Pure iodine-123 production by small cyclotron for medical use

For improvement of radionuclidic purity of¹²³I a method was elaborated to obtain highly enriched [¹²³Te] tellurium. Using this new TeO₂ target the optimum irradiation conditions have been investigated for the production of¹²³I via¹²³Te (p,n)¹²³I and the radionuclide impurity levels were also determined.     

Iodine-123 production at a small cyclotron for medical use

An improved method has been developed to obtain highly enriched [¹²³Te] tellurium for the production of medically important¹²³I. Excitation function of the¹²³Te(p,n)¹²³I reaction, production yields and radionuclidic impurity levels were determined as a function of bombarding energy and target thickness.     

Cyclotron production of high-purity iodine-123 for medical applications

Iodine-123 is recognized today as the best radioiodine available for use in diagnostic nuclear medicine. At UC Davis, a continuous flow method was developed and has been operational since 1974 providing high-purity¹²³I made indirectly by means of the¹²⁷I(p, 5n)¹²³Xe→¹²³I reaction. Targetry and radiochemical systems are described, as well as in-progress developments for total system automation. A comparison of different quality¹²³I products is made based upon radionuclidic and dosimetry considerations. The high-purity, no-carrier-added¹²³I produced at Crocker Nuclear Laboratory is being used in many research labeling efforts in proteins, amino acids, antibiotics, fatty acids, and hormones.     

Hippuran-123I: Preparation and quality control

A kit-like procedure is described for the labelling of Hippuran by exchange in a melt with carrier-free iodide-123 directly formed from the decay of¹²³Xe. Decay and subsequent melting for 15 min at 180°C are performed in one and the same ampoule. This results in a transfer of 95% of the¹²³I-activity into Hippuran with a residual¹²³I-content of <1.0%. Quality control is based on thin-layer chromatography. Contaminants are discussed and a comparison is made with commercial preparations of Hippuran-¹³¹I.     

Experiences in the routine production of123I via the124Te(p, 2n)123I reaction with a low energy cyclotron

This paper deals with the results and experimental observations obtained in routine production of¹²³I via¹²⁴Te(p, 2n)¹²³I reaction, using the low energy cyclotron (protons, E_max=22 MeV) at the German Cancer Research Center in Heidelberg. The reaction was studied during the past 4 years using¹²⁴TeO₂ targets with various levels of enrichment. The purpose of the study was to determine which target material provided the highest quality and most economical production of¹²³I. A viable routine production was defined as one in which¹²³I could be conveniently and reproducably prepared in reasonable purity while maintaining a low cost for the entire process. Different methods of sublimation of¹²³I activity from the¹²⁴TeO₂ target were examined to determine the optimal conditions for recovery of radioactivity and recycling of target material. A rapid method is described which permits quantitative separation of¹²³I while allowing only a negligible loss of¹²⁴TeO₂.     

An iodine-123 generator/iodination kit: A preliminary report

Preliminary results are described of a¹²³Xe filled device to serve as a combination¹²³I generator/iodination kit.¹²³X was produced in the Brookhaven Linac Isotope Producer (BLIP) by the reaction¹²⁷I(p, 5n)¹²³Xe. The device consists of a small glass ampoule containing an internal glass breakseal and a flanged neck on which was crimped a multi-injection type septum. The ampoule contained a hydrogen sulfide atmosphere to assure that the iodine generated from the decay of the xenon was in the form of iodide. Following an adequate period for¹²³Xe to decay (this period can be used for shipment), a needle is forced through the septum breaking the seal and residual gases are pumped off. The¹²³I in the form of iodide can then be rinsed from the ampoule with any desired solvent or reagent added directly to the device to carry out an iodination in an enclosed environment. Preliminary results of both iodine recovery and iodinations have been promising. This research was supported by the US Department of Energy under Contract No. DE-ACO2-76CH0016.     

Anion-exchange and solvent extraction studies on the separation of radioiodine with particular reference to the production of 123I via proton irradiation of 123Te metal target

The separation of radioiodine was investigated using two wet chemical procedures, namely anion-exchange and solvent extraction. Some factors affecting the separation, such as HCl, NaOH and tetrabutyl ammonium bromide (TBAB) concentrations, used solvents ethyl acetate, benzene and carbon tetrachloride and different quaternary ammonium salts were studied. For each procedure the optimum conditions were deduced. The separation of ¹²³I was effected from proton-irradiated ¹²³Te target under the optimized conditions of the two procedures. The yield of ¹²³I obtained using the Dowex 21k anion-exchanger and tetrabutyl ammonium bromide solution as eluting agent was 88±3%; the radionuclidic purity was high and the time needed was 60 minutes. In solvent extraction process using TBAB in ethyl acetate as the extracting agent, the yield of ¹²³I was low (47±3%), the radionuclidic purity was not as good as in the anion-exchange method, and the time needed was 150 minutes. Therefore, the anionexchange method is preferable. A comparison of this wet chemical method of separation of ¹²³I with the commonly used dry distillation method is given. The wet method appears to be more suitable when a ¹²³Te metal target is used.     

Iodination methods for routine preparation of 17-123I-heptadecanoic acid and 15-(123I-phenyl)-pentadecanoic acid

The diagnosis of the myocardial diseases with 17¹²³I-heptadecanoic acid and recently 15-(p-¹²³I-phenyl)-pentadeconoic acid has been applied successfully. A high labeling yield and short reaction time is desired for routine applications. The over-all yield of the complete procedure is the most important consideration. Different labeling approaches were evaluated to increase the yield of the entrire procedure. So each laboratory is able to select the method appropriate for their individual demands and possibilities.     

Excitation functions of proton-induced nuclear reactions on124Xe: Production of123I

Highy enriched gaseous¹²⁴Xe /99.9%/ is used to perform instrumental measurements of excitation functions of the¹²⁴Xe/p, 2n/¹²³Cs and¹²⁴Xe/p, pn/¹²³Xe reactions up to the proton energy of 33 MeV. Differential and integral yields of¹²³I have also been determined /6.6 h after irradiation/.     

Kinetics of 17-(123I) iodoheptadecanoic acid in myocardium of rats

Myocardial uptake and turnover of 17-(¹²³I)-iodoheptadecanoic acid, injected i.v., was studied in rats. Kinetics of radioactivity incorporated into myocardial tissue and heart lipids as well as myocardial radioactivity recovered as¹²³I iodide were determined. Maximal heart uptake of IHA (7.9% dose/g heart) was observed as early as 30 sec., p.i., followed by mono-component elimination period. Already 10 to 30 sec p.i. 70 to 80% of total myocardial radioactivity was recovered as¹²³I iodide. IHA was incorporated only in modest amounts into myocardial phospholipids and triglycerides. Time course of total myocardial radioactivity grossly paralleled that recovered as¹²³I iodide. These findings indicate stringent limitations in utility of IHA as a tracer for assessment of β-oxidation.     

Synthesis of [123I] iodoantipyrine to study the high-LET characteristics of Auger electrons in mammalian cells

4-Iodoantipyrine was synthesised from phenazone, labeled with¹²³I and administered to cells in culture. 4-[¹²³I]iodoantipyrine carries the radionuclide across the cell membrane allowing one to study the biological effects of the very short ranged Auger electrons emitted by this isotope. The formulation used to prepare this compound proves to be free of reagents that may have an adverse effect on the mitotic activity of cells in culture. By observing micronuclei frequencies in human lymphocytes and CHO-K1 cells the high-LET characteristics of Auger electrons could be demonstrated. Compared to extracellular disintegrations from [¹²³I]NaI and¹²³I-human serum albumin, a substantial reduction in the variation in radiosensitivity of these cell types was noted when treated with 4-[¹²³I] iodoantipyrine.     

123I production at the Milan AVF cyclotron

The production of¹²³I from enriched¹²⁴Te is described. Preliminary experiments on a distillation separation of iodine from the Te target have been performed and the method seems promising in comparison to the time-consuming chemical separation technique.     

Chemical processing of 123I with a modified Bio-Rex 5 resin

The Bio-Rex 5 resin was used for the recovery of ¹²³I, producedin a cyclotron by irradiation of a ¹²⁴ Xe target. Initially fouranion exchange resins AG1-X8, AG2-X8, Amberlite IRA-93 and Bio-Rex 5 wereused, but none of them gave good separations. Bio-Rex 5, consisting of a largeportion of tertiary and a smaller portion of quaternary amino groups, wasthen modified so that the resin contained only tertiary amine functional groupsand this modified resin was used for the separation. The concentrations ofiodide solutions were ca 5 ppb and the volumes about 120 ml. For measurementof iodide, ¹³¹I was added as tracer. In this study 6 columns ofvarious sizes were used and the best of them, in terms of maximum recoveryand minimum volume of NaOH for elution, was selected for routine production.     

Production of123I and28Mg by high-energy nuclear reactions for applications in life sciences

The advantages of high energy cyclotrons as compared to small compact cyclotrons for the production of special radionuclides are outlined. The routine production of¹²³I (T=13.3 h) and²⁸Mg (T=21.1 h) by means of high energy nuclear reactions at the Jülich Isochronous Cyclotron is described. The reaction¹²⁷I(d,6n)^{123 123}I at 78 to 64 MeV is used for the production of¹²³I with thick target yields of 8 mCi/μAh and high radionuclidic purity. The practical experience in the application of this process, which is well suited for the production of Na¹²³I and for¹²³Xe-exposure labelling techniques, is reported.²⁸Mg is produced by the²⁷Al(α, 3p)²⁸Mg reaction at E_α=140 to 30 MeV with thick target yields of 40 μCi/μAh. The carrier-free²⁸Mg is separated from the matrix activities by coprecipitation and anion exchange with chemical yields of 80%.     

Experiences in routine production of123I in Manitoba for delivery to other Canadian centres

An experience at¹²³I production with a low beam current cyclotron used in combination with the¹²⁴Te(p, 2n)¹²³I reaction on 90.8% enrichment¹²⁴Te is described.     

Enriched stable isotopes for 123I production: Pathways and prospects

Large-scale production of radioisotopes for medical application was impeded by limited capabilities of the electromagnetic separation. Nowadays the centrifuge separation process involves more than two dozens of chemical elements. The cost of isotopes is incomparably lower than of those produced by electromagnetic separation, which has made enriched isotopes more practicable and has extended their application scope. The development of new isotope targets has ensured the realization of more effective schemes of ¹²³I production. The processes of ¹²⁴Xe and ¹²³Te production are reviewed.     

123 Phases in CeLa2Cu2MgO8 samples

A tetragonal 123 phase with the composition close to CeLa₂ { Cu ₂ ²⁺ } [Mg²⁺]O₈ (the braces indicate the Cu(2) positions; the brackets indicate the Cu(1) positions) with the parameters a = b = 0.3909(3) nm, c = 1.6591(8) nm was prepared at 860°C under an oxygen atmosphere with an elevated oxygen pressure. When the lanthanum-for-barium substitution was incomplete, the resulting 123 phase had the composition close to CeLa_1.7Ba_0.3{ Cu _1.7 ²⁺ } [Mg]O₈ with the unit cell parameters a = b = 0.3868(3) nm, c = 1.6578(8) nm that contains Cu³⁺ in the Cu(2) positions. The partial substitution of barium for lanthanum (the melting point of barium oxide is almost 500°C lower that of the lanthanum oxide) appreciably facilitated the synthesis: the 123 phase in this sample was more than 90%. The existence of Cu³⁺ in the Cu(2) positions enhanced the electrical conductivity of the sample.     

A facility for the production of iodine-123 by spallation of caesium

A facility for the continuous production of iodine-123 by spallation of elemental caesium by 482 MeV protons has been in operation at a TRIUMF beam dump for about 2 years. Radioxenon from the target is efficiently trapped on alumina which is subsequently used to remove the¹²¹Te decay product. The yield is 100 mCi/h from a 20 gm/cm² target at 10 μA. Impurities are¹²⁵I<2% and¹²¹Te<0.2% at 27 hours after end of production. The¹²³I consists mainly of iodide along with significant iodate impurity. The product is used extensively in Canadian clinics for thyroid analyses and for labelling radiopharmaceuticals.     

Improving the radiochemical purity determination of 123I-labeled metaiodobenzylguanidine

The HPLC method originally applied at the Nuclear Engineering Institute (IEN) for the radiochemical purity determination of ¹²³iodine labeled m-iodobenzylguanidine (¹²³I-mIBG) takes 18.5 min. The final product release also depends on this result, and to facilitate this stage, we aimed to decrease this analysis time. We also intended to use fewer toxic compounds, if feasible. The optimization approach used herein was a combination of factorial and mixture designs to study simultaneously the selected variables. Analysis time, resolution and chromatograms aspect were the measured responses. The qualitative analysis of these responses provided the best chromatographic separation conditions that were 52 mM KH₂PO₄ in a solution of ethanol and water (1:1), applying a flow rate of 0.50 mL min^?1 and C18 column (4.6 × 250 mm, 5 μm). These optimum conditions not only decreased the analysis time in 61 %, but also allowed the reduction of mobile phase toxicity. To assure reliable data, method validation was performed for these conditions. The method has proved its specificity, the detection limit found was 3.70 × 10^?4 MBq mL^?1 and the quantification limit has corresponded to 1.11 × 10^?3 MBq mL^?1. Repeatability and intermediate precision has not exceeded 3 and 5 %, respectively, and the accuracy has matched the interval of 95–105 %. This new method has been routinely applied in the radiochemical purity determination of ¹²³I-mIBG at IEN.     

A rapid and high-yield aqueous phase preparation procedure for123I-labelled meta-iodobenzylguanidine

A new, aqueous phase preparation procedure for¹²³I-mIBG /meta-iodobenzylguanidine/ is described. It comprises a copper-catalyzed exchange reaction between aqueous¹²³I-iodide and mIBG at 150 °C for 45 min, a purification via anion-exchange chromatography, and a sterilization via micropore filtration. Overall preparative yield, radiochemical purity and specific activity amount to >90%, >99.7% and >10¹⁵ Bq.mol^–1 mIBG, respectively. Other features are simplicity /no evaporation of water or other solvents/, reproducibility of labelling yield and radiochemical purity, and speed /total time required 1.5 h/.