Calibration of the LNMRI Secondary Standard Ionization Chamber for 131I capsules used in nuclear medicine

The radionuclide ¹³¹I has been increasingly used in nuclear medicine therapy procedures. Nowadays, the ¹³¹I source administered to the patient is manufactured in two different geometries: solution and capsules. The purpose of this study is the accurate measurement of the activity present in a ¹³¹I capsule without destroys it. The methodology to determine the capsules activity is to obtain the calibration factor of an IG12 secondary standard activity measurement system based on the IG12 well-type ionization chamber set up at Brazilian national metrology laboratory for ionizing radiation (LNMRI) of institute of radiation protection and dosimetry (IRD).The result obtained, 6.4670?±?0.0381?×?10^?18?A?Bq^?1, is quite similar to the calibration factor of the ¹³¹I solution contained in the standard ampoule geometry, 6.4515?±?0.0368?×?10^?18?A?Bq^?1. After obtaining the calibration factor it was used to measure ¹³¹I therapy capsules in order to check the performance of radionuclide calibrators of some Brazilian nuclear medicine centers.     

Reuse of decayed tellurium dioxide target for production of iodine-131

Iodine-131 was generated by irradiation of natural tellurium dioxide in a nuclear reactor. After irradiation the tellurium dioxide was transferred to hot cell and heated in a quartz furnace at ~700 °C. The Iodine-131 was distilled and collected in carbonate/bicarbonate buffer and used for thyroid cancer patients. The tellurium dioxide used was >99 % pure. During nuclear reaction nanogram tellurium was consumed to produce ¹³¹I, although significant loss of target material may occur in heating process. In dry distillation technique no chemical was added to irradiated target material. After ¹³¹I separation tellurium dioxide was decayed for 8 years in radioactive waste management facility. The decayed TeO₂ was recovered, melted and crushed for desired mesh size. The TeO₂ was sealed in Al capsule for re-irradiation purposes. The separation of ¹³¹I was carried out via dry distillation. The purity and yield of ¹³¹I separated from both of the irradiated new and irradiated re-used tellurium dioxide targets were comparable.     

Rapid radiochemical analysis of 131I in environmental samples using a well-type Ge-detector

Large-scale production of ¹³¹I in a nuclear reactor, the gaseous nature of ¹³¹I, and its selective uptake by the human thyroid gland, make this radioisotope a health hazard in the event of a nuclear accident. The maximum concentration of ¹³¹I in drinking water has been set at 1 pCi/l. Human ingestion of ¹³¹I through the grass-cow-milk pathway makes milk an environmentally significant matrix to be monitored for. In this paper, we report a simple and a rapid radiochemical procedure for the analysis of ¹³¹I in water and milk samples. A quick single-step separation on anion-exchange resin concentrates radioiodine from large sample volumes. The resin is then directly counted in the cavity of a low-background well-type HPGe detector that has high counting efficiency for X-rays and low-energy -radiation. Chemical recovery is evaluated from the intensity of the 29.6 keV X-rays of the ¹²⁹I spike, and ¹³¹I is assayed through the intensity of its 364.5 keV g-peak. The method's minimum detection limit is 0.5 pCi ¹³¹I based on a 1 liter sample and a 200-minute count.     

Diphosphine Capsules for Transition‐Metal Encapsulation

Self‐assembly and characterization of novel heterodimeric diphosphine capsules formed by multiple ionic interactions and composed of one tetracationic diphosphine ligand and one complementary tetraanionic calix[4]arene are described. Encapsulation of a palladium atom within a diphosphine capsule is achieved successfully by using the metal complex of the tetracationic diphosphine ligand for the assembly process. In this templated approach to metal encapsulation, the transition‐metal complex is an integrated part of the capsule with the transition metal located inside the capsule and is not involved in the assembly process. We present two approaches for capsule assembly by mixing solutions of the precharged building blocks in methanol and mixing solutions of the neutral building blocks in methanol. The scope of the diphosphine capsules and the metallodiphosphine capsules is easily extended by applying tetracationic diphosphine ligands with different backbones (ethylene, diphenyl ether, and xanthene) and cationic binding motifs (p‐C₆H₄‐CH₂‐ammonium, m‐C₆H₄‐ammonium, and m‐C₆H₄‐guanidinium). These tetracationic building blocks with different flexibilities and shapes readily associate into capsules with the proper capsular structure, as is indicated by ¹H NMR spectroscopy, 1D NOESY, ESI‐MS, and modeling studies.     

An extraction method for the determination of the Rose Bengal content in the preparations of Rose Bengal labelled with131I

The paper describes an extraction radiometric method for the determination of Rose Bengal content in the radiopharmaceutical preparations of Rose Bengal labelled with¹³¹I. Two methods have been studied. The first one is based on the addition of an excess and substoichiometric amounts of Septonex /carbetoxypentadecyltrimethylammonium bromide/ to the sample of Rose Bengal-¹³¹I and on the activity measuring of the chloroform extracts. The second method is based on the extraction of Rose Bengal-¹³¹I with substoichiometric amount of Septonex from the sample of Rose Bengal-¹³¹I and the sample of Rose Bengal-¹³¹I diluted with a known amount of an inactive Rose Bengal preparation.     

Current status and future plan for the production of radioisotopes using HANARO Research Reactor

The Korea Atomic Energy Research Institute (KAERI) completed the High-flux Advanced Neutron Application Reactor (HANARO) in 1995 and the radioisotope production facilities(RIPF) in 1997. Many devices and handling tools were developed and applied for the production of radioisotopes. Emphasis on RI production plan was placed on the development of new radiopharmaceuticals, the development of new radiation sources for industrial use and the steady production of selected radioisotopes. The selected items are ¹⁶⁶Ho-based pharmaceuticals, fission ⁹⁹Mo/^99mTc generators, and products of ¹³¹I and ¹⁹²Ir and ⁶⁰Co sources for industrial use. Now KAERI regularly produces radioisotopes (¹³¹I, ^99mTc, ¹⁶⁶Ho, ¹⁹²Ir, ⁶⁰Co etc.) and labeled compounds including ^99mTc cold kits. Newly developed therapeutic agents are a ¹⁶⁶Ho-chitosan complex for liver cancer treatment, a ¹⁶⁶Ho patch for skin cancer treatment and devices such as the stent and balloon for the prevention against restenosis of the coronary artery. Feasibility studies on the installation of a ^99mTc generator loading facility and on ⁶⁰Co production for food irradiation were finished. The ¹⁹²Ir sealed source assembly for NDT has been supplied to domestic users since May 2001. The fission moly process, separation process of non-sealed sources (¹²⁵I, ³³P, ⁸⁹Sr, ¹⁵³Sm, ¹⁸⁸Re) and fabrication process of sealed sources (¹⁶⁹Yb, ⁷⁵Se) are also under development. For the quality assurance of our final products, we obtained ISO certification in 2000. We are carrying out a feasibility study on a new research reactor for the stable supply of radioisotopes in Korea.     

Possibilities of the determination of3H,14C and131I individually and in mixtures,by the method of amplitude attenuation using liquid scintillators

Possibilities of the determination by radioactivity measurements of³H,¹⁴C and¹³¹I are described for the individual nuclides and their mixtures, with the use of liquid scintillators. The changes in the counting efficiency have been determined as a function of the parameters of the measuring equipment, and parameters are suggested which make possible the determination of³H,¹⁴C and¹³¹I individually, or in the pairs³H−¹⁴C,³H−¹³¹I,¹⁴C−¹³¹I, and finally, in the triplet³H−¹⁴C−¹³¹I.     

Separation of iodine produced from fission with a porous metal silver column in99Mo production

In Argentina, at the Ezeiza Atomic Center,¹³¹I is produced by wet distillation of natural tellurium dioxide irradiated with thermal neutrons in a pool-type reactor. In order to recover the¹³¹I present in the production process of fission⁹⁹Mo obtained by irradiation of UAL_x/Al targets (with 90% enriched uranium) a separation method was developed. Iodine isotopes can be separated from a sodium hydroxide solution containing fission products using a column filled with alternate beds of glass microspheres and porous metal silver. Tests with tracers were performed in radiochemical laboratory. Following this results, a series of tests with higher activities (3 TBq of⁹⁹Mo and 0.7 TBq of¹³¹I) were carried out in hot cells. Molybdenum passes through the silver column, while¹³¹I retention was 92–97% in tracer test and 90% in optimised hot cell tests. This result depends on several facts that are discussed. An initial separation of iodine isotopes diminishes radiation damage on ion-exchange resin used in the subsequent molybdenum purification, improving its retention and elution yield.     

Some observations on the radionuclidic and radiochemical control of radiopharmaceuticals at the N.R.C. Democritos

In the production of¹³¹I, the presence of a contamination extractable with organic solvents has been detected and its source discovered. The influence of overheating was established in the preparation of^99m Tc by the extraction method. Finally, details are given of the procedure used for the estimation of¹⁹⁹Au present in¹⁹⁸Au.     

Preparation of high purity labelled Rose-Bengal with radioiodine

The exchange of Rose-Bengal in the mono-sodium salt with elementary¹³¹I in an organic medium allows for the preparation of a labelled product substantially higher in radiochemical purity than that produced by other methods. Purification of the starting material before the labelling process has been done by adsorption chromatography. Under the conditions described a radiochemical yield more than 97% can be obtained within 30–60 minutes. The product was stable during sterilization and storage for 10 days and was found to be free of¹³¹I.     

Assembly of Alternated Multivalent Ion/Polyelectrolyte Layers on Colloidal Particles. Stability of the Multilayers and Encapsulation of Macromolecules into Polyelectrolyte Capsules

Alternating adsorption of multivalent ions and oppositely charged polyelectrolytes on colloid particles has been investigated. Multilayer films composed of Tb³⁺/polysterene sulfonate (PSS) and 4-pyrene sulfate/polyallylamine (PAH) were successfully assembled on polysterene sulfonate (PS) and melamine formaldehyde (MF) latex particles. The amount of assembled material was estimated by fluorescence and the linear growth of the film versus the number of layers was demonstrated. These multilayers are not stable and can be decomposed by salt and temperature. Dissolution of MF particles leads to formation of hollow capsules consisting of multivalent ion/polyelectrolyte multilayers. Comparative analysis of the capsules was done by confocal and scanning force microscopy. Complex hollow spheres consisting of Tb³⁺/PSS or 4-PS/PAH as an inner shell and stable PSS/PAH as an outer shell were produced. Due to selective permeability of the outer shell after degradation of the inner shell the multivalent ions are released out of the capsule while the polyelectrolytes fill the capsule interior. This is indicative of swelling of the capsule by osmotic pressure. The filled capsules were studied by confocal and scanning electron microscopy. Possibilities of encapsulating macromolecules in defined amounts per capsule are discussed.     

Synthesis,radiolabeling and biodistribution of morphine glucuronide (mor-glu)

The aim of this study was to synthesize a glucuronide conjugated morphine derivative which could be labeled with ¹³¹I, as a radiopharmaceutical, and to investigate its radiopharmaceutical potential using biodistribution studies in male Albino Wistar rats. Morphine was extracted from dry capsules of the opium poppy (Papaver somniferum L.). It was conjugated with UDP-glucuronic acid by using UDP-glucuronyl transferase (UDPGT) enzyme rich microsomes, purified by high performance liquid chromatography (HPLC) and characterized by nuclear magnetic resonance (NMR), infrared (IR) spectroscopy and liquid chromatography mass spectroscopy (LC-MS/MS). Normal and receptor blockage biodistribution studies were performed in male Albino Wistar rats. The results of the tissue distribution studies showed that ¹³¹I labeled morphine glucuronide (¹³¹I-mor-glu) uptake in the small intestine, large intestine and urinary bladder was higher than in the other tissues of the rats in the blocked receptor and unblocked receptor. A greater uptake of the radio labeled substance was observed in the hypothalamus and mid brain than in the other branches of the rats’ brains.     

EPR Studies of the Binding Properties,Guest Dynamics,and Inner‐Space Dimensions of a Water‐Soluble Resorcinarene Capsule

Nitroxide free radicals have been used to study the inner space of one of Rebek’s water‐soluble capsules. EPR and ¹H NMR spectroscopy, ESI‐MS, and DFT calculations showed a preference for the formation of 1:2 complexes. EPR titrations allowed us to determine binding constants (K_a) in the order of 10⁷ M ^?2. EPR spectral‐shape analysis provided information on the guest rotational dynamics within the capsule. The interplay between optimum hydrogen bonding upon capsule formation and steric strain for guest accommodation highlights some degree of flexibility for guest inclusion, particularly at the center of the capsule where the hydrogen bond seam can be barely distorted or slightly disturbed.     

Radiochemical separation of110mAg,210Pb,127Te and131I from aqueous nitric acid solution by bis-2-(butoxyethyl ether)

A bis-2-(butoxyethyl ether) (DBC) solvent extraction method has been developed for the radiochemical separation of^110mAg,²¹⁰Pb,¹²⁷Te and¹³¹I in varying concentrations of aqueous HNO₃. Various factors were examined to determine the optimum conditions of extraction. The effect of various masking agents has been studied. The extraction of¹³¹I is enhanced to 99% at 2.4M HNO₃ in the presence of KSCN.¹³¹I was stripped into aqueous sodium hydroxide from the oxygenated organic extractant. The method was then applied for the recovery of¹³¹I from neutron irradiated tellurium metal. The mechanism and reactivity of DBC with metal ions is described.     

Apparent Neutron Emissions from Polyethylene Capsules during Neutron Activation and Delayed Neutron Counting

At Imperial College uranium is determined at very low levels in environmental samples by delayed neutron counting. High density polyethylene capsules are used for transporting the samples in a pneumatic transfer system, from the reactor, to the neutron detection rig. The detector has a background of 3.6 counts per minute, however the empty transport capsules produce 11.0 counts above the background. We have determined that neither uranium in the polyethylene or from contamination of the capsule nor ¹⁷N from the ¹⁷O(n,p)¹⁷N and ¹⁸O(n,d)¹⁷N reactions are the cause. This paper reports the results of the investigation into the source of the extra counts.     

Studies on the preparation of a131Ba−131Cs generator

¹³¹Cs has been a useful radionuclide for myocardial scanning and localisation of certain tumors in man. It has a half-life of 9.7 days and the decay product of¹³¹Ba (T=11.6 d). The authors have developed a¹³¹Ba−¹³¹Cs generator based on ion exchange chromatography over hydrous zirconium oxide yielding¹³¹Cs quantitatively and in a pure form. This method can also be employed in any isotope laboratory for the large scale production of¹³¹Cs.     

Comparison of the radiopharmaceutical potentials of dithizone radiolabeled with 131I and with 99mTc

In this study, dithizone (diphenylthiocarbazone) has been separately radiolabeled with ¹³¹I and with ^99mTc for preliminarily testing their radiopharmaceutical potentials on male albino rabbits. ¹³¹I-dithizone and ^99mTc-dithizone were intravenously injected to rabbits via their ear veins after anesthetizing with a mixture of Alfazyne and Alfamine (Serva) to determine their dynamic and static statuses in the metabolism. Also, ^99mTc as pertechnetate and ¹³¹I as iodate were administered to rabbits as controls. Dynamic and static scintigrams were obtained using a gamma camera (Diacan Instruments). Dynamic scintigrams were obtained over the first half hour with frames of 1 minute following the administrations of the labeled compounds. Static images were obtained from posterior projection at different time intervals up to about 3 hours following the administration of the radiolabeled compounds. ^99mTc-dithizone was significantly uptaken by the pancreas in contrast to free ^99mTc. In the case of ¹³¹I-dithizone, the distribution of ¹³¹I activity in the metabolism was clearly different than the case of free ¹³¹I and the uptake of ¹³¹I-dithizone at the pancreas zone was also significant. These preliminary tests have clearly indicated that especially ^99mTc-dithizone has a significant potential to be used as a pancreatic radiopharmaceutical.     

Synthesis of radioiodinated 4-[*I]iodoantipyrine via isotopic exchange

Radioiodinated 4-[*I]iodoantipyrine labeled with radioiodine (i.e., ¹²³I or ¹²⁵I or ¹³¹I) has been used for modeling radiation damage on cell nuclei of tumor cells where the characteristic high linear energy transfer (high-LET) of the Auger electron could be demonstrated. Also, the compound is currently used for the measurement of regional cerebral blood flow (rCBF) in autoradiography. 4-[¹³¹I]iodoantipyrine was synthesized by two methods via a nucleophilic isotopic exchange reaction between ¹³¹I as iodide ion [¹³¹I^–] and inactive 4-[¹²⁷I]iodoantipyrine: either in absolute ethyl alcohol catalyzed by ammonium acetate or in dry state molten ammonium acetate (m.p. 114 °C) as an isotopic exchange medium without carrier addition. The first one is called wet method: where a solution of 4-iodoantipyrine and ammonium acetate in absolute ethyl alcohol and lyophilized Na¹³¹I was heated briefly up to boiling (80 to 90 °C) for 30 minutes under reflux. The second one is called dry state-molten method: where the alcoholic solution containing 4-iodoantipyrine and ammonium acetate and the lyophilized Na¹³¹I were heated briefly in a nitrogen stream to dryness at 120 to 125 °C for 5 minutes or melted by gradual heating at 150 to 160 °C for 5 minutes. A radiochemical yield ranged between 90%–95% in each method has been obtained for 4-[¹³¹I]iodoantipyrine. In both methods, the reaction proceeds properly without carrier addition by an addition – elimination mechanism. The physico-chemical parameters affecting the radiochemical yield of the isotopic exchange reaction [i.e., reaction time, temperature, exchange medium, concentration of the reactants, carrier (KI) addition and pH] were investigated. Chromatographic analysis i.e., TLC and HPLC were used to determine the radiochemical yield as well as the purity of the final product, which was as pure as 99.9%.     

Uranyl–Peroxide Capsule Self-Assembly in Slow Motion

Uranyl-peroxide capsules are the newest family of polyoxometalates. Although discovered 13 years previously with over 70 topologies reported, there is a lack in the fundamental understanding of assembly mechanisms, particularly the role of the alkali counterions. Herein, the reaction pathway and assembly of uranyl peroxide capsules is reported by tracking the conversion from K⁺ uranyl triperoxide monomer to the K⁺ uranyl-peroxide U₂₈ capsule by means of small-angle X-ray scattering and Raman spectroscopy. For the first time, the K⁺ uranyl-peroxide pentamer face is isolated and structurally characterized, giving credence to the long-held belief that these geometric faces serve as building blocks to the fully formed capsules. Once isolated and re-dissolved, the pentamer face undergoes rapid conversion to capsule forms, underlining its high reactivity that challenges its isolation. Calorimetric measurements of the studied species confirms the pentamer lies on the energy landscape between the monomer and capsule.     

New developments in the production of theranostic pairs of radionuclides

A brief historical background of the development of the theranostic approach in nuclear medicine is given and seven theranostic pairs of radionuclides, namely ^44gSc/⁴⁷Sc, ⁶⁴Cu/⁶⁷Cu, ⁸³Sr/⁸⁹Sr, ⁸⁶Y/⁹⁰Y, ¹²⁴I/¹³¹I, ¹⁵²Tb/¹⁶¹Tb and ¹⁵²Tb/¹⁴⁹Tb, are considered. The first six pairs consist of a positron and a β^?-emitter whereas the seventh pair consists of a positron and an α-particle emitter. The decay properties of all those radionuclides are briefly mentioned and their production methodologies are discussed. The positron emitters ⁶⁴Cu, ⁸⁶Y and ¹²⁴I are commonly produced in sufficient quantities via the (p,n) reaction on the respective highly enriched target isotope. A clinical scale production of the positron emitter ^44gSc has been achieved via the generator route as well as via the (p,n) reaction, but further development work is necessary. The positron emitters ⁸³Sr and ¹⁵²Tb are under development. Among the therapeutic radionuclides, ⁸⁹Sr, ⁹⁰Y and ¹³¹I are commercially available and ¹⁶¹Tb can also be produced in sufficient quantity at a nuclear reactor. Great efforts are presently underway to produce ⁴⁷Sc and ⁶⁷Cu via neutron, photon and charged particle induced reactions. The radionuclide ¹⁴⁹Tb is unique because it is an α-particle emitter. The present method of production of ¹⁵²Tb and ¹⁴⁹Tb involves the use of the spallation process in combination with an on-line mass separator. The role of some emerging irradiation facilities in the production of special radionuclides is discussed.