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.     

Differential solubility labelling and purification of ortho-iodo-hippuric acid with 123I

A simple method is described for the production of high quality clinical ¹²³I hippuran at TRIUMF. The first feature is that solid ortho-iodo-hippuric acid (IHA) is heated with aqueous [¹²³I]iodide creating a single phase where labelling occurs. When subsequently cooled to room temperature, IHA crystallizes. The second feature is employed at this stage. A density gradient is created with NaCl to remove the supernatant fluid from the IHA crystals. The IHA is then neutralized for pharmaceutical use. The product purity is consistantly >99% by TLC and by HPLC analysis that is described. The initial tag is typically 96% and the useful recovery is 85% by this process. Iodine-123 has been used up to 100 mCi per batch from the 500 MeV ¹³³Cs (p, 2p, 9n) ¹²³Xe reaction and from the ¹²⁴Xe (p, 2n) ¹²³Xe reaction.     

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.     

Cyclotron production of high-purity 123I I. A revision of excitation functions,thin-target and cumulative yields for 127I(p,xn) reactions

Excitation functions, thin-target and cumulative yields for the proton-induced reactions on ¹²⁷I targets were measured in the 67.5- to 5.3-MeV energy region. These results were used primarily to define the proton-energy ranges and target thicknesses to optimize radionuclide yields and purities for ¹²³I production from its 2.08-h ¹²³Xe parent. Other reactions producing radioxenons of interest in nuclear medicine (i.e. 36.406-d ¹²⁷Xe, 17.3-h ¹²⁵Xe, 20.1-h ¹²²Xe, and 38.85-min ¹²¹Xe), were also measured. These results are compared to other previously reported values.     

(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.     

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.     

A new binary compound for the production of 124I via the 124Te(p,n)124I reaction.

The binary compound, aluminum telluride (Al(2)Te(3)), was investigated as a target material for the production of (124)I by way of the (124)Te(p,n)(124)I reaction on a low-energy cyclotron. The high melting point and formation of a glassy matrix upon heating provided a stable target material at irradiations up to 20 microA of 11 MeV protons. The 87% tellurium mass fraction and 95% iodine separation yield led to significantly higher quantities of iodine compared to traditional TeO(2)/6%Al(2)O(3) admixtures. Radiochemical analysis of distilled samples using ion chromatography showed that the product remained in the iodide form while supported in weak buffer solutions. Stable Te impurities in the radioiodine product were less than 0.5 microg following purification by ion exchange chromatography. Average thick target yields of 229+/-18 microCi/microAh were achieved, and typical production runs at 18 microA for three hours yielded 12 mCi at the end-of-bombardment. Total losses of the target material after each irradiation and distillation cycle were approximately 2%.     

Radioiodination of 1-(2-deoxy-beta-D-ribofuranosyl)-2,4-difluoro-5-iodobenzene (dRFIB), a putative thymidine mimic nucleoside for cell proliferation studies

Iodine-124 was produced via the (124)Te(p,n)(124)I reaction by 15 MeV proton irradiation of an in-house solid mass tellurium dioxide target, using the Tübingen PETtrace (General Electric Medical Systems) cyclotron. 1-(2-Deoxy-beta-D-ribofuranosyl)-2,4-difluoro-5-iodobenzene (dRFIB), a stable, non-polar thymidine mimic nucleoside, was synthesized in 5 steps following a literature method, for radioiodination with [(124)I] iodide via isotope exchange in the presence of copper sulphate and ammonium sulphate in methanol-water. The radiolabelling procedure was optimized with respect to temperature, amount of dRFIB, amount of sodium hydroxide and reaction time, to produce radiochemical yields of up to 85% with a 1-h reaction at 140 degrees C. With routine I-124 production of 30 MBq/run, relatively high specific activities, approaching 100 MBq/mmol, can be expected. The activation energy for dRFIB radioiodination was calculated from temperature-time RCY data to be approximately 100 kJ/mol using no-carrier-added [(124)I]iodide.     

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.     

123I research and production at Brookhaven National Laboratory

The procedures for preparing high purity ¹²³I at the Brookhaven Linac Isotope Producer using the ¹²⁷I(p, 5n)¹²³Xe reaction on a NaI target are described. The activity is supplied in a glass ampoule with anhydrous ¹²³I deposited on the interior walls, allowing maximum flexibility in subsequent iodinations. Preliminary experience with a continuous flow target is also described. The results of a series of measurements of specific activity by neutron activation, x-ray fluorescence, u.v. absorption, and wet chemistry generally showed no detectable carrier. HPLC methods to analyze the chemical form of radioiodine and to characterize various iodinated radiopharmaceuticals have been developed. These methods provide higher sensitivity, speed and resolution than commonly used techniques.     

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.     

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.     

Critical cerebral blood flow thresholds studied by SPECT using xenon-133 and iodine-123 iodoamphetamine

Regional cerebral blood flow (rCBF) was assessed in patients with cerebrovascular diseases (CVD) by single photon emission computed tomography (SPECT) using 133Xe and N-isopropyl-p-[123I]iodoamphetamine ([123I]IMP). The purpose of this study was to determine the infarcted and symptomatic blood flow thresholds of cerebral cortex by SPECT. In the 133Xe inhalation method rCBF was calculated by employing the Celsis modification of the Kanno and Lassen algorithm. In the [123I]IMP SPECT quantitation was obtained by counting-rate ratio for the low flow lesion to the contralateral homologous region which was presumed to be normal (Lesion/Normal ratio, L/N ratio). The infarcted and symptomatic blood flow thresholds by 133Xe SPECT was 19-23 and 33-36 ml/100 g/min, respectively. While, those of L/N ratio in the [123I]IMP SPECT were 39-48 and 65-72%, respectively. There was a significant correlation between the ischemic degrees evaluated by 133Xe and [123I]IMP SPECT studies.     

Comparative study of regional cerebral blood flow images by SPECT using xenon-133, iodine-123 IMP, and technetium-99m HM-PAO

Regional cerebral blood flow (rCBF) was measured by single photon emission computed tomography (SPECT) using 133Xe, N-isopropyl-p-[123I]iodoamphetamine ([123I]IMP) and [99mTc] hexamethylpropyleneamine oxime ([99mTc]HM-PAO) in 24 patients with cerebrovascular diseases. The greatest advantage of 133Xe SPECT was to be able to provide absolute rCBF values without arterial sampling. However, its image quality was very poor. Iodine-123 IMP SPECT provided rCBF images of higher quality and it had good correlation to 133Xe SPECT. Iodine-123 IMP SPECT provided the best images to detect mild ischemic lesions. It could detect obstructive or stenotic changes of large cerebral arteries very well except for a moderate stenosis of internal carotid artery. Technetium-99m HM-PAO SPECT also provided very good rCBF images and it had good correlation to 133Xe SPECT. However, the count-density ratios for the ischemic lesions to the contralateral presumed normal areas of [99mTc] HM-PAO SPECT were significantly higher than those of [123I]IMP SPECT.     

Dual-isotope brain SPECT imaging with technetium-99m and iodine-123: clinical validation using xenon-133 SPECT.

Our phantom studies indicate that the energy resolution (9.7% FWHM) of a new three-headed single-photon tomograph (PRISM-3000) separates the distribution of 99mTc from 123I for 10% asymmetric or 15% or 10% centered 99mTc windows when combined with a 10% asymmetric 123I window. This technique is now applied to the simultaneous measurement of resting rCBF and changes induced by vasodilation (1 g acetazolamide) in 10 subjects with cerebrovascular disease. Resting and vasodilated 133Xe SPECT images were obtained first. Within 48 hr, 99mTc HMPAO was given at rest, acetazolamide injected, and after 20 min either [123I] IMP or [123I] HIPDM was administered. Subjects were scanned for 99mTc and 123I simultaneously using 10% asymmetric windows. Regression analyses demonstrated a linear relationship between 133Xe SPECT and dual-isotope SPECT measurements of lesion-to-cerebellum ratios in baseline (r = 0.92), vasodilated (r = 0.86) and rest-minus-vasodilated data (r = 0.85). Technetium-99m and 123I images obtained through dual-isotope imaging are by definition in perfect anatomic registration.     

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.     

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.     

Iodine-123 labelled Z-(R,R)-IQNP: a potential radioligand for visualization of M(1 )and M(2) muscarinic acetylcholine receptors in Alzheimer's disease.

Z-(R)-1-Azabicyclo[2.2.2]oct-3-yl (R)-alpha-hydroxy-alpha-(1-iodo-1-propen-3-yl)-alpha-phenylacetate (Z-IQNP) has high affinity to the M(1 )and M(2) muscarinic acetylcholine receptor (mAChR) subtypes according to previous in vitro and in vivo studies in rats. In the present study iodine-123 labelled Z-IQNP was prepared for in vivo single-photon emission tomography (SPET) studies in cynomolgus monkeys. SPET studies with Z-[(123)I]IQNP demonstrated high accumulation in monkey brain (>5% of injected dose at 70 min p.i.) and marked accumulation in brain regions such as the thalamus, the neocortex, the striatum and the cerebellum. Pretreatment with the non-selective mAChR antagonist scopolamine (0.2 mg/kg) inhibited Z-[(123)I]IQNP binding in all these regions. The percentage of unchanged Z-[(123)I]IQNP measured in plasma was less than 10% at 10 min after injection, which may be due to rapid hydrolysis, as has been demonstrated previously with the E-isomer of IQNP. Z-[(123)I]IQNP showed higher uptake in M(2)-rich regions, compared with previously obtained results with E-[(123)I]IQNP. In conclusion, the radioactivity distribution from Z-[(123)I]IQNP in monkey brain indicates that Z-[(123)I]IQNP binds to the M(1)- and M(2)-rich areas and provides a high signal for specific binding, and is thus a potential ligand for mAChR imaging with SPET.     

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.