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.     

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.     

New cross section data on68Zn(p, 2n)67Ga andnatZn(p,xn)67Ga nuclear reactions for the development of a reference data base

Excitation functions were measured by stacked-foil technique for the⁶⁸Zn(p, 2n)⁶⁷Ga,⁶⁸Zn(p,3n)⁶⁶Ga,^natCu(p,xn)⁶²Zn,^natZn(p,xn)⁶⁷Ga,^natZn(p,xn)⁶⁶Ga,^natZn(p,px)⁶²Zn and^natZn(p,αx)⁶¹Cu nuclear reactions in the energy range from 15–35 MeV. The experimental excitation functions were compared with published data. Our present measurements not only increase the number of available cross section data points for the above reactions, but for some reactions (and in some energy regions) values are presented for the first time.     

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.     

Radiochemistry,Production Processes,Labeling Methods,and ImmunoPET Imaging Pharmaceuticals of Iodine-124

Target-specific biomolecules, monoclonal antibodies (mAb), proteins, and protein fragments are known to have high specificity and affinity for receptors associated with tumors and other pathological conditions. However, the large biomolecules have relatively intermediate to long circulation half-lives (>day) and tumor localization times. Combining superior target specificity of mAbs and high sensitivity and resolution of the PET (Positron Emission Tomography) imaging technique has created a paradigm-shifting imaging modality, ImmunoPET. In addition to metallic PET radionuclides, ¹²⁴I is an attractive radionuclide for radiolabeling of mAbs as potential immunoPET imaging pharmaceuticals due to its physical properties (decay characteristics and half-life), easy and routine production by cyclotrons, and well-established methodologies for radioiodination. The objective of this report is to provide a comprehensive review of the physical properties of iodine and iodine radionuclides, production processes of ¹²⁴I, various ¹²⁴I-labeling methodologies for large biomolecules, mAbs, and the development of ¹²⁴I-labeled immunoPET imaging pharmaceuticals for various cancer targets in preclinical and clinical environments. A summary of several production processes, including ¹²³Te(d,n)¹²⁴I, ¹²⁴Te(d,2n)¹²⁴I, ¹²¹Sb(α,n)¹²⁴I, ¹²³Sb(α,3n)¹²⁴I, ¹²³Sb(³He,2n)¹²⁴I, ^natSb(α, xn)¹²⁴I, ^natSb(³He,n)¹²⁴I reactions, a detailed overview of the ¹²⁴Te(p,n)¹²⁴I reaction (including target selection, preparation, processing, and recovery of ¹²⁴I), and a fully automated process that can be scaled up for GMP (Good Manufacturing Practices) production of large quantities of ¹²⁴I is provided. Direct, using inorganic and organic oxidizing agents and enzyme catalysis, and indirect, using prosthetic groups, ¹²⁴I-labeling techniques have been discussed. Significant research has been conducted, in more than the last two decades, in the development of ¹²⁴I-labeled immunoPET imaging pharmaceuticals for target-specific cancer detection. Details of preclinical and clinical evaluations of the potential ¹²⁴I-labeled immunoPET imaging pharmaceuticals are described here.     

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.     

Production of123I using the CV-28 cyclotron at IPEN-CNEN/SP

These studies had the purpose of establishing the optimal conditions for the production of¹²³I through the¹²⁴Te (p, 2n)¹²³I reaction, using the CV-28 Cyclotron (E_max=24 MeV for protons) at IPEN-CNEN/SP. Two different targets (TeO₂ and TeO₂+2% Al₂O₃) were irradiated in order to check their physical resistance against beam current (up to 12 A) and length of irradiation (10 min — 2h), and to evaluate the recovery of the radioiodine produced, by a dry distillation process with a high frequency induction furnace. Later on, enriched¹²⁴TeO₂ (96.2%) targets were irradiated, and¹²³I was produced routinely with a production yield of (3. 31±0.07) mCi/Ah, 1.7% of¹²⁴I at EOB and radiochemically pure.     

Determination of70Ge(n,p)70Ga and74Ge(n,p)74Ga reaction cross sections for a fission neutron spectrum

The fission neutron spectrum averaged cross-sections for the reactions⁷⁰Ge(n,p)⁷⁰Ga and⁷⁴Ge(n,p)⁷⁴Ga have been determined. The averages of four determinations are, respectively, (3.10±0.30) mb and (0.00938±0.00059) mb. The present values are, to the authors' knowledge, the first experimental data on the fission averaged cross-section for these reactions.     

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.     

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/.     

Development of a process for routine production of123I using the127I(p, 5n)123Xe→123I reaction

The object of this paper is to give details of a production method for¹²³I, now in routine use at Harwell. We employ the (p, 5n) reaction, irradiating a liquid target of di-iodomethane (CH₂I₂) spiked with additional iodine, with 58 MeV protons. A yield of ∼9 mCi/μAh is obtained; the only detectable radionuclidic impurity is¹²⁵I, present to the extent of ∼0.15% by activity at the time of separation of Xe from I.     

Quality assurance of iodine-124 produced via the nuclear reaction124Te (d, 2n)124I

For more than a year,¹²⁴I (T=4.15 d) has been produced routinely with a compact cyclotron by irradiation of¹²⁴TeO₂ with 14 MeV deuterons, followed by dry distillation of the iodine radioisotopes formed from irradiated target materials. The following by-products have been measured and compiled in each charge: 13.2-d¹²³I, 60-d¹²⁵I, 13.0-d¹²⁶I, 12.4-h¹³⁰I and 8.02-d¹³¹I. The data show that after 45 h decay time, the sum of the activities of these nuclides is less than 5% of the¹²⁴I activity. Observation of this limit has been required by the Swiss Regulatory Agencies for a PET study of cell proliferation in human brain tumors using [¹²⁴I] IUdR.     

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.     

Cross section measurements for (n, p) and (n, 2n) reactions of rare-earth isotopes at neutron energies from 13.5 to 14.6 MeV

Cross sections for (n, p) and (n, 2n) reactions have been measured on some rare-earth isotopes at neutron energies of 13.5-14.6 MeV using activation technique. Data are reported for the following reactions:¹⁵⁰Nd(n, 2n) ¹⁴⁹Nd, ¹⁴⁸Nd(n, 2n) ¹⁴⁷Nd, ¹⁴²Nd(n, 2n) ¹⁴¹Nd, ¹⁶⁰Gd(n, 2n) ¹⁵⁹Gd, ¹⁵⁸Gd(n, p) ¹⁵⁸Eu, ¹⁴⁶Nd(n, p) ¹⁴⁶Pr, ¹⁴¹Pr(n, p) ¹⁴¹Ce and ¹³⁹La(n, p) ¹³⁹Ba. The neutron fluences are determined by the cross sections of ²⁷Al(n, a) ²⁴Na and ⁹³Nb(n, 2n) ^92mNb reactions. This revised version was published online in August 2006 with corrections to the Cover Date.     

Activation cross-sections for some (n, 2n), (n,p) and (n, γ)-reactions

The average fission neutron cross-sections of the reactions²³³U(n, 2n)²³²U,⁶⁰Ni(n, p)⁶⁰Co and²⁷Al(n, p)²⁷Mg and the resonance integrals of the (n, γ)-reactions of the nuclides¹⁸¹Ta,¹⁷⁶Lu,¹⁷⁵Lu,⁶⁴Ni,⁵⁹Co and²⁶Mg have been determined by the activation method following the well-known conventions. The results verify some of the existing values and present data for hitherto unknown or poorly known reactions.     

Analysis of excitation functions of (p,n) reactions for the stable isotopes of zinc and copper up to 40 MeV

Journal of Radioanalytical and Nuclear Chemistry - The excitation functions of 63Cu(p,n)63Zn, 65Cu(p,n)65Zn, 66Zn(p,n)66Ga, 67Zn(p,n)67Ga and 68Zn(p,n)68Ga reactions were computed using the...     

Ethylene dicysteine (EC) and ethyl cysteinate dimer (ECD) complexes of Ga(III) and In(III)

Ethylene dicysteine (EC) and ethyl cysteinate dimer (ECD) complexes of⁶⁷Ga and¹¹¹In were prepared and the complexation yield and radiochemical purity estimated by paper chromatography, paper electrophoresis and solvent extraction into chloroform.¹¹¹In-EC was found to be anionic, whereas¹¹¹In-ECD was neutral. EC complexes of⁶⁷Ga and¹¹¹In were stable upto 6 hours and expectedly less lipophilic than ECD complexes. ECD complexes of⁶⁷Ga and¹¹¹In were unstable in aqueous medium, but highly stable in chloroform. The utility of the work for stabilisation of products as organic extract and the possible role and limitation for the development of new⁶⁸Ga radiopharmaceuticals and of bifunctional chelating agent (BCA) for¹¹¹In are discussed.     

Excitation functions of proton induced nuclear reactions on natural tellurium up to 18 MeV for validation of isotopic cross sections

Summary Excitation functions of proton induced nuclear reactions on natural Te were investigated up to 18 MeV. Cross sections for production of ^{121,123,124,126,128,130g}I and ^121gTe were measured. The new experimental data were compared with the results of ALICE-IPPE model calculations and with data found in the literature and measured on natural or enriched Te targets. The new data can be effectively used for validation of recommended cross sections of medically relevant ¹²³I and ¹²⁴I.     

Optimization of irradiation parameters for67Ga production fromnatZn (p,xn) nuclear reactions

Excitation functions for^natZn (p, xn) and (p, pxn) nuclear reactions in the 5–45 MeV proton energy range were measured. Evaluations were made both of target thickness and proton energy in order to optimize the⁶⁷Ga production rate, at the same time minimizing contamination by the⁶⁶Ga. Optimal irradiation conditions, depending both on the beam current available and on the power dissipated into the target were determined.     

Determination of the 54Fe(n, 2n)53gFe and 54Fe(n, 2n)53mFe cross sections averaged over a 235U fission neutron spectrum

The reaction cross sections averaged over a ²³⁵U fission neutron spectrum have been measured for the ⁵⁴Fe(n, 2n)^53gFe and ⁵⁴Fe(n, 2n)^53mFe threshold reactions. The values found are, respectively: (1.14±0.13) mb, and (0.52±0.16) mb. The measured cross sections are referred to the (111±3) mb standard cross section of the ⁵⁸Ni(n, p)^58m+gCo reaction. The (81.7±2.2) mb standard cross section value for the ⁵⁴Fe(n, p)⁵⁴Mn reaction, was also used as a monitor to check the results obtained with the Ni standard, leading to an excellent agreement.