Optimization of 124I production via 124Te(p,n)124I reaction.

(124)I was produced, via (124)Te(p,n)(124)I reaction, in greater than 3.7GBq (100 mCi, EOB) amount by bombarding (124)TeO(2) targets at 24 microA current for about 8h. This was achieved by keeping the target at 37 degrees relative to the beam during irradiation, by sweeping the beam across the target and by keeping the incident energy of the proton at 14.1MeV. The time-averaged yield of our 8h run was 21.1 MBq/microAh (0.57 mCi/microAh), which was 90% of the theoretical yield calculated using thick target yield data obtained from the reported excitation function for the reaction. At the end of bombardment, the level of (125)I and (126)I impurities, co-produced with (124)I, were 0.03% and 0.007%, respectively.     

Excitation functions of 124Te(d,xn)124,125I reactions from threshold up to 14 MeV: comparative evaluation of nuclear routes for the production of 124I.

Excitation functions of the nuclear reactions 124Te(d,xn)124-125I were measured from their respective thresholds up to 14.0 MeV via the stacked-foil technique. Thin samples were prepared by electrolytic deposition of 99.8% enriched 124Te on Ti-backing. The excitation function of the 124Te(d,n)125I reaction was measured for the first time. The present data for the 124Te(d,2n)124I reaction are by an order of magnitude higher than the literature experimental data but are in good agreement with the results of a hybrid model calculation. From the measured cross sections, integral yields of 124,125I were calculated. The energy range Ed = 14 --> 10 MeV appears to be the best compromise between 124I-yield and 1251-impurity. The calculated 124I-yield amounts to 17.5 MBq/microA h and the 125I-impurity to 1.7%. A critical evaluation of the three nuclear routes for the production of 124I, viz. 124Te(d,2n)-, 124Te(p,n)- and 125Te(p,2n)-processes, is given. The reaction studied in this work proved to be least suitable. The 124Te(p,n)-reaction gives 124I of the highest radionuclidic purity, and a small-sized cyclotron is adequate for production purposes. The 125Te(p,2n)-reaction is more suitable at a medium-sized cyclotron: the yield of 124I is four times higher than in the other two reactions but the level of 0.9% 125I-impurity is relatively high.     

Excitation functions of 125Te(p, xn)-reactions from their respective thresholds up to 100 MeV with special reference to the production of 124I.

Excitation functions of the nuclear reactions 125Te(p, xn) (119,120m, 120g, 121,122,123,124,125)I were measured for the first time from their respective thresholds up to 100 MeV using the stacked-foil technique. Thin samples were prepared by electrolytic deposition of 98.3% enriched 125Te on Ti-backing. In addition to experimental studies, excitation functions were calculated by the modified hybrid model code ALICE-IPPE. The experimental and theoretical data generally showed good agreement. From the measured cross section data, integral yields of (123,124,125)I were calculated. The energy range Ep 21 --> 15 MeV appears to be very suitable for the production of the medically interesting radionuclide 124I (T(1/2) = 4.18 d; I(beta)+ = 25%). The thick target yield of 124I amounts to 81 MBq/microA h and the level of 125I-impurity to 0.9%. The 125Te(p,2n)124I reaction gives 124I yield about four times higher than the commonly used 124Te(p,n)124I and 124Te(d,2n)124I reactions. The proposed production energy range is too high for small cyclotrons but large quantities of 124I can be produced with medium-sized commercial machines.     

Some optimisation studies relevant to the production of high-purity 124I and 120gI at a small-sized cyclotron.

Optimisation experiments on the production of the positron emitting radionuclides 124I(T(1/2) = 4.18d) and (120g)I (T(1/2) = 1.35 h) were carried out. The TeO(2)-target technology and dry distillation method of radioiodine separation were used. The removal of radioiodine was studied as a function of time and the loss of TeO(2) from the target as a function of oven temperature and time of distillation. A distillation time of 15 min at 750 degrees C was found to be ideal. Using a very pure source and comparing the intensities of the annihilation and X-ray radiation, a value of 22.0 +/- 0.5% for the beta(+) branching in 124I was obtained. Production of 124I was done using 200 mg/cm(2) targets of 99.8% enriched 124TeO(2) on Pt-backing, 16 MeV proton beam intensities of 10 microA, and irradiation times of about 8 h. The average yield of 124I at EOB was 470 MBq(12.7 mCi). At the time of application (about 70 h after EOB) the radionuclidic impurity 123I (T(1/2) = 13.2 h) was <1%. The levels of other impurities were negligible (126I < 0.0001%;125I = 0.01%). Special care was taken to determine the 125I impurity. For the production of (120g)I only a thin 30 mg target (on 0.5 cm(2) area) of 99.9% enriched 120TeO(2) was available. Irradiations were done with 16 MeV protons for 80 min at beam currents of 7 microA. The 120gI yield achieved at EOB was 700 MBq(19 mCi), and the only impurity detected was the isomeric state 120 mI(T(1/2) = 53 min) at a level of 4.0%. The radiochemical purity of both 124I and 120gI was checked via HPLC and TLC. The radioiodine collected in 0.02 M NaOH solution existed >98% as iodide. The amount of inactive Te found in radioiodine was <1 microg. High purity 124I and 120gI can thus be advantageously produced on a medium scale using the low-energy (p,n) reaction at a small-sized cyclotron.     

Alpha-particle induced reactions on natSb and 121Sb with particular reference to the production of the medically interesting radionuclide 124I.

Excitation functions of the reactions (nat)Sb(alpha,xn)(123,124,125,126)I and (121)Sb(alpha,xn)(123,124)I were measured from their respective thresholds up to 26 MeV, with particular emphasis on data for the production of the medically important radionuclide (124)I. The conventional stacked-foil technique was used, and the samples for irradiation were prepared by a sedimentation process. The measured excitation curves were compared with the data available in the literature. From the experimental data the theoretical yields of the investigated radionuclides were calculated as a function of the alpha-particle energy. The calculated yield of (124)I from the (nat)Sb(alpha,xn)(124)I process over the energy range E(alpha) = 22-->13 MeV amounts to 1.02 MBq/microA x h and from the (121)Sb(alpha,n)(124)I reaction over the same energy range to 2.11 MBq/microA x h. The radionuclidic impurity levels are discussed. Use of (nat)Sb as target material would not lead to high-purity (124)I. Using highly enriched (121)Sb as target, production of (124)I of high radionuclidic purity is possible; the batch yield, however, is low.     

Preparation of 124I solutions after thermodistillation of irradiated 124TeO2 targets.

The 4.15-d radionuclide 124I is produced via the nuclear reaction 124Te(d, 2n) 124I by irradiation of 96% enriched 124TeO2 with 14 MeV deuterons, followed by thermodistillation. In order to minimise the loss of 124I, the quartz distillation tube was fitted to a stainless steel helix capillary trap directly behind the end of the furnace. Using this device, distillation yields of more than 80% were routinely obtained, and the activity was concentrated in markedly less than 100 microL solution. The 124I produced by this method proved to be useful for labelling proteins and IUdR.     

(3)He-particle-induced reactions on (nat)Sb for production of (124)I.

Excitation functions of the reactions (nat)Sb((3)He,xn)(124,123,121)I were measured from their respective thresholds up to 35 MeV, with particular emphasis on data for the production of the medically important radionuclide (124)I. The conventional stacked-foil technique was used. From the experimental data the theoretical yields of the three investigated radionuclides were calculated. The yield of (124)I over the energy range E9(30He) = 35 --> 13 MeV amounts to 0.95 MBq/microA h. The radionuclidic impurities are discussed. A comparison of (3)He- and alpha-particle-induced reactions on antimony for production of (124)I is given. The alpha-particle-induced reaction on enriched (121)Sb and the (3)He-particle-induced reaction on enriched (123)Sb would lead to comparable (124)I yields, but the level of impurities in the latter case would be somewhat higher.     

PET quantitation and imaging of the non-pure positron-emitting iodine isotope 124I.

A series of PET studies using phantoms is presented to characterize the imaging and quantitative performance of the positron-emitting iodine isotope 124I. Measurements were performed on the 2D-PET scanner GE 4096+ as well as on the Siemens PET scanner HRR+ operated in both 2D and 3D modes. No specific correction was applied for the gamma-rays emitted together with the positrons. As compared to 18F, in studies with 124I there is a small loss of image resolution and contrast, and an increase in background. The quantitative results varied between different scanners and various acquisition as well as reconstruction modes, with an average relative difference of -6 +/- 13% (mean+/-SD) in respect of the phantom radioactivity as measured with gamma-ray spectroscopy. We conclude that quantitation of a radiopharmaceutical labelled with 124I is feasible and may be improved by the development of specific corrections.     

Evaluation of excitation functions of proton and deuteron induced reactions on enriched tellurium isotopes with special relevance to the production of iodine-124

Cross-section data for the production of medically important radionuclide ¹²⁴I via five proton and deuteron induced reactions on enriched tellurium isotopes were evaluated. The nuclear model codes, STAPRE, EMPIRE and TALYS, were used for consistency checks of the experimental data. Recommended excitation functions were derived using a well-defined statistical procedure. Therefrom integral yields were calculated. The various production routes of ¹²⁴I were compared. Presently the ¹²⁴Te(p,n)¹²⁴I reaction is the method of choice; however, the ¹²⁵Te(p,2n)¹²⁴I reaction also appears to have great potential.     

Evaluation of irradiation parameters of enriched (124)Xe target for (123)I production in cyclotrons.

The production of high-purity (123)I that utilizes an isotopically enriched (124)Xe target and bombardment with 30MeV protons, through the reactions (124)Xe (p, 2n) (123)Cs-->(123)Xe-->(123)I and (124)Xe (p, pn) (123)Xe-->(123)I, is described. The aim of this work was to improve the production parameters, such as (124)Xe load pressure, beam current, decay time and target heating to recover (123)I to obtain high-production (123)I yield at low cost.     

Assessment of the short-lived non-pure positron-emitting nuclide 120I for PET imaging

Purpose The non-pure positron-emitting iodine isotope ¹²⁰I (T _1/2=81 min) is a short-lived alternative to ¹²⁴I. ¹²⁰I has a positron abundance more than twice that of ¹²⁴I and a maximum positron energy of 4 MeV. This study was undertaken to evaluate and characterise the qualitative and quantitative PET imaging of ¹²⁰I.Methods ¹²⁰I was produced via the ¹²⁰Te(p,n) reaction on highly enriched ¹²⁰Te. The measurements were done with the Siemens scanner HR+ and the 2D PET scanner GE PC4096+. A cylinder containing three cold inserts and a phantom resembling a human brain slice were used to evaluate half-life, positron abundance and background correction. To analyse the image resolution, a 1-mm tube placed in water was filled with ¹²⁰I and ¹⁸F. Comparisons with ¹⁸F, ¹²⁴I and ¹²³I (measured with SPECT) were made using the Hoffman 3D brain phantom.Results The half-life of 81.1 min was reproduced by the PET measurements. The PET-based positron abundance ranged from 47.9% to 55.0%. The reconstructed image resolution found with the HR+ was 5.4 mm FWHM (12.3 mm FWTM), in contrast to 4.6 mm (8.6 mm) when using ¹⁸F. Erroneous positive and negative numbers of radioactivity found in the cold inserts became nearly zero when the background of γ-coincidences was corrected for. Images of the Hoffman phantom were inferior to those obtained when ¹⁸F or ¹²⁴I was applied but superior to the ¹²³I-SPECT images.Conclusion Our data show that ¹²⁰I of high radionuclidic purity can be regarded as a suitable nuclide for the PET imaging of radioiodine-labelled pharmaceuticals.     

A simple and rapid technique for radiochemical separation of iodine radionuclides from irradiated tellurium using an activated charcoal column

A simple and inexpensive method for the separation of medically useful no-carrier-added (nca) iodine radionuclides from bulk amounts of irradiated tellurium dioxide (TeO₂) target was developed. The β⁻ emitting ¹³¹I radionuclide, produced by the decay of ¹³¹Te through the ^natTe(n, γ)¹³¹Te nuclear reaction, was used for standardization of the radiochemical separation procedure. The radiochemical separation was performed by precipitation followed by column (activated charcoal) chromatography. Quantitative post-irradiation recovery of the TeO₂ target material (98–99%), in a form suitable for reuse in future irradiations, was achieved. The overall radiochemical yield for the complete separation of ¹³¹I was 75–85% (n=8). The separated nca ¹³¹I was of high, 99%, radionuclidic and radiochemical purities and did not contain detectable amounts of the target material. This method can be adopted for the radiochemical separation of other different iodine radionuclides produced from tellurium matrices through cyclotron as well as reactor irradiation.     

c-erbB2 protein overexpression in breast cancer as a target for PET using iodine-124-labeled monoclonal antibodies.

ICR 12, one of a panel of rat monoclonal antibodies recognizing the external domain of the human c-erb B2 proto-oncogene product, (Styles, 1990) was chosen as a candidate for radiolabeling with 124I for positron emission tomography of selected patients with breast cancer. By using N-bromosuccinimide (NBS), optimal labeling conditions were established using 125I. The labeling efficiency was determined using instant thin-layer chromatography (ITLC) and gel filtration (HPLC). The antibody was then labeled with the positron emitter 124I, and a labeling efficiency of 96% and immunoreactivity of 80%-90% was obtained. The product was stable, with less than 5% of the radiolabel being eluted after six days storage in plasma at 37 degrees C. Immunolocalization studies were performed in athymic mice bearing human breast carcinoma xenografts overexpressing the c-erb B2 gene product using as controls 125I labeled isotype-matched rat antibody, and antigen-negative tumors. Good uptake of 124I-labeled ICR12 was obtained in c-erb B2 expressing tumors (up to 12% injected dose per gram at intervals up to 120 hr), with localization indices of 3.4-6.2. Tumor xenografts of 6 mm diameter were successfully imaged with high resolution at 24, 48 and 120 hr using the RMH/ICR MUP-PET camera. We suggest that 124I-labeled ICR12 is a suitable agent to image and quantify immunolocalization in patients whose tumors overexpress the c-erb B2 proto-oncogene product.     

NCL-6-124I: a PET agent for the adrenal

The radiopharmaceutical 6β-[¹²⁴I]iodomethyl-19-norcholest-5(10)-en-3β-ol (NCL-6-¹²⁴I) was synthesized. The product was less sensitive to autoradiolytic decomposition in chloroform, than when stored as an injectable solution at 5°C.     

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.     

Cryogenic target design considerations for the production of [18F]fluoride from enriched [18O]carbon dioxide

Four cryogenic target designs are described for the production of fluorine-18 in the chemical form of fluoride using oxygen-18-enriched carbon dioxide gas utilizing the (18)O(p,n)18F nuclear reaction. The targets are conical in shape and made of copper or silver and the carbon dioxide is frozen into the cone at liquid nitrogen temperatures. Three of the targets (2 copper and 1 silver) have four cooling fins extending radially and are different lengths, and one target has only a single heat sink at the rear of the cone. The targets with four cooling fins could be run with 17.4 MeV protons incident on the target material at a beam current of 25 microA with no detectable volatilization of the target material, although yields did decrease slightly when compared with lower current runs. The target with the single cooling block showed volatilization at about 8 microA. The two copper targets of different lengths did not show a difference in the volatilization of the target material at the beam current limit of our cyclotron (25 microA). The shorter target did maintain production with a lower amount of gas frozen into the target, while the longer target maintained production at higher beam currents. Targets of this type are compatible with low energy, high current accelerators because very thin windows may be used.     

Acquisition settings for PET of 124I administered simultaneously with therapeutic amounts of 131I.

Radiation dosimetry of thyroid cancer therapy with 131I can be performed by coadministration of 124I followed by longitudinal PET scans over several days. The photons emitted by 131I may affect PET image quality. The aim of this study was to assess the influence of large amounts of 131I on PET image quality and accuracy with various acquisition settings. METHODS: Noise equivalent count (NEC) rates of 124I only were measured with a standard clinical PET scanner. Apart from the standard 350- to 650-keV energy window, 425- to 650-keV and 460- to 562-keV windows were used and data were acquired both with (2-dimensional) and without (3-dimensional [3D]) septa. A phantom containing 6 hot spheres, filled with a combination of 131I and 124I and with a sphere-to-background ratio of 18:1, was scanned repeatedly with energy window settings as indicated and emission and transmission scan durations of 7 and 3 min, respectively. NEC rates were calculated and compared with those measured with the phantom filled with only 124I. Sphere-to-background ratios in the reconstructed images were determined. One patient with known metastatic thyroid cancer was scanned using energy window settings and scan times as indicated 3 and 6 d after administration of 5.5 GBq of 131I and 75 MBq of 124I. RESULTS: The highest 124I-only NEC rates were obtained using a 425- to 650-keV energy window in 3D mode. In the presence of (131)I, the settings giving the highest NEC rate and contrast were 425-650 keV and 460-562 keV in 3D mode, with the clinical scans giving the highest quality images with the same settings. CONCLUSION: Acquisition in 3D mode with a 425- to 650-keV or 460- to 562-keV window leads to the highest image quality and contrast when imaging 124I in the presence of large amounts of 131I using a standard clinical PET scanner.     

Performance of collimators used for tomographic imaging of I-123 contaminated with I-124

Iodine-123 prepared from the 124Te(p,2n)123I reaction is contaminated with between 3% to 5% I-124 when imaging is performed. The effects of such a mixture were evaluated for medium-energy and low energy general-purpose collimators on a commercially available rotating gamma camera equipped to perform tomography. The planar sensitivity for I-123 was less for the general-purpose collimator, varying between 0.84 and 0.85 in water relative to that measured for the medium energy-collimator. Counts due to scattering or septal penetration of I-124 photons were greater for the general-purpose collimator (36%) than for the medium-energy collimator (15%). Evaluation of the higher-frequency components of the modulation transfer functions confirmed that the low-energy general-purpose collimator is expected to offer significantly more contrast information at frequencies above 0.21 cycles/cm. This is expected to contribute to image quality when studies are performed with collimators of similar design.     

A simple method to quantitate iodine-124 contamination in iodine-123 radiopharmaceuticals

Iodine-123 (123I) produced by the 124Te(p,2n)123I reaction contains several percent 124I radionuclidic contamination at the time of imaging. Since 124I degrades the quality of the images and causes unnecessary radiation absorbed dose to the patient, it is important to know the amount present in radiopharmaceuticals at the time of administration. A simple approach is described which uses a radionuclide dose calibrator and lead shield. The sample is assayed both shielded and unshielded and the ratio of readings depends uniquely upon the percent 124I present. The technique can be adopted for any type of dose calibrator, sample container, and Pb shield, but use of the numeric constants reported here should be restricted to the specified equipment.     

Three-dimensional positron emission tomography imaging with 124I and 86Y

BACKGROUND: Impure positron emitters have physical characteristics that degrade image quality compared to conventional positron emitters like 18F. Two impure positron emitters with potentially interesting applications are 124I and 86Y. The degradation in image quality due to the imperfection of these isotopes is quantified for a human three-dimensional (3-D) positron emission tomography (PET) system. An acquisition protocol to obtain similar image quality as for 18F imaging is determined by Monte Carlo simulations. METHODS: The effects of larger positron range, associated singles and the other decay modes on image quality are determined by extensive Monte Carlo simulations of the Allegro scanner. Spatial resolution was evaluated for both isotopes and compared to spatial resolution of 18F. The loss in sensitivity due to triple coincidences was determined as a function of the axial acceptance angle of the PET scanner. The performance of the scanner at low count rates was studied by determining the noise equivalent count (NEC) values for different upper energy thresholds. The image degrading effect of spurious coincidences is taken into account by adding another factor to the NEC calculation. This allowed the contribution of spurious coincidences to be minimized by using a setting for the appropriate energy window. For this optimal energy window the amount of spurious and scattered coincidences was quantified. Simulations of count rate performance were also done to determine the peak NEC and the activity at which the maximum occurred. RESULTS: Spatial resolution degradation, compared to 18F, is about 0.5 mm for 86Y and 1 mm for 124I. Associated singles have a similar effect as scattered coincidences, as they also add a background to the image. The effect, however, is less important than the effect of scatter. The fraction of triple coincidences is quite small for a 3-D PET scanner used for humans as the axial acceptance angle is still moderate. For the Allegro with an energy resolution of 18% the optimal upper energy threshold was determined at 600 keV. For 124I this leads to 2.5% extra contamination that needs to be added to the scatter fraction. For 86Y this fraction is about 5.5%. CONCLUSION: 3-D PET images of 124I and 86Y have lower spatial resolution. For PET scanners used for humans the difference is not as important as for scanners used for animals. The limited positron decay fraction of both isotopes can be compensated by increasing the imaging time by a factor of 3-5 (same activity). A short coincidence window limits the contamination from other decay modes. Good energy resolution allows setting a selective upper energy threshold to limit the effect of spurious coincidences. With an appropriate setting of the energy window it should be possible to obtain good image quality in a relatively short time because of the high sensitivity of 3-D PET scanners.