<Superscript>137</Superscript>Cs/<Superscript>137m</Superscript>Ba radioisotope generator based on 6-tungstocerate(IV) column matrix

Summary Barium-137m radioisotope generator of the chromatographic column elution mode based on loading 1.5 g 6-tungstocerate(IV) gel matrix with ~54 kBq of fission-produced ¹³⁷Cs is described. The elution performance of the generated ^137mBa radionuclide was investigated as a function of chemical composition of the eluent, flow rate, elution frequency, and age of the generator system. At comparable conditions, ^137mBa eluates with 0.9% NaCl-0.1M HCl eluent had higher elution yields and radionuclidic purity than with 0.1M NH₄Cl-0.1M HCl eluent. The generator has been repeatedly eluted for 311 days by passing 4810 ml of the saline eluent (10 ml × 481 elution operations) at a flow rate of 3.0 ml/min. Barium-137m eluates of high and reproducible elution yields, chemical and radionuclidic purities of (≥ 99.99%) were obtained.     

<Superscript>99</Superscript>Mo/<Superscript>99m</Superscript>Tc generators based on aluminum molybdate gel matrix prepared by nano method

A procedure for preparation of ⁹⁹Mo/^99mTc radioisotope generator based on low specific activity neutron activated ⁹⁹Mo was developed. Aluminum molybdate(VI)-⁹⁹Mo of high Mo(VI) content (~?364 mg/g Al⁹⁹Mo) was prepared by mixing low specific activity molybdate(VI)-⁹⁹Mo and aluminum mixture solution with isoamyl alcohol. Al⁹⁹Mo gel matrix was precipitated when the pH of the mixture solution was raised to ~?5 by addition of NaOH to the mixture. Radiometric measurements indicate the strong fixation of Molybdate(VI)-⁹⁹Mo species in the form of the sparingly insoluble Al⁹⁹Mo gel matrix. The prepared AlMo gel matrix was physiochemically characterized. Al⁹⁹Mo gel matrix was used as a base material for preparation of ⁹⁹Mo/^99mTc generator. The ^99mTc eluted from ⁹⁹Mo/^99mTc radioisotope generator was found to have relatively high elution yield (84?±?2.3%), radionuclidic (≥?99.99%), radiochemical (98.1?±?0.9%) and chemical purity.     

Separation of <Superscript>113m</Superscript>In from <Superscript>113</Superscript>Sn based on activated carbon used as column matrix

The activated carbon was prepared by using corncobs and characterized by sorpatometer for using as an exchanger material to separate the generated ^113mIn from ¹¹³Sn and ^124,125Sb. To optimize the separation process, the different parameters like acetone percentage, HCl concentration were studied. The exchange capacity of Sn(IV) is 7.6 meq/g onto the activated carbon and the elution efficiency of ^113mIn > 80% by using 10 mL of 0.2 M HCl-80% acetone with flow rate 1 mL/min. The radionuclidic purity and radiochemical purity of the eluted ^113mIn were examined and clarified the presence of ^124,125Sb with relatively high level as radio impurities, so further separation was carried out by using Dowex 1×8 as an anion exchanger below the activated carbon matrix on the same separation column to adsorb the ¹¹³Sn and ^124,125Sb, which escape from the activated carbon matrix.     

Zirconium silicotungstate matrix as a prospective sorbent material for the preparation of <Superscript>113</Superscript>Sn/<Superscript>113m</Superscript>In generator

The zirconium silicotungstate (ZrSiW) was studied as an effective sorbent material to be used in the ¹¹³Sn/^113mIn generator. The results elucidated that the distribution coefficient of ¹¹³Sn (3700 mL/g) is greater than ^113mIn (275 mL/g) from 0.1 M HCl acid solution to the ZrSiW material. The maximum sorption capacity of Sn (IV) was found to be 33 mg per gram ZrSiW (~?0.3 mmol/g). The elution yield of ^113mIn was found to be >?78?±?6.4% with an acceptable purity of radionuclidic and radiochemical (≥?99.99 and 96.8%, respectively). The rigorous separation of ^113mIn from the ¹²⁵Sb was carried out due to its long half-life (2.758 years) and beta emission that causes tissue damage. Zr, W and Si levels are below the permitted limit in the ^113mIn eluate.     

Analytical and radioanalytical quality control of purity and stability of radiopharmaceutical compound [186gRe]Re-HEDP for bone metastases pain palliation

Summary The nuclear properties of ^186gRe make it a useful agent for radionuclide therapy and imaging. The coordination compound [^186gRe]Re-HEDP has proved to be a successful bone seeking agent for palliation of metastatic bone pain. Chemical, radiochemical and radionuclidic purity of commercial radiopharmaceutical [^186gRe]Re-HEDP have been checked by means by γ- and β-spectrometries, INAA and paper radio-chromatography. The results indicate a good radionuclidic purity, with levels of contamination from the short-lived ¹⁸⁸Re well below the required specifications. After injection of the radiopharmaceutical, the radiochemical measurements conducted in vivo, on biological matrices, blood, plasma and urine, have shown that, entering the systemic circulation, ^186gRe dissociates from the bis-phosphonate complex as hydrosoluble [^186gRe]ReO₄-, and the two chemical species follow different biokinetics.     

<Superscript>103</Superscript>Ru/<Superscript>103m</Superscript>Rh generator

^103mRh is a very promising radionuclide for Auger electron therapy due to its very low photon/electron ratio. The goal of the present work was the elaboration a method for production of large quantities of ^103mRh for generator system. It was found that the combination of solvent extraction with evaporation of ¹⁰³RuO₄ followed by decomposition of H₅IO₆ makes it possible to produce ^103mRh of high radionuclidic and chemical purity.     

Synthesis of maghemite nano-particles and its application as radionuclidic adsorbant to purify <Superscript>109</Superscript>Cd radionuclide

Maghemite nano-particles were synthesized by a solid-state chemical reaction for its highly selective use as, cyclotron-produced, ¹⁰⁹Cd (462.9 days) purification method of choice. ¹⁰⁹Cd radiochemical separation starts with Ag activities precipitated with HCl 0.0015 M followed by, on a second step, ¹⁰⁹Cd separation from Cu carrier and ⁶⁵Zn (243.8 days) using Ca (NO₃)₂ 0.01 M. Experimental parameters such, pH and sorbent concentration, on ¹⁰⁹Cd extraction efficiency were investigated. Phase morphology, nanostructure and size of nano-particles were studied by X-ray diffraction (XRD) and scanning electron microscopy (SEM). A 10–20 nm average grain size was derived from XRD line broadening and SEM data. Heat treatment on Fe³⁺:Fe²⁺ ratios equal to 2:1, produced powders, resulting in tetragonal (maghemite) structure at 300 °C and rhombohedra (hematite) at 600 °C. ¹⁰⁹Cd chemical and radionuclidic purity were determined by ICP-AES and HPGe detector gamma-ray spectrometry. The overall recovery and radionuclide purity were 80.0% from obtained 129.63 kBq/C MeV (70 kBq/μAh) initial activity and 91.4%, respectively.     

Pyridyl derivatives provide new pathways for labeling protein with fac-[<Superscript>188</Superscript>Re(CO)<Subscript>3</Subscript>(H<Subscript>2</Subscript>O)<Subscript>3</Subscript>]<Superscript>+</Superscript>

The purpose of this work was to indirect label IgG with fac-[¹⁸⁸Re(CO)₃(H₂O)₃]⁺ and to check the radiochemical behavior of the labeled product. The compound of (bis(2-pyridylmethyl)-amino)-acetic acid (L²H) was synthesized and labeled with fac-[¹⁸⁸Re(CO)₃(H₂O)₃]⁺. The labeling yield of ¹⁸⁸Re(CO)₃–L²H was more than 90%. The effects of protein concentration, reaction time, pH and reaction temperature of labeling of IgG with ¹⁸⁸Re(CO)₃–L²H were investigated. The conjugation conditions were optimized. The labeled product was analyzed by size exclusion HPLC and TLC. The stability of ¹⁸⁸Re(CO)₃–L²H–IgG in vitro was high. The results of this study may be useful for [¹⁸⁸Re(CO)₃(H₂O)₃]⁺ labeling of protein for radioimmunotherapy.     

Synthesis of pyridyl derivatives for the future functionalization of biomolecules labeled with the fac-[<Superscript>188</Superscript>Re(CO)<Subscript>3</Subscript>(H<Subscript>2</Subscript>O)<Subscript>3</Subscript>]<Superscript>+</Superscript> precursor

In this paper, we investigated three ligand systems, symmetric and asymmetric pyridyl-containing tridentate ligands (L¹NH₂ = (bis(2-pyridylmethyl)-amino)-ethylamine, L²H = (bis(2-pyridylmethyl)-amino)-acetic acid, L³NH₂ = [(6-amino-hexyl)-pyridyl-2-methyl-amino]-acetic acid) as bifunctional chelating agents for labeling biomolecules. These ligands reacted with the precursor fac-[¹⁸⁸Re(CO)₃(H₂O)₃]⁺ and yielded the radioactive complexes fac-[¹⁸⁸Re(CO)₃L] (L = three ligands), which were identified by RP-HPLC. The corresponding stable rhenium tricarbonyl complexes (1–3) were allowed for macroscopic identification of the radiochemical compounds. ¹⁸⁸Re tricarbonyl complexes, with log P _o/w values ranging from −1.36 to −0.32, were obtained with yields of ≥90% using ligand concentrations within the 10⁻⁶−10⁻⁴M range. Challenge studies with cysteine and histidine revealed the high stability properties of these radioactive complexes, and biodistribution studies in normal mice indicated a fast rate of blood clearance and high rate of total radioactivity excretion, primarily through the renal-urinary pathway. In summary, these asymmetric and symmetric pyridyl-containing tridentate ligands are potent bifunctional chelators for the future biomolecules labeling of fac-[¹⁸⁸Re(CO)₃(H₂O)₃]⁺.     

Radionuclide purity assessment and calibration of <Superscript>90</Superscript>Y(<Superscript>177</Superscript>Lu) glass particles using gamma-ray spectrometry

Intra-hepatic administration of radioactive glass microspheres is a treatment for patients with primary liver cancer and hepatic metastases. The purpose of this study was radionuclide purity assessment of new glass particles containing two radionuclide, ⁹⁰Y as a therapeutic source and also ¹⁷⁷Lu as a source of diagnostic gamma. For the mixed source, activity measurement using a dose calibrator cannot be used and we need new calibration methods. YAS (Yb) and YAS compositions were sol–gel derived glass particles and production of ⁹⁰Y (¹⁷⁷Lu) and ⁹⁰Y particles was performed using the Tehran Research Reactor. The radionuclide purity was carried out using γ-spectrometry with HPGe detector. A non-destructive spectroscopic assay was employed due to a newly updated low uncertainty positron branching ratio of ⁹⁰Y that emit 511 keV annihilation radiations. In another method, a new calibration of ⁹⁰Y using a non-destructive spectroscopic assay of ⁸⁸Y were investigated. Potential radionuclide impurity include: ⁸⁸Y, ¹⁵²Eu, ⁶⁰Co with activity 100, 50 and 5 Bq per 1 mg of that are not harmful for patients due to delivering radioactive particles about 20–50 mg in ⁹⁰Y(¹⁷⁷Lu) glass microspheres. Among of radionuclide impurity, ¹⁵²Er with a half life of 13.54 years and ⁸⁸Y with a half life of 106.65 days was important in the residual delivery device. For calibration of ⁹⁰Y with monitoring of 511 keV, errors were12.2–21%. In calibration of ⁹⁰Y using gamma spectroscopic assay of ⁸⁸Y, there was an error less than 14%. Spectroscopic assay of ⁸⁸Y can be performed easily and has more repeat for our purpose.     

An improved tungsten-188/rhenium-188 gel generator based on zirconium tungstate

An improved¹⁸⁸W-¹⁸⁸Re gel generator based on Zr tungstate is described. The influence of synthesis parameters and pre-treatment conditions on¹⁸⁸Re elution yields and the¹⁸⁸W breakthrough was studied with 0.15M aqueous solution of NaCl at pH 5.3 to 7.3 as well as with some organic solvents. An elution efficiency of 80% was achieved during 3 month of explotation with 0.15M NaCl at pH=6.3. The¹⁸⁸W breakthrough was 10^–4 to 10^–3%. The¹⁸⁸W breakthrough may be decreased to 10^–6% when converted into tandem generator with an alumina column. However,¹⁸⁸Re yields are reduced by 8–12% with a tandem generator.     

Development of an in vivo radionuclide generator by labeling bleomycin with <Superscript>191</Superscript>Os

Bleomycin (BLM) has been labeled with various radioisotopes and widely used in therapy and diagnosis. ¹⁹¹Os is a parent radionuclide with 15.4 day half-life and decays by beta emission to ^191mIr, which is a radionuclide with 4.96 s half-life. BLM was labeled with ¹⁹¹Os-hexachloro-osmate and its distribution and stability in wild-type mice was determined. The complex was obtained at the pH 2 in normal saline at 90 °C in 48 h. Radio-TLC showed an overall radiochemical yield of 93–97%, radio-chemical purity > 97%. The biodistribution study for ¹⁹¹Os-hexachloro-osmate and ¹⁹¹Os-BLM were carried in wild type-mice up to 14 days. Lungs, liver and spleen uptake increased 24–72 h after administration of ¹⁹¹Os-BLM. 24 h after administration, the radioactivity of the kidney increased and remained constant.     

Evaluation of fresh and old eluate of <Superscript>99</Superscript>Mo/<Superscript>99m</Superscript>Tc generators used for labeling of different pharmaceutical kits

Summary Sixty ⁹⁹Mo/^99mTc wet column generators, loaded with two different ⁹⁹Mo activities, were analyzed in order to assess the quality of their eluates. Each elution was used for labeling of different radiopharmaceuticals, in order to evaluate whether “risky” elutions, namely those performed just after generator delivery and at 72 hours or more from the last elution, could be conveniently employed when fresh available radioactivity is not enough for the planned labeling or when shipping problems arise, or delay in delivery of a new generator occurs. Radiochemical quality control of all radiopharmaceuticals labeled with these elutions was performed. The elutions differed mainly in ⁹⁹Tc ground state (^99gTc) and amounts of oxidizing impurities. Radiolabeling procedures, however, were not affected, suggesting that these “risky” elutions might be appropriately used, in “emergency” conditions, for labeling radiopharmaceuticals although their radiochemical purity control is recommended prior to patient administration.     

Rapid isocratic HPLC investigation of radiochemical purity for <Superscript>90</Superscript>Y-DOTATATE

DOTA-conjugated peptides, such as [DOTA⁰, Tyr³]ocreotide (DOTATOC) and [DOTA⁰, Tyr³]octreotate (DOTATATE) can be labeled with radionuclides such as ⁹⁰Y, ¹⁷⁷Lu and ¹¹¹In at high specific activities. These radiolabelled somatostatin analogues are used for peptide receptor radionuclide therapy (PRRT). Currently, radio-high performance liquid chromatography (radio-HPLC) and radio-thin layer chromatography (radio-TLC) are the methods of choice for the analysis of the labeled compounds. In literature, radiochemical purity of the radiolabelled DOTATATE was investigated using gradient reversed-phase radio-HPLC. However, these studies indicate long retention time of the radiolabelled compound of 14.52 min. In our study, a new simple and rapid reversed-phase isocratic system enables the radiochemical purity of the radiolabelled DOTATATE within a few minutes.     

Sequential separation of <Superscript>99</Superscript>Tc, <Superscript>94</Superscript>Nb, <Superscript>55</Superscript>Fe, <Superscript>90</Superscript>Sr and <Superscript>59/63</Superscript>Ni from radioactive wastes

A sequential separation procedure has been developed for the determination of ⁹⁹Tc, ⁹⁴Nb, ⁵⁵Fe, ⁹⁰Sr and ^59/63Ni in various radioactive wastes generated from nuclear power plants. Ion exchange and extraction chromatography were adopted for individual separation of the radionuclides. Precipitation was supplementarily utilized for both purification of the individual radionuclides and preparation of the radionuclide sources for use in a radioactivity measurement. The chromatographic separation behavior of the radionuclides both from the sample matrix metals and from one another was investigated using stable metals, Re (as a surrogate of ⁹⁹Tc), Nb, Fe, Sr and Ni. The validity of the procedure for reliability and applicability was evaluated by measuring the recovery of the metal carriers added to synthetic radioactive waste solutions. The recoveries by the chromatographic separation were in the range of 84.8 to 102.2% with 2s of less than 8.6%, the recoveries by the precipitation being in the range of 84.3 to 97.3% with 2s of less than 10.9%.     

Systematic radiochemical separation for the determination of <Superscript>99</Superscript>Tc, <Superscript>90</Superscript>Sr, <Superscript>94</Superscript>Nb, <Superscript>55</Superscript>Fe and <Superscript>59,63</Superscript>Ni in low and intermediate radioactive waste samples

A simple and rapid separation procedure was systemized for the determination of ⁹⁹Tc, ⁹⁰Sr, ⁹⁴Nb, ⁵⁵Fe and ^59,63Ni in low and intermediate level radioactive wastes. The integrated procedure involves precipitation, anion exchange and extraction chromatography for the separation and purification of individual radionuclide from sample matrix elements and from other radionuclides. After separating Re (as a surrogate of ⁹⁹Tc) on an anion change resin column, Sr, Nb, Fe and Ni were sequentially separated as follows; Sr was separated as Sr (Ca-oxalate) co-precipitates from Nb, Fe and Ni followed by purification using Sr-Spec extraction chromatographic resin. Nb was separated from Fe and Ni by anion exchange chromatography. Fe was separated from Ni by anion exchange chromatography. Ni was separated as Ni-dimethylglyoxime precipitates after the removal of ^134,137Cs and ^110mAg by Cs-phosphotungstate and AgCl precipitation, respectively. Finally, the radionuclide sources were prepared by precipitation for their radioactivity measurements. The reliability of the procedure was evaluated by measuring the recovery of chemical carriers added to a synthetic radioactive waste solution.     

Accurate determination of half-life and radionuclidic purity of reactor produced <Superscript>177g</Superscript>Lu (<Superscript>177m</Superscript>Lu) for metabolic radiotherapy

Thanks to its favorable decay characteristics, ^177gLu is finding several applications in nuclear medicine, especially for palliative metabolic radiotherapy of cancer and radioimunotherapy. ^177gLu is produced in thermal nuclear reactor either by direct neutron capture ¹⁷⁶Lu(n,γ)^177(m+g)Lu on either natural or enriched ¹⁷⁶Lu target, or by reaction on enriched ¹⁷⁶Yb target followed by negatron decay. The latter method does produce a high radionuclidic purity and high specific activity radionuclide in no-carrier-added form, since ¹⁷⁷Yb decays solely to the ground state ^177gLu. Conversely, the first method does produce a low specific activity ^177gLu in carrier-added form,¹ contaminated by the long-lived radioisotopic impurity ^177mLu. The accurate determination of radionuclidic purity and half-life of ^177gLu carried out by HPGe and LSCS is presented in some details.     

Separation of Clinical Grade 188Re from 188W Using Polymer Embedded Nanocrystalline Titania

Currently, ¹⁸⁸Re is obtained from ¹⁸⁸W/¹⁸⁸Re chromatographic generator containing alumina which has a limited capacity (~80 mg Wg^?1) for ¹⁸⁸W. This results in high bolus volumes of ¹⁸⁸Re, which often needs to be concentrated before radiolabeling. We have demonstrated the feasibility of using polymer embedded nano crystalline titania (TiP), a novel high capacity sorbent material (~300 mg Wg^?1), for developing a ¹⁸⁸W/¹⁸⁸Re chromatographic generator. A TiP based chromatographic ¹⁸⁸W/¹⁸⁸Re generator was developed in which ¹⁸⁸Re could be eluted with 0.9% saline solution. About 90% of the ¹⁸⁸Re could be recovered in the first 4–5 mL of total activity with more than 80% yield. The purity of ¹⁸⁸Re is adequate for clinical applications.     

Development of [<Superscript>64</Superscript>Cu]-DOTA-anti-CD20 for targeted therapy

Copper-64 was produced as a by-product of ⁵⁵Co via ⁶⁴Ni(p,n)⁶⁴Cu by 15 MeV proton bombardment of ^natNi resulting in a thick target yield of 5.31 MBq/μAh (143.5 μCi/μAh) and a radiochemical separation yield of 95% (radionuclide purity >97% after 25 hours of bombardment). Rituximab was successively labeled with [⁶⁴Cu]-CuCl₂. N-succinimidyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA-NHS) was prepared at 25 °C using DOTA and N-hydroxy succinimide (NHS) in CH₂Cl₂ followed by the addition of 1 ml of a Rituximab pharmaceutical solution. Radiolabeling was performed at 37 °C in 3 hours. Radio thin-layer chromatography showed an overall radiochemical purity of 90–95% at optimized conditions (specific activity=30 GBq/mg, labeling efficacy; 82%) using various chromatography systems. The final isotonic ⁶⁴Cu-DOTA-Rituximab complex was passed through a 0.22 μm filter and checked by gel electrophoresis for radiolysis control. Stability of the final product was checked in the formulation and in presence of human serum at 37 °C.     

Separation of Clinical Grade 188Re from 188W Using Polymer Embedded Nanocrystalline Titania

Currently, ¹⁸⁸Re is obtained from ¹⁸⁸W/¹⁸⁸Re chromatographic generator containing alumina which has a limited capacity (~80 mg Wg⁻¹) for ¹⁸⁸W. This results in high bolus volumes of ¹⁸⁸Re, which often needs to be concentrated before radiolabeling. We have demonstrated the feasibility of using polymer embedded nano crystalline titania (TiP), a novel high capacity sorbent material (~300 mg Wg⁻¹), for developing a ¹⁸⁸W/¹⁸⁸Re chromatographic generator. A TiP based chromatographic ¹⁸⁸W/¹⁸⁸Re generator was developed in which ¹⁸⁸Re could be eluted with 0.9% saline solution. About 90% of the ¹⁸⁸Re could be recovered in the first 4–5 mL of total activity with more than 80% yield. The purity of ¹⁸⁸Re is adequate for clinical applications.