EP0288284A2 - Méthode pour produire de l'iode 124 et méta-iodobenzylguandine contenant de l'iode 124 - Google Patents

Méthode pour produire de l'iode 124 et méta-iodobenzylguandine contenant de l'iode 124 Download PDF

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Publication number
EP0288284A2
EP0288284A2 EP88303603A EP88303603A EP0288284A2 EP 0288284 A2 EP0288284 A2 EP 0288284A2 EP 88303603 A EP88303603 A EP 88303603A EP 88303603 A EP88303603 A EP 88303603A EP 0288284 A2 EP0288284 A2 EP 0288284A2
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EP
European Patent Office
Prior art keywords
solution
iodine124
target
target means
placing
Prior art date
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Application number
EP88303603A
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German (de)
English (en)
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EP0288284A3 (fr
Inventor
Muhammad A. Qureshi
Munawwar Sajjad
Richard M. Lambrecht
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
King Faisal Specialist Hospital and Research Centre
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King Faisal Specialist Hospital and Research Centre
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Application filed by King Faisal Specialist Hospital and Research Centre filed Critical King Faisal Specialist Hospital and Research Centre
Publication of EP0288284A2 publication Critical patent/EP0288284A2/fr
Publication of EP0288284A3 publication Critical patent/EP0288284A3/fr
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    • G—PHYSICS
    • G21—NUCLEAR PHYSICS; NUCLEAR ENGINEERING
    • G21G—CONVERSION OF CHEMICAL ELEMENTS; RADIOACTIVE SOURCES
    • G21G1/00—Arrangements for converting chemical elements by electromagnetic radiation, corpuscular radiation or particle bombardment, e.g. producing radioactive isotopes
    • G21G1/04—Arrangements for converting chemical elements by electromagnetic radiation, corpuscular radiation or particle bombardment, e.g. producing radioactive isotopes outside nuclear reactors or particle accelerators
    • G21G1/10—Arrangements for converting chemical elements by electromagnetic radiation, corpuscular radiation or particle bombardment, e.g. producing radioactive isotopes outside nuclear reactors or particle accelerators by bombardment with electrically charged particles

Definitions

  • This invention relates generally to a method for synthesising 124I and 124I-m-IBG. More specifically, this method comprises an innovative technique for preparing an irradiation target, irradiating the prepared target, and finally collecting the resulting 124I; in one embodiment of the invention, the method is further characterized by the synthesis of 124I-m-IBG.
  • Iodine123 and Iodine131 radioisotopes are presently used in medical diagnosis and radiation therapy.
  • Meta-­Iodobenzylguanidine sulfate (m-IBG) labelled with 123I and 131I has been used clinically in the diagnosis and treatment of pheochromocytomas, neuroblastomas and other paragagliomas.
  • Iodine124 is another iodine isotope which is useful in nuclear medicine. Iodin124 decays by positron emission (25%) and can therefore be used in positron emission tomography for non-invasive quantitative physiological studies. When m-IBG is labelled with 124I-iodide (124I-m-IBG), it is useful in obtaining quantitative images of the brain, adrenal, and myocardium.
  • Iodine124 and 124I-m-IBG are not commonly available substances.
  • a known method of producing Iodine124 is by the 124Te(p,n)124I reaction disclosed in Kondo K., Lambrecht, R.M., Norton E.F. and Wolf A.P., 28 Int. J. App. Rad. and Isotopes 765 (1977). However, this reaction is not efficient and typically results in low yields.
  • a further object of this invention is to provide an efficient and commercially feasible method for synthesizing 124I-m-IBG.
  • a further object of this invention is to provide a method of synthesizing Iodine124 which is safe and reliable.
  • a further object of this invention is to provide a method of synthesizing 124I-m-IBG which is safe and reliable.
  • This invention relates to a method for synthesising 124I and 124I-m-IBG comprising an innovative technique for preparing an irradiation target, irradiating the prepared target, and finally collecting the resulting 124I.
  • the method is further characterized by the synthesis of 124I-m-IBG which is useful in nuclear medicine applications.
  • a copper metal plate is first milled and uniformly lapped to the dimensional specifications required for ultimately placing the target matrix in the accelerated subatomic particle path of a nuclear accelerator apparatus.
  • the surface of the copper plate is sanded, washed with distilled water, and dried.
  • the copper plate is then placed in a nickel plating solution prepared from a salt, such as nickel sulfate hexahydrate, and is then electroplated using a platinum electrode as the anode.
  • the copper plate is then placed in a tellurium plating solution comprising isotopically enriched Tellurium124 dioxide dissolved in a solution of potassium hydroxide.
  • the tellurium is electroplated onto the copper plate using a platinum electrode.
  • the target thickness of the Tellurium124 is typically 10-14 milligrams per square centimeter for routine production targets.
  • the irradiated Tellurium124 is dissolved from the copper plate by means of a sodium hydroxide solution, preferably 5 molar, and about 30% hydrogen peroxide and water.
  • a sodium hydroxide solution preferably 5 molar, and about 30% hydrogen peroxide and water.
  • the solution is transferred to a vessel containing about 250 milligrams of aluminum powder.
  • the solution is purged with air, then carbon dioxide gas.
  • the solution volume may be reduced by boiling the solution.
  • the solution is then passed through a filter to collect solid materials for subsequent recovery of the isotopically enriched Tellurium124 by use of methods known to those skilled in the art.
  • Table 2 illustrates Iodine124 production yields and levels of Iodine126 impurity 48 hours after irradiation of the Tellurium124 target of greater than 95% isotopic enrichment.
  • Radioanalysis by gamma-ray spectrometry was performed to assess the radionuclidic purity and to identify the impurities.
  • Irradiation conditions in the examples range from 25 to 80 microampere deutron beam current with irradiation doses ranging from 100 to 550 microampere hours.
  • the Iodine124 was prepared in quantities of greater than 100 mCi by 15 megavolt deuteron irradiation of enriched Tellurium124 by the 124Te(d,2n)124I nuclear reaction.
  • Enriched Tellurium124 was plated in the quantity of about 13 mg/cm2 on a nickel plated copper target. These targets were irradiated in the internal beam line of the King Faisal Specialist Hospital and Research Centre CS-30 Cyclotron. The current was varied from 25 to 60 micro-amperes, and the irradiation time was varied from 4-8 hours. Iodine124 was separated from the tellurium target using the chemical procedure already discussed.
  • the 124I-I was passed through a cation-exchange column to remove trace tellurium.
  • the radioanalysis was done by gamma-ray spectrometry.
  • the gamma-spectrum was obtained by using a 45-­Cm3 Ge(Li) detector (full width at half-maximum of 1.87 KeV at 1.33 MeV photopeak of 60Co, peak-to-compton ratio of 32:1 and an efficiency of 7.7%) and a Canberra Series 80 pulse height analyzer.
  • Non-radioactive m-IBG was synthesized by the method of Wieland, disclosed in Wieland, D.M., Wu, Jiann-long, Brown, L.E., Mangner,l T.J., Swanson, D.P., Beierwaltes, W.H., 21 Journal of Nulear Medicine 349 (1980).
  • Mass spectrum analysis (direct probe insertion) was performed on a Finnegan MAT Model-311: molecular ion (M+) and a base peak (rel. intensity 100%) at m/z 276, a peak (rel. intensity 060%) at m/z 233 (M-43) representing the split of the -C group.
  • HNMR analysis was performed on a Varian Model T-60A: (DMSO-d6); delta 7-7.8(m,4H aromatic), the benzylic CH2 group is overmasked by the water peak at delta 3.4. Melting point: 167.3° (corr), Lit. 167.0° (uncorr).
  • 124I-m-IBG was analyzed by TLC on silica gel plates with ethylacetate: ethanol: H2O (20:20:1) as the developing solvent (R f , I ⁇ : 0.75; 124I-m-IBG: 0.00).
  • High pressure liquid chromatography (HPLC) analysis of m-IBG was performed on a Varian 5000 HPLC System. Column effluent was passed first through a variable UV detector (254 nm), and then through a radioactivity detector (NaI) connected in series with the UV detector ( Figure 1).
  • Iodine124 can be produced in higher yields and final product purity by using this reaction rather than by the 124Te(p,n)124I reaction.
  • the yields for the 124Te(d,2n)124I was 0.57mCi/micro-ampere, compared to 0.093 mCi/micro-ampere-h for the124Te(p,n) 124I reaction reported in Kondo K., Lambrecht, R. M., Norton E. F. and Wolf A. P., 28 Int. J. App. Rad.

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  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Engineering & Computer Science (AREA)
  • General Engineering & Computer Science (AREA)
  • High Energy & Nuclear Physics (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
EP88303603A 1987-04-24 1988-04-21 Méthode pour produire de l'iode 124 et méta-iodobenzylguandine contenant de l'iode 124 Withdrawn EP0288284A3 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US4212987A 1987-04-24 1987-04-24
US42129 1987-04-24

Publications (2)

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EP0288284A2 true EP0288284A2 (fr) 1988-10-26
EP0288284A3 EP0288284A3 (fr) 1990-07-25

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EP88303603A Withdrawn EP0288284A3 (fr) 1987-04-24 1988-04-21 Méthode pour produire de l'iode 124 et méta-iodobenzylguandine contenant de l'iode 124

Country Status (3)

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EP (1) EP0288284A3 (fr)
JP (1) JPH0323203A (fr)
AU (1) AU1503888A (fr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2005210411B2 (en) 2004-02-05 2008-01-31 Nippon Shokubai Co., Ltd. Particulate water absorbing agent and method for production thereof, and water absorbing article
EP2474525B1 (fr) * 2006-12-26 2020-04-15 Lantheus Medical Imaging, Inc. Ligands pour l'imagerie de l'innervation cardiaque
NZ604233A (en) 2010-05-11 2014-10-31 Lantheus Medical Imaging Inc Compositions, methods and systems for the synthesis and use of imaging agents

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, vol. 87, 1977, page 491, abstract no. 30460p, Columbus, Ohio, US; R.M. LAMBRECHT et al.: "Excitation functions, targetry and radiochemistry for iodine-123 and iodine-124 production by the (p,2n) and (p,n) reaction on tellurium-124", & J. LABELLED COMPD. RADIOPHARM. 1977, 13(2), 278 *
CHEMICAL ABSTRACTS, vol. 88, 1978, page 330, abstract no. 42745u, Columbus, Ohio, US; K. KONDO et al.: "Cyclotron isotopes and radiopharmaceuticals. XXII. Improved targetry and radiochemistry for production of iodine-123 ans iodine-124", & INT. J. APPL. RADIAT. ISOT, 1977, 28(9), 765-71 *
CHEMICAL ABSTRACTS, vol. 97, 1982, page 496, abstract no. 99643z, Columbus, Ohio, US; J. BURDE et al.: "The excited states in the odd-odd iodine-124 nucleus produced by the (p,n) reaction", & NUCL. PHYS. A 1982, A385(1), 29-42 *

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Publication number Publication date
JPH0323203A (ja) 1991-01-31
AU1503888A (en) 1988-10-27
EP0288284A3 (fr) 1990-07-25

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