PRODUCTION OF CARRIER-FREE 123I USING THE 127l(p,5n)123Xe REACTION M. A. Fusco, N. F. Peek, J. A. Jungerman, F. W. Zielinski, S. J. DeNardo, and G. L. DeNardo University of California at Davis, Davis, California Iodine is notable among the elements which are part iodine were present but did not indicate the amount of man's composition in that it has more different ra- of these contaminants. Sodd, et al (J) and other dioisotopes than any other element natural to man. investigators (4-8) have provided an extensive list These radioisotopes of iodine have different physical of nuclear reactions leading to the production of 123I. characteristics and no one radioisotope is optimal Their list does not include the production method for all biomédicalapplications. Iodine-123 has physi to be described in this publication (Table 1). Most cal characteristics which are optimal for most in vivo of the previously described methods for the produc medical procedures, particularly those which are tion of 123Iresult in contamination with 124Iwhich completed within 24 hr. Iodine-123 decays solely reduces the spatial resolution of imaging procedures by electron capture; the photon-to-electron ratio is and increases the radiation dose to the patient (9). high, indicating a low level of undesirable paniculate We wish to describe a new method for the produc radiation. Iodine-123 emits 159-keV gamma rays in tion of 123Iwhich eliminates virtually all radioactive 84% of the disintegrations, thus providing a high contaminants (Table 2). yield of photons suitable for use with imaging sys tems. The 13.1-hr half-life of 123Iis long enough to MATERIALS AND METHODS allow for target processing, chemical manipulation, Research irradiations. The 123Xeproduction cross- purification, extensive quality control, delivery to the section information was collected using a small iodine patient, and subsequent development of clinical in target. A tantalum plate with a recess 1.2 mm deep formation. In all respects then, '123Iis a more ideal and 6.5 mm in diam was used as the target holder gamma radionuclide than any other radioisotope of for resublimed high-purity natural iodine. To prevent iodine for in vivo diagnostic procedures (1). In 1962 Myers, et al (2) described the merits of 123Iand several methods for production. They indi Received Jan. 31, 1972; revision accepted Apr. 27. 1972. For reprints contact: Neal Peek. Crocker Nuclear Lab cated that contaminants of other radioisotopes of oratory, University of California, Davis, Calif. 95616. 1^1ActivityReactionTABLE 1. COMPARISON OF VARIOUS REPORTED METHODS OF PRODUCTION OF mlI21Sb(a,2n)12''l (mCi/M/hr) »,0.62 US, Réf.ni w\ ni«iaTe(d,n)ial 0.23 0.00190.19 0.015 30.96 ni ni'•" 0.13 0.0061 0.12 3ni 0.07 '-r"1TcIcK.jn)l 1 \1 --v AC / rt —_ . ^Teond"3!"'M=T ( 0.009ni.5 0.03 3ni ni ni^JÕS-*"("u"'.)?«»!* 0.007 nini ni 3ni ni "'^Tela^nJ^Xe °-°°14 nini ni 3ni ni ni1!nl(p^n)12aXe 0.3 ni— <0.2 7— ni —* 3.0 0.1 —m\ — Présentwork Not indicated in publication.12<| Volume 13, Number 10 729 FUSCO, PEEK, JUNGERMAN, ZIELINSKI, DENARDO, AND DENARDO et al (7) was used to separate the xenon from the target. At the end of the irradiation, the target block was remotely removed from the cyclotron and trans ferred to the radiochemical laboratory. The iodine target was dissolved in an aqueous solution of po tassium iodide. Helium was circulated in a closed system through the dissolved sample and subse quently through dry-ice-acetone and liquid-nitrogen traps (Fig. 2). Water vapor and iodine released from the dissolution flask were removed by the dry-ice- acetone-cooled trap and the xenon gas was collected in the liquid nitrogen-cooled trap. Cooling was main tained for about 6 hr to allow the 123Xe to decay 50 55 to 123I. E protón (MeV) Methods of identification and assay. Serial gamma- FIG. 1. Relative yield of u>:ilas function of incident proton en ray spectroscopy was used to identify the kinds and ergy. 121Utargets used were about 2.5 MeV thick. Yield is given in amounts of radionuclides present by virtue of their arbitrary units. Some uncertainty results because of possible loss of xenon from iodide crystal lattice if target is overheated by inci characteristic photopeak energies and half-lives. A dent beam of protons. 30 cc Ge(Li) detector coupled to a 4,096-channel analyzer was used for the gamma-ray spectroscopy of the irradiated target and the final product. The resulting spectra were processed using a PDF 15/40 computer to integrate the area under the respective gamma-ray photopeaks. Yields were determined by IODINE TARGET ON TANTALUM PLATE comparison with an IAEA 22Na calibrated standard source counted in a standard geometry. Figure 3 MAGNETIC BAR LIQUIDN2 shows the gamma-ray spectrum of the final 123I t-196'C) MAGNETIC STIRRING product. MOTOR To further establish product purity and suitabil TARGET DISSOLUTION ity for clinical use, paper and cellulose acetate elec- trophoresis of 123I dissolved in distilled water was FIG. 2. System for isolation of xenon isotopes from 'L target performed. Paper electrophoresis for 75 min at 170 following proton irradiation. volts in 0.05 ionic strength barbitol buffer (Beckman buffer B-l, pH 8.6) and cellulose acetate electro loss of volatile products during irradiation a 0.25- phoresis for 15 min at 340 volts in the same buffer mm-thick tantalum cover foil was used. The assem system were followed by a determination of the bled chemical target block was cooled by circulating distribution of the radioactivity by radiochromato- water on the back and helium across the front of graphic scanning. the target. A series of irradiations were made at The product 123Iwas tested for sterility according proton energies increasing from 42.5 to 62 MeV to the U. S. Pharmacopeia using thioglycollate me in 2.5-MeV steps to establish the optimum proton dium incubated at 32°Cfor 7 days and Sabouraud energy for producing 123Xe (Fig. 1). medium incubated at 25 °Cfor 10 days. Production irradiations. Having established the relative cross sections as a function of proton energy RESULTS for the 127I(p,5n)123Xe and 127I(p,3n)125Xe reac Yields measured as a function of proton energy tions, a system was designed for the production and showed that the optimum energy for 12SXeproduc recovery of large quantities of carrier-free 123I for tion is about 54 MeV for a thin target (Fig. 1). The subsequent chemical and biomédicalstudies. The 123I activity recovered from the liquid-nitrogen- area of iodine target was increased to 4.5 cm2, the cooled trap 6 hr after the termination of a production thickness to 1.6 mm, and the beam intensity to 6 /¿A irradiation was 24 mCi. This figure is based on the of 57.5-MeV protons. To minimize the production following experimental conditions: 127Itarget thick of 125Xe, it was decided to irradiate the target for ness of 1.0 gm/cm2 (7 MeV thick) with an irradia 3 hr, which would produce 63 % saturation of 123Xe. tion time of 1.0 hr at 6 /uA at 57.5 MeV and target Methods of separation and recovery. A cyclic or area of 4.5 cm2. batch processing method similar to that of Sodd, Because the isotopes of xenon, including 123Xe, 730 JOURNAL OF NUCLEAR MEDICINE PRODUCTION OF CARRIER-FREE 123I FIG. 3. Gamma spectrum of final product. Only !l !l is observed after sepa SCO 600 ration. Line energies are given in keV. CHANNEL can be readily separated from the target and final product, which was cultured in Sabouraud and thio- product, the only contaminants in the product are glycollate media to establish clinical suitability fur isotopes of iodine from xenon decay (Table 2). Ra- ther, was found to be sterile. dionuclides of iodine produced directly in the target remain in the dissolution flask. Furthermore, 124Xe DISCUSSION and 126Xe are stable so they do not result in 124I The merits of 123Ifor diagnostic biomedicai appli and 126I.Xenon-125 is a contaminant initially (17-hr half-life) which constitutes about 5% of the 123Xe cations have been appreciated for some time; its (2.1-hr half-life) activity at the end of irradiation advantages of decreased radiation exposure and in with 57.5-MeV protons. If the residual xenon is re creased spatial resolution can only be fully realized moved at the optimal time for maximum 123Iactivity if other radioactive contaminants are absent or negli (6 hr), only 22% of the I25Xe will have decayed to gible. A variety of production methods have been 126I. This results in 125Icontamination of 0.1% of proposed or developed (Table 1). These production methods may be direct, that is, the I23I is produced the 123Iactivity. Also some 122Xe (20-hr half-life) is produced by 127I(p,6n)122Xe. This isotope is not immediately in the target by the irradiation, or in direct, that is, 123Xe is produced in the target and a problem because the 122Xeis removed as described subsequently decays to 123I. Several investigative previously, and the 122Idaughter promptly decays groups (2,4,5,6,10) have described a variety of di to stable tellurium with a half-life of 3.5 min. rect methods for the production of 123I.These meth Electrophoresis of the final aqueous 123Iproduct indicates that the 123Imigrates as one substance and ods also result in the production of radioactive contaminants including 124I, 125I, 12«I,130I, and 1S1I in the same manner as the I2r'I-iodide standard.