹Rb, ⁸²Kr(p,n)^82mRb, ⁸³Kr(p,2n)^82mRb, ⁸⁴Kr(p,3n)^82mRb, ⁸³Kr(p,n)⁸³Rb, ⁸⁴Kr(p,2n)⁸³Rb, ⁸⁴Kr(p,n)⁸⁴Rb and ⁸⁶Kr(p,3n)⁸⁴Rb. From those data the differential and integral thick target yields of ⁸¹Rb were calculated. The method of choice for the production of ⁸¹Rb(^81mKr) generator radionuclide is the ⁸²Kr(p,2n)-process on highly enriched ⁸²Kr. Our results show that the optimum energy range for production is E_p = 27 → 19 MeV: the thick target yield of ⁸¹Rb amounts to 48 mCi (1776 MBq)/μAh and the level of 6.47 h ^82mRb impurity to ∼7%. Due to the high yield of the process sufficient quantities of ⁸¹Rb can be produced even at cyclotrons with E_p ≈ 20 MeV.     

Excitation functions of proton-induced reactions on natFe and enriched 57Fe with particular reference to the production of 57Co

Excitation functions of the reactions ^natFe(p,xn)^55,56,57,58Co, ^natFe(p,x)⁵¹Cr, ^natFe(p,x)⁵⁴Mn, ⁵⁷Fe(p,n)⁵⁷Co and ⁵⁷Fe(p,α)⁵⁴Mn were measured from their respective thresholds up to 18.5 MeV, with particular emphasis on data for the production of the radionuclide ⁵⁷Co (T_1/2=271.8 d). The conventional stacked-foil technique was used, and the samples for irradiation were prepared by an electroplating or sedimentation process. The measured excitation curves were compared with the data available in the literature as well as with results of nuclear model calculations. From the experimental data, the theoretical yields of the investigated radionuclides were calculated as a function of the proton energy. Over the energy range E_p=15→5 MeV the calculated yield of ⁵⁷Co from the ⁵⁷Fe(p,n)⁵⁷Co process amounts to 1.2 MBq/μA h and from the ^natFe(p,xn)⁵⁷Co reaction to 0.025 MBq/μA h. The radionuclidic impurity levels are discussed. Use of highly enriched ⁵⁷Fe as target material would lead to formation of high-purity ⁵⁷Co.     

Investigation of the natZn(p,x)62Zn nuclear process up to 70 MeV: a new 62Zn/62Cu generator

The excitation function of the ^natZn(p,x)⁶²Zn nuclear process was measured by the stacked-foil technique up to a proton energy of 70 MeV to obtain accurate data for production of the ‘mother nuclide’ (⁶²Zn) of the PET related β⁺ emitting radioisotope ⁶²Cu. Investigations were also made on the ⁶⁶Zn(p,x)⁶²Zn and ^natZn(p,xn)⁶⁶Ga processes and on the ⁶⁶Zn(p,n)⁶⁶Ga reaction using ^natZn and highly enriched ⁶⁶Zn. The excitation functions were compared with the published data. Thick target yields for the ^natZn(p,x)⁶²Zn and ^natCu(p,xn)⁶²Zn processes were also calculated up to 70 MeV. On the basis of these calculations the ^natZn+p process results in higher yield for ⁶²Zn above 50 MeV than the ^natCu+p process. The latter process is presently used for practical production of ⁶²Zn. In an energy window from 70 to 30 MeV the available EOB yield of the ^natZn+p reactions is around 19 mCi/μA h (0.7 GBq/μAh) that makes the ^natZn(p,x)⁶²Zn process a good candidate for routine generator production.     

Calculation of induced reactions of 3He-particles on natSb in 10–34 MeV energy range

Calculations for the excitation functions of the ¹²¹Sb(³He, xn) ^121,122,123I, and ¹²³Sb(³He xn) ^{122,123,124,125}I reactions have been carried out using statistical and pre-equilibrium nuclear reaction models in 10−34 MeV energy range. These excitation functions have been used to derive the excitation functions of the ^natSb(³He, xn)^121,123,124I reactions and compared with reported measurements. For studying the improvement with measurements two values of the diffuseness parameter a_w equal to 0.9 and 0.7 fm have been used in the calculations. The dependence of pre-equilibrium calculations on the initial exciton numbers has also been considered.     

Excitation functions of (alpha,xn) reactions on (nat)Rb and (nat)Sr from threshold up to 26 MeV: possibility of production of (87)Y, (88)Y and (89)Zr.

Excitation functions were measured by the stacked-foil technique for (nat)Rb(alpha,xn)(87m,87m+g,88)Y and (nat)Sr(alpha,xn)(86,88,89)Zr reactions from their respective thresholds up to 26 MeV. The samples for irradiation were prepared by sedimentation and pellet pressing techniques. The measured data were compared with those available in the literature. From the excitation functions, integral yields of the products were calculated. The suitable energy ranges for the production of (87)Y and (88)Y via (nat)Rb(alpha,xn) processes and of (89)Zr via the (nat)Sr(alpha,xn) process are E(alpha)=26-->20 MeV, E(alpha)=26-->5 MeV and E(alpha)=20-->8.5 MeV, respectively. The respective yields amount to 8.2, 0.08 and 0.9 MBq/microA h. Production of (88)Y is feasible if a waiting time of about 2 months is allowed to let the impurities decay out. Also, (87)Y can be produced with a relatively low impurity of (88)Y. The yields of both (88)Y and (87)Y via the present routes are, however, appreciably lower than those via the (nat)Sr(p,xn) processes. There is a possibility to produce (89)Zr via the alpha-particle irradiation of (nat)Sr. The yield is rather low but would be considerably increased if enriched (86)Sr would be used as target material. The radionuclidic impurity levels in all the three products are discussed.     

Study of the excitation function for the deuteron induced reaction on 64Ni(d,2n) for the production of the medical radioisotope 64Cu

The production of ⁶⁴Cu, a radioisotope of considerable interest for the application in nuclear medicine for PET imaging and radioimmunotherapy, was investigated by deuteron bombardment of enriched ⁶⁴Ni target up to E_d=20.5 MeV. The experimental excitation function for the reaction ⁶⁴Ni(d,2n)⁶⁴Cu was measured using the stacked foil irradiation technique followed by HPGe γ-ray analysis at 1346 keV and is compared with earlier literature values. Cross-section data for the ⁶⁴Ni(d,p)⁶⁵Ni reaction are determined for the first time. Thick target yields are derived and compared with results of other production routes.     

Cross sections and production yields of 66Ga and 67Ga for proton reactions in natural zinc

Cross sections and production yields of ⁶⁶Ga and ⁶⁷Ga for the Zn(p,xn) ^66,67Ga reactions were measured in the energy region from 4 to 31 MeV. The results were compared with the data available in the literature.     

Production of 73Se via the 70Ge(α, n)-process using high current target materials

Some development work relevant to the production of ⁷³Se via the ⁷⁰Ge(α, n)-process was carried out. A copper-germanium alloy with Ge content of about 40% was found to withstand 28 MeV α-particle extracted beams of up to 30 μA. For irradiations with internal beams of up to 80 μA a Cu₃ Ge intermetallic compound (Ge content 27.4%), obtained via simultaneous electrodeposition of germanium and copper on a Cu-backing, proved to be more suitable. A thermochromatographic method was developed to separate radioselenium; at 900°C the removal yield was >90%. The chemical state of the radioselenium taken up in H₂O₂ was ⁷³SeO₃²⁻. Using ∼97% enriched ⁷⁰Ge in the intermetallic compound an experimental ⁷³Se batch yield (at EOB) of ∼57 mCi (2.1 GBq) was achieved. The product was of high radionuclidic and chemical purity. A technique combining anodic oxidation and solvent extraction was developed to recover enriched ⁷⁰Ge from the used target.     

Excitation function measurements of 40Ar(p,3n)38K, 40Ar(p,2pn)38Cl and 40Ar(p,2p)39Cl reactions

For the production of ³⁸K, excitation functions of the ⁴⁰Ar(p,3n)³⁸K reaction and its accompanying reactions ⁴⁰Ar(p,2pn)³⁸Cl, and ⁴⁰Ar(p,2p)³⁹Cl were measured at the proton energy of 20.5–39.5 MeV to determine the optimum conditions of irradiation. Target cells containing argon gas were prepared using specially developed tools in an argon-replaced glove box. In the ⁴⁰Ar(p,3n)³⁸K, ⁴⁰Ar(p,2pn)³⁸Cl, and ⁴⁰Ar(p,2p)³⁹Cl reactions, the maximum cross sections were 6.7±0.7, 34±3.3 and 11±1.2mbarn at 37.6, 39.5 and 32.0 MeV, respectively, and the saturation thick target yields were calculated to be 560, 2200, and 1300¹ MBq/μA, respectively, at an incident energy of 39.5 MeV (¹ integral yield above 21 MeV).     

Cyclotron production of PET radionuclides: No-carrier-added fluorine-18 (109.77 min; β + 96.9%; EC 3.1%) with high-energy protons on sodium targets

The production of no-carrier-added (NCA) ¹⁸F from reactions induced by high-energy protons on Na-containing targets was studied. Single (mCi/μAh) and cumulative yields (mCi/μAh) for ¹⁸F were measured in the 67.5–20 MeV proton energy range. Total cross sections (mbarns) were then calculated from the experimental radionuclide yields. Preliminary results of a radiochemical process to separate and purify NCA ¹⁸F from Na targets are also reported and evaluated. The production of ¹⁸F from Na is compared with other existing techniques as well as with other high-energy proton-induced reactions on solid targets (Al, Mg) reported previously. Other radionuclides (i.e. ²⁴Na, ²²Na, ⁷Be and ^34mCl) were also produced with protons on NaCl and Na₂CO₃ targets. The effects of these radiocontaminants is also discussed. Finally, a comparison is made for the ²³Na(p,x) excitation function, measured experimentally and calculated using the ALICE82 nuclear reaction code.     

Cyclotron production of PET radionuclides: 34mCl (33.99 min; β + 53%; IT 47%) with protons on natural isotopic chlorine-containing targets

Thin- and thick-target yields for the production of ^34mCl (31.99 min; β + 53%; IT 47%) with high-energy protons on natural isotopic chlorine targets were measured in the 67.5–20.0 MeV energy range. The total cross section for the reactions ³⁵Cl(p,pn) (Q = -12.8 MeV) and ³⁷Cl(p,p3n) (Q = -31.7 MeV) was measured. The total cross section peaked at 30 MeV with a value of 108±14.6 (13.5%) mbarn. The ^34mCl cumulative yield reached 591±80 (13.5%) mCi/μAh with a 67.5-MeV proton beam exiting at 20 MeV. The potential to produce ^34mCl for research and radiopharmaceutical syntheses is discussed based upon current accelerator capabilities. Other aspects of the potential use of ^34mCl (i.e. radionuclidic, radiochemical purities, specific activities) are also discussed.