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Sample records for 32p 90y 188re

  1. Therapeutic Radionuclide Generators: 90Sr/90Y and 188W/188Re Generators

    Radionuclide therapy using radiopharmaceuticals has been in existence for over 60 years and offers substantial benefits to cancer patients, in particular, patients suffering from thyroid cancer. Numerous clinical trials for treating other types of cancer using therapeutic radiopharmaceuticals are in progress, and their success will increase the demand for therapeutic radionuclides in the coming years. Those radioisotopes having short physical half-lives ranging from a few hours to a few days are useful for radionuclide therapy. The use of short lived radioisotopes for radionuclide therapy involves important challenges including the transport of the radionuclides and the need for frequent shipments. Radionuclide generators represent an efficient means for making short lived therapeutic radionuclides more widely available throughout the world. To meet the requirements for sustained growth and future expansion of the application of therapeutic radiopharmaceuticals in nuclear medicine, particularly in oncology, it is important to develop and maintain a constant and reliable supply of therapeutic radionuclides of the required quality in the desired quantities. The IAEA has several activities to support programmes that foster the enhanced availability of therapeutic radionuclides and radiopharmaceuticals in Member States. One such activity was the coordinated research project (CRP) on the development of generator technologies for therapeutic radionuclides, which ran from 2004 to 2007, in which participants from 13 countries worked to develop generator technologies for the preparation of 90Y and 188Re usable for radionuclide therapy. The objectives of the CRP were: (a) To develop reproducible methodologies for the preparation of 90Sr/90Y and 188W/188Re generators; (b) To standardize quality control techniques for generator eluted therapeutic radionuclides; (c) To optimize technologies for post-elution concentration of 188Re; (d) To prepare chromatography adsorbents having

  2. Development of Radiopharmaceuticals Based on 188Re and 90Y for Radionuclide Therapy at BARC. Chapter 6

    During the last decade, the group at Bhabha Atomic Research Centre (BARC), India, has focused attention on the development of 90Y based radiopharmaceuticals for therapy. Because the 90Sr/90Y generator is the primary source of high specific activity 90Y, local availability of the generator is crucial in the successful development of 90Y radiopharmaceuticals. In this context, 90Sr/90Y generators based on SLM and electrochemical techniques were designed and deployed at BARC for the elution of 90Y to be used for preparation of 90Y labelled products. This work formed a part of the IAEA CRP entitled Development of Generator Technologies for Therapeutic Radionuclides: 90Y and 188Re. In this chapter, work on the development of 90Y labelled products for treatment of NHL and liver cancer is reported. In addition, validation of the EPC technique for determination of 90Sr contamination in 90Y eluates and its comparison with the United States Pharmacopeia recommended method is presented. (author)

  3. Country report: Brazil. Development of Radiopharmaceuticals Based on 188Re and 90Y for Radionuclide Therapy at IPEN-CNEN/SP

    The overall objective of this CRP is to develop radiopharmaceuticals for targeted therapy using 188Re and 90Y and to study the performance of generators with long lived parent radionuclides as well as to validate the QC control procedures for estimating the purity of generator eluents. The CRP is expected to enhance the capability in production of 90Y and 188Re radiopharmaceuticals to meet the increasing demand of therapeutic products for clinical applications, in particular in Brazil. In this period efforts were made towards the assembling of 90Sr-90Y generators, quality control of 90Y, the labelling of DMSA(V) and anti-CD20 with 188Re and the labelling of Hydroxiapatite(HA) with 90Y. (author)

  4. Country report: Cuba. Local Production of 90Y And 188Re Radionuclides and Development of Radiopharmaceuticals for Therapy

    During the first period of this CRP we could test an efficient and reliable generator system based on ion-chromatography to obtain 90Y from its parent radionuclide 90Sr. This production scheme for 90Y was outlined in the previous CRP related with the development of generator technologies. Quality parameters such as trace metals that can potentially interfere in the labeling of biomoléculas, 90Y recovery, 90Sr/90Y ratio and radiation dose to bed matrix were evaluated. The results showed that high recovery and radionuclidic purity could be obtained for 90Y during its repeated separation from the 90Sr cow. No replacement or treatment of the cow were necessary and low waste generation and 90Sr losses less that 0.1% after each run were also observed during the present study. A Fab’ fragment was enzimatically produced and purified from the monoclonal antibody h-R3 (Nimotuzumab®). The fragment and the parent antibody were successfully conjugated with DOTA and labeled with 90Y. The radioinmunoconjugate thus obtained also exhibited a good 24 h in-vitro stability in an excess of DTPA. A 90Y radiocoloid was prepared in a cromic phosphate particle for radiosynoviorthesis with promising results in animal models. Two alumina based 188W/188Re generators were prepared and their eluates were used in the labeling of hR3-DOTA conjugates. Quality control and in vivo evaluation in comparison with 99mTc-hR3 showed very good results and similar pattern of distribution and pharmacokinetic and will be used in clinical trials for cancer patients. (author)

  5. Report on the 2nd Research Coordination Meeting on The Development of Therapeutic Radiopharmaceuticals Based on 188Re and 90Y for Radionuclide. Working Document

    Radionuclide therapy is practiced for the treatment of malignant disorders of various organs and tissues as well as for treating certain other diseases such as rheumatoid arthritis. Advances in understanding tumor biology as well as developments in peptide chemistry and monoclonal antibody technology are opening new opportunities for the development of therapeutic radiopharmaceuticals, thereby widening the scope of radionuclide therapy. In addition, particulate based radiopharmaceuticals are useful for treating hepatocarcinoma as well as in radiation synovectomy. With the establishment of new products the demand and application of therapeutic nuclear medicine is expected to grow rapidly. While there are a large number of radioisotopes proposed for targeted therapy, practical considerations had been limiting the number of usable isotopes. Generator-produced radionuclides are an attractive option for the large scale on-site availability of therapeutic isotopes. The IAEA’s CRP on the ‘Development of generator technologies for therapeutic radionuclides’ (2004-2007) was successful in developing technologies for the preparation of 188W/188Re and 90Sr/90Y generators for eluting 188Re and 90Y of high radionuclidic and chemical purity usable for research applications in the development of therapeutic radiopharmaceuticals. The IAEA’s CRP on ‘The development of therapeutic radiopharmaceuticals based on 188Re and 90Y for radionuclide therapy’ was formulated to focus on enhancing the capacity of the 90Sr/90Y generator; to develop and validate quality control methods for the generator eluate; and to develop therapeutic radiopharmaceuticals based on 188Re and 90Y. The first RCM of the CRP was held in Polatom, Warsaw, Poland from 30 June to 4 July 2008. The meeting reviewed the work going on in the different participating laboratories, and the facilities, expertise and capabilities of the different participating groups, and formulated the work plan of the CRP. The work

  6. 166Ho and 90Y labeled 6D2 monoclonal antibody for targeted radiotherapy of melanoma: Comparison with 188Re radiolabel

    Introduction: An approach to radioimmunotherapy (RIT) of metastatic melanoma is the targeting of melanin pigment with monoclonal antibodies (mAbs) to melanin radiolabeled with therapeutic radionuclides. The proof of principle experiments were performed using a melanin-binding antibody 6D2 of IgM isotype radiolabeled with a β emitter 188Re and demonstrated the inhibition of tumor growth. In this study we investigated the efficacy of 6D2 antibody radiolabeled with two other longer lived β emitters 90Y and 166Ho in treatment of experimental melanoma, with the objective to find a possible correlation between the efficacy and half-life of the radioisotopes which possess high energy β (Emax > 1.5 MeV) emission properties. Methods: 6D2 was radiolabeled with longer lived β emitters 90Y and 166Ho in treatment of experimental melanoma in A2058 melanoma tumor-bearing nude mice. The immunoreactivity of the radiolabeled 6D2 mAb, its in vitro binding to the MNT1 human melanoma cells, the biodistribution and therapy in A2058 human melanoma bearing nude mice as well as dosimetry calculations were performed. Results: When labeled with the longer lived 90Y radionuclide, the 6D2 mAb did not produce any therapeutic effect in tumor bearing mice while the reduction of the tumor growth by 166Ho-6D2 was very similar to the previously reported therapy results for 188Re-6D2. In addition, 166Ho-labeled mAb produced the therapeutic effect on the tumor without any toxic effects while the administration of the 90Y-labeled radioconjugate was toxic to mice with no appreciable anti-tumor effect. Conclusions: 166Ho-labeled mAb to melanin produced some therapeutic effect on the tumor without any toxic effects while the administration of the 90Y-labeled radioconjugate was toxic to mice with no appreciable anti-tumor effect. We concluded that the serum half-life of the 6D2 carrier antibody matched well the physical half-life of 166Ho to deliver the tumoricidal absorbed dose to the tumor. Further

  7. Evaluation of S-values and dose distributions for 90Y, 131I, 166Ho, and 188Re in seven lobes of the rat liver

    Purpose: Rats have been widely used in radionuclide therapy research for the treatment of hepatocellular carcinoma (HCC). This has created the need to assess rat liver absorbed radiation dose. In most dose estimation studies, the rat liver is considered as a homogeneous integrated target organ with a tissue composition assumed to be similar to that of human liver tissue. However, the rat liver is composed of several lobes having different anatomical and chemical characteristics. To assess the overall impact on rat liver dose calculation, the authors use a new voxel-based rat model with identified suborgan regions of the liver. Methods: The liver in the original cryosectional color images was manually segmented into seven individual lobes and subsequently integrated into a voxel-based computational rat model. Photon and electron particle transport was simulated using the MCNPX Monte Carlo code to calculate absorbed fractions and S-values for 90Y, 131I, 166Ho, and 188Re for the seven liver lobes. The effect of chemical composition on organ-specific absorbed dose was investigated by changing the chemical composition of the voxel filling liver material. Radionuclide-specific absorbed doses at the voxel level were further assessed for a small spherical hepatic tumor. Results: The self-absorbed dose for different liver lobes varied depending on their respective masses. A maximum difference of 3.5% was observed for the liver self-absorbed fraction between rat and human tissues for photon energies below 100 keV. 166Ho and 188Re produce a uniformly distributed high dose in the tumor and relatively low absorbed dose for surrounding tissues. Conclusions: The authors evaluated rat liver radiation doses from various radionuclides used in HCC treatments using a realistic computational rat model. This work contributes to a better understanding of all aspects influencing radiation transport in organ-specific radiation dose evaluation for preclinical therapy studies, from tissue

  8. Development, Preparation and Quality Assurance of Radiopharmaceuticals Based on 188Re and 90Y for Radionuclide Therapy: In House Production of Radioisotopes at Vinča Instute of Nuclear Sciences. Chapter 10

    The objective of the project described in this chapter was the development of different radiolabelled compounds with 188Re and 90Y and optimization of labelling procedures. Four different groups of compounds were evaluated as follows: different polyphosphonates (HEDP, MDP and (2-hydroxy-3,4-dioxopentyl) phosphate (DPD)) and DMSA; HA particles; colloids like antimony trisulphide and tin colloid for radiosynovectomy and/or HCC; and biodegradable microspheres of HSA for HCC. During the project, the work was focused on the development of a 90Sr/90Y electrochemical generator, quality control methods for radionuclidic purity of 90Y, use of 90Y for radiometallation of a DOTA conjugated somatostatin analogue, [DOTA, Tyr3] octreotate, and preparation of 90Y DOTATATE for peptide receptor radionuclide therapy (PRRT). In vitro and in vivo evaluation of the labelled molecules and collection of data of promising radiotracers for clinical trials were also carried out. (author)

  9. Country report: Serbia. Development, Preparing and Quality Assurance of Radiopharmaceuticals Based on 188Re and 90Y for Radionuclide Therapy: The Possibilities for their Production in Laboratory for Radioisotopes, Ins «Vinča»

    The main object of the research planed for this project was to optimize the procedures for the 90Y and 188Re labelling of different compounds as well as their in vitro and in vivo evaluation. The work has been involved setting up the facilities, standardization of preparing protocols, and improving existing quality assurance/quality control (QA/QC) procedures in order to supply reliable products to the national nuclear medicine community

  10. Monte Carlo Calculation of Radioimmunotherapy with 90Y-, 177Lu-, 131I-, 124I-, and 188Re-Nanoobjects: Choice of the Best Radionuclide for Solid Tumour Treatment by Using TCP and NTCP Concepts

    S. Lucas

    2015-01-01

    Full Text Available Radioimmunotherapy has shown that the use of monoclonal antibodies combined with a radioisotope like 131I or 90Y still remains ineffective for solid and radioresistant tumour treatment. Previous simulations have revealed that an increase in the number of 90Y labelled to each antibody or nanoobject could be a solution to improve treatment output. It now seems important to assess the treatment output and toxicity when radionuclides such as 90Y, 177Lu, 131I, 124I, and 188Re are used. Tumour control probability (TCP and normal tissue complication probability (NTCP curves versus the number of radionuclides per nanoobject were computed with MCNPX to evaluate treatment efficacy for solid tumours and to predict the incidence of surrounding side effects. Analyses were carried out for two solid tumour sizes of 0.5 and 1.0 cm radius and for nanoobject (i.e., a radiolabelled antibody distributed uniformly or nonuniformly throughout a solid tumour (e.g., Non-small-cell-lung cancer (NSCLC. 90Y and 188Re are the best candidates for solid tumour treatment when only one radionuclide is coupled to one carrier. Furthermore, regardless of the radionuclide properties, high values of TCP can be reached without toxicity if the number of radionuclides per nanoobject increases.

  11. Phosphate Suspension Chromium (III) radiolabelled with 32P and 90Y

    Chronic synovitis is a manifestation common joint of rheumatoid arthritis, hemophilia and other systemic diseases. The modalities of treatment of this complication radiosynoviorthesis stands out for its good response, ease of implementation and lower total cost. In the United States, Europe and some countries in Latin America they are used to this different radioactive colloids and suspensions. In Cuba it was developed and is approved suspension Chromic Phosphate 32P-labeled. At work the consistency of the production process of this suspension is examined. As a result of the evaluation was found that the suspension is characterized by a radiochemical purity of 94 ± 1% and particle size predominantly of 91 ± 3 between 0.2-10 microns. The results achieved in regular production and application to patients with rheumatic diseases and hemophiliacs, with follow-up to one year prove their efficacy and safety, the latter associated with low leakage articular detected and the absence of adverse reactions. Also at work the results achieved in the development of a technology for the production of suspension Phosphate Chromium (III) labeled with 90Y, similarly to existing 32P composition is exposed, and properties even more favorable, in particular radiochemical purity of 97%, favoring the registration of a radiopharmaceutical with better technical and economic characteristics, which must ensures the use of this form of treatment in the country. (author)

  12. Evaluation of S-values and dose distributions for {sup 90}Y, {sup 131}I, {sup 166}Ho, and {sup 188}Re in seven lobes of the rat liver

    Xie Tianwu; Liu Qian; Zaidi, Habib [Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074 (China) and Key Laboratory of Biomedical Photonics of Ministry of Education, Huazhong University of Science and Technology, Wuhan 430074 (China); Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074 (China); Key Laboratory of Biomedical Photonics of Ministry of Education, Huazhong University of Science and Technology, Wuhan 430074 (China) and Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, CH-1211 Geneva (Switzerland); Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, CH-1211 Geneva (Switzerland); Geneva Neuroscience Center, Geneva University, CH-1211 Geneva (Switzerland) and Department of Nuclear Medicine and Molecular Imaging, University Medical Center Gronigen, University of Groningen, 9700 RB Groningen (Netherlands)

    2012-03-15

    Purpose: Rats have been widely used in radionuclide therapy research for the treatment of hepatocellular carcinoma (HCC). This has created the need to assess rat liver absorbed radiation dose. In most dose estimation studies, the rat liver is considered as a homogeneous integrated target organ with a tissue composition assumed to be similar to that of human liver tissue. However, the rat liver is composed of several lobes having different anatomical and chemical characteristics. To assess the overall impact on rat liver dose calculation, the authors use a new voxel-based rat model with identified suborgan regions of the liver. Methods: The liver in the original cryosectional color images was manually segmented into seven individual lobes and subsequently integrated into a voxel-based computational rat model. Photon and electron particle transport was simulated using the MCNPX Monte Carlo code to calculate absorbed fractions and S-values for {sup 90}Y, {sup 131}I, {sup 166}Ho, and {sup 188}Re for the seven liver lobes. The effect of chemical composition on organ-specific absorbed dose was investigated by changing the chemical composition of the voxel filling liver material. Radionuclide-specific absorbed doses at the voxel level were further assessed for a small spherical hepatic tumor. Results: The self-absorbed dose for different liver lobes varied depending on their respective masses. A maximum difference of 3.5% was observed for the liver self-absorbed fraction between rat and human tissues for photon energies below 100 keV. {sup 166}Ho and {sup 188}Re produce a uniformly distributed high dose in the tumor and relatively low absorbed dose for surrounding tissues. Conclusions: The authors evaluated rat liver radiation doses from various radionuclides used in HCC treatments using a realistic computational rat model. This work contributes to a better understanding of all aspects influencing radiation transport in organ-specific radiation dose evaluation for

  13. Production cross-section calculations of medical {sup 32}P, {sup 117}Sn, {sup 153}Sm and {sup 186,188}Re radionuclides used in bone pain palliation treatment

    Demir, Bayram [Istanbul Univ. (Turkey). Physics Dept.; Kaplan, A.; Capali, V. [Univ. Isparta (Turkey). Physics Dept.; Sarpuen, I.H. [Afyon Kocatepe Univ., Afyonkarahisar (Turkey). Physics Dept.; Aydin, A. [Kirikkale Univ. (Turkey). Physics Dept.; Tel, E. [Univ. Osmaniye (Turkey). Physics Dept.

    2015-03-15

    In this study, production cross-section calculations of {sup 32}P, {sup 117}Sn, {sup 153}Sm and {sup 186,188}Re radionuclides used in bone pain palliation treatment produced by {sup 30}Si(d,γ){sup 32}P, {sup 118}Sn(γ,n){sup 117}Sn, {sup 116}Sn(n,γ){sup 117}Sn, {sup 150}Nd(α,n){sup 153}Sm, {sup 154}Sm(n,2n){sup 153}Sm, {sup 152}Sm(n,γ){sup 153}Sm, {sup 186}W(d,2n){sup 186}Re, {sup 187}Re(γ,n){sup 186}Re, {sup 185}Re(n,γ){sup 186}Re and {sup 187}Re(n,γ){sup 188}Re reactions have been investigated in the different incident energy range of 0.003-34 MeV. Two-component exciton and generalised superfluid models of the TALYS 1.6 and exciton and generalised superfluid models of the EMPIRE 3.1 computer codes have been used to pre-equilibrium (PEQ) reaction calculations. The calculated production cross-section results have been compared with available experimental results existing in the experimental nuclear reaction database (EXFOR). Except the {sup 118}Sn(γ,n){sup 117}Sn, {sup 150}Nd(α,n){sup 153}Sm and {sup 185}Re(n,γ){sup 186}Re reactions, the two-component exciton model calculations of TALYS 1.6 code exhibit generally good agreement with the experimental measurements for all reactions used in this present study.

  14. Simulation of a 32P sourcewire and a 90Sr/90Y sourcetrain using MCNP4b and EGS4

    The two simulated sources, the 32P sourcewire and the 90Sr/90Y sourcetrain, are parts of catheter-based systems developed for vascular brachytherapy. Percutaneous transluminal coronary angioplasty is a widely accepted therapy for symptomatic coronary disease, but within the first 6 months often restenosis occur. For dosimetry and treatment planning, the knowledge of the source is essential. Therefore we simulated the depth dose curve and the change of the energy-spectra in dependence on the depth in polymethyl methacrylate. (orig.)

  15. Country report: Pakistan. Second Research Co-ordination Meeting on Development of Radiopharmaceuticals Based on 188Re and 90Y for Radionuclide Therapy, 22-26 March 2010, Vienna

    Various experiments were carried out for the separation of 90Y from 90Sr using colloid formation behavior of 90Y in basic pH range. When the acidic solution of 90Sr/90Y was treated with NaOH and passed through a small glass wool column, more than 95% 90Y was retained on glass wool, which was further washed with 0.1 M NaOH. The 90Y was extracted in 1 M HCl. Radionuclidic purity was determined by half life measurement. The contamination of parent was less than 0.0001%. Similarly when the colloid was passed through membrane filter more than 95% 90Y was retained which was recovered by 1 M HCl. The contamination of 90Sr was less than 0.0001%. The stock solution of 90Sr/90Y in NH4OH/NaOH was again passed through Millipore filter paper or glass wool after one week. The retention of 90Y was insignificant. The equilibrium mixture of 90Sr/90Y was acidified with HCl and again precipitated with addition of NH4OH or NaOH. The basic solution was passed through the Millipore filter or glass wool. More than 90% activity of 90Y was retained, which was finally extracted in 1 M HCl It was concluded that for recovery of 90Y from 90Sr by colloid formation, the acidic solution of 90Sr/90Y shall be freshly precipitated by NH4OH or NaOH. It was also observed that the adsorption of 90Y was quite high when the 90Sr solution was left in a glass vial for the growth of 90Y. However it can be easily extracted after keeping it in boiling water bath for few minutes. The separated 90Y via colloid formation was used for the labeling of EDTMP. Labeling efficiency of 90Y-EDTMP was more than 98%

  16. Production of 186Re and 188Re, and synthesis of 188Re-DTPA

    Production of radioactive rhenium isotopes 186Re and 188Re, and synthesis of 188Re-DTPA have been studied. For 186Re, a production method by the 185Re(n, γ) 186Re reaction in a reactor has been established. For 188Re, a production method by the double neuron capture reaction of 186W, which produces a 188W/188Re generator, has been established. For synthesis of 188Re-DTPA, the optimum conditions, including pH, the amounts of regents and so on, have been determined. (author)

  17. Development of a 188W/188Re Generator, Post-Elution Concentration of 99mTc and Evaluation of High Capacity Adsorbents

    The objective of the coordinated research project was the development of techniques for the preparation of 90Sr/90Y and 188W/188Re generators. The research at IPEN-CNEN/SP focused on developing a generator technology using high specific activity 188W imported from the Russian Federation. The development of a 188Re gel type generator, using the experience acquired by IPEN in recent years through the 99mTc gel generator project, is discussed. Quality control procedures were developed to ensure the purity of the eluted 188Re, and special attention was given to post-elution concentration of 188Re. (author)

  18. Studies of HEDP labelled with 188Re from different generators of 188W /188Re

    The widespread interest in 188Re for therapeutic applications, is due to its attractive 16,9 hours half-life, emission of a β- particle with maximum energy of 2.12 MeV and gamma-ray of 155 keV suitable for imaging. This work presents the radiolabelling of HEDP (etidronate) with 188Re eluted from alumina-based 188W/188Re generators and tungstate-based 188W/188Re gel generators. Dependence of the yield of the 18'8Re-HEDP on the concentration of the reduction agent, p H, reaction time, temperature and addition of carrier Re2O7 were evaluated. The radiolabelling of 188Re-HEDP procedure using the optimum conditions resulted a yield >= 98% for liquid and lyophilized kits. This basic formulation contains: 30 mg de HEDP, 7 mg de SnCl2, 3 mg de ascorbic acid and addition of 20 mug of Re2O7. The reactions were carried out with heating in boiling water for 30 minutes followed by 60 minutes of incubation. Another important aspect of this work was the radiochemical quality control comparing the results of PC, TLC and ion chromatography, along with the experiments with HPLC. The biological distribution proved the adequate bone uptake and in vivo stability of 188Re-HEDP complexes. (author)

  19. Preparation of 188Re complexes for nuclear medicine

    Synthesis conditions for 188Re complexes without carrier and with methylenediphosphonic, 1-hydroxyethylenediphosphonic and dimercaptosuccinic acids are studied 188Re is produced using 188W/188Re generator. Tin dichloride is used for rhenium reduction and ascorbic acid is taken as antioxidant. Effect of reducer concentration, p H, process duration, antioxidant nature, temperature and carrier introduction on the complex yield is investigated. Under the optimal conditions the yield makes up over 95% both for 188Re with and without carrier. The complex stability in relation to p H and salt background change is studied

  20. Synthesis of {sup 188}Re-DMSA complex using carrier-free {sup 188}Re

    Hashimoto, Kazuyuki; Izumo, Mishiroku [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; Islam, M.S.

    1997-03-01

    The synthesis of rhenium-DMSA labelled compound using carrier-free {sup 188}Re from the {sup 188}W/{sup 188}Re generator has been carried out. Stannous chloride was used as the reducing agent for reduction of rhenium and ascorbic acid was used as an antioxidant in the reaction media. The dependence of the yield of Re-DMSA complex upon the concentration of reducing agent, pH, reaction time, anti-oxidant, carrier and temperature was investigated. Under optimum conditions, the yield of Re-DMSA complexes were more than 98% for the carrier-free as well as carrier-added {sup 188}Re. The stability of the Re-DMSA complexes at different pH and time were also investigated. It was found that the Re-DMSA complex was very stable and did not undergo any changes or decomposition with the changes of pH from its initial values even after 48 hours of pH change for carrier-free as well as carrier-added complexes. (author)

  1. 188W/188Re Generator System and Its Therapeutic Applications

    A. Boschi

    2014-01-01

    Full Text Available The 188Re radioisotope represents a useful radioisotope for the preparation of radiopharmaceuticals for therapeutic applications, particularly because of its favorable nuclear properties. The nuclide decay pattern is through the emission of a principle beta particle having 2.12 MeV maximum energy, which is enough to penetrate and destroy abnormal tissues, and principle gamma rays (Eγ=155 keV, which can efficiently be used for imaging and calculations of radiation dose. 188Re may be conveniently produced by 188W/188Re generator systems. The challenges related to the double neutron capture reaction route to provide only modest yield of the parent 188W radionuclide indeed have been one of the major issues about the use of 188Re in nuclear medicine. Since the specific activity of 188W used in the generator is relatively low (<185 GBq/g, the eluted Re188O4- can have a low radioactive concentration, often ineffective for radiopharmaceutical preparation. However, several efficient postelution concentration techniques have been developed, which yield clinically useful Re188O4- solutions. This review summarizes the technologies developed for the preparation of 188W/188Re generators, postelution concentration of the 188Re perrhenate eluate, and a brief discussion of new chemical strategies available for the very high yield preparation of 188Re radiopharmaceuticals.

  2. Labelling of Biotin with 188Re. Chapter 8

    Different chemical strategies have been employed for labelling biotin using 188Re with the aim to develop a sterile and pyrogen free kit formulation that is suitable for clinical use. A number of biotin conjugated 188Re complexes were prepared and evaluated to determine their affinity for avidin. The most difficult challenge was to devise an efficient reaction pathway that was able to obtain the final radiocompounds in a high radiochemical yield. This work describes the molecular design and the chemical strategy that were followed to obtain reliable preparation of the new radiopharmaceuticals starting from generator produced [188ReO4]–. (author)

  3. Extraction centrifugal W-188/Re-188 generator for radiotherapeutic applications

    188 Re extraction generator for medical purposes development results are presented. The main advantage of such generator is the possibility to use as starting material the tungsten oxide of natural isotope composition irradiated in react or with mean neutron flux (1.0– 1.4·10 14 n ⋅ cm-2 ⋅ s-1). The parent (188 W) and daughter radionuclides were separated using centrifugal semicounter -current extractor developed at Physical Chemistry and Electrochemistry Institute under RAS (Russian Academy of Sciences). In the course of simulated solution experiments, optimal operating conditions were established for 188 Re production process. For this purpose, it is proposed to recover 188 Re by methylethylketone from alkaline solution (2.5 M KON + 2.5 M K2CO3) containing up to 200 g/l of W element. Methylethylketone is subsequently evaporated to dryness and residue is dissolved in isotonic solution of NaCl. An extraction generator model was built in hot cell; the process developed was then tested on radioactive solutions. The test has shown that the yield is 89% in the average and the radiochemical purity of 188 Re solution is ~ 97%. The activity of 188 W was less than 1·10-3 relative to that of 188 Re. Activity of other radioisotopes was below 1·10-4 . The content of inorganic impurities in 188 Re solution is determined only by the purity of aqueous solutions used for 188 Re dissolution. The generator model may be recommended as a basis for creation of commercial prototype of 188 Re extraction generator. Key words: extraction, generator, methylethylketone, radiopharmaceutical, metastases, preclinical research

  4. Specific energy from Auger and conversion electrons of 131I, 188Re-anti-CD20 to a lymphocyte's nucleus

    Torres-García, E.; Carrillo-Cazares, T. A.

    2011-01-01

    The typical radionuclides used to label anti-CD20 in the treatment of non-Hodgkin's lymphoma are 90Y, 131I, and 188Re, with the emission of beta particles, Auger electrons, and conversion electrons for the latter two. The aim of the present work was to calculate the contribution of high linear energy transfer radiation as Auger electrons (AE) and conversion electrons (CE) of 131I and 188Re-anti-CD20 to mean specific energy into the cell nucleus by Monte Carlo simulation (MCS), so as to infer therapeutic effectiveness on a dosimetric basis. MCS was used to quantify the frequency-mean specific energy into the cell nucleus, where the cell was modeled by two concentric spheres, considering two cell models. The results showed that 10% and 33% of the mean-specific energies (z¯) per disintegration imparted to the cell nucleus for both geometries are due to AE and CE; on the other hand, if the hit of AE and CE occurs, the contribution to (z¯) is about 64% and 86% for 131I and 188Re, respectively. According to the amount of specific energy from AE and CE into the cell nucleus by positive event, they can cause catastrophic effects in the nuclear DNA in the treatment of non-Hodgkin's lymphoma with 131I, 188Re-anti-CD20.

  5. Development of a 188W/188Re Generator

    The fabrication of a 188W/188Re generator is described in detail, including the stability testing and quality control methods used. Studies of the elution profiles of four generators showed that about 90% of the available activity was contained in a 4 mL volume of saline solution with high radioactive concentration. The generators were usable for over 6 months, and the quality of the eluate was within the approved specifications. An illustration of a shielding container made of tungsten for a 188Re eluate vial is also included. (author)

  6. Production of carrier-free 188Re in the past ten years in Taiwan

    Twenty clinical scale alumina-based 188W/188Re generators and carrier-free 188Re has been produced at the Institute of Nuclear Energy Research (INER-Taiwan) for over ten years. 2845.6 GBq (76.9 Ci) of 188Re-perrhenate solution has been eluted from generators during the past ten years. We have used the harvesting 188Re solution for labeling radiopharmaceuticals, such as 188Re-HEDP, 188Re-MDP, 188Re-microsphere, 188Relipiodol, and 188Re-sulfur colloid, etc. The average eluting yield of 188Re is 78.6±5.8% that was investigated at 1115 harvesting times from 20 generators. Each generator can be used more than six months but the Millipore needs to be changed every two months for smooth harvesting and high yield of 188Re solution. (author)

  7. Labeling of MDP with 188Re for bone tumour therapy

    188Re is one of the most attractive radioisotopes for a variety of therapeutic applications in nuclear medicine, due to its physical decay properties, such as β- emission of 2.12 MeV, γ emission of 155 keV and half life of 16.9 hours. Biphosphonates are potent inhibitors of osteoclastic bone resorption and are effective in several diseases that cause bone fragility and bone metastases. Because of these characteristics, labeled biphosphonates have been studied for bone pathologies, also acting as palliation of bone pain in case of metastasis.The aim of this study was to optimize the labeling of a phosphonate-MDP (Sodium Methylene Diphosphonate) with 188Re for use in bone pain palliation. 188Re was obtained by eluting a 188W-188Re generator from POLATOM. The labeling was performed at room temperature using MDP, SnCl2 as reducing agent and ascorbic acid. The variables studied were: Mass of ligand (3, 6 and 10 mg), reducing agent mass (5, 7, 10 and 11 mg), ascorbic acid mass (1, 3, 5 and 6 mg), pH (1 and 2) and time of reaction (15, 60, 120, 360 and 4320 minutes), that also reflected the stability of the radiopharmaceutical. The radiochemical control, that also measures the labeling efficiency was evaluated by paper chromatography using Whatman 3MM paper and the solvents acetone and 0.9%NaCl. The best formulation was the following: Mass of ligand MDP: 10 mg, mass of SnCl2: 5 mg, ascorbic acid mass: 3 mg, time of reaction: 30 minutes, pH: 1. Under optimum conditions, 188Re MDP radiolabeling yield was 98,07% and the radiopharmaceutical was stable up to 72 h. (author)

  8. A kit for preparation of 188Re sulfide suspension

    The 188Re sulfide suspension could be prepared quickly by a kit. The kit consists of three 10 mL vials. All the procedures were carried out in sterility circumstance. Vial A consisted of 1 mL KReO4 and Na2S2O3 (mole ratio 1:70) solution with excipient. Vial B was 5 mol/L HCl solution. Vial C consisted of 1.5 mL PVP and NaOH solution (mole ratio 1000:1). Vial B was sealed, Vial A and C were freeze-dried. Bacterium check, endotoxin check and security check were qualified. Kits were kept at ambient temperature and the Labelling efficiency of 188Re sulfide suspension was more than 98% with 2 months. The particle sizes were 1-5 μm (60.1 +- 12.7)%; 5-10 μm (30.9 +- 8.1)%; > 10 μm (9.0 +- 4.7)%. The radiochemical purity of 188Re sulfide suspension made by the kit was higher than 98% in 5 days with particle sizes 1-5 μm (49.9 +- 14.4%); 5-10 μm (41.1 +- 5.4)%; > 10μm (9.0 +- 3.3)%

  9. β-radiation exposure with 188Re-labelled pharmaceuticals

    Aim: The number of therapies with radiopharmaceuticals labelled with 188Re is increasing requiring the documentation of the beta radiation exposure Hp(0.07) of the staff at all working and production sites and during the application and follow-up of the patient according to the new German Radiation Protection Law (StrlSchV). However, data for β-radiation exposure are rare. Therefore, we determined the personal dose Hp(0.07) of the skin of the hands handling 188Re radiopharmaceuticals to identify steps of high radiation exposure and to optimize working conditions. Method: Thermoluminescence dosimeters (TLD 100) were fixed to the fingertips of the radiochemist, the physician and the nurse and compared to official ring dosimeters. In addition, to monitor radiation exposure continuously readable electronic beta- and gamma dosimeters EPD (Siemens) were used. At eight days in which therapies were performed these readings were evaluated. Results: Considering one therapy with a 188Re-labelled radiopharmaceutical the middle finger of the radiochemist (production) and the physician (application) showed a radiation burden of 894 and 664 μSv/GBq, respectively. The cumulative dose of the fingertips after eight days of therapy was 249 and 110 mSv for the radiochemist and physician, respectively. A cumulative finger dose after eight days of therapy of 17 and 39 μSv/GBq was found for physician and nurse leading to a Hp(0.07) of 3 and 6 mSv, respectively. Preparing the radiopharmaceutical labelled with 20 GBq of 188Re the reading of the personal electronic dosimeter of the radiochemist showed a γ-dose rate Hp(10) of 55 μSv/h and a β-dose rate Hp(0.07) of 663 μSv/h which are obviously not representative for the true radiation dose to the skin of the fingertips. Conclusion: During therapy with 188Re-labelled radiopharmaceuticals the true radiation dose to the skin of the finger tips exceeds by far the readings of the official ring dosimeters as well as the continuously

  10. Labelling of aminomethylenephosphonate derivatives with generator-produced 188Re and their stability

    In this study, the labelling of aminomethylenephosphonate derivatives (EDTMP Ethylenediamine-N,N,N',N' -tetrakis(methylenephosphonic acid), EDBMP - Ethylenediamine- N,N'-bis(methylenephosphonic acid) and NTMP - nitrilotris(methylenephosphonic acid)) with carrier-free 188Re from the 188W/188Re generator was investigated in detail. Stannous chloride was used as the reducing agent for the reduction of rhenium. The labelling studies were carried out by mixing all the solutions (ligand, I-ascorbic acid, a solution for pH adjustment, 188Re and stannous chloride) in a vial. The dependence of the labelling yield upon the reaction conditions such as the concentrations of the reducing agent and the ligand (aminomethylenephosphonate), pH, temperature and the addition of a carrier was examined. The stability of the 188Re complex against pH change and dilution with saline was also studied. It was found that the formation condition of the 188Re complex, that is the temperature, pH and the addition of a carrier, influenced the stability of 188Re complex. The carrier-added 188Re complex was more stable than the carrier-free 188Re complex. Furthermore, the stability decreased in the order 188Re-EDTMP > 188Re-EDBMP > 188Re-NTMP for the carrier-free 188Re complex

  11. Study on the preparation and stability of 188Re biomolecules via EHDP

    A direct labelling technique via ethane-1-hydroxy-1,1-diphosphonic acid (EHDP) as a weak competing ligand was developed for the preparation of several biomolecules: 188 Re-monoclonal antibody ior cea1 against carcinoembryonic antigen (188 Re-MoAb), biotinylated 188Re-MoAb (188 Re-MoAb-biotin), 188 Re-polyclonal IgG (188 Re-IgG), 188 Re-peptide (somatostatine analogue peptide b-(2-naphtyl)-D-Ala-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-amide), 188 Re-MoAb fragments (188 Re-F(ab')2) and biotinylated 188 Re-F(ab')2 (188 Re-F(ab')2-biotin). The reaction conditions such as pH, temperature, weak ligand concentration and stannous chloride concentration were optimized during the radiolabelling of each biomolecule. Before the labelling procedure, disulphide bridge groups of the biomolecules were reduced with 2-mercaptoethanol (2-ME). To obtain 188 Re labelled antibodies and peptides in high radiochemical yields (>90%) via EHDP, it was necessary to use acidic conditions and a high concentration of stannous chloride to allow the redox reaction Re+7→Re+5:Re+4. The labelling of MoAb and F(ab')2 with 188Re via EHDP was also evaluated employing a pretargeted technique by avidin-biotin strategy in normal mice, demonstrating that the 188Re-labelled biotinylated antibodies are stable complexes in vivo. The 188Re-peptide complex prepared by this method, was stable for 24 h and no radiolytic degradation was observed. (author)

  12. Labelling of aminomethylenephosphonate derivatives with generator-produced {sup 188}Re and their stability

    Hashimoto, K. [Japan Atomic Energy Research Insttitute, Tokai-mura, Ibaraki-ken, (Japan). Department of Radioisotopes

    1997-10-01

    In this study, the labelling of aminomethylenephosphonate derivatives (EDTMP Ethylenediamine-N,N,N`,N` -tetrakis(methylenephosphonic acid), EDBMP - Ethylenediamine- N,N`-bis(methylenephosphonic acid) and NTMP - nitrilotris(methylenephosphonic acid)) with carrier-free {sup 188}Re from the {sup 188}W/{sup 1}8{sup 8R}e generator was investigated in detail. Stannous chloride was used as the reducing agent for the reduction of rhenium. The labelling studies were carried out by mixing all the solutions (ligand, I-ascorbic acid, a solution for pH adjustment, {sup 188}Re and stannous chloride) in a vial. The dependence of the labelling yield upon the reaction conditions such as the concentrations of the reducing agent and the ligand (aminomethylenephosphonate), pH, temperature and the addition of a carrier was examined. The stability of the {sup 188}Re complex against pH change and dilution with saline was also studied. It was found that the formation condition of the {sup 188}Re complex, that is the temperature, pH and the addition of a carrier, influenced the stability of {sup 188}Re complex. The carrier-added {sup 188}Re complex was more stable than the carrier-free {sup 188}Re complex. Furthermore, the stability decreased in the order {sup 188}Re-EDTMP > {sup 188}Re-EDBMP > {sup 188}Re-NTMP for the carrier-free {sup 188}Re complex 20 refs., 12 figs.

  13. Intratumoral injection of 188Re labeled cationic polyethylenimine conjugates: a preliminary report.

    Kim, Eun-Mi; Jeong, Hwan-Jeong; Heo, Young-Jun; Moon, Hyung-Bae; Bom, Hee-Seung; Kim, Chang-Guhn

    2004-10-01

    188Re (Rhenium) is easily obtained from an in-house 188W/188Re generator that is similar to the current 99Mo/99mTc generator, making it very convenient for clinical use. This characteristic makes this radionuclide a promising candidate as a therapeutic agent. Polyethylenimine (PEI) is a cationic polymer and has been used as a gene delivery vector. Positively charged materials interact with cellular blood components, vascular endothelium, and plasma proteins. In this study, the authors investigated whether intratumoral injection of 188Re labeled transferrin (Tf)-PEI conjugates exert the effect of radionuclide therapy against the tumor cells. When the diameters of the Ramos lymphoma (human Burkitt's lymphoma) xenografted tumors reached approximately 1 cm, 3 kinds of 188Re bound compounds (HYNIC-PEI-Tf, HYNIC-PEI, 188Re perrhenate) were injected directly into the tumors. There were increases in the retention of 188Re inside the tumor when PEI was incorporated with 188Re compared to the use of free 188Re. The 188Re HYNIC-Tf-PEI showed the most retention inside the tumor (retention rate=approximately 97%). H&E stain of isolated tumor tissues showed that 188Re labeled HYNIC-PEI-Tf caused extensive tumor necrosis. These results support 188Re HYNIC-PEI-Tf as being a useful radiopharmaceutical agent to treat tumors when delivered by intratumoral injection. PMID:15483337

  14. Experimental study of 188Re-BAC5 radioimmunotherapy on nasopharyngeal carcinoma

    The feasibility of radioimmunotherapy for NPC with 188Re-BAC5, a kind of monoclonal antibody to NPC, was investigated. The 188Re-BAC5 was prepared by direct labeling method and its biological activity was determined. The MTT method was used to determine the inhibition effect of the 188Re-BAC5 on CNE-2 cell line culture, and the destruction effect on CNE-2 multicellular spheroids model was also observed. The control group were 188Re-BSA and 188ReO4-. The biological activity of BAC5 was 1:780000 after purification. The labeling yield of 188Re-BAC5 was above 80%. The immuno-activity of 188Re-BAC5 was 61% ± 15%. The results of MTT showed that the inhibition effect of 188Re-BAC5 group was much stronger than the control group (P188Re-BAC5 had a obvious destruction effect on spheroids, and there was a significant difference between 188Re-BAC5 and the control group. In conclusion, 188Re-BAC5 may serve a possible way in the treatment of NPC in the near future

  15. Labeling Lanreotide with 125I and 188Re

    Lanreotide is a new somatostatin analogue. It can bind to human somatostatin receptor (hSSTR) subtype 2 through 5 with high affinity and to hSSTR subtype I with low affinity. We investigate labeling condition, quality control and stability in vitro of 125I-Lanreotide and 188Re-lanreotide respectively. (A) Lanreotide is labeled with 125I using Chloramine T. The effect of reaction condition (such as reaction time, pH value, Lanreotide amount, quantity of Chloramine T and reaction volume) on labeling yield is investigated in detail. (B) The labeling yield and radiochemical purity (RP) is measured with paper chromatography (PC) and Sep-Pak C18 Cartridge. (C) The stability of 125I-Lanreotide in vitro is investigated by labeling compound incubating for 48 hours at 37 deg C in the 0.9% sodium chloride solution and RP is tested by PC at specific time intervals. (D) Lanreotide is labeled directly with 188Re via the mixture of citrate and tartate using stannous chloride as reduced agent. The influence of reaction conditions such as pH, temperature, amount of stannous chloride, amount of Lanreotide and reaction time on labeling yield is investigated in detail. At the time, the stability in vitro quality control and animal test are evaluated

  16. Experimental study of the biological properties of 188Re-Hepama-1 biologic superparamagnetic nanoparticles

    Objective: To investigate a new biologic-superparamagnetic nanoparticles's characteristics of immunological activity, biological distributing in vivo, targeting and inhibiting tumor effect. Methods: The experimental group 188Re-Hepama-l-superparamagnetic nanoparticles, and control groups, including 188ReO4-, 188Re-Hepama-1, and 188Re-superparamagnetic nanoparticles, were set up. The distributions were measured after injection 4 h and 24 h by caudal vein of Kuming mice. The magnetic targeting experiments in vivo were clone with and without magnetic field in liver after injection in New Zealand rabbit. The inhibiting tumor effect on hepatic cancer cell lines SMMC-7721 of the above four 188Re labeled products were measured by mono nuclear cell direct cytotoxicity assay method. Results: After injection 4 h and 24 h by vein, the liver taking was highest in group 188Re-Hepama-l-superparamagnetic nanoparticles. The radiative activity in liver in magnetism zoo was higher than in non magnetism zoo in 188Re- Hepama-1-superparamagnetic nanoparticles after applying magnetic field in left lobe of liver, and the ratio of in magnetism zoo to non magnetism zoo was 1.87. And the half effective inhibition radioactive concentrations (IC50) in 188Re-Hepama-l-superparamagnetic nanoparticles was one forth of 188ReO4-. Conclusion: 188Re- Hepama-l-superparamagnetic nanoparticles showed its fine stability in intro, good immunological activity and significant liver target. (authors)

  17. Peptide labeling using 188Re, 188Re-MAG3 and 153Sm-H1ETA. A comparison on their in vitro lipophilicity

    Lanreotide peptide was labeled with 153Sm-H1ETA and 188Re-MAG3 in order to evaluate whether or not their conjugation to the peptide produce significant differences of the in vitro lipophilicity with respect to the 188Re-lanreotide prepared by the direct labeling method (highly lipophilic). The differences of lipophilicity between the complexes, were evaluated using a reverse phase HPLC system. The measured lipophilicity of 153Sm-H1ETA-lanreotide, 188Re-MAG3-lanreotide and 188Re-lanreotide was taken to be the capacity factor [k' = (tR - t0)/t0 where tR is the retention time and t0 is the dead time] for each of the complexes under identical chromatography conditions. Results showed that the in vitro lipophilicity decreased in the order 188Re-lanreotide (direct labeling), 188Re-MAG3-lanreotide and 153Sm-H1ETA-lanreotide. Since the last one has a capacity factor (k') similar to that of 188Re-MAG3, some renal elimination for 153Sm-H1ETA-lanreotide could be expected, which probably would reduce the unnecessary radiation dose to normal tissues. (author)

  18. Preparation of 188W/188Re generator in a clinical-scale

    A 188W/188Re generator based on acid-treated alumina is prepared for medical application. 188Re can be eluted into vacuum vial with 0.9% NaCl solution in the presence or absence of ascorbic acid. The elution yield of 188Re is more than 70% during a period of three months. The 188W leakage is less than 10 - 4 %. Both the radiochemical purity and radionuclide purity are more than 99%

  19. Synthesis and primary biological evaluation of 188ReN-NEMPTDD

    A new nitrido-188Re complex, 188ReN-NEMPTDD, was synthesized through a modified method in high yield. This complex was stable in vitro. The biodistribution in normal mice showed that this ReN complex accumulated in the liver and was eliminated quickly from almost all organs. VX2 carcinoma was grown in the livers of rabbits. Transcatheter arterial embolization (TAE) was performed using 188ReN-NEMPTDD/lipiodol solution. The SPECT images showed that the lipiodol solution could be concentrated in the tumor for about 12 hours. These results indicated that 188ReN-NEMPTDD/lipiodol could be a potential radiopharmaceutical for liver cancer. (author)

  20. An alternative approach to the preparation of 188Re radiopharmaceuticals from generator-produced [188ReO4]-: efficient synthesis of 188Re(V)-meso-2,3-dimercaptosuccinic acid

    A new efficient approach for the preparation of 188Re radiopharmaceuticals starting from [188ReO4]-, produced at a carrier-free level through the 188W/188Re generator system, is described. The reaction procedure was based on the combined action of different reagents and has been applied in detail to the preparation of the therapeutic agent 188Re(V)-DMSA (H2DMSA [meso-2,3-dimercaptosuccinic acid]). The most efficient combination required the use of SnCl2, oxalate ions, and γ-cyclodextrin. These were reacted with [188ReO4]- and H2DMSA to afford the final radiopharmaceutical in high radiochemical purity, at room temperature, and in weakly acidic solution. The role played by the various reagents in the reaction was investigated. It was found that SnCl2 behaved as the actual reducing agent, whereas oxalate and γ-cyclodextrin greatly enhanced the ease of reduction of [188ReO4]- through the action of two hypothetical mechanisms. In the first step of the reaction, oxalate ions gave rise to the formation of Re(VII) complexes with the concomitant expansion of the coordination sphere of the metal. This process strongly favored the electron transfer between Sn2+ and Re+7 centers, giving rise to intermediate reduced rhenium complexes. These species were further stabilized by the formation of transient host-guest aggregates with γ-cyclodextrin and finally converted into 188Re(V)-DMSA through simple replacement of the coordinated ligands by H2DMSA

  1. Exploitation of nano alumina for the chromatographic separation of clinical grade 188Re from 188W: a renaissance of the 188W/188Re generator technology.

    Chakravarty, Rubel; Shukla, Rakesh; Ram, Ramu; Venkatesh, Meera; Tyagi, Avesh Kumar; Dash, Ashutosh

    2011-08-15

    The (188)W/(188)Re generator using an acidic alumina column for chromatographic separation of (188)Re has remained the most popular procedure world over. The capacity of bulk alumina for taking up tungstate ions is limited (∼50 mg W/g) necessitating the use of very high specific activity (188)W (185-370 GBq/g), which can be produced only in very few high flux reactors available in the world. In this context, the use of high-capacity sorbents would not only mitigate the requirement of high specific activity (188)W but also facilitate easy access to (188)Re. A solid state mechanochemical approach to synthesize nanocrystalline γ-Al(2)O(3) possessing very high W-sorption capacity (500 mg W/g) was developed. The structural and other investigations of the material were carried out using X-ray diffraction (XRD), transmission electron microscopy (TEM), Brunauer Emmett Teller (BET) surface area analysis, thermogravimetric-differential thermal analysis (TG-DTA), and dynamic light scattering (DLS) techniques. The synthesized material had an average crystallite size of ∼5 nm and surface area of 252 ± 10 m(2)/g. Sorption characteristics such as distribution ratios (K(d)), capacity, breakthrough profile, and elution behavior were investigated to ensure quantitative uptake of (188)W and selective elution of (188)Re. A 11.1 GBq (300 mCi) (188)W/(188)Re generator was developed using nanocrystalline γ-Al(2)O(3), and its performance was evaluated for a period of 6 months. The overall yield of (188)Re was >80%, with >99.999% radionuclidic purity and >99% radiochemical purity. The eluted (188)Re possessed appreciably high radioactive concentration and was compatible for the preparation of (188)Re labeled radiopharmaceuticals. PMID:21726091

  2. Labeling Lanreotide with 125I and 188Re. China

    Lanreotide (D-β-Nal-Cys-Try-D-Trp-Lys-Val-Cys-Thr-NH2) is a new somatostatin analogue. It can bind to human somatostatin receptor (hSSTR) subtype 2 through 5 with high affinity and to hSSTR subtype 1 with low affinity. We investigate labeling condition, quality control and stability in vitro of 125I-Lanreotide and 188Re-lanreotide respectively. (A) Lanreotide is labeled with 125I using Chloramine T. The effect of reaction condition (such as reaction time, pH value, Lanreotide amount, quantity of Chloramine T and reaction volume) on labeling yield is investigated in detail. (B) The labeling yield and radiochemical purity (RP) is measured with paper chromatography (PC) and Sep-Pak C18 Cartridge. For PC method, 125I-Lanreotide is spotted on the Whatman No.1 paper and developed in the mixture of CH3CH2CH2CH2OH and CH3CH2OH and NH4OH (v/v/v=5:2:1), the Rf value of every component in the mobile phase is given in table 1. For Sep-Pak C18 Cartridge methods each cartridge is washed with 10 ml of ethanol followed by 10 ml of iso-CH3CH2CH2OH solution. Aliquots of 0.1 mI sample is loaded onto the cartridge, unbound peptide (sodium iodine-125) is eluted with 5 ml of 0.5mol/L sodium acetate solution, 125I-Lanreotide is eluted with 5 mI of 95% aqueous ethanol solution. (C) The stability of 125I-Lanreotide in vitro is investigated by labeling compound incubating for 48 hours at 37 deg. C in the 0.9% sodium chloride solution and RP is tested by PC at specific time intervals. (D) Lanreotide is labeled directly with 188Re via the mixture of citrate and tartate using stannous chloride as reduced agent. The influence of reaction conditions such as pH, temperature, amount of stannous chloride, amount of Lanreotide and reaction time on labeling yield is investigated in detail. At the time, the stability in vitro quality control and animal test are evaluated

  3. A comparative study of {sup 188}Re(V)-meso-DMSA and {sup 188}Re(V)-rac-DMSA: preparation and in vivo evaluation in nude mice xenografted with a neuroendocrine tumor

    Park, Jun-Young [Department of Biomedical Laboratory Science, College of Health Science, Yonsei University, Wonju 220-710 (Korea, Republic of); Department of Nuclear Medicine, Yonsei University Health System, Seoul 120-752 (Korea, Republic of); Lee, Tae-Sup; Choi, Tae-Hyun; Cheon, Gi-Jeong; Choi, Chang-Woon [Laboratory of Nuclear Medicine, Korea Institute of Radiological and Medical Science, Seoul 139-706 (Korea, Republic of); Awh, Ok-Doo [Department of Nuclear Medicine, Yonsei University Health System, Seoul 120-752 (Korea, Republic of)], E-mail: immunoch@yonsei.ac.kr

    2007-11-15

    Dimercaptosuccinic acid (DMSA) exists in meso and racemic (rac) forms. Unlike a meso isomer, rac-2,3-DMSA is very soluble in water, strongly acidic solutions and organic solvents. Despite these differences, rac-2,3-DMSA has not been studied as a radiopharmaceutical. In this study, {sup 188}Re complexes with diastereomeric DMSA were prepared to compare the properties of {sup 188}Re(V)-rac-DMSA with those of {sup 188}Re(V)-meso-DMSA in in vitro and in vivo models. Methods: rac-2,3-DMSA was synthesized and radiolabeled with {sup 188}Re. The biodistribution and gamma camera imaging of {sup 188}Re(V)-meso-DMSA and {sup 188}Re(V)-rac-DMSA were performed in nude mice subcutaneously implanted with PC-12 cell lines. Results and conclusions: Both {sup 188}Re(V)-meso-DMSA and {sup 188}Re(V)-rac-DMSA showed excellent radiochemical purity and stability at room temperature. Compared with {sup 188}Re(V)-meso-DMSA, {sup 188}Re(V)-rac-DMSA needed a higher concentration of rac-DMSA and metabisulfite for maximum yields. {sup 188}Re(V)-meso-DMSA showed high labeling efficiency at pH 2, whereas {sup 188}Re(V)-rac-DMSA showed maximum yields at pH 5. The tumor uptake of {sup 188}Re(V)-rac-DMSA was 3.5 times higher than that of {sup 188}Re(V)-meso-DMSA at 1 h (P<.01). Gamma camera images showed that {sup 188}Re(V)-rac-DMSA was more selectively localized than {sup 188}Re(V)-meso-DMSA at the tumor region in a xenograft model. These results demonstrate that {sup 188}Re(V)-rac-DMSA may have better potential than {sup 188}Re(V)-meso-DMSA as a therapeutic agent against neuroendocrine tumors.

  4. A comparative study of 188Re(V)-meso-DMSA and 188Re(V)-rac-DMSA: preparation and in vivo evaluation in nude mice xenografted with a neuroendocrine tumor

    Dimercaptosuccinic acid (DMSA) exists in meso and racemic (rac) forms. Unlike a meso isomer, rac-2,3-DMSA is very soluble in water, strongly acidic solutions and organic solvents. Despite these differences, rac-2,3-DMSA has not been studied as a radiopharmaceutical. In this study, 188Re complexes with diastereomeric DMSA were prepared to compare the properties of 188Re(V)-rac-DMSA with those of 188Re(V)-meso-DMSA in in vitro and in vivo models. Methods: rac-2,3-DMSA was synthesized and radiolabeled with 188Re. The biodistribution and gamma camera imaging of 188Re(V)-meso-DMSA and 188Re(V)-rac-DMSA were performed in nude mice subcutaneously implanted with PC-12 cell lines. Results and conclusions: Both 188Re(V)-meso-DMSA and 188Re(V)-rac-DMSA showed excellent radiochemical purity and stability at room temperature. Compared with 188Re(V)-meso-DMSA, 188Re(V)-rac-DMSA needed a higher concentration of rac-DMSA and metabisulfite for maximum yields. 188Re(V)-meso-DMSA showed high labeling efficiency at pH 2, whereas 188Re(V)-rac-DMSA showed maximum yields at pH 5. The tumor uptake of 188Re(V)-rac-DMSA was 3.5 times higher than that of 188Re(V)-meso-DMSA at 1 h (P188Re(V)-rac-DMSA was more selectively localized than 188Re(V)-meso-DMSA at the tumor region in a xenograft model. These results demonstrate that 188Re(V)-rac-DMSA may have better potential than 188Re(V)-meso-DMSA as a therapeutic agent against neuroendocrine tumors

  5. Hydroxyapatite Based 99Mo-99mTc and 188W-188Re Generator Systems

    This paper describes studies evaluating the use of hydroxyapatite as the adsorbent material for both 99Mo-99mTc and 188W-188Re generator systems. Hydroxyapatite is an insoluble solid with anion exchange properties. A study of the sorption behaviour of 99Mo, 99mTc, 188W and 188Re on hydroxyapatite in NaCl medium was evaluated by batch experiments. The results demonstrated that while 99Mo, 99mTc and 188Re are not adsorbed by the hydroxyapatite in NaCl solutions (Kd 188W is strongly adsorbed (Kd >500). On the basis of these measurements, hydroxyapatite 188W-188Re generator systems were then constructed and eluted in NaCl solutions. The hydroxyapatite based 188W-188Re generator performances are presented

  6. Pharmacokinetics of radioimmunotherapeutic agent of direct labeling mAb 188Re-HAb18

    Chao Lou; Zhi-Nan Chen; Hui-Jie Bian; Jie Li; Shou-Bo Zhou

    2002-01-01

    AIM: To labed Anti-hepatoma monoclonal antibody (mAb)fragment HAb18 F (ab')2 was labeled with 188 Re for thepharmacokinetic model of 188 Re-HAb18 F (ab')2 and toevaluate its pharmacokinetic parameters in hepatoma-bearing nude mice.METHODS: HAb18 F(ab')2 was directly labeled with 188Reusing 2-mercaptoethanol (2-ME) as reducing agents.Labeling efficiency and immunoreactivity of 188 Re-HAb18 F( ab')2 were evaluated by Whatman 3MM paperchromatography and live cell assay, respectively.Biodiatribution analysis was also conducted in nude micebearing human hepatoma in which animals were sacrificed atdifferent time points(1, 4, 18, 24 and 24h) after 188Re-HAb18F(ab' )2 was injected through tail-vein into hepatoma-bearingnude mice. The blood and radioactivity of organs and masswere measured. The concentrations of 188 Re-HAb18 F(ab')2were evaluated with a pharmacokinetic 3P97 software.RESULTS: The optimum labeling efficiency andimmunoreactive fraction were 91.7% and 0.78%,respectively. The parameters of 188Re-HAb18 F(ab')2 were:T1/2, 2.29h; Vd, 1.49 × 10-9L@ Bq- 1; AUC, 20.49 × 109Bq@ h@L-1 ;CL, 0.45 × 10-3L@ h- 1. 188Re- HAb18 F(ab')2 could locatespecially in hepatoma with high selective reactivity of HAb18F(ab')2. 188 Re-HAb18 F(ab')2 was mainly eliminated bykidney. The maximal tumor to blood ratio was at 48h, andmaximal tumor to liver ratio was at 18h.CONCLUTION: The pharmacokinetics of 188Re-HAb18 F(ab')2fit a I-compartment model. 188 Re-HAb18 F(ab')2 can beuptaken selectively at the hepatoma site.

  7. Formulation of a freeze-dried kit for 188Re-MAG3 and its quality control

    The synthesis of 188Re-MAG3 is described using 188Re, which was obtained from the alumina based 188W/188Re generator. Dependence of the radiolabeling yields of 188Re-MAG3 on reducing agent concentration, Bz-MAG3 concentration, pH, temperature and incubation time was examined. In the case of optimum conditions the yield of 188Re-MAG3 was 98%. TLC and HPLC techniques were employed to monitor the different species formed. Biodistribution study of 188Re-MAG3 was carried out in rats and compared with behavior of 99mTc-MAG3. (author)

  8. Extractive 90Y generator

    The generator for 90Y production is made up of two units - an extractive unit and a unit for deep purification. Contrary to the well-known methods of 90Y separation two mineral acids are used in the developed technology. The solutions of nitric acid are used for preliminary separation of 90Y and the solutions of hydrochloric acid are used for the deep purification of 90Y from 90Sr and stripping. The optimum conditions for carrying out this technology were found. The following results are reported: the carry-over of the stationary phase is excluded in this generator; the separation time is 30-60 minutes; the yield of the final product is not less than 95%; impurity of 90Sr is not more than 10-9---10%; the content of the chemical (nonactive) impurities is not more than the allowed one for radiopharmaceuticals

  9. Stability of 188Re Labeled antibody for radioimmunotherapy and the effect of stabilizing agents

    For clinical application of beta-emitter labeled antibody, high specific activity is important. Carrier-free 188Re from 188W/ 188Re generator is an ideal radionuclide for this purpose. However, low stability of 188Re labeled antibody, especially in high specific activity, due to radiolytic decomposition by high energy (2.1 MeV) beta ray was problem. We studied the stability of 188Re labeled antibody, and stabilizing effect of several stabilizers. Pre-reduced monoclonal antibody (CEA79.4) was labeled with 188Re by incubating with generator-eluted 188Re-perrhenate in the presence of stannous tartrate for 2 hr at room temperature. Radiochemical purity of each preparation was determined by chromatography. Human serum albumin was added to the labeled antibodies (2%). Stability of 188Re-CEA79.4 was investigated in the presence of ascorbic acid, ethanol, or Tween 80 as stabilizing agents. Labeling efficiencies were 88±4% (n=12). Specific activities of 1.25 ∼4.77 MBq/μg were obtained. If stored after purging with N2, all the preparations were stable for 10 hr. However, stability decreased in the presence of air. Perrhenate and 188Re-tartrate was major impurity in declined preparation. Colloid-formation was not a significant problem in all cases. Addition of ascorbic acid stabilized the labeled antibodies either under N2 or under air by reducing the formation of perrhenate. High specific activity 188Re labeled antibody is unstable, especially, in the presence of oxygen. Addition of ascorbic acid increased the stability

  10. Rhenium-188: Availability from the W-188/Re-188 Generator and Status of Current Applications

    Pillai, M R A [Bhabha Atomic Research Centre, Mumbai, India; Dash, A [Bhabha Atomic Research Centre, Mumbai, India; Knapp Jr, Russ F [ORNL

    2012-01-01

    Rhenium-188 is one of the most readily available generator derived and useful radionuclides for therapy emitting - particles (2.12 MeV, 71.1% and 1.965 MeV, 25.6%) and imageable gammas (155 KeV, 15.1%). The 188W/188Re generator is an ideal source for the long term (4-6 months) continuous availability of no carrier added (nca) 188Re suitable for the preparation of radiopharmaceuticals for radionuclide therapy. The challenges associated with the double neutron capture route of production of the parent 188W radionuclide have been a major impediment in the progress of application of 188Re. Tungsten-188 of adequate specific activity can be prepared only in 2-3 of the high flux reactors operating in the World. Several useful technologies have been developed for the preparation of clinical grade 188W/188Re generator. Since the specific activity of 188W used in the generator is relatively low (<5 Ci/g), the eluted 188ReO4- can have low radioactive concentration often insufficient for radiopharmaceutical preparation. However, several efficient post elution concentration techniques have been developed that yield clinically useful 188ReO4-. Rhenium-188 has been used for the preparation of therapeutic radiopharmaceuticals for the management of diseases such as bone metastasis, rheumatoid arthritis and primary cancers. Several early phase clinical studies using radiopharmaceuticals based on 188Re-labeled phosphonates, antibodies, peptides, lipiodol and particulates have been reported. This article reviews the availability, and use of188Re including a discussion of why broader use of 188Re has not progressed as ecpected as a popular radionuclide for therapy.

  11. Preparation and biodistribution of 188Re-labeled folate conjugated human serum albumin magnetic cisplatin nanoparticles (188Re-folate-CDDP/HSA MNPs in vivo

    Tang QS

    2011-11-01

    Full Text Available Qiu-Sha Tang1,*, Dao-Zhen Chen2,*, Wen-Qun Xue2, Jing-Ying Xiang2, Yong-Chi Gong1, Li Zhang2, Cai-Qin Guo21Department of Pathology and Pathophysiology, Medical College, Southeast University, Nanjing, Jiangsu; 2Central Laboratory, Wuxi Hospital for Maternal and Child Health Care, Affiliated Medical School of Nanjin, Wuxi, Jiangsu, China *Authors contributed equally to this workBackground: The purpose of this study was to develop intraperitoneal hyperthermic therapy based on magnetic fluid hyperthermia, nanoparticle-wrapped cisplatin chemotherapy, and magnetic particles of albumin. In addition, to combine the multiple-killing effects of hyperthermal targeting therapy, chemotherapy, and radiotherapy, the albumin-nanoparticle surfaces were linked with radionuclide 188Re-labeled folic acid ligand (188Re-folate-CDDP/HSA.Methods: Human serum albumin was labeled with 188Re using the pre-tin method. Reaction time and optimal conditions of labeling were investigated. The particles were intravenously injected into mice, which were sacrificed at different time points. Radioactivity per gram of tissue of percent injected dose (% ID/g was measured in vital organs. The biodistribution of 188Re-folate-CDDP/HAS magnetic nanoparticles was assessed.Results: Optimal conditions for 188Re-labeled folate-conjugated albumin combined with cisplatin magnetic nanoparticles were: 0.1 mL of sodium gluconate solution (0.3 mol/L, 0.1 mL of concentrated hydrochloric acid with dissolved stannous chloride (10 mg/mL, 0.04 mL of acetic acid buffer solution (pH 5, 0.2 mol/L, 30 mg of folate-conjugated albumin combined with cisplatin magnetic nanoparticles, and 188ReO4 eluent (0.1 mL. The rate of 188Re-folate-CDDP-HSA magnetic nanoparticle formation exceeded 90%, and radiochemical purity exceeded 95%. The overall labeling rate was 83% in calf serum at 37°C. The major uptake tissues were the liver, kidney, intestine, and tumor after the 188Re-folate-CDDP/HSA magnetic nanoparticles

  12. Automation of the synthesis of highly concentrated 188Re-MAG3 for intracoronary radiation therapy

    We have developed an efficient method and an automated synthetic system for the preparation of highly concentrated 188Re-MAG3. Routine production of 188Re-MAG3 for use in intracoronary radiation therapy was performed by compressed air driven semi-automated shielded system. 188Re-MAG3 was prepared with a commercial kit and reducing agents, purified and concentrated by C18 Sep-Pak cartridges to desired radioactivity and volume. Using this automated system, reproducible radiolabeling yields of 80-85% were obtained

  13. MicroSPECT/CT imaging and pharmacokinetics of 188Re-(DXR)-liposome in human colorectal adenocarcinoma-bearing mice.

    Chen, Min-Hua; Chang, Chih-Hsien; Chang, Ya-Jen; Chen, Liang-Cheng; Yu, Chia-Yu; Wu, Yu-Hsien; Lee, Wan-Chi; Yeh, Chung-Hsin; Lin, Feng-Huei; Lee, Te-Wei; Yang, Chung-Shi; Ting, Gann

    2010-01-01

    Nanoliposome can be designed as a drug delivery carrier to improve the pharmacological and therapeutic properties of drug administration. (188)Re-labeled nanoliposomes are useful for diagnostic imaging as well as for targeted radionuclide therapy. In this study, the in vivo nuclear imaging, pharmacokinetics and biodistribution of administered nanoliposomes were investigated as drug and radionuclide carriers for targeting solid tumor via intravenous (i.v.) administration. The radiotherapeutics ((188)Re-liposome) and radiochemotherapeutics ((188)Re-DXR-liposome) were i.v. administered to nude mice bearing human HT-29 colorectal adenocarcinoma xenografts. (188)Re-liposome and (188)Re-DXR-liposomes show similar biodistribution profile; both have higher tumor uptake, higher blood retention time, and lower excretion rate than (188)Re-N,N-bis(2-mercaptoethyl)-N',N'-diethylenediamine (BMEDA). In contrast to tumor uptake, the area under the curve (AUC) value of tumor for (188)Re-liposome and (188)Re-DXR-liposome was 16.5- and 11.5-fold higher than that of free (188)Re-BMEDA, respectively. Additionally, (188)Re-liposome and (188)Re-DXR-liposome had a higher tumor-to-muscle ratio at 24 h (14.4+/-2 .7 and 17.14+/-4.1, respectively) than (188)Re-BMEDA (1.6+/-0.1). The tumor targeting and distribution of (188)Re-(DXR)-liposome (representing (188)Re-DXR-liposome and (188)Re-liposome) can also be acquired by signal photon-emission computed tomography/computed tomography images as well as whole body autoradiograph. These results suggest that (188)Re-(DXR)-liposomes are potentially promising agents for passive targeting treatment of malignant disease. PMID:20150618

  14. Preparation of 188 Re-lanreotide as a potential tumor therapeutic agent

    Radiolabeled peptides hold unlimited potential in diagnostic applications and therapy of malignant tumor. Somatostatin analogue peptide (Lanreotide) is labeled directly with 188Re via the mixture of citrate and tartrate. The influences of reaction conditions such as pH, temperature, amount of stannous chloride, Lanreotide quantity, reaction time on labeling yield are investigated in detail. At the same time, the stability in vitro, quality control and animal test are evaluated. The experimental results show that Lanreotide reacts with 188Re for 40 min at pH 2 - 3 and 60 degree C, the labeling yield is at range of 88% - 94%. After purification of 188Re-Lanreotide with Sep-Pak C18 reverse phase extraction cartridge, the radiochemical purity (RP) is more than 95%. 188Re-Lanreotide is eliminated rapidly from the blood and is excreted through liver, the uptake of lung and intestine is high

  15. Labeling procedures for the preparation of 188Re- DMSA(V)

    188Re has received a lot of attention in the past decade, due to its favorable nuclear characteristics [t1/2 16.9 h, Eβmax 2.12 MeV and Eγ 155 keV (15%) suitable for imaging], including the fact that it is carrier-free and can be obtained cost-effectively through the generator 188W-188Re. Besides the therapeutic usefulness of 188Re, the emission of the 155 keV gamma photon is an added advantage since the biodistribution of 188Re-labeled agents can be evaluated in vivo with a gamma camera. Biodistribution studies of 188Re-DMSA(V) have shown that its general pharmacokinetic properties are similar to that of 99mTc-DMSA(V), so this agent could be used for targeted radiotherapy of the same tumors, i.e., medullary thyroid carcinoma, bone metastases, soft tissue, head and neck tumors. The aim of this work is to evaluate two labeling procedures for the preparation of 188Re- DMSA(V). 188Re-DMSA(V) was prepared by two methods. The first method was prepared using a commercial kit of DMSA(III) for labeling with 99mTc, at high temperature (100 deg C). The second method was prepared in a vial containing 2.5 mg of DMSA, 1.00 mg of SnCl2.2H2O and 30 mg of sodium oxalate, in a total volume of 1.1 mL. The pH was adjusted to 5 with 37% HCl. After labeling the solution was stirred and incubated for 15 min at room temperature. The radiochemical purity was determined using TLC-SG developed with two different solvent systems. Preliminary results for both methods of labeling 188Re-DMSA(V) showed that the labeling yield was >90%. (author)

  16. Intracoronary radionuclide therapy with liquid 188Re-filled balloons; radiopharmaceutical and dosimetric studies

    Percutaneous transluminal coronary angioplasty associated with radioactive liquid-filled balloons has demonstrated to be useful to inhibit the growth of neo intimal tissue. The present study pursued optimizing the relation risk/benefit during a procedure of brachytherapy with 188Re associated to angioplasty. Since the possibility of balloon rupture exists, to increase the security during the treatment different agents such as 188Re-DTPA, 188Re-Citrate and 188Re-EC vs 188ReO4 were evaluated. Dosimetric studies using Mirdose 3, after iv injection to Wistar rats, evaluation of a number of safety requirements in order to estimate radiation dose delivered to operating personnel and absorbed doses estimated by Monte Carlo method (PENELOPE). It is a safe procedure, both for the patient and the working staff; in case of ballon rupture the use of the above mentioned radiopharmaceuticals increases its security. 188Reβ emitor achieves a local dosis, diminishing the dose in healthy tissue (au)

  17. External beam radiotherapy synergizes 188Re-liposome against human esophageal cancer xenograft and modulates 188Re-liposome pharmacokinetics

    Chang CH

    2015-05-01

    Full Text Available Chih-Hsien Chang,1,2 Shin-Yi Liu,3 Chih-Wen Chi,3 Hsiang-Lin Yu,1 Tsui-Jung Chang,1 Tung-Hu Tsai,4 Te-Wei Lee,1 Yu-Jen Chen3–5 1Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan; 2Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, 3Department of Medical Research MacKay Memorial Hospital, 4Institute of Traditional Medicine, National Yang-Ming University, 5Department of Radiation Oncology, MacKay Memorial Hospital, Taipei, Taiwan Abstract: External beam radiotherapy (EBRT treats gross tumors and local microscopic diseases. Radionuclide therapy by radioisotopes can eradicate tumors systemically. Rhenium 188 (188Re-liposome, a nanoparticle undergoing clinical trials, emits gamma rays for imaging validation and beta rays for therapy, with biodistribution profiles preferential to tumors. We designed a combinatory treatment and examined its effects on human esophageal cancer xenografts, a malignancy with potential treatment resistance and poor prognosis. Human esophageal cancer cell lines BE-3 (adenocarcinoma and CE81T/VGH (squamous cell carcinoma were implanted and compared. The radiochemical purity of 188Re-liposome exceeded 95%. Molecular imaging by NanoSPECT/CT showed that BE-3, but not CE81T/VGH, xenografts could uptake the 188Re-liposome. The combination of EBRT and 188Re-liposome inhibited tumor regrowth greater than each treatment alone, as the tumor growth inhibition rate was 30% with EBRT, 25% with 188Re-liposome, and 53% with the combination treatment at 21 days postinjection. Combinatory treatment had no additive adverse effects and significant biological toxicities on white blood cell counts, body weight, or liver and renal functions. EBRT significantly enhanced the excretion of 188Re-liposome into feces and urine. In conclusion, the combination of EBRT with 188Re-liposome might be a potential treatment modality for esophageal cancer. Keywords: Radionuclide

  18. Imaging, Autoradiography, and Biodistribution of 188Re-Labeled PEGylated Nanoliposome in Orthotopic Glioma Bearing Rat Model

    Huang, Feng-Yun J.; LEE, TE-WEI; Kao, Chih-Hao K.; Chang, Chih-Hsien; Zhang, Xiaoning; Lee, Wan-Yu; Chen, Wan-Jou; Wang, Shu-Chi; Lo, Jem-Mau

    2011-01-01

    The 188Re-labeled pegylated nanoliposome (abbreviated as 188Re-Liposome) was prepared and evaluated for its potential as a theragnostic agent for glioma. 188Re-BMEDA complex was loaded into the pegylated liposome core with pH 5.5 ammonium sulfate gradient to produce 188Re-Liposome. Orthotopic Fischer344/F98 glioma tumor-bearing rats were prepared and intravenously injected with 188Re-Liposome. Biodistribution, pharmacokinetic study, autoradiography (ARG), histopathology, and nano-SPECT/CT ima...

  19. Comparative studies of antibody anti-CD20 labeled with {sup 188}Re; Estudo comparativo da marcacao do anticorpo anti-CD20 com {sup 188}Re

    Dias, Carla Roberta de Barros Rodrigues

    2010-07-01

    Nuclear Medicine is an unique and important modality in oncology and the development of new tumor-targeted radiopharmaceuticals for both diagnosis and therapy is an area of interest for researchers. Rituximab (RTX) is a quimeric monoclonal antibody (mAb) (IgG 1) that specifically binds to CD20 antigen with high affinity and has been successfully used for the treatment of Non-Hodgkin Lymphoma (NHL) of cell B. The CD20 antigen is expressed over more than 90% of cell B NHL. Technetium-99m ({sup 99m}Tc) and rhenium-188 ({sup 188}Re) are an attractive radionuclide pair for clinical use due to their favorable decay properties for diagnosis ({sup 99m}Tc: T{sub 1/2} = 6 h, {gamma} radiation = 140 keV) and therapy ({sup 188}Re: T{sub 1/2} = 17 h, maximum {beta} energy = 2.12 MeV) and to their availability in the form of {sup 99}Mo/{sup 99}mTc and {sup 188}W/{sup 188}Re generators. The radionuclides can be conjugated to mAb using similar chemical procedures. The aim of this work was to study the labeling of anti-CD20 mAb (RTX) with {sup 188}Re using two techniques: the direct labeling method [{sup 188}Re(V)] and the labeling method via the carbonyl nucleus [{sup 188}Re(I)]. Besides the quality control, the radiolabeled mAb was submitted to in vivo, in vitro and ex vivo biological studies. For the direct labeling, RTX was reducing by incubation with 2-mercaptoethanol for generating sulphydryl groups (-SH) and further labeled with {sup 188}Re(V), in a study of several parameters in order to reach an optimized formulation. The labeling via the carbonyl nucleus both {sup 99}mTc and {sup 188}Re were employed through 2 different procedures: (1) labeling of intact RTX with {sup 99}mTc(I) and (2) reduced RTX (RTX{sub red}) labeled with {sup 99}mTc(I)/{sup 188}Re(I). Also a parameter study was performed to obtain an optimized formulation. The quality control method for evaluating the radiochemical purity showed a good labeling yield (93%) for the direct method. The labeling method

  20. Evaluation of 188Re-MAG2-RGD-bombesin for potential prostate cancer therapy

    Glu-RGD-bombesin (RGD-BBN) is a heterodimeric peptide that contains motifs recognizing both integrin αvβ3 and gastrin releasing peptide receptor (GRPR). We evaluated here 188Re (t1/2 = 16.9 h) labeled RGD-BBN as a potential agent for radionuclide therapy of prostate cancer. RGD-BBN was conjugated with S-benzoylmercaptoacetylglycylglycyl (MAG2), and then labeled with 99mTc or 188Re, respectively. The dual-receptor binding affinity of MAG2-RGD-BBN was investigated by a radioligand competition binding assay. Biodistribution study of 188Re-MAG2-RGD-BBN was carried out in normal BALB/c mice and PC-3 human prostate tumor-bearing nude mice. Gamma imaging studies were performed in PC-3 tumor-bearing nude mice. Biodistribution in normal mice showed that both 99mTc and 188Re-labeled MAG2-RGD-BBN possessed high pancreas uptake due to the high GRPR expression of this organ. Gamma imaging with both 99mTc and 188Re-labeled RGD-BBN in PC-3 tumor-bearing nude mice demonstrated high tumor uptake. The PC-3 tumors were clearly visible at 1 postinjection, with high contrast to the contralateral background. The use of chelator MAG2 enables successful and high-yield 99mTc and 188Re radiolabeling of RGD-BBN with favorable tumor targeting specificity. Further optimization may allow potential clinical application of 188Re-MAG2-RGD-BBN for tumor-targeted radionuclide therapy

  1. Dosimetric evaluation of anti-CD20 labelled with 188Re

    Radioimmunotherapy has the potential to deliver lethal radiation energy directly to malignant cells via targeting of radioisotope-conjugated monoclonal antibodies (MAbs) to specific antigens. B-cell lymphoma is a particularly good candidate for radioimmunotherapy because the disease is inherently radiosensitive, malignant cells in the blood, bone marrow, spleen and lymphonodes are accessible, and MAbs have been developed to B-cell surface antigens that do not shed or modulate. Rituximab (RTX), the human IgG1-type chimeric form of the parent murine antibody ibritumomab, is specifically targeted against CD20, a surface antigen expressed by pre-B and mature human B lymphocytes. The use of rhenium-188 from a 188W/188Re generator system represents an attractive alternative radionuclide for therapy. 188Re is produced from beta decay of the 188W parent. In addition to the emission of high-energy electrons (Eβ= 2118 keV), 188Re also decays with emission of a gamma photon with an energy of 155 keV in 15% abundance. Besides the therapeutic usefulness of 188Re, the emission of gamma photon is an added advantage since the biodistribution of 188Re-labeled antibodies can be evaluated in vivo with a gamma camera. Also, rhenium has chemical properties similar to technetium. Thus, both can be conjugated to antibodies using similar chemistry methods. The objective of this work is to prove the usefulness of this radiopharmaceutical based on dosimetric studies, that are also required by the Brazilian Regulatory Agency (ANVISA). (author)

  2. A review on the current status and production technology for 188W-188Re generator system

    The current status of 188W-188Re generator production technology were reviewed in PART 1. Main interests were given to the aspects of 188W reactor production, irradiated targets reprocessing and generator loading technologies, such as alumina type and gel type generators. In order to develop the more convenient and advanced 188W-188Re generator, further studies must be carried out to get the precise evaluation of production and burn-up cross section of 188W, the more easily realizable generator loading procedure, and also to optimize the column and generator design to compensate the deterioration of generator performance because of parent radionuclide decay. By irradiation of 186W enriched sample, 188W-188Re generator production experiments were performed to evaluate the possibility of 188W-188Re generator production using HANARO, and PART 2 describes about the experiments. The experimental results shows the possibility of practical 188W-188Re generator production using of low-specific activity 188W produced in HANARO. (author). 79 refs., 4 tabs., 26 figs

  3. In vivo examination of 188Re(I)-tricarbonyl-labeled trastuzumab to target HER2-overexpressing breast cancer

    Introduction: Trastuzumab (Herceptin), a humanized IgG1 monoclonal antibody directed against the extracellular domain of the HER2 protein, acts as an immunotherapeutic agent for HER2-overexpressing human breast cancers. Radiolabeled trastuzumab with β- or α emitters can be used as radioimmunotherapeutic agent for the similar purpose but with additional radiation effect. Methods: In this study, trastuzumab was labeled with 188Re for radioimmunotherapy of HER2/neu-positive breast cancer. 188Re(I)-tricarbonyl ion, [188Re(OH2)3(CO)3]+, was employed as a precursor for directly labeling the monoclonal antibody with 188Re. The immunoreactivity of 188Re(I)-trastuzumab was estimated by competition receptor-binding assay using HER2/neu-overexpressive BT-474 human breast cancer cells. The localization properties of 188Re(I)-trastuzumab within both tumor and normal tissues of athymic mice bearing BT-474 human breast cancer xenografts (HER2/neu-overexpressive) and similar mice bearing MCF-7 human breast cancer xenografts (HER2/neu-low expressive) were investigated. Results: When incubated with human serum albumin and histidine at 25oC, 188Re(I)-trastuzumab was found to be stable within 24 h. The IC50 of 188Re(I)-trastuzumab was found to be 22.63±4.57 nM. 188Re(I)-trastuzumab was shown to accumulate specifically in BT-474 tumor tissue in in vivo biodistribution studies. By microSPECT/CT, the image of 188Re localized BT-474 tumor was clearly visualized within 24 h. In contrast, 188Re(I)-trastuzumab uptake in HER2-low-expressing MCF-7 tumor was minimal, and the 188Re image at the localization of the tumor was dim. Conclusion: These results reveal that 188Re(I)-trastuzumab could be an appropriate radioimmunotherapeutic agent for the treatment of HER2/neu-overexpressing cancers.

  4. Study of 188Re(V)-DMSA for treatment of cancer: radiolabeling and biodistribution

    The purpose of this study was to examine the radiolabeling and biodistribution of 188Re(V)-DMSA as a therapeutic cancer radiopharmaceutical. We made a DMSA kit(NaHCO3 1.5 mg, meso-2,3-dimercaptosuccinic acid 1.0 mg, L(+)-ascorbic acid 0.7 mg, SnCl2·2H2O 0.34 mg, pH 2.9) for labeling with 188Re. In this kit, 188ReO4 5 mCi/2 ml added and boiled at 100 .deg. C for 3 hr in water bath. The final pH adjusted to 7.5 with 7% NaHCO3 solution. We checked the labelling efficacy with TLC-SG(n-butanol : acetic acid : H2O= 3 : 2: 3) and examined the stability both in room temperature and in serum at 37 .deg. C. Biodistribution (1, 3, 13, 24, 48 hr) of 188Re(V)-DMSA compound was evaluated in Sarcoma 180 tumor-bearing mice. Each labeling efficiency and stability at room temperature for 48 hours was over 98% and 95%, respectively. The stability in serum were 82% (6 hr) and 85% (48 hr). Tumor uptake of 188Re(V)-DMSA in Sarcoma 180-bearing mice were 0.66±0.15% (1 hr), 0.51±0.10% (3 hr), 0.19±0.05%(24 hr) and 0.13±0.02%(48 hr). These result are consistent with those of 99mTc(V)-DMSA which were reported previously. In conclusion, 188Re(V)-DMSA may be a useful therapeutic radiopharmaceutical for treating some cancers and metastatic bone lesion

  5. Labeling procedures for the preparation of {sup 188}Re- DMSA(V)

    Brambilla, Tania P.; Osso Junior, Joao A., E-mail: taniabrambilla@yahoo.com.b, E-mail: jaosso@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2009-07-01

    {sup 188}Re has received a lot of attention in the past decade, due to its favorable nuclear characteristics [t{sub 1/2} 16.9 h, E{sub beta}{sub max} 2.12 MeV and E{sub gamma} 155 keV (15%) suitable for imaging], including the fact that it is carrier-free and can be obtained cost-effectively through the generator {sup 188}W-{sup 188}Re. Besides the therapeutic usefulness of {sup 188}Re, the emission of the 155 keV gamma photon is an added advantage since the biodistribution of {sup 188}Re-labeled agents can be evaluated in vivo with a gamma camera. Biodistribution studies of {sup 188}Re-DMSA(V) have shown that its general pharmacokinetic properties are similar to that of {sup 99}mTc-DMSA(V), so this agent could be used for targeted radiotherapy of the same tumors, i.e., medullary thyroid carcinoma, bone metastases, soft tissue, head and neck tumors. The aim of this work is to evaluate two labeling procedures for the preparation of {sup 188}Re- DMSA(V). {sup 188}Re-DMSA(V) was prepared by two methods. The first method was prepared using a commercial kit of DMSA(III) for labeling with {sup 99m}Tc, at high temperature (100 deg C). The second method was prepared in a vial containing 2.5 mg of DMSA, 1.00 mg of SnCl{sub 2}.2H2{sub O} and 30 mg of sodium oxalate, in a total volume of 1.1 mL. The pH was adjusted to 5 with 37% HCl. After labeling the solution was stirred and incubated for 15 min at room temperature. The radiochemical purity was determined using TLC-SG developed with two different solvent systems. Preliminary results for both methods of labeling {sup 188}Re-DMSA(V) showed that the labeling yield was >90%. (author)

  6. Preliminary study of metabolic radiotherapy with 188Re via small animal imaging

    Baldazzi, G; Muciaccio, A; Navarria, Francesco Luigi; Pancaldi, G; Perrotta, A; Zuffa, M; Boccaccio, P; Uzunov, N; Bello, M; Bernardini, D; Mazzi, U; Moschini, G; Riondato, M; Rosato, A; Garibaldi, F; Pani, R; Antoccia, A; De Notaristefani, F; Hull, G; Cencelli, V O; Sgura, A; Tanzarella, C

    2006-01-01

    188Re is a beta- (Emax = 2.12 MeV) and gamma (155 keV) emitter. Since its chemistry is similar to that of the largely employed tracer, 99mTc, molecules of hyaluronic acid (HA) have been labelled with 188Re to produce a target specific radiopharmaceutical. The radiolabeled compound, i.v. injected in healthy mice, is able to accumulate into the liver after a few minutes. To study the effect of metabolic radiotherapy in mice, we have built a small gamma camera based on a matrix of YAP:Ce crystals, with 0.6x0.6x10 mm**3 pixels, read out by a R2486 Hamamatsu PSPMT. A high-sensitivity 20 mm thick lead parallel-hole collimator, with hole diameter 1.5 mm and septa of 0.18 mm, is placed in front of the YAP matrix. Preliminary results obtained with various phantoms containing a solution of 188Re and with C57 black mice injected with the 188Re-HA solution are presented. To increase the space resolution and to obtain two orthogonal projections simultaneously we are building in parallel two new cameras to be positioned at...

  7. Preliminary study of metabolic radiotherapy with {sup 188}Re via small animal imaging

    Antoccia, A. [Dept. of Biology, Univ. Roma3, V.le G. Marconi, I-00146 Rome (Italy); INFN, Sezione Roma3, Via della Vasca Navale 84, I-00146 Rome (Italy); Baldazzi, G. [Dept. of Physics, Univ. Bologna, V.le C. Berti-Pichat 6/2, I-40127 Bologna (Italy); INFN, Sezione Bologna, V.le C. Berti-Pichat 6/2, I-40127 Bologna (Italy); Bello, M. [Dept. of Physics, Univ. Padova, Via F. Marzolo 8, I-35131 Padova (Italy); INFN - LNL, V.le dell' Universita 2, I-35020 Legnaro(Italy)

    2006-01-15

    {sup 188}Re is a {beta}{sup -} (Emax=2.12 MeV) and {gamma} (155 keV) emitter. Since its chemistry is similar to that of the largely employed tracer, {sup 99m}Tc, molecules of hyaluronic acid (HA) have been labelled with {sup 188}Re to produce a target specific radiopharmaceutical. The radiolabeled compound, i.v. injected in healthy mice, is able to accumulate into the liver after a few minutes. To study the effect of metabolic radiotherapy in mice, we have built a small gamma camera based on a matrix of YAP:Ce crystals, with 0.6x0.6x10 mm{sup 3} pixels, read out by a R2486 Hamamatsu PSPMT. A high-sensitivity 20 mm thick lead parallel-hole collimator, with hole diameter 1.5 mm and septa of 0.18 mm, is placed in front of the YAP matrix. Preliminary results obtained with various phantoms containing a solution of {sup 188}Re and with C57 black mice injected with the {sup 188}Re-HA solution are presented. To increase the space resolution and to obtain two orthogonal projections simultaneously we are building in parallel two new cameras to be positioned at 90 degrees. They use a CsI(Tl) matrix with 1x1x5 mm{sup 3} pixels read out by H8500 Hamamatsu Flat panel PMT.

  8. Synthesis of polyacrylamide modified magnetic nanoparticles and radiolabeling with 188Re for magnetically targeted radiotherapy

    Magnetic nanoparticles were synthesized, modified with polyacrylamide, and then characterized by TEM, FTIR, VSM and PCS. Rhenium-188 (188Re) was bound to the nanoparticles by imidazolyl groups of histidine immobilized on the surface. The labeling yield was about 90% with good in vitro stability. Such nanoparticles might be useful for magnetically targeted radiotherapy

  9. 188Re-ethylene dicysteine: a novel agent for possible use in endovascular radiation therapy.

    Das, T; Banerjee, S; Samuel, G; Sarma, H D; Ramamoorthy, N; Pillai, M R

    2000-10-01

    Several agents, such as 188ReO4-, 188Re-MAG3 and 188Re-DTPA are currently under investigation as radiation sources in liquid-filled balloons for prevention of restenosis following coronary angioplasty. Bearing in mind the risk factor associated with leakage of radioactivity in the event of balloon rupture, the criteria sought in selecting suitable agents for endovascular radiation therapy (EVRT) are rapid clearance and low dose to vital organs. Since 99Tcm labelled ethylene dicysteine (EC) is a well established agent for renal tubular function imaging, the use of 186Re-ethylene dicysteine as a potential agent for prevention of restenosis after angioplasty has been evaluated previously. Therefore, it was of interest to evaluate the applicability of the more potential isotope of rhenium, 188Re, a high energy beta-emitter (Ebetamax = 2.12 MeV) with a suitable T 1/2 = 16.9 h, obtainable carrier-free from the 188W-188Re generator, as an attractive and alternative radionuclide for labelling with L,L-EC. In this paper, the preparation and pharmacological behaviour of the 188Re complex of ethylene dicysteine are reported. The complex can be prepared in high yields (99.5%) under optimized conditions of pH 2-3, at a ligand concentration of 15 mM, 50 microg (0.18 mM) carrier rhenium and using 2 mg x mL(-1) stannous chloride. On storage at 4 degrees C, the RC purity was more than 97% after 48 h when prepared under optimum conditions. Biodistribution studies in Wistar rats showed the desired characteristics of fast blood clearance and low retention of activity in the vital organs (< 2% in intestine, < 1% in stomach, < 0.5% in liver) with a high renal excretion (90.65+/-0.6%) at 3 h post-injection. These results confirm the advantages of using the 188Re-EC complex compared with perrhenate and other rhenium radiopharmaceuticals currently being used in balloons for EVRT. PMID:11130335

  10. Very stable 188Re-S4 chelates for labelling biomolecules. Preparation with highly concentrated perrhenate eluates

    Aim: The preparation and stability of a new 188Re-S4-complex [S4 (1-aza-18-crown-6)(O)C-C(SH)-C(SH)-C(O)NH-(CH2)3-NH-(CH2)3-NHC(O)- = C(SH)- C(SH )-C(O)(1-aza-18-crown-6)] was studied at therapeutic relevant radioactive concentrations. The results were compared with 188Re-MAG3 (MAG3: mercaptoacetyltriglycine) and 188Re-DMSA preparations (DMSA: dimercaptosuccinic acid) performed with the same highly concentrated [188Re]perrhenate solution (12-15 GBq/ml). Methods: The 188Re complexes were prepared by direct reduction of perrhenate (188Re-S4-complex) as well as via the 188Re-EDTA precursor complex (188Re-MAG3, 188Re-DMSA). The preparations were stabilised with 15 mg of ascorbic acid and analysed after 1, 2, and 24 hours by TLC and HPLC. Additionally, in vitro and in vivo stability studies were performed with the purified complexes. Results: After stabilisation with 15 mg of ascorbic acid, all of the complexes were nearly stable under nitrogen for hours, and only 2-8% of perrhenate was observed after 24 h. In contrast, only the 188Re-S4 complex was completely stable in vitro and in all investigated in vivo samples after separation of ligand excess and reducing agent by HPLC. Conclusion: The bridging amine group or free carboxylic groups of the S4-ligand framework make available reactive positions for coupling biomolecules to the chelate. Thus it appears that the new 188Re-S4 complexes offer the possibility of stable and high specific activity labelling of biomolecules for therapeutic application. (orig.)

  11. Comparative studies of antibody anti-CD20 labeled with 188Re

    Nuclear Medicine is an unique and important modality in oncology and the development of new tumor-targeted radiopharmaceuticals for both diagnosis and therapy is an area of interest for researchers. Rituximab (RTX) is a quimeric monoclonal antibody (mAb) (IgG 1) that specifically binds to CD20 antigen with high affinity and has been successfully used for the treatment of Non-Hodgkin Lymphoma (NHL) of cell B. The CD20 antigen is expressed over more than 90% of cell B NHL. Technetium-99m (99mTc) and rhenium-188 (188Re) are an attractive radionuclide pair for clinical use due to their favorable decay properties for diagnosis (99mTc: T1/2 = 6 h, γ radiation = 140 keV) and therapy (188Re: T1/2 = 17 h, maximum β energy = 2.12 MeV) and to their availability in the form of 99Mo/99mTc and 188W/188Re generators. The radionuclides can be conjugated to mAb using similar chemical procedures. The aim of this work was to study the labeling of anti-CD20 mAb (RTX) with 188Re using two techniques: the direct labeling method [188Re(V)] and the labeling method via the carbonyl nucleus [188Re(I)]. Besides the quality control, the radiolabeled mAb was submitted to in vivo, in vitro and ex vivo biological studies. For the direct labeling, RTX was reducing by incubation with 2-mercaptoethanol for generating sulphydryl groups (-SH) and further labeled with 188Re(V), in a study of several parameters in order to reach an optimized formulation. The labeling via the carbonyl nucleus both 99mTc and 188Re were employed through 2 different procedures: (1) labeling of intact RTX with 99mTc(I) and (2) reduced RTX (RTXred) labeled with 99mTc(I)/188Re(I). Also a parameter study was performed to obtain an optimized formulation. The quality control method for evaluating the radiochemical purity showed a good labeling yield (93%) for the direct method. The labeling method via carbonyl group, the results showed that the - SH groups of RTXred are a possible way of labeling. The formulation of 99m

  12. Formulation, radiopharmaceutical kinetics and dosimetry of the {sup 188}Re(V)-DMSA complex; Formulacion, radiofarmacocinetica y dosimetria del complejo {sup 188}Re(V)-DMSA

    Garcia S, L.; Ferro F, G. [Departamento de Materiales Radiactivos. Instituto Nacional de Investigaciones Nucleares, C.P. 52045 Salazar, Estado de Mexico (Mexico); Murphy, C.A. de; Pedraza L, M. [Departamento de Medicina Nuclear, Instituto Nacional de la Nutricion, Salvador Zubiran, Mexico D.F. (Mexico); Azorin N, J. [Departamento de Fisica, Universidad Autonoma Metropolitana Iztapalapa, Mexico D.F. (Mexico)

    1999-07-01

    It was developed through experimental design (ANOVA), a formulation to prepare the {sup 188} Re(V)-Dmsa complex. Likewise, there were realized studies of radiopharmaceutical kinetics and internal dosimetry in animals, its normal and with induced tumors, considering an open bi compartmental model using the MIRD methodology. The {sup 188} Re(V)-Dmsa complex was obtained with a radiochemical purity greater than 95% incubating 30 min at 90 Centigrade under the following formulation: [SnCl{sub 2}] = 1.4 mg/ml, [ascorbic acid] = 0.5 mg/ml, p H = 2.0 - 3.0. The stability test of the formulation, shows that after 48 h of its preparation, does not produce radiolytic degradation neither chemical decomposition. The radiopharmaceutical kinetics data show an average residence time 7.2h, velocity constant {alpha} = 0.6508h{sup -1} and {beta} = 0.1046 h{sup -1} with an apparent distribution volume 6.9 l. The main elimination via was renal and it was observed osseous caption with an accumulated activity 522.049 {+-} 62 MBq h (residence time 14.1094 {+-} 1.69h). In according with the dosimetric calculations, by each 37 MBq injected, the equivalent dose at the tumor was 9.67{+-} 0.33 Sv/g, for an effective dose 0.292 {+-} 0.0017 mSv/MBq. The images obtained in the gamma camera of the mice with induced tumors, show that do not have significant accumulation in the metabolic organs. The caption in bone and in tumors induced of the {sup 188} Re(V)-Dmsa complex, show its potential for be used as a palliative agent for pain in patients with osseous metastasis and in the treatment of tumors of soft tissue. (Author)

  13. Labeling of MDP with {sup 188}Re for bone tumour therapy

    Barbezan, Angelica B.; Osso Junior, Joao A., E-mail: jaosso@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    {sup 188}Re is one of the most attractive radioisotopes for a variety of therapeutic applications in nuclear medicine, due to its physical decay properties, such as {beta}{sup -} emission of 2.12 MeV, {gamma} emission of 155 keV and half life of 16.9 hours. Biphosphonates are potent inhibitors of osteoclastic bone resorption and are effective in several diseases that cause bone fragility and bone metastases. Because of these characteristics, labeled biphosphonates have been studied for bone pathologies, also acting as palliation of bone pain in case of metastasis.The aim of this study was to optimize the labeling of a phosphonate-MDP (Sodium Methylene Diphosphonate) with {sup 188}Re for use in bone pain palliation. {sup 188}Re was obtained by eluting a {sup 188}W-{sup 188}Re generator from POLATOM. The labeling was performed at room temperature using MDP, SnCl{sub 2} as reducing agent and ascorbic acid. The variables studied were: Mass of ligand (3, 6 and 10 mg), reducing agent mass (5, 7, 10 and 11 mg), ascorbic acid mass (1, 3, 5 and 6 mg), pH (1 and 2) and time of reaction (15, 60, 120, 360 and 4320 minutes), that also reflected the stability of the radiopharmaceutical. The radiochemical control, that also measures the labeling efficiency was evaluated by paper chromatography using Whatman 3MM paper and the solvents acetone and 0.9%NaCl. The best formulation was the following: Mass of ligand MDP: 10 mg, mass of SnCl{sub 2}: 5 mg, ascorbic acid mass: 3 mg, time of reaction: 30 minutes, pH: 1. Under optimum conditions, {sup 188}Re MDP radiolabeling yield was 98,07% and the radiopharmaceutical was stable up to 72 h. (author)

  14. Intracoronary radionuclide therapy with liquid 188Re-filled balloons: Radiopharmaceutical and dosimetric studies

    Full text: Percutaneous transluminal coronary angioplasty (PCTA) associated with radioactive liquid-filled balloons has demostrated useful to inhibit the growth of neointimal tissue and as consequence offers a potential method to decrease restenosis rate. Near 40 to 60% of the patients suffered from restenosis, being necessary to reiterate angioplasty. The spectrum of late effects from the variety of sources types, dosimetric aspects and delivery systems has not became clear. An attractive radionucleid for this purpose is 188Re, that is eluated from a 188W/188Re generator. The generator can be used during 6 months, depending on the initial activity. The specific activity can be increased by a concentration system up to a maximum of 20 GBq/mL. The present study had the purpose of optimizing the relation risk/benefit during a procedure of brachytherapy with 188Re associated to angioplasty. The possibility of balloon rupture exists, with the passage of the radioactive solution towards the patient bloodstream. In order to increase the security during the treatment the evaluation of different agents such as 188Re- DTPA, 188Re-Citrate and 188Re-EC vs 188ReO4- (as the standard agent) was performed. Labelling procedures were optimized considering pH, temperature, reaction time and carrier adition. Dosimetric studies using Mirdose 3, after iv injection to Wistar rats of the three radiopharmaceuticals were performed. Biodistrubion at 1 and 3 hs post-administration and dose estimation showed no difference between all the radiopharmaceuticals, presenting low uptake in thyroid and stomach, and faster renal elimination than 188ReO4-, with smaller residence times in all the organs. As the preparation of 188Re-Citrate and 188Re-EC required less strong conditions than 188Re-DTPA, one of these radiopharmaceuticals could be selected to improve the security of the procedure. A second point of this study was the evaluation of a number of safety requirements in order to estimate

  15. Assessment of 188Re marked anti MHC class Ⅱ antibody by peripheral blood mononuclear cells stimulated by donor alloantigen

    DING Guo-ping; CAO Li-ping; LIU Jie; LIU Da-ren; QUE Ri-sheng; ZHU Lin-hua; ZHOU Yi-ming; MAO Ke-jie; HU Jun-an

    2011-01-01

    Background Previous studies showed that anti MHC-Ⅱ monoclone antibody (MAb) only had partial inhibiting effect of alloreactive mixed lymphocyte reaction (MLR) in vitro and it was unsteady and non-persistent. The aim of this research was to determine whether radioactive isotope 188Re marked MHC-Ⅱ antibody could benefit the allograft acceptance in transplantation as compared to normal MHC-Ⅱ antibody.Methods 188Re was incorporated to 2E9/13F(ab')2 which is against swine MHC class Ⅱ antigen (MAb-188Re). Porcine peripheral blood mononuclear (PBMC) cells were examined for proliferation and cytokine mRNA expression after stimulation with MHC-Ⅱ MAb or MAb-188Re.Results The proliferative response of recipient PBMCs in mixed lymphocyte reaction (MLR) to donor alloantigen showed that the stimulation index of MAb-188Re group was significantly lower than the MHC-Ⅱ MAb group and control (P<0.05). mRNA expression of interleukin 2, interferon Y and tumor necrosis factor α (type 1 cytokines) was lower in MAb-188Re group than the MHC-Ⅱ MAb group, while interleukin 10 (type 2 cytokines) was higher in MAb-188Re group in the first 24 hours.Conclusion MAb-188Re could help the graft acceptance by inhibiting T cell proliferation, lowering the expression of type 1 cytokines and elevating the type 2 cytokines produced by PBMC.

  16. Dosimetric evaluation of nanotargeted 188Re-liposome with the MIRDOSE3 and OLINDA/EXM programs

    The OLINDA/EXM computer code was created as a replacement for the widely used MIRDOSE3 code for radiation dosimetry in nuclear medicine. A dosimetric analysis with these codes was performed to evaluate nanoliposomes as carriers of radionuclides (188Re-liposomes) in colon carcinoma-bearing mice. Pharmacokinetic data for 188Re-N, N-bis (2-mercaptoethyl)-N', N'-diethylethylenediamine (188Re-BMEDA) and 188Re-liposome were obtained for estimation of absorbed doses in normal organs. Radiation dose estimates for normal tissues were calculated using the MIRDOSE3 and OLINDA/EXM programs for a colon carcinoma solid tumor mouse model. Mean absorbed doses derived from 188Re-BMEDA and 188Re-liposome in normal tissues were generally similar as calculated by MIRDOSE3 and OLINDA/EXM programs. One notable exception to this was red marrow, wherein MIRDOSE3 resulted in higher absorbed doses than OLINDA/EXM (1.53- and 1.60-fold for 188Re-BMEDA and 188Re-liposome, respectively). MIRDOSE3 and OLINDA have very similar residence times and organ doses. Bone marrow doses were estimated by designating cortical bone rather than bone marrow as a source organ. The bone marrow doses calculated by MIRDOSE3 are higher than those by OLINDA. If the bone marrow is designated as a source organ, the doses estimated by MIRDOSE3 and OLINDA programs will be very similar. (author)

  17. Labelling of biorelated compounds and monoclonal antibodies with 188-Re,186-Re and 99mTc

    Some bio-related compounds were labelled with 188Re and 186Re 188Re was obtained from 188W/188Re generator which was produced by neutron irradiation of enriched 186WO3 target (99.79%) in JRR-2 and 186Re was supplied by Production Div., Department of Radioisotopes, JAERI, Japan. Rhenium labelling involved reduction of perrhenate with SnCl2.2H20 in HCI. Bio-related compounds citrate and gluconate were then labelled with reduced rhenium. The labelling yield of labelled compounds as determined by thin-layer chromatography were greater than 98% and 94% for 188Re-citrate and gluconate, respectively. Monoclonal antibodies (mouse,lgG2A and lgG;Fab'2, human lgG2A; anti-hepatoma and IgG) were also successfully labelled with 188Re, 186Re, and 99mTc by direct method using citrate and glucoheptonate as transchelating agents

  18. Experimental study on target treatment of nasopharyngeal carcinoma using 188Re-BAC5 combined with PYM-BAC5

    Objective: Combination of radiation and chemical agents was supposed to have better effect on nasopharyngeal cancer. This study compared the in vitro inhibiting effects of 188Re-monoclonal anti- body (BACs) with or without pingyangmycin conjugated BACs (PYM-BAC5) on nasopharyngeal carcinoma cells (CNE2). Methods: 188Re-BAC5 was prepared using 2-mereaptoethanol (ME), citric acid and tartaric acid as reducing and transchelation agents. Oxidized dextran T-40 (polyaldehyde dextran, PAD ) was used to conjugate PYM to BAC5. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenylte-trazolium bromide (MTT) method was applied to assess anti-tumor effects of 188Re-BAC5 and PYM-BAC5 on CNE2 cells. Results: The labeling efficiency of 188Re-BACs was 92%-95% with a radioactive concentration of 5254 kBq/ml. The composition of PYM-BAC5 was m (PYM): m (BAC5)=1: 0.526, or n (PYM): n(BAC5)=1:51. The inhibition effects of each treatment regime were in a dose dependent manner. The 50% inhibition doses (IC50) of 188Re-BAC5, 188Re-mIgG and 188ReO4- were 264, 1062 and 882 kBq/ml, respectively. The IC50 of the PYM-BAC5 and free PYM were 10.07 and 63.60 μg/ml, respectively. Combining 188Re-BAC5 and PYM-BACs reduced the IC50 of 1'88Re-BAC5 and PYM-BACs down to 32.1 kBq/ml and 1.70 μg/ml. Conclusions: It was proved that targeted therapy had better anti-tumor effect. The combination of targeted radiation and chemical agents (188Re-BAC5 + PYM-BAC5) obtained the best therapeutic effect on cultured CNE2 cells. (authors)

  19. Development of a technology for the preparation of 188W-188Re generators

    A big interest has recently arisen concerning the use of Rhenium-188 (188Re) for various medical applications. Tumor therapy with antibodies labeled with 188Re is the main application, but it is being studied its application in carcinomas of medullar thyroid, bone pain palliation and radionuclide synovectomy, among others. Rhenium-188 decays 79% to the ground state of stable 188Os (Eβ1max - 2,11 MeV) and 20% to the first excited state (Eβ2max = 1,97 MeV). The deexcitation of this state gives a 155 keV gamma ray (15r%) which can be detected by imaging. Another great advantage is the viability of carrier-free 188Re from the decay of 188W (t1/2 = 69.4 days) in a generator system. The objective of this work is the development of the technology for the preparation of 188W- 188Re generators. To accomplish this, the steps of the work are: preparation of the targets of W; irradiation of W targets in order to measure the activation and radionuclidic impurities; development of 188W-188Re generators; development of a method for the quality control of 188Re: chemical, radiochemical and radionuclidic purities. The study of alumina-based generators was performed with the irradiation of targets of natural metallic W and W03 and showed that this kind of generator will only be viable with the importation of 188W, due to the low neutron flux of the Reactor IEA-R1 Reactor for the commercial routine production of this radioisotope, but the technology of production and quality control were successful. The gel type chromatographic generators of WZr were produced with natural WO3 targets and showed that, if enriched targets are to be used and with the power upgrade of the IEA-R1 Reactor, they can be produced by the Radiopharmacy Center at IPEN-SP. The quality control methodology were determined and the results were inside the limits given by the Pharmacopoeia. (author)

  20. Improved conditions for labeling EDTMP with 188Re for bone pain palliation

    Introduction: Ethilenediamine tetramethylene phosphonate (EDTMP) is a tetraphosphonate ligand which, when labeled with 188Re, can be used for relief of metastatic bone pain. The preferential localization of phosphonate complexes in bone is attributed to their affinity for calcium, and tetraphosphonates may be equal or superior to diphosphonates in this regard. In the present study, it was aimed to determine optimal conditions for preparation of a kit of EDTMP to be labeled with 188Re. Methods: EDTMP was dissolved in NaOH 1N, and alkalinity was reversed with HCl till pH 2, when SnCl2. 2H20 and also ascorbic acid were introduced in the mixture, followed by Na188ReO4. The preparation was incubated in water bath for 30 minutes and after cooling radiochemical purity was assessed. Optimization of the process consisted in varying the values of EDTMP mass (20, 30, 40 mg) SnCl2.2H20 concentration (0.5, 1.0, 2.0 and 3.0 mg/mL), and reaction time (15 and 30 minutes). Radiochemical purity and stability were ascertained in vitro and also in Swiss mice. Bone/muscle uptake ratio was calculated from %ID/g of these organs. Results: The best 188Re-EDTMP complex was obtained with 40 mg of the ligand and 2 mg/mL of stannous chloride heated during 15 minutes, and the product was radiochemically stable during 24 hours. Kidney and bone uptake were very significant (respectively 4.5 ± 0.5% and 3.1 ± 0.3 %ID/g). Bone/muscle ratio observed four hours post-injection was also very adequate (28.5). Conclusions: A stable and biologically useful complex of 188Re-EDTMP can be prepared with high concentration of EDTMP and considerable uptake by bone. It compares favorably with 153Sm-EDTMP, as 188Re has more advantageous radioisotopic properties than 153Sm, and it can be recommended for further studies in conditions of painful bone metastases

  1. Synthesis and in Vitro evaluation of ''1''8''8Re-biotinyl-hydrazino-etda

    Pretargeting strategies have overcome many drawbacks associated with the use of directly labelled MoAbs in the diagnosis / treatment of various solid tumors. In particular the avidin-biotin system has received much attention due to extremely high affinity between avidin and biotin. An EDTA derivative of biotin has been synthesized (yield-35%). In order or label biotin derivative (biotinyl-hydrazino-EDTA) , stannous ion was used to reduce ''1''8''8ReO4 (VII) to lower oxidation state and weak chelating agent glucoheptonate as stabilizer and trans chelating agent. Thin layer chromatography and high performance liquid chromatography techniques were employed to monitor the radiolabeling efficiency. The radiolabeling yield of ''1''8''8Re-EDTAB1 was >95%. The radiolabeled product was found to bind to avidin (70-80%), thereby demonstrating retention of its biological integrity

  2. Radioimmunotherapy of fungal infection with 213-Bi- and 188-Re-labeled antibody

    Aim: Radioimmunotherapy (RIT) is a therapeutic modality that utilizes monoclonal antibodies (mAb) radiolabeled with therapeutic radioisotopes to selectively deliver lethal doses of radiation to cells. We hypothesized that 18B7 mAb (murine IgG1), specific for Cryptoccocus neoformans (CN) polysaccharide capsule, may be used to deliver fungicidal doses of radioisotopes to the sites of CN infection in vitro and in vivo. Materials and Methods: 18B7 mAb was radiolabeled with either the beta-emitter 188-Rhenium (188Re) or with the alpha-emitter 213-Bismuth (213Bi). The biodistribution of radiolabeled 18B7 was measured in BALB/c mice with and without intratracheal CN infection. For in vitro killing assays 105 CN cells/well were treated with 0-3.2 μCi 213Bi-18B7 (3 h incubation), 32 μCi 188Re-18B7 (48 h incubation) or with radiolabeled IgG1 MOPC21 as a control and minimal inhibitory concentrations (MIC) were determined. To compare the activity of radiolabeled mAb's against CN infection with an established antifungal drug, we evaluated the susceptibility of CN strain to Amphoterecin B. In vivo therapy of CN was conducted in groups of 10 A/JCr mice infected intravenously with 105 CN cells 24 h prior to treatment with 50-200 μCi 213Bi- or 188Re-18B7, 213Bi- or 188Re-MOPC21, unlabeled 18B7 or saline. Student's t test for unpaired data was used to analyze in vitro data, and log-rank test - for animal survival data. Results: MAb 18B7 preserved its immunoreactivity post-labeling and delivered 10% ID/g to the lungs of the CN-infected BALB/c mice in 24 h after injection. Two-log reduction in colony forming units (CFU) was achieved in treatment of CN with 213Bi-18B7 and 188Re-18B7, which compared favorably with Amphoterecin B. MIC's were determined to be 0.4 μCi/1.5 mg and 4 μCi/1.25 mg mAb for 213Bi-18B7 and 188Re-18B7, respectively. The fungicidal activity of irrelevant mAb 213Bi-or 188Re-MOPC21 was negligible (P213Bi-18B7 and of 100 μCi 188Re-18B7 significantly (P<0

  3. Development of methods of labeling pentavalent DMSA with 99mTc and 188Re

    Technetium-99 m is the most useful radionuclide in diagnostic imaging procedures in Nuclear Medicine, more than 80 percent of radiopharmaceuticals are 99mTc-labeled compounds. 99mTc-DMSA(V) has been used for imaging of soft tissue, head and neck tumors. It shows a particularly high specificity for medullary thyroid carcinoma and bone metastases in a variety of cancers. Biodistribution studies of 188Re-DMSA(V) have shown that its general pharmacokinetic properties are similar to that of 99mTc-DMSA(V), so this agent could be used for targeted radiotherapy of these tumors. The aim of this work is the development of methods of labeling DMSA(V) with 99mTc and 188Re. 99mTc-DMSA(V) can be prepared by two methods. One of them is the indirect one, through the use of a commercial kit of DMSA (III), by adjusting the pH from 2.5 to ∼ 8.5 with NaHCO3. This method was evaluated and optimized presenting high labeling yields. The other method is the direct one, through the preparation of a lyophilised kit ready for labeling with 99mTc, being the method of interest of this work, due to the easy of its clinical use. The most adequate formulation of the kit was: 1.71 mg of DMSA, 0.53 mg of SnCl2.2H2O and 0.83 mg of ascorbic acid (pH 9). Labeling yields higher than 95% were achieved labeling this kit with 1 to 2 m L of 99mTc with activities up to 4736 MBq (128 mCi). The kit was stable up to 6 months and biodistribution studies confirmed the quality of the DMSA (V) labeled with 99mTc using this kit. The reduction potential of Re is lower than the one for Tc, so the labeling conditions of 188Re-DMSA(V) are different from the ones used for 99mTc- DMSA(V). 188Re-DMSA(V) is prepared in acid solution, that makes it possible to use the DMSA (III) commercial kit developed for labeling with 99mTc, prepared in pH 2.5, for labeling with 188Re. Labeling yields higher than 95% were achieved with this methodology, with a rection time of 30 minutes at 100 deg C using no more than 1 m L of 188ReO4

  4. Vascular responses to endovascular irradiation of 188Re in the rabbit model after angioplasty

    The effects on vascular restenosis of intravascular radiation delivery from 188Rhenium (Re)-perrhenate liquid-filled balloon through beta-particle radiation are controversial. To determine the effect of beta-radiation on vascular injury in hypercholesterolemic rabbits, thirty rabbits fed with a high cholesterol diet were enrolled into this study. All the rabbits underwent percutaneous transluminal balloon overstretch over left iliac artery. After balloon overstretch, the catheter was withdrawn and immediately followed by irradiation using low dose 188Re solution (10 Gray) in the vascular wall 0.5 mm distal to intimal surface. After 2 and 6 weeks, arteries were harvested for histological and immunological analysis. This rabbit study suggest that endovascular 188Re low dose irradiation at the non-injury segment of iliac artery may enhance intima hyperplasia and smooth muscle cell proliferation. (author)

  5. Biological behavior of 188Re-biotin chelate for multistep therapy with the avidin-biotin system

    The purpose of this study was to test the three-step targeting of tumors in mice using biotinylated antibody, streptavidin and radiolabeled biotin for radioimmunotherapy (RAIT). Three-step pretargetting can potentially decreases harmful radiation to normal tissues in radioimmunotherapy. 188Re from 188W-188Re generator, is recently introduced in therapeutic nuclear medicine and made it possible to use whenever needed. We studied biotin-chelates MGB for use in the avidin/biotin pretargetting system. Chelates that hold radiometals with high stability under physiological conditions are essential to avoid excessive radiation damage to non-target cells. We synthesized MAG2GABA-Biocytin (MGB), labeled with 188Re and evaluated biological behavior of 188Re-MGB. biotinyl MAG2GABA bind the therapeutic radiometal 188Re with excellent in vitro stability and have the required physiological properties for pretargetted therapy. In normal mice, 188Re-MGB was excreted via hepatobiliary pathway, %ID/g of GI tract was 52.1 at 120min. In Raji cells tumor bearing nude mice, liver and colon were higher than those of normal mouse. Tumor uptake at 120min was 0.05%ID/g. 188Re-MGB may have a role in pretargetted radioimmunotherapy

  6. Rhenium-188 Production in Hospitals, by W-188/Re-188 Generator, for Easy Use in Radionuclide Therapy

    Maria Argyrou; Alexia Valassi; Maria Andreou; Maria Lyra

    2013-01-01

    Rhenium-188 (Re-188) is a high energy β-emitting radioisotope obtained from the tungsten-188/rhenium-188 (W-188/Re-188) generator, which has shown utility for a variety of therapeutic applications in nuclear medicine, oncology, and interventional radiology/cardiology. Re-188 decay is accompanied by a 155 keV predominant energy γ-emission, which could be detected by γ-cameras, for imaging, biodistribution, or absorbed radiation dose studies. Its attractive physical properties and its potential...

  7. Novel and efficient preparation of precursor [188Re(OH2)3(CO)3]+ for the labeling of biomolecules.

    Park, Sang Hyun; Seifert, Sepp; Pietzsch, Hans-Jurgen

    2006-01-01

    A novel and efficient method for preparing 188Re(I) tricarbonyl precursor [188Re(OH2)3(CO)3]+ has been developed by reacting [188Re]perrhenate with Schibli's kit in the presence of borohydride exchange resin (BER) as a reducing agent and an anion scavenger. The precursor was produced in more than 97% yield by reacting a solution of tetrahydroborate exchange resin (BER, 3 mg), borane-ammonia (BH3.NH3, 3 mg), and potassium boranocarbonate (K2[H3BCO2], 3 mg) in 0.9% saline with a solution of sodium perrhenate (Na188ReO4) with up to 50 MBq and concentrated phosphoric acid (85%, 7 microL) at 60 degrees C for 15 min. HPLC and TLC revealed 0% unreacted [188Re]perrhenate ion and <3% of colloidal 188ReO2. Since the precursor is produced with high radiochemical purity and labeling efficiency under the milder conditions than those required for the conventional reducing agents, the latter can be replaced. PMID:16417272

  8. Formulation, radiopharmaceutical kinetics and dosimetry of the 188Re(V)-DMSA complex

    It was developed through experimental design (ANOVA), a formulation to prepare the 188 Re(V)-Dmsa complex. Likewise, there were realized studies of radiopharmaceutical kinetics and internal dosimetry in animals, its normal and with induced tumors, considering an open bi compartmental model using the MIRD methodology. The 188 Re(V)-Dmsa complex was obtained with a radiochemical purity greater than 95% incubating 30 min at 90 Centigrade under the following formulation: [SnCl2] = 1.4 mg/ml, [ascorbic acid] = 0.5 mg/ml, p H = 2.0 - 3.0. The stability test of the formulation, shows that after 48 h of its preparation, does not produce radiolytic degradation neither chemical decomposition. The radiopharmaceutical kinetics data show an average residence time 7.2h, velocity constant α = 0.6508h-1 and β = 0.1046 h-1 with an apparent distribution volume 6.9 l. The main elimination via was renal and it was observed osseous caption with an accumulated activity 522.049 ± 62 MBq h (residence time 14.1094 ± 1.69h). In according with the dosimetric calculations, by each 37 MBq injected, the equivalent dose at the tumor was 9.67± 0.33 Sv/g, for an effective dose 0.292 ± 0.0017 mSv/MBq. The images obtained in the gamma camera of the mice with induced tumors, show that do not have significant accumulation in the metabolic organs. The caption in bone and in tumors induced of the 188 Re(V)-Dmsa complex, show its potential for be used as a palliative agent for pain in patients with osseous metastasis and in the treatment of tumors of soft tissue. (Author)

  9. Automation of labelling of Lipiodol with high-activity generator-produced {sup 188}Re

    Lepareur, Nicolas, E-mail: n.lepareur@rennes.fnclcc.f [Service de Medecine Nucleaire, Centre Regional de Lutte Contre le Cancer Eugene Marquis, CS 44229, 35042 Rennes (France); INSERM U-991, Foie, Metabolismes et Cancer, 35033 Rennes (France); Universite Europeenne de Bretagne, Rennes (France); Ardisson, Valerie [Service de Medecine Nucleaire, Centre Regional de Lutte Contre le Cancer Eugene Marquis, CS 44229, 35042 Rennes (France); INSERM U-991, Foie, Metabolismes et Cancer, 35033 Rennes (France); Universite Europeenne de Bretagne, Rennes (France); Noiret, Nicolas [Universite Europeenne de Bretagne, Rennes (France); Ecole Nationale Superieure de Chimie de Rennes, UMR CNRS 6226, Chimie Organique et Supramoleculaire, Avenue du General Leclerc, CS 50837, 35708 Rennes Cedex 7 (France); Boucher, Eveline; Raoul, Jean-Luc [INSERM U-991, Foie, Metabolismes et Cancer, 35033 Rennes (France); Universite Europeenne de Bretagne, Rennes (France); Service d' Oncologie Digestive, Centre Regional de Lutte Contre le Cancer Eugene Marquis, CS 44229, 35042 Rennes (France); Clement, Bruno [INSERM U-991, Foie, Metabolismes et Cancer, 35033 Rennes (France); Garin, Etienne [Service de Medecine Nucleaire, Centre Regional de Lutte Contre le Cancer Eugene Marquis, CS 44229, 35042 Rennes (France); INSERM U-991, Foie, Metabolismes et Cancer, 35033 Rennes (France); Universite Europeenne de Bretagne, Rennes (France)

    2011-02-15

    This work describes optimisation of the kit formulation for labelling of Lipiodol with high-activity generator-produced rhenium-188. Radiochemical purity (RCP) was 92.52{+-}2.3% and extraction yield was 98.56{+-}1.2%. The synthesis has been automated with a TADDEO module (Comecer) giving a mean final yield of 52.68{+-}9.6%, and reducing radiation burden to the radiochemist by 80%. Radiolabelled Lipiodol ({sup 188}Re-SSS/Lipiodol) is stable for at least 7 days (RCP=91.07{+-}0.9%).

  10. The tolerance to 188Re-HEDP treatment in patients with bone pain from osseous metastases

    Objective: To study the tolerance to 188Re-1-hydroxy-1 ,1-ethylidene disodium phosphonate (HEDP) in patients with bone pain caused by osseous metastases. Methods: Thirty-one patients (10 with prostate cancer, 9 with breast cancer, 3 with lung cancer, 5 with liver cancer, 2 with rectal cancer, 1 with esophageal cancer and 1 with renal cancer) received a single injection dose of 188Re-HEDP. The patients were divided into four groups according to the injection dose: 20 MBq/kg (6 patients), 30 MBq/kg(6 patients), 40 MBq/kg (9 patients), and 50 MBq/kg (10 patients). Haematological toxicity (WHO grading) of grade III- IV was considered unacceptable. Vital signs and adverse effects after injection were recorded for 8 weeks. Blood counts were measured weekly during a period of 8 weeks. Biochemical parameters and electrocardiogram were assayed at week 4 and 8. Statistical analysis was performed for per-protocol (pp) population (t-test). Results: Twenty-seven patients belonged to PP population with 5 in the group of 20 MBq/kg, 5 in the group of 30 MBq/kg, 8 in the group of 40 MBq/kg and 9 in the group of 50 MBq/kg. No obvious adverse effects and no significant change of vital signs, electrocardiogram, liver and renal function were found after injection. Alkaline phosphatase was slightly higher than baseline at week 4 and 8 after therapy, but the difference was not statistically significant. In the 20 MBq/kg group, reversible grade I leucopenia was noted in 1 patient. In the 30 MBq/kg group, 2 patients showed reversible grade I leucopenia including 1 alone with reversible grade III thrombopenia. In the 40 MBq/kg group, reversible grade I leucopenia and thrombopenia was observed in 1 patient and reversible grade II leucopenia and thrombopenia in another patient. In the 50 MBq/kg group, 3 patients showed reversible grade II leucopenia. The lowest level of thrombopenia was at week 4(143.5 x 109/L), leucopenia at week 6 (5.4 x 109/L) and anaemia at week 8 (t =3.1325, 3.3156, 3

  11. The Dresden in-stent restenosis radiation trial (DIRRT) with liquid-filled 188Re balloon

    Full text: In some studies intracoronary radiation therapy (IRT) to minimize the restenosis rate after PTCA proved to be effective. We evaluated the performance, safety and effectiveness of IRT with 188Re-perrhenate filled into a standard PTCA balloon. This kind of IRT allows a self-centering homogenous dose distribution to the vessel wall. 107 patients (pts) with a mean age of 63 years (81 m, 26 fin) with in-stent restenosis (type B in 39 %, type C in 61 %) and proven ischemia were included. After routine re-PTCA with or without additional stent implantation a second standard balloon was placed into the PTCA area and filled with β--emitting liquid 188Re at 3 atm. Irradiation time was 525 ± 167 sec to achieve a dose of 30 Gy at 0.5 mm depth of the vessel wall. In only one procedure there was a disconnection of the 188Re containing system and the catheter but no contamination of the cath table or lab was measured. In 16 coronaries 21 stents were additionally implanted. In the follow-up 4 stent thromboses (1 day, 37 days, 2 x 6 months) with subsequent myocardial infarction were noticed, all in pts with additionally implanted stents. 57 pts had control angiography after 4 to 6 months after therapy and 41 after one year. Restenosis (stenosis > 50 % of luminal diameter) was shown in 9 out of 12 pts (75 %) with additionally implanted stents but only in 4 out of 24 pts (17 %) with PTCA alone. Reocclusion was noticed in 3 (25 %) pts with additional stent but only in 1 pt (4 %) without. No re-restenosis occurred in 20 patients which were without finding after 6 months. Intracoronary radiation therapy (IRT) with β--emitting liquid-filled 188Re balloon is a safe and effective therapy method which might be used routinely. Long-term results seem satisfactory in a patient group with in-stent restenosis and high risk of re-restenosis. But the positive effect of irradiation is abolished if an additional stent after PTCA is needed. (author)

  12. Effect of 188Re-IGF-1 analogue in proliferation inhibition and apoptosis induction in pancreatic carcinoma cells

    Objective: To investigate the effect of 188Re-IGF-1 analogue (IGF-1A) in proliferation inhibition and apoptosis induction in human pancreatic carcinoma cell line Patu8988. Methods: IGF-1A was labeled with 188Re. Patu8988 cells were divided into an un-treated control group, IGF-1A group (1, 5, 10, 20 μg), 188ReO4-group (0.37, 1.85, 3.70, 7.40 MBq) and 188Re-IGF-1A group (0.37, 0.74, 1.85 MBq). The cell proliferation inhibition effects by the 188Re-IGF-1A and 188ReO4--were detected every day by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) test from 1 d to 7 d after administration, while the IGF-1 A group was tested every day from 1 d to 6 d after treatment. Inhibition rates were calculated. At 3 d after treatment with 188ReO4-and 188Re-IGF-1A (1.85, 3.70, 7.40 MBq), cell apoptosis was detected by flow cytometry. For biodistribution studies of 188Re-IGF-1A, 36 nude mice bearing Patu8988 cell xenografts were divided into 6 groups. At different time points (15 min, 1 h, 4 h, 1 d, 3 d and 5 d), 36 mice (n=6 per time point) were sacrificed and organs of interest were removed, weighted and measured for radioactivity by a gamma counter. The absorbed doses of organs were calculated as % ID/g. One-way analysis of variance was used. Results: After 4 d, inhibition rate of Patu8988 cell proliferation in the 188Re-IGF-1A group (1.85 MBq) was (90.75 ±5.20)%,higher than that in 188ReO4-group or IGF-1A group ((49.50±2.39)%, (23.00±4.21)%; F=554.724, P<0.01). At 3 d after treatment with different doses of 188Re-IGF-1A (1.85, 3.70, 7.40 MBq), floating cell ratios were (16.56 ± 0.95)%, (33.39 ±5.93)% and (43.76 ± 1.38)%, respectively. Apoptosis ratios in the floating cells treated by 188Re-IGF-1A (1.85, 3.70, 7.40 MBq) were (12.70±2.27)%, (17.80±1.51)% and (23.23 ±1.22)%, respectively. Distribution in tumors was (39.30 ± 17.98), (10.59 ± 9.39), (5.32 ± 1.53) and (5.30 ±2.28)% ID/g at the 15 min, 1 d, 3 d, and 5 d time points after intratumoral

  13. Pharmacokinetics, micro-SPECT/CT imaging and therapeutic efficacy of 188Re-DXR-liposome in C26 colon carcinoma ascites mice model

    The pharmacokinetics and internal radionuclide therapy of intraperitoneally administrated 188Re-N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA)-labeled pegylated liposomal doxorubicin (188Re-DXR-liposome) were investigated in the C26 murine colon carcinoma ascites mouse model. After intraperitoneal administration of the nanotargeted bimodality 188Re-DXR-liposome, the ascites and tumor accumulation of the radioactivity were observed, the levels of radioactivity within the ascites were maintained at relatively higher levels before 48 h and the levels of radioactivity in the tumor were maintained at steady levels after 4 h. The AUC(o→∞) of 188Re-DXR-liposome in blood, ascites and tumor was 9.3-, 4.2- and 4.7-fold larger than that of 188Re-BMEDA, respectively. The maximum tolerated dose of intraperitoneally administrated 188Re-DXR-liposome was determined in normal BALB/c mice. The survival, tumor and ascites inhibition of mice after 188Re-DXR-liposome (22.2 MBq of 188Re, 5 mg/kg of DXR) treatment were evaluated. Consequently, radiochemotherapeutics of 188Re-DXR-liposome attained better survival time, tumor and ascites inhibition (decreased by 49% and 91% at 4 days after treatment; P188Re-liposome or chemotherapeutics of Lipo-Dox did. Therefore, intraperitoneal administration of novel 188Re-DXR-liposome could provide a benefit and promising strategy for delivery of passive nanotargeted bimodality radiochemotherapeutics in oncology applications

  14. Prediction of the correct measured activity of 186Re and 188Re from reactor produced natural rhenium using an artificial neural network

    To optimize the cost effectiveness of 186Re and 188Re production, which have recently been used as radio pharmaceuticals for therapeutic purposes, we designed an artificial neural network (ANN) to evaluate the activity of combined 186Re + 188Re. One of the production ways is the (n,γ) reaction of natural rhenium which leads to combined 186Re + 188Re. Using the counted activity of 186Re + 188Re mixtures by a well type isotope calibrator, the precise activity of 186Re and 188Re is obtained by the ANN. A back-propagation ANN was trained using 30 activities of mixed 186Re + 188Re. The performance of the ANN was tested by Early-Stopping validation method, and the ANN was optimized with respect to its architecture. The response of the ANN shows significant precision that may be used for medical application of 186Re + 188Re mixtures.

  15. Evaluation of S-values and dose distributions for (90)Y, (131)I, (166)Ho, and (188)Re in seven lobes of the rat liver

    Xie, Tianwu; Liu, Qian; Zaidi, Habib

    2012-01-01

    Rats have been widely used in radionuclide therapy research for the treatment of hepatocellular carcinoma (HCC). This has created the need to assess rat liver absorbed radiation dose. In most dose estimation studies, the rat liver is considered as a homogeneous integrated target organ with a tissue composition assumed to be similar to that of human liver tissue. However, the rat liver is composed of several lobes having different anatomical and chemical characteristics. To assess the overall ...

  16. Radiolabeling and biodistribution of RGD peptide with 188Re-tricarbonyl complex

    Three amino acids residues of Arg-Gly-Asp (RGD) are often the primary site of recognition by integrins which are responsible for tumor invasion and metastasis. In this research, one peptides containing RGD: HCRGD(D)FC were radiolabeled with 188Re-tricarbonyl complex. High radiolabeling ratios (>90%) were achieved under the reaction condition of 75 degree C, 30 min. The radiolabeled peptide got high stability in PBS at room temperature for 4 hours. The hemolysis of red blood cells was not observed during incubation at at 37 degree C for 3 hours. Biodistribution studies were performed in normal male mice and S180-bearing mice, respectively. the radioactivities were rapidly eliminated by the hepatobiliary and urinary systems. Tumor/Muscle ratios were 4.4075 ± 0.1139, 5.1510 ± 0.5375, 4.4727 ± 0.4895 and 4.8788 ± 3.16 at 1h, 4h, 24h and 48h after injection. The results showed that 188Re-tricarbonyl peptide containing RGD was a potential agent for tumor treatment. (authors)

  17. 188Re-labelled anti-CD20 monoclonal antibody: Labelling and quality control studies

    Immunotherapy with human chimeric antibody rituximab (Rituxan, IDEC pharmaceuticals) has been a major advance in treatments of patients with CD20-positive B-cell non Hodgkin's lymphoma (NHL). Radioimmunotherapy (RIT) uses the targeting features of monoclonal antibody to deliver radiation from an attached readionuclide and it is an appeling concept that has received widespread attention. Here, we report our experience using rhenium-188 (188Re)- radiolabeled chimeric anti-CD20 antibody (rituximab). A stable antibody-labeling technique had been developed for 188Re. The 188Re-direct labeling of anti-CD20 monoclonal antibody, the methods for quality control: paper chromatography, instant thin layer chromatographysilica gel (ITLC-SG) and HPLC technique, the immunoreactivity and biological recognition of the target antigen assessment of the radiolabeled molecule, in vitro stability and the assessment of in vivo stability through biodistribution studies in normal WISTAR rats are described. For the direct radiolabeling, the reduction of monoclonal antibody (mAb) was performed with 2-mercaptoethanol (2-ME), based on Schwarz's method at a molar ratio 2000:1 (2- ME:mAb). By means of this method some of the disulfide bonds of the antibody are reduced to sulfhydryl groups (we obtained 4-5 groups) and these groups provide sites for the formation of very strong bond between the reduced rhenium and the antibody. The methodology used in this work has been tested in a phase I radioimmunotherapy clinical trial using the humanized mAb hR3 for loco-regional treatment of brain tumours. The labeling efficiency (> 95 %) of this method showed that the final product needs no further purification for clinical purposes (low level formation of colloidal species). In vitro stability studies of the labeled anti-CD20 were performed at room temperature at 4 h, 24 h and 48 h in cysteine, human serum and saline. In the presence of normal human serum, during the first 4h, transchelation of about 15

  18. Production of carrier free 188Re radioisotope generator based on aluminum tungstate matrix

    Improved radionuclide generator include a substantially insoluble salt of a radioactive parent which may be directly packed in column for subsequent elution of the daughter radionuclide. An improved 188Re generator was prepared by reacting a radioactive tungsten (188W) as parent radionuclide incorporated with aluminum chloride to obtain an insoluble radioactive aluminum tungstate matrix. The investigated matrix was characterized on the basis of the chemical composition, IR, thermal analysis and mechanical stabilities. The factors affecting the elution performance were studied such as influence of pH, molar ratio and drying temperature. From the obtained data, the molar ratio W:Al was 1.5:1 at pH = 4, the matrix dried at 105 deg C for 2 h. Chromatographic and multichannel analysis has been currently used to investigate the radiochemical and radionuclidic purity respectively on eluted 188Re. An elution yield more than 80%, with radiochemical purity 188W break through >10-4% of the column. The Al+3 and W contents value were about 2 and 3 μg/mL eluate. The obtained data approved the stability of the prepared generator and its suitability for medical application. (author)

  19. PRODUCTION OF CARRIER-FREE 188Re RADIOISOTOPE GENERATOR BASED ON ALUMINUM TUNGSTATE MATRIX

    An improved 188Re generator was prepared by reacting solutions of radioactive tungsten (188 W as parent radionuclide) with aluminum chloride to obtain an insoluble radioactive aluminum tungstate incorporated-188W matrix. The investigated matrix was characterized on the basis of the chemical composition, IR, thermal analysis and physical analysis. The factors affecting the elution performance were studied such as influence of pH, molar ratio and drying temperature. From the obtained data, the W : Al molar ratio was 1.5:1 at pH=4 for the matrix dried at 1050C for 2 hr. Chromatographic and multichannel analysis have been currently used to investigate the radiochemical and radionuclidic purity, respectively, of eluted 188Re. An elution yield more than 80% with radiochemical purity ≥ 98 % and radionuclidic purity ≥ 99.99% with a 188 W break through ≤ 10-4 % of the column tungsten activity. The values of Al3+ and W contents were about 2 and 3μg/ml elute

  20. Analysis of effectiveness of the palliative treatment of metastatic bone's pain with 188Re-HEDP

    The objective of the study was to evaluate the treatment effectiveness with 188Re-HEDP in a group of 27 patients, who had received 36 doses. A pharmaceutical care programme was also added in order to improve drug follow-up after treatment. Two levels of doses were administered: 30 or 60 mCi. Initially a trace dose was given in order to estimate the therapeutic dose, which was individualise according to bone uptake of the radiopharmaceutical. Bone uptake was determined measuring radioactivity in urine samples (0, 1, 2, 4 and 6 hs), because the radiopharmaceutical showed only renal elimination. Multiple dose schedules with with 3 months between both doses were also tried. Seventy two percent showed an algesic effect during the first week post-treatment, with was kept during one month, while seven tenn (17%) percent of the patients the effect was kept for two of more months. Opioid analgesic (third level of OMS scale) were diminished in eighty two percent of the patients and AINES drugs in seventy one percent. The pharmaceutical care programme also showed the importance of the radio pharmacist role to improve treatment outcomes. 188Re-HEDP effectiveness was achieved in 100% of the patients, but with different pain palliation response in time and/or drug intake, with a suitable radiological safety

  1. Biokinetic and dosimetric studies of {sup 188}Re-hyaluronic acid: a new radiopharmaceutical for treatment of hepatocellular carcinoma

    Melendez-Alafort, Laura [Dipartimento di Scienze Farmaceutiche, Universita degli Studi di Padova, 35131 Padua (Italy)], E-mail: laura.melendez@unipd.it; Nadali, Anna; Zangoni, Elena [Dipartimento di Scienze Farmaceutiche, Universita degli Studi di Padova, 35131 Padua (Italy); Banzato, Alessandra; Rondina, Maria [Dipartimento di Scienze Oncologiche e Chirurgiche, Universita degli Studi di Padova, Padua (Italy); Rosato, Antonio [Dipartimento di Scienze Oncologiche e Chirurgiche, Universita degli Studi di Padova, Padua (Italy); Istituto Oncologico Veneto, IOV, Padova, Padua (Italy); Mazzi, Ulderico [Dipartimento di Scienze Farmaceutiche, Universita degli Studi di Padova, 35131 Padua (Italy)

    2009-08-15

    Hepatocellular carcinoma (HCC) is the most common primary liver cancer and has very limited therapeutic options. Recently, it has been found that hyaluronic acid (HA) shows selective binding to CD44 receptors expressed in most cancer histotypes. Since the trend in cancer treatment is the use of targeted radionuclide therapy, the aim of this research was to label HA with rhenium-188 and to evaluate its potential use as a hepatocarcinoma therapeutic radiopharmaceutical. Methods: {sup 188}Re-HA was prepared by a direct labelling method to produce a ReO(O-COO){sub 2}-type coordination complex. {sup 188}Re-HA protein binding and its stability in saline, phosphate buffer, human serum and cysteine solutions were determined. Biokinetic and dosimetric data were estimated in healthy mice (n=60) using the Medical Internal Radiation Dose methodology and mouse model beta-absorbed fractions. To evaluate liver toxicity, alanine aminotranferase (AST) and aspartate aminotranferase (ALT) levels in mice were assessed and the liver maximum tolerated dose (MTD) of {sup 188}Re-HA was determined. Results: A stable complex of {sup 188}Re-HA was obtained with high radiochemical purity (>90%) and low serum protein binding (2%). Biokinetic studies showed a rapid blood clearance (T{sub 1/2}{alpha}=21 min). Four hours after administration, {sup 188}Re-HA was almost totally removed from the blood by the liver due to the selective uptake via HA-specific receptors (73.47{+-}5.11% of the injected dose). The liver MTD in mice was {approx}40 Gy after 7.4 MBq of {sup 188}Re-HA injection. Conclusions: {sup 188}Re-HA complex showed good stability, pharmacokinetic and dosimetric characteristics that confirm its potential as a new agent for HCC radiation therapy.

  2. Biokinetic and dosimetric studies of 188Re-hyaluronic acid: a new radiopharmaceutical for treatment of hepatocellular carcinoma

    Hepatocellular carcinoma (HCC) is the most common primary liver cancer and has very limited therapeutic options. Recently, it has been found that hyaluronic acid (HA) shows selective binding to CD44 receptors expressed in most cancer histotypes. Since the trend in cancer treatment is the use of targeted radionuclide therapy, the aim of this research was to label HA with rhenium-188 and to evaluate its potential use as a hepatocarcinoma therapeutic radiopharmaceutical. Methods: 188Re-HA was prepared by a direct labelling method to produce a ReO(O-COO)2-type coordination complex. 188Re-HA protein binding and its stability in saline, phosphate buffer, human serum and cysteine solutions were determined. Biokinetic and dosimetric data were estimated in healthy mice (n=60) using the Medical Internal Radiation Dose methodology and mouse model beta-absorbed fractions. To evaluate liver toxicity, alanine aminotranferase (AST) and aspartate aminotranferase (ALT) levels in mice were assessed and the liver maximum tolerated dose (MTD) of 188Re-HA was determined. Results: A stable complex of 188Re-HA was obtained with high radiochemical purity (>90%) and low serum protein binding (2%). Biokinetic studies showed a rapid blood clearance (T1/2α=21 min). Four hours after administration, 188Re-HA was almost totally removed from the blood by the liver due to the selective uptake via HA-specific receptors (73.47±5.11% of the injected dose). The liver MTD in mice was ∼40 Gy after 7.4 MBq of 188Re-HA injection. Conclusions: 188Re-HA complex showed good stability, pharmacokinetic and dosimetric characteristics that confirm its potential as a new agent for HCC radiation therapy.

  3. DNA damage in lymphocytes after irradiation with 211At and 188Re. Quantification by alkaline and neutral comet assay

    Aim: Ionising radiation produces many types of DNA lesions of different complexity. High linear energy transfer (LET) types of radiation are biological more effective than low LET radiation. In the present work we applied the single cell gel electrophoreses (comet assay) to study the induction of initial DNA damage, efficiency of repair and residual DNA damage in lymphocytes after treatment with 211At and 188Re. Methods: Peripheral blood mononuclear cells (PBMC) were isolated from heparinized blood of healthy donors and irradiated with 211At and 188Re at different doses. The comet assay was performed under alkaline and neutral conditions in order to detect the initial DNA damage and its repair. The measure of damage was% tail DNA (percentage of DNA in the tail). Results: After treatment of cells with 188Re the initial DNA damage (% tail DNA) detected with the alkaline comet assay was higher than the damage measured for 21lAt. The neutral comet assay estimated higher tail intensities for 211At in contrast to 188Re. Compared with the complete repair (10%) after irradiation with 188Re, the radiotoxicity of alpha particles indicated reduced rejoining of DNA strand breaks (60-80% residual damage). Rejoining of DNA damage measured by the neutral comet method detected about 70% unrepaired strand breaks for 211At and 188Re. Conclusions: There are major differences between the repair of strand breaks caused by 188Re and 211At detected by the alkaline comet assay. The DNA-damage induced by the high LET Emitter 211At remains nearly unrepaired detected by both alkaline and neutral comet assay. Represented data following irradiation of lymphocytes with alpha and beta particles demonstrated higher biological effectiveness of 211At by factors of 2.0-2.5. (orig.)

  4. A review on the current status and production technology for {sup 188}W-{sup 188}Re generator system

    Kuznetsov, R. A.; Han, H. S.; Cho, W. K.; Park, U. J.; Kim, Y. M

    1998-11-01

    The current status of {sup 188}W-{sup 188}Re generator production technology were reviewed in PART 1. Main interests were given to the aspects of {sup 188}W reactor production, irradiated targets reprocessing and generator loading technologies, such as alumina type and gel type generators. In order to develop the more convenient and advanced {sup 188}W-{sup 188}Re generator, further studies must be carried out to get the precise evaluation of production and burn-up cross section of {sup 188}W, the more easily realizable generator loading procedure, and also to optimize the column and generator design to compensate the deterioration of generator performance because of parent radionuclide decay. By irradiation of {sup 186}W enriched sample, {sup 188}W-{sup 188}Re generator production experiments were performed to evaluate the possibility of {sup 188}W-{sup 188}Re generator production using HANARO, and PART 2 describes about the experiments. The experimental results shows the possibility of practical {sup 188}W-{sup 188}Re generator production using of low-specific activity {sup 188}W produced in HANARO. (author). 79 refs., 4 tabs., 26 figs.

  5. {sup 188}Re-labeled bisphosphonates as potential bifunctional agents for therapy in patients with bone metastases

    El-Mabhouh, Amal [Faculty of Pharmacy and Pharmaceutical Sciences, 3118 Dentistry Pharmacy Center, University of Alberta, Edmonton Alta, T6G-2N8 (Canada); Mercer, John R. [Faculty of Pharmacy and Pharmaceutical Sciences, 3118 Dentistry Pharmacy Center, University of Alberta, Edmonton Alta, T6G-2N8 (Canada); Faculty of Medicine, 3118 Dentistry Pharmacy Center, University of Alberta, Edmonton Alta, T6G-2N8 (Canada)]. E-mail: john.mercer@ualberta.ca

    2005-04-01

    Two new bisphosphonates have been examined for their ability to bind {sup 188}Re and deliver it selectively to bone. The bisphosphonates are prototype compounds with potential to deliver rhenium radionuclides and a second therapy modality to bone metastases. A conjugate between diethylenetriaminepentaacetic acid and bisphosphonate (DTPA/BP) and a conjugate between 5-fluorouracil and bisphosphonate (5-FU/BP) were prepared and labeled at high radiochemical purity with {sup 188}Re and biodistribution studies were carried out in normal Balb/C mice. The compounds showed rapid blood clearance and elimination from soft tissues with substantial retention of activity in the bone comparable to {sup 188}Re-hydroxyethylidine diphosphonate used as a control. At 8 h bone activity was 3.51% of injected dose for {sup 188}Re-DTPA/BP and 6.38% of injected dose for {sup 188}Re-5-FU/BP representing 69.6% and 80.6% of total body radioactivity, respectively. The two compounds show the potential for combination therapy of painful bone metastases.

  6. Synthesis, characterization and biological evaluation of [{sup 188}Re(N)(cys{approx})(PNP)]{sup +/0} mixed-ligand complexes as prototypes for the development of {sup 188}Re(N)-based target-specific radiopharmaceuticals

    Thieme, Stefan [Institute of Radiopharmacy, Forschungszentrum Dresden Rossendorf, P.O. Box 510 119, 01314 Dresden (Germany); Agostini, Stefania [Department of Pharmaceutical Sciences, University of Padua, Via Marzolo 5, 35131 Padova (Italy); Bergmann, Ralf; Pietzsch, Jens; Pietzsch, Hans-Juergen [Institute of Radiopharmacy, Forschungszentrum Dresden Rossendorf, P.O. Box 510 119, 01314 Dresden (Germany); Carta, Davide; Salvarese, Nicola [Department of Pharmaceutical Sciences, University of Padua, Via Marzolo 5, 35131 Padova (Italy); Refosco, Fiorenzo [ICIS-CNR, Corso Stati Uniti 4, 35127 Padova (Italy); Bolzati, Cristina, E-mail: bolzati@icis.cnr.i [Department of Pharmaceutical Sciences, University of Padua, Via Marzolo 5, 35131 Padova (Italy); ICIS-CNR, Corso Stati Uniti 4, 35127 Padova (Italy)

    2011-04-15

    We report on an efficient procedure for the preparation of [{sup 188}Re(N)(PNP)]-based complexes (where PNP is diphosphinoamine) useful in the development of target-specific radiopharmaceuticals. The radiochemical yield of the compounds was optimized considering such reaction parameters as nature of the nitrido nitrogen donor, reaction times and pH level. The chemical identity of the {sup 188}Re agents was determined by high-performance liquid chromatography comparison with the corresponding well-characterized cold Re compounds. {sup 188}Re(N) mixed compounds have been evaluated with regard to stability toward transchelation with GSH and degradation by serum enzymes. The clearance of selected radiocompounds from normal tissues and their in vivo stability were evaluated in rats by biodistribution and imaging studies. [{sup 188}Re(N)(cys{approx})(PNP)]{sup +/0} mixed-ligand compounds were efficiently prepared in aqueous solution from perrhenate using a multistep procedure based on the preliminary formation of the labile {sup 188}Re{sup III}-EDTA species, which easily undergo oxidation/ligand exchange reaction to afford the [{sup 188}Re{sup V{identical_to}}N]{sup 2+} core in the presence of dithiocarbazate. The final mixed-ligand compounds were obtained, at 100{sup o}C, by adding the two bidentate ligands to the buffered [{sup 188}Re{sup V{identical_to}}N]{sup 2+} solution (pH 3.2-3.6). However, a relatively high amount of cys{approx} ligand was required to obtain a quantitative radiochemical yield. The complexes were stable toward reoxidation to perrhenate and ligand exchange reactions. In vivo studies showed rapid distribution and elimination of the complexes from the body. No specific uptakes in sensitive tissues/organs were detected. A positive correlation of the distribution of the complexes estimated with biodistribution studies (%ID) and with micro-SPECT semiquantification imaging analysis (standard uptake values) was observed. These results support the

  7. Radiolabeling RGD-peptide using fac-[188Re(CO)3(H2O)3]+

    Integrin αvβ3 is a member of the integrin family, which plays an important role in angiogenesis and tumour metastasis. The peptides containing arginine-glycine-aspartic acid(RGD) sequence can bind to integrin αvβ3 selectively. In the present study, we labeled two RGD-peptides via fac-[188Re(CO)3(H2O)3]+. The results show that the labeling yields are more than 90% for both of radiolabeled compounds, and they are all stable in phosphate buffered saline and new-born calf serum, even challenged in histidine or cysteine solution. We will evaluate their biological properties to develop radiolabeled agents for tumor therapy. (authors)

  8. Stability of 186Re- and 188Re-DMSAs and removal of impurity in the product

    Complex compound of 186Re- and 188Re with meso-2,3-dimercaptosuccinic acid (DMSA) is expected to be effective against cancerous disease. This compound is synthesized with high radiochemical yield by use of SnCl2 as reducing reagent. However, the product contains a large amount of SnCl2 which is harmful to humans body. The removal of tin impurity was tested with cation exchange resin. 186Re-DMSA complex was also obtained with high radiochemical yield by use of other harmless reducing agents (L-ascorbic acid, Na2-SO3, H3PO3). Synthesized 186Re-DMSA by use of SnCl2 was stable in sodium acetate buffer for 5 hours, while survival amount of 186Re-DMSA synthesized by other reducing agents decreased in a short time. (author)

  9. Research on labelling chemistry of o-phenanthroline with 99mTc, 188Re and stable Re

    With SnCl2 as reductant, tartrate as intermediate ligand, and with the aid of paper chromatography on three kinds of developing agents, the 99mTc, 188Re and stable rhenium labelling chemistry with regard to o-phenanthroline (Phen) have been studied. The labelling ratio of 99mTc-Phen can reach to 95%. For different pH values of media and at different labelling temperatures, the 99mTc-Phen products cna be different, and they can have different paper chromatographic behavior in some developing agents. The labelling of 188Re and stable rhenium is more difficult than that of 99mTc. Even if large quantity of SnCl2 is used, the labelling ratio of 188Re-phen is significantly lower than 99mTc-Phen: the highest labelling ratio is only 50%

  10. Bifunctional Bisphosphonate Complexes of 99mTc and 188Re for Diagnosis and Therapy of Bone Metastases. Chapter 13

    A simple method to purify the rhenium tricarbonyl precursor for labelling small molecules and biomolecules with 188Re is reported in this chapter. The synthesis of a new radiopharmaceutical for the radionuclide therapy of bone metastases and of the corresponding 99mTc analogue is also described. In contrast with the clinically approved 186/188Re HEDP, this new 188Re agent forms an inert, single species that has been well characterized and displays superior stability, selective bone targeting and retention properties. Similarly, a new bone seeking 99mTc tracer prepared using the 99mTc nitrido core as a prereduced intermediate shows prolonged retention in bone and higher stability and binding to serum proteins compared to 99mTc MDP. (author)

  11. Animal experiment on 188Re-radioactive nanometre particle esophageal stent

    Objective: To investigate the mechanism and clinical reliability of applying 188Re-radioactive nanometre particle esophageal stent. Methods: An elastic meshed esophageal stent made of double membranous nickel-titanium alloy and loaded with 188Re-radioactive nanometre particles was used . The stent was introduced into the esophagus of eight experimental pigs and fixed in place. Two pigs served as controls. With the pig aneasthetized, the stent with good expandability was placed in the proper position. Radioactive MBq was applied to the 8 experiment pigs while the two control pigs received only the stent without the radioactive material. Three hours after the insertion of the stent, the pigs were allowed to feed, without any choking observed. Results: Seven days after the treatment of pathologic experiment pigs showed infla mmatory celluar infilfration, congestion and edema in the mucosa and submucous layer. After 21 days, some parts of the esophageal mucosa showed thickening of the vascular layer of the blood vessels and scanty fibrous hyperplasia. Seven days after application of larger dose of 259 MBq stent, pathology examination carried out in the experiment pigs showed extensive infla mmatory cellular infilfration, edema and congestion in the muscles and submucosa, and patch-like necrosis. Twenty-one days after application, repairing fibrous hyperplasia appeared. In the control pigs, not even any traumatic damage was observed. Periodic checking of the stool did not show any leakage of radioactivity and there was no displacement of the stents as confirmed by X-ray exam. Conclusions: The stent is effective to maintain an unobstructed passage of food . The loaded radioactive particles can be concentrated in the target area and adjusted by a body surface magnetic modulation and inhibit the intraluminal epithelial growth of esophageal mucosa without any severe radiation reaction or damage. It is quite promising to resolve the obstruction of advanced esophageal cancer

  12. A YAP camera for the biodistribution of 188Re conjugated with Hyaluronic-Acid in 'in vivo' systems

    The aim of the SCINTIRAD experiment is to determine the radio-response of 188Rhenium (Re) in in vitro cells and the biodistribution in different organs of in vivo mice, and subsequently to assess the therapeutic effect on liver tumours induced in mice. Both the γ- and β- emissions of 188Re have been exploited in the experiment. The in vivo biodistribution in mice was studied also with a γ-camera using different parallel hole collimators. In the 188Re spectrum, while the 155 keV γ-peak is useful for imaging, the photons emitted at larger energies and the β-particles act as noise in the image reconstruction. The γ-cameras previously used to image biodistributions obtained with 99Tc are, therefore, not optimized for use with 188Re. A new setup of the γ-camera has been studied for 188Re: 66x66 YAP:Ce crystals (0.6x0.6x10 mm3, 5 μm optical insulation) guarantee a FOV of 40x40 mm2, a Hamamatsu R2486 PSPMT, 3 in. diameter, converts their light into an electrical signal and allows reconstructing the spatial coordinates of the light spot; incoming photon directions are selected through a lead collimator with 1.5 mm diameter hexagonal holes, 0.18 mm septa, 40 mm thickness. Using this setup, results have been obtained both with 99Tc filled and 188Re filled capillaries and wells. The energy spectrum of the collected photons and the spatial resolutions obtainable with the 188Re source will be presented

  13. Evaluating the potential of {sup 188}Re-SOCTA-trastuzumab as a new radioimmunoagent for breast cancer treatment

    Luo, T.-Y. [Isotope Application Division, Institute of Nuclear Energy Research, P.O. Box 3-27, Longtan, Taoyuan 325, Taiwan (China)], E-mail: tylo@iner.gov.tw; Tang, I-C.; Wu, Y.-L.; Hsu, K.-L. [Isotope Application Division, Institute of Nuclear Energy Research, P.O. Box 3-27, Longtan, Taoyuan 325, Taiwan (China); Liu, S.-W. [Chemistry Division, Institute of Nuclear Energy Research, Taoyuan 325, Taiwan (China); Kung, H.-C. [Department of Electrical Engineering, Tung Nan University, Taipei 222, Taiwan (China); Lai, P.-S. [Department of Chemistry, National Chung Hsing University, Taichung 402, Taiwan (China); Lin, W.-J. [Isotope Application Division, Institute of Nuclear Energy Research, P.O. Box 3-27, Longtan, Taoyuan 325, Taiwan (China)

    2009-01-15

    Introduction: Radioimmunotherapy, which utilizes monoclonal antibodies and therapeutic radioisotopes against antigen-expressing tumor tissues, is an attractive therapeutic approach for cancer therapy. Trastuzumab (Herceptin) is a humanized anti-HER-2/neu monoclonal antibody for breast cancer treatment. In this paper, we introduce a new radioimmunoagent, {sup 188}Re-trastuzumab, via a bifunctional ligand, succinimidyl 3,6-diaza-5-oxo-3-[2-((triphenylmethyl)thio)ethyl] -8-[(triphenylmethyl)thio]octanoate (SOCTA), and evaluate its potential to be a therapeutic radiopharmaceutical for breast cancer treatment. Methods: Equimolar amounts of SOCTA and trastuzumab were selected to react, and the conjugation ratio of SOCTA-trastuzumab was evaluated by the MALDI-TOF method. The immunoreactivity of SOCTA-trastuzumab was compared with nonconjugated trastuzumab in HER-2/neu overexpressing human breast cancer cell BT-474. Biodistribution experiment and microSPECT/CT images of {sup 188}Re-SOCTA-trastuzumab being administered intravenously to SCID mice bearing xenografted BT-474 breast cancer were investigated to evaluate the tumor-targeting capability. Results: The covalent attachment of SOCTA to trastuzumab (at 1:1 molar ratio) resulted in the averaged conjugation ratio of 0.27{+-}0.06 (n=3). The complex could easily be labeled with {sup 188}Re and achieve 95% radiochemical purity (RCP) after 1 h of reaction at room temperature. The in vitro stability study also revealed that the RCP of {sup 188}Re-SOCTA-trastuzumab was at a value of more than 85% after 48 h of incubation with human serum. The immunoreactivity evaluation showed that SOCTA-trastuzumab and nonconjugated trastuzumab had similar binding capacity (B{sub max}) to HER-2/neu receptor in BT-474 cells. The animal experiments showed that {sup 188}Re-SOCTA-trastuzumab accumulated more intensively in the tumor site as compared to normal tissue. Conclusion: We suggest that {sup 188}Re-SOCTA-trastuzumab could be a potential

  14. 188Re-HTDD-lipiodol solution as a new therapeutic agent for transhepatic arterial administration in liver cancer: a preclinical study using liver-cancer model in rabbit

    188Re-HTDD-lipiodol solution was developed and reported to be a new therapeutic material for transhepatic arterial embolization (TAE) of liver cancer. In this study we compared the tissue retention of 188Re-HTDD-lipiodol with that of 188Re-TDD-lipiodol using liver-cancer model in rabbit. Cancer cell line VX2 was inoculated into 7 rabbits and grown up to larger than 3 cm. TAE was performed with 188Re-TDD-lipiodol in 3 rabbits and with 188Re-HTDD-lipiodol in 4 rabbits. Conjugated planar scans were performed at 1, 2, 6, 24, 48 hours after TAE. From these images, the mean life of radioactivity retention in tumor was calculated, and the required dose for human application as also calculated from the mean life and MIRDOSE3 software. The mean lifes of radioactivity in liver were 10.2±1.0 hr in TDD group and 17.6±0.8 hr in HTDD group (p188Re-HTDD-lipiodol for 5.7 cm-sized tumor and 88 mCi for 9,7 cm-sized tumor. By the introduction of long chain alkyl group, 188Re-HTDD-lipiodol showed significantly better tumor retention than that of 188Re-TDD-lipiodol. And the required dose of radiation for human application was calculated to be 18 ∼ 88 mCi when using 188Re-HTDD-lipiodol

  15. Pharmacokinetics, micro-SPECT/CT imaging and therapeutic efficacy of (188)Re-DXR-liposome in C26 colon carcinoma ascites mice model.

    Chen, Liang-Cheng; Chang, Chih-Hsien; Yu, Chia-Yu; Chang, Ya-Jen; Wu, Yu-Hsien; Lee, Wan-Chi; Yeh, Chung-Hsin; Lee, Te-Wei; Ting, Gann

    2008-11-01

    The pharmacokinetics and internal radionuclide therapy of intraperitoneally administrated (188)Re-N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA)-labeled pegylated liposomal doxorubicin ((188)Re-DXR-liposome) were investigated in the C26 murine colon carcinoma ascites mouse model. After intraperitoneal administration of the nanotargeted bimodality (188)Re-DXR-liposome, the ascites and tumor accumulation of the radioactivity were observed, the levels of radioactivity within the ascites were maintained at relatively higher levels before 48 h and the levels of radioactivity in the tumor were maintained at steady levels after 4 h. The AUC((o-->infinity)) of (188)Re-DXR-liposome in blood, ascites and tumor was 9.3-, 4.2- and 4.7-fold larger than that of (188)Re-BMEDA, respectively. The maximum tolerated dose of intraperitoneally administrated (188)Re-DXR-liposome was determined in normal BALB/c mice. The survival, tumor and ascites inhibition of mice after (188)Re-DXR-liposome (22.2 MBq of (188)Re, 5 mg/kg of DXR) treatment were evaluated. Consequently, radiochemotherapeutics of (188)Re-DXR-liposome attained better survival time, tumor and ascites inhibition (decreased by 49% and 91% at 4 days after treatment; Ppassive nanotargeted bimodality radiochemotherapeutics in oncology applications. PMID:19026950

  16. Intravascular β-irradiation with a liquid 188Re-filled balloon for the prevention of restenosis in rabbit model

    Objective: To investigate the effects of intravascular β-irradiation with a liquid 188Re-filled balloon on restenosis in rabbit model, and to evaluate the feasibility of the intravascular irradiation. Methods: The bilateral iliac arteries of 14 rabbits were injured by catheter balloon overdilation. A random side iliac artery of the rabbit was irradiated by a liquid 188Re-filled balloon with the radioactivity of 15 Gy at a depth of 0.5 mm beneath the skin close to the artery, and the other iliac artery served as a control. At 12 weeks after operation, quantitative angiography, histopathology and immunohistochemistry analysis were performed in the injured iliac arteries to evaluate the effects of irradiation. Results: There was significant increase in iliac artery diameter [(1.94 +- 0.19) vs (1.77 +- 0.28) mm, P2, P188Re-filled balloon irradiation group compared with control group. Conclusions: Intravascular β-irradiation by a liquid 188Re-filled balloon with 15 Gy at 0.5 mm tissue depth beneath the skin close to the artery in rabbit model could inhibit neointimal proliferation and prevent restenosis. The intravascular brachytherapy with irradiation for prevention of restenosis is technically feasible

  17. Pharmacokinetics, micro-SPECT/CT imaging and therapeutic efficacy of {sup 188}Re-DXR-liposome in C26 colon carcinoma ascites mice model

    Chen, L.-C.; Chang, C.-H.; Yu, C.-Y.; Chang, Y.-J.; Wu, Y.-H.; Lee, W.-C.; Yeh, C.-H.; Lee, T.-W. [Institute of Nuclear Energy Research, Taoyuan, Taiwan (China); Ting Gann [National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan (China)], E-mail: gann.ting@msa.hinet.net

    2008-11-15

    The pharmacokinetics and internal radionuclide therapy of intraperitoneally administrated {sup 188}Re-N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA)-labeled pegylated liposomal doxorubicin ({sup 188}Re-DXR-liposome) were investigated in the C26 murine colon carcinoma ascites mouse model. After intraperitoneal administration of the nanotargeted bimodality {sup 188}Re-DXR-liposome, the ascites and tumor accumulation of the radioactivity were observed, the levels of radioactivity within the ascites were maintained at relatively higher levels before 48 h and the levels of radioactivity in the tumor were maintained at steady levels after 4 h. The AUC{sub (o{yields}{infinity})} of {sup 188}Re-DXR-liposome in blood, ascites and tumor was 9.3-, 4.2- and 4.7-fold larger than that of {sup 188}Re-BMEDA, respectively. The maximum tolerated dose of intraperitoneally administrated {sup 188}Re-DXR-liposome was determined in normal BALB/c mice. The survival, tumor and ascites inhibition of mice after {sup 188}Re-DXR-liposome (22.2 MBq of {sup 188}Re, 5 mg/kg of DXR) treatment were evaluated. Consequently, radiochemotherapeutics of {sup 188}Re-DXR-liposome attained better survival time, tumor and ascites inhibition (decreased by 49% and 91% at 4 days after treatment; P<.05) in mice than radiotherapeutics of {sup 188}Re-liposome or chemotherapeutics of Lipo-Dox did. Therefore, intraperitoneal administration of novel {sup 188}Re-DXR-liposome could provide a benefit and promising strategy for delivery of passive nanotargeted bimodality radiochemotherapeutics in oncology applications.

  18. Intratumoral injection with [188Re]rhenium sulfide suspension for treatment of transplanted human liver carcinoma in nude mice

    Hepatocellular carcinoma (HCC) is one of the most common malignancies in China. Direct intratumoral injection of non removable radioactive material has been widely studied because it could deliver high doses of radiation to target sites and minimize radiation leakage to non-target organs or tissues. Thirty nude mice bearing SMMC 7721 human liver carcinoma were used for the biodistribution study after intratumoral injection of [188Re]rhenium sulfide suspension or sodium [188Re]perrhenate solution. Another 30 tumor-bearing mice were divided into six groups, four groups of which were treated with a 0.1 ml [188Re]rhenium sulfide suspension at doses of 3.7, 7.4, 18.5, 29.6 MBq by a single intratumoral injection. For control studies, to study the tumor inhibiting ratio, the remaining two groups were injected with nonradioactive rhenium sulfide suspension and Hanks' balanced salt solution, respectively. The injections were repeated 6 days later. The retention percentages of radioactivity (%ID) in tumors injected with [188Re]rhenium sulfide suspension were 90.96 ± 6.63%, 86.09 ± 22.58% and 87.62 ± 13.97% at 1, 24 and 48 h, respectively. Tumor inhibition ratios are as high as 89% when the outer space of tumor (0.5-0.6 cm from center) received about 507.6 Gy doses. Intratumoral injection of [188Re]rhenium sulfide suspension results in high tumor retention indicating this approach has strong potential for the treatment of hepatic carcinoma

  19. Development of 188Re-HEDP as radiopharmaceutical for palliative bone pain

    Full text: The optimized condition for labeling HEDP with Re-188 was assessed by wet labeling. The mixture solution of 10 mg HEDP, 3 mg SnCl2.2H2O, 4 mg Gentisic acid and 50 ?g of NH4ReO4 was labeled with 3- 10 mCi ReO-4 at pH1 with heating temperature at 100 ?C for 15 minutes. After adjusting pH to 5-6 with 0.3 M NaOAc pH 8 and NaOH, radiochemical purity of the labeled product was checked by TLC. Labeling efficiency was high as 98.88%. The HEDP ligand was prepared in form of lyophilized kits then labeled and controlled for labeling efficiency. Labeling yield of labeled HEDP kits were more than 94% for 5 months storage. Biodistribution of 188Re-HEDP in rat measured in % injected dose/g of bone at time 2, 4 and 24 hours was 1.372%, 1.302% and 1.154%, respectively

  20. Decay of 188Re and TRS calculations for its daughter nuclide 188Os

    The γ-ray spectra of 188Re decay have been studied by using a Compton-suppressed spectrometer and a three parameters γ-γ-T list coincidence system. Experimental data analysis demonstrated that six γ-rays at 557, 810, 1463, 1867, 1936 and 2022 keV and three levels at 1443, 1936 and 2022 keV are confirmed again. Seven new γ-rays at 309.60±0.04, 826.90±0.02, 979.29±0.08, 1103.7±0.4, 1828.2±0.1, 1842.5±0.2 and 1982.5±0.2 keV have been identified, three new levels at 309.60, 1828.2 and 1982.5 keV are assigned. The β- decay branching ratio is deduced. In addition, in order to study this γ-unstable nucleus, shape calculations using the Hartree–Fock–Bogoliubov-like formalism were carried out for positive-parity states in 188Os. The TRS plots reveal that, as the spin increases up the band, the triaxiality parameter γ changes. (author)

  1. Microwave assisted facile one-pot synthesis of 188Re-complex using a tetrahydroborate exchange resin. A bifunctional chelating agent for radiopharmaceuticals

    A facile one-pot synthesis of 188Re-complex as a bifunctional chelating agent for the preparation of therapeutic radiopharmaceuticals was accomplished with good labeling yields and radiochemical purity by using a tetrahydroborate exchange resin as a reducing agent for a disulfide ligand as well as the [188Re] perrhenate ion under microwave irradiation. (author)

  2. Preparation, biodistribution, and dosimetry of 188Re-Labeled MoAb ior cea1 and its f(ab')2 fragments by avidin-biotin strategy

    The biotinylated monoclonal antibody (MoAb) ior cea1 and its F(ab')2 fragments were labeled with Re-188 by combination of avidin-biotin strategy. 188Re-MoAb, 188Re-MoAb-biotin, 188Re-F(ab')2, and 188Re-F(ab')2-biotin preparations were produced for these studies with specific activities of 1.30±0.18 GBq/mg and from instant freeze-dried kit formulations using ethane-1-hydroxy-1,1-diphosphonic acid (EHDP) as a weak competing ligand. There were no significant differences (p>0.05) between the biodistribution in mice of biotinylated and unbiotinylated 188Re-labeled immunoconjugates. When avidin was injected as a chase after injection of 188Re-MoAb-biotin or 188Re-F(ab')2-biotin, the blood radioactivity level decreased approximately 75% (cumulated activity) and the effective dose decreased almost 25% with respect to that of the radioimmunoconjugates in which the chase effect was not used. Our results suggest that 188Re-labeled biotinylated MoAb ior cea1 and its F(ab')2 fragments prepared by this method are stable complexes in vivo

  3. Pharmacokinetics, dosimetry and comparative efficacy of 188Re-liposome and 5-FU in a CT26-luc lung-metastatic mice model.

    Chen, Liang-Cheng; Wu, Yu-Hsien; Liu, I-Hshiang; Ho, Chung-Li; Lee, Wan-Chi; Chang, Chih-Hsien; Lan, Keng-Li; Ting, Gann; Lee, Te-Wei; Shien, Jui-Hung

    2012-01-01

    The biodistribution, pharmacokinetics, dosimetry and comparative therapeutic efficacy of intravenously administrated (188)Re-N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA)-labeled pegylated liposome ((188)Re-liposome) and 5-FU were investigated in a CT26-luc lung-metastatic model. After intravenous administration of (188)Re-liposome, tumor accumulation from the radioactivity was observed. Levels of radioactivity in tumors were maintained at steady levels (from 5.40 to 5.67 %ID/g) after 4 to 24 h. In pharmacokinetics, the AUC((0→∞)), MRT((0→∞)) and Cl of (188)Re-liposome in blood via intravenous route were 998 h %ID/ml, 28.7 h and 0.1 ml/h, respectively. The total excreted fractions of feces and urine were 0.61 and 0.26, respectively. Absorbed doses for (188)Re-liposome in the liver and red marrow were 0.31 and 0.08 mSv/MBq, respectively. Tumor-absorbed doses for (188)Re-liposome ranged from 48.4 to 1.73 mGy/MBq at 10 to 300 g tumor spheres. In therapeutic efficacy, the survival times of mice after (188)Re-liposome [80% maximum tolerated dose (MTD); 29.6 MBq], 5-FU (80% MTD; 144 mg/kg), liposome or normal saline treatments were evaluated. Consequently, radiotherapeutics of (188)Re-liposome attained a longer lifespan (increase of 34.9%; P=.005) in mice than in the normal saline group. The increase in lifespan of the (188)Re-liposome group was 2.5-fold greater than that of the 5-FU group. Therefore, intravenous administration of (188)Re-liposome could provide a benefit and it is a promising strategy for delivery of passive nanotargeted radiotherapeutics in oncology applications. PMID:21958858

  4. Pharmacokinetics, dosimetry and comparative efficacy of 188Re-liposome and 5-FU in a CT26-luc lung-metastatic mice model

    The biodistribution, pharmacokinetics, dosimetry and comparative therapeutic efficacy of intravenously administrated 188Re-N,N-bis(2-mercaptoethyl)-N′,N′-diethylethylenediamine (BMEDA)-labeled pegylated liposome (188Re-liposome) and 5-FU were investigated in a CT26-luc lung-metastatic model. After intravenous administration of 188Re-liposome, tumor accumulation from the radioactivity was observed. Levels of radioactivity in tumors were maintained at steady levels (from 5.40 to 5.67 %ID/g) after 4 to 24 h. In pharmacokinetics, the AUC(0→∞), MRT(0→∞) and Cl of 188Re-liposome in blood via intravenous route were 998 h %ID/ml, 28.7 h and 0.1 ml/h, respectively. The total excreted fractions of feces and urine were 0.61 and 0.26, respectively. Absorbed doses for 188Re-liposome in the liver and red marrow were 0.31 and 0.08 mSv/MBq, respectively. Tumor-absorbed doses for 188Re-liposome ranged from 48.4 to 1.73 mGy/MBq at 10 to 300 g tumor spheres. In therapeutic efficacy, the survival times of mice after 188Re-liposome [80% maximum tolerated dose (MTD); 29.6 MBq], 5-FU (80% MTD; 144 mg/kg), liposome or normal saline treatments were evaluated. Consequently, radiotherapeutics of 188Re-liposome attained a longer lifespan (increase of 34.9%; P=.005) in mice than in the normal saline group. The increase in lifespan of the 188Re-liposome group was 2.5-fold greater than that of the 5-FU group. Therefore, intravenous administration of 188Re-liposome could provide a benefit and it is a promising strategy for delivery of passive nanotargeted radiotherapeutics in oncology applications.

  5. Biodistribution of 188Re-labeled stannic sulfur colloid in rabbit orthotopic liver cancer model by intratumoral injection

    Objective: To study the biodistribution of 188Re-labeled stannic sulfur colloid in rabbit orthotopic VX2 liver cancer model by intratumoral injection and to evaluate its potential for endoradiotherapy. Methods: 188Re-labeled stannic sulfur colloid was prepared with direct labeling method. The labeling efficiency and radiochemical purity were measured. Twelve rabbits xenografted by orthotopic VX2 liver cancer were used to determine the biodistribution of 188Re-labeled stannic sulfur colloid. Under CT guidance, 37 MBq (0.1 ml) 188Re-labeled stannic sulfur colloid was injected directly into the center of the tumor. Four rabbits were sacrificed after gamma imaging at 1, 24, 48 h post injection. The organ uptake was calculated as %ID/g, the absorbed dose and T/NT ratio were calculated. One-way analysis of variance was used to analyze the data. Results: The labeling efficiency of 188Re-labeled stannic sulfur colloid was (98.23±0.25)%. The radiochemical purity was (94.23±0.54) % at 48 h. The radioactivity essentially accumulated in the tumor area and remained trapped up to 48 h. The radioactivity in other organs was at background level. The T/NT ratios were 88.22± 11.57, 32.87±9.13 and 31.65± 10.11 at 1, 24 and 48 h post injection respectively, with the corresponding tumor uptakes of (43.318±11.931) %ID/g, (39.875±9.290) %ID/g and (37.761±6.849) %ID/g, which were much higher than those in normal tissues (F=77.350, 97.577, 417.072, all P<0.01). Radiation dose to the tumor was (88.12 ± 12.21) Gy. Conclusions: 188Re-labeled stannic sulfur colloid may have a stable distribution at the site of orthotopic VX2 liver cancer after intratumoral injection. Thus it may have potential for the endoradiotherapy of liver cancer. (authors)

  6. Development of methods of labeling pentavalent DMSA with {sup 99m}Tc and {sup 188}Re; Desenvolvimento de metodos para marcacao de DMSA pentavalente com {sup 99m}Tc e {sup 188}Re

    Brambilla, Tania de Paula, email: jtoniolo@ipen.br

    2009-07-01

    Technetium-99 m is the most useful radionuclide in diagnostic imaging procedures in Nuclear Medicine, more than 80 percent of radiopharmaceuticals are {sup 99m}Tc-labeled compounds. {sup 99m}Tc-DMSA(V) has been used for imaging of soft tissue, head and neck tumors. It shows a particularly high specificity for medullary thyroid carcinoma and bone metastases in a variety of cancers. Biodistribution studies of {sup 188}Re-DMSA(V) have shown that its general pharmacokinetic properties are similar to that of {sup 99m}Tc-DMSA(V), so this agent could be used for targeted radiotherapy of these tumors. The aim of this work is the development of methods of labeling DMSA(V) with {sup 99m}Tc and {sup 188}Re. {sup 99m}Tc-DMSA(V) can be prepared by two methods. One of them is the indirect one, through the use of a commercial kit of DMSA (III), by adjusting the pH from 2.5 to {approx} 8.5 with NaHCO{sub 3}. This method was evaluated and optimized presenting high labeling yields. The other method is the direct one, through the preparation of a lyophilised kit ready for labeling with {sup 99m}Tc, being the method of interest of this work, due to the easy of its clinical use. The most adequate formulation of the kit was: 1.71 mg of DMSA, 0.53 mg of SnCl{sub 2}.2H{sub 2}O and 0.83 mg of ascorbic acid (pH 9). Labeling yields higher than 95% were achieved labeling this kit with 1 to 2 m L of {sup 99m}Tc with activities up to 4736 MBq (128 mCi). The kit was stable up to 6 months and biodistribution studies confirmed the quality of the DMSA (V) labeled with {sup 99m}Tc using this kit. The reduction potential of Re is lower than the one for Tc, so the labeling conditions of {sup 188}Re-DMSA(V) are different from the ones used for {sup 99m}Tc- DMSA(V). {sup 188}Re-DMSA(V) is prepared in acid solution, that makes it possible to use the DMSA (III) commercial kit developed for labeling with {sup 99m}Tc, prepared in pH 2.5, for labeling with {sup 188}Re. Labeling yields higher than 95% were

  7. Studies on biodistribution and imaging of 188Re labeled insulin-like growth factor-1 analogue in nude mice bearing human pancreatic carcinoma

    Objective: To evaluate the biodistribution and planar gamma camera imaging characteristics of 188Re labeled insulin-like growth factor 1 analogue (188Re-IGF-1A) in tumor-bearing mice. Methods: (1)To label IGF-1A with 188Re directly and to determine the labeling efficiency. (2)To establish nude mice model which bearing human pancreatic carcinoma cell Patu8988. (3)To scan those nude mice at 15 min, 1 h, 4 h, 24 h, 3 d and 5 d after intratumor injection with 188Re-IGF-1A into their tumors. (4)To scan those nude mice at 15 min, 1 h, 2 h, 4 h and 24 h after intratumor injection with 188ReO4- into their tumors. To calculate the tumor to normal tissue ratio (T/NT) and the percentages of injected dose per gram tissue (%ID/g) of different organs. Results: (1)The labeling efficiency of 188Re-IGF-1A was (94.07 ± 0.32)%. (2)The largest uptake of tumors was (42.38 ± 17.82)%ID/g at 4 h after injection of 188Re-IGF-1A. Then the tumor to normal tissue ratios 5ncreased and the largest tumor to muscle ratio was 6531.79 ± 4930.26 at 5 d after injection. (3) 188ReO4- was major distributed in thyroid glands, stomachs, tumors and blood in nude mice after injection at first. Then %ID/g decreased rapidly in tumors. (4) The difference of %ID/g was significant (t=5.877, t=13.287, P188Re-IGF-1A group than in 188ReO4- group. The largest ratio of tumors in the two groups was 74.10 at 24 h after injection. (5) After being injected, 188Re-IGF-1A formed clear images in tumors, 5 d later, nothing but tumors can be seen. Conclusions: 188Re-IGF-1A has good affinity with human pancreatic cancer, and the tumor to muscle ratios in nude mice is high. So 188Re-IGF-1A is expected to be used for targeting therapy of human pancreatic carcinoma. (authors)

  8. Uptake of the 188Re(V)-DMSA complex by cervical carcinoma cells in nude mice: pharmacokinetics and dosimetry

    The uptake of the rhenium-188 (188Re(V)-DMSA) complex of dimercaptosuccinic acid by cervical carcinoma cells in nude mice was evaluated. The pharmacokinetics and dosimetry calculations in normal rats were also evaluated. The images obtained in mice did not show significant accumulation in metabolic organs and the biodistribution studies showed that 3.52±0.76% of the injected activity per gram (n=4) was taken up by the tumor. This percentage produces a cumulated activity of 35.63±8.40 MBq h and an equivalent dose per injected activity of 260±8.91 mSv/MBq. Pharmacokinetics and dosimetry of the 188Re(V)-DMSA complex indicate that this radiopharmaceutical could be evaluated in patients with soft tissue tumors, since the risk of radiation damage to the kidney or red bone marrow could not be an obstacle for its application in therapeutic nuclear medicine

  9. Studies of gel metal-oxide composite samples as filling materials for W-188/Re-188 generator column

    Iller, E.; Polkowska-Motrenko, H.; Lada, W.; Wawszczak, D.; Sypula, M.; Doner, K.; Konior, M.; Milczarek, J.; Zoladek, J.; Ráliš, Jan

    2009-01-01

    Roč. 281, č. 1 (2009), s. 83-86. ISSN 0236-5731. [9th International Conference on Nuclear Analytical Methods in the Life Sciences. Lisbon, 07.09.2008-12.09.2008] Institutional research plan: CEZ:AV0Z10480505 Keywords : W-188/Re-188 generator * W-Zr gels * W-Zr composites * Sol-gel process Subject RIV: CH - Nuclear ; Quantum Chemistry Impact factor: 0.631, year: 2009

  10. 188Re-labelled McAb 3H11 used as preventive for the peritoneal micro-metastasis of gastric cancer

    In advancing gastric cancer, especially when the serous is invaded, the plantation of cancer cells in peritoneal is common and it affects patients' survival time severely. Based on successfully labelled McAb (monoclonal antibody) 3H11 with 188Re, the authors investigated the effect of RIT (Radio-immuno-Therapy) with 188Re-3H11 on preventing the peritoneal micro-metastasis of gastric cancer cells in nude mice to increase the survival time. After 1 x 106 BGC-823 gastric cancer cells were injected into the peritoneal cavity of each mouse, 45BABL/C nude mice were divided into 9 groups. Each group received different doses of 188Re-3H11 or 188Re-IgG, or saline I.P.16 hours post operation. The injected volume of each mouse was 1.0 mL. The results showed that the survival time depended on the injected dose during 0 to 37 MBq. The survival time was 170 +- 25.3 d after 37 MBq 188Re-3H11 were treated. It was over 5 times more than that for the saline group and about 3 times more than that for 37 MBq 188-Re IgG group (p 188Re-3H11 I.P. is effective and safe for the prevention of intra-peritoneal injected gastric cancer cells from surviving, growing and disseminating in nude mice

  11. Prediction of the correct measured activity of {sup 186}Re and {sup 188}Re from reactor produced natural rhenium using an artificial neural network

    Leila Moghaddam, B., E-mail: lmoghaddam@aut.ac.i [Faculty of Nuclear Engineering and Physics, Amirkabir Technical University (Tehran Polytechnic), Hafez Street, Tehran (Iran, Islamic Republic of); Setayeshi, Saeed; Maragheh, Mohammad G.; Gholipour, Reza [Faculty of Nuclear Engineering and Physics, Amirkabir Technical University (Tehran Polytechnic), Hafez Street, Tehran (Iran, Islamic Republic of)

    2009-11-15

    To optimize the cost effectiveness of {sup 186}Re and {sup 188}Re production, which have recently been used as radio pharmaceuticals for therapeutic purposes, we designed an artificial neural network (ANN) to evaluate the activity of combined {sup 186}Re + {sup 188}Re. One of the production ways is the (n,gamma) reaction of natural rhenium which leads to combined {sup 186}Re + {sup 188}Re. Using the counted activity of {sup 186}Re + {sup 188}Re mixtures by a well type isotope calibrator, the precise activity of {sup 186}Re and {sup 188}Re is obtained by the ANN. A back-propagation ANN was trained using 30 activities of mixed {sup 186}Re + {sup 188}Re. The performance of the ANN was tested by Early-Stopping validation method, and the ANN was optimized with respect to its architecture. The response of the ANN shows significant precision that may be used for medical application of {sup 186}Re + {sup 188}Re mixtures.

  12. {sup 99m}Tc/{sup 188}Re-labelled lipid nanocapsules as promising radiotracers for imaging and therapy: formulation and biodistribution

    Ballot, Sandrine; Noiret, Nicolas; Rajerison, Holisoa [Institut de Chimie de Rennes, Ecole Nationale Superieure de Chimie de Rennes UMR CNRS 6052 ' Syntheses et Activations de Biomolecules' , Rennes-Beaulieu (France); Hindre, Francois; Denizot, Benoit; Benoit, Jean-Pierre [Ingenierie de la Vectorisation Particulaire' , Inserm U 646, Angers (France); Garin, Etienne [Centre Eugene Marquis, Service de Medecine Nucleaire, Rennes (France)

    2006-05-15

    This study focusses on a promising carrier system for imaging and therapeutic purposes using lipid nanocapsules. To assess their potential for clinical use, we labelled nanocapsules with {sup 99m}Tc and {sup 188}Re and analysed some kinetic biodistribution parameters after intravenous injection in rats. Lipophilic complexes [{sup 99m}Tc/{sup 188}Re(S{sub 3}CPh){sub 2}(S{sub 2}CPh)] ({sup 99m}Tc/{sup 188}Re-SSS) were encapsulated within the nanoparticles during their manufacture with quantitative yield and satisfactory radiochemical purity. Rats were injected intravenously with 3.7 MBq {sup 99m}Tc/{sup 188}Re-labelled nanocapsules and sacrificed at 5, 15 and 30 min and 1, 2, 4, 8, 12, 16, 20 and 24 h. Dynamic scintigraphic acquisitions showed predominant hepatic uptake, and ex vivo counting indicated a long circulation time of labelled nanocapsules, with a half-life of 21{+-}1 min for {sup 99m}Tc and 22{+-}2 min for {sup 188}Re. Very weak urinary elimination was observed, indicating good stability of {sup 99m}Tc and {sup 188}Re labelling. {sup 99m}Tc/{sup 188}Re-SSS nanocapsules can be obtained with high yield and satisfactory radiochemical purity. The biodistributions of {sup 99m}Tc/{sup 188}Re-labelled nanocapsules are close to those of classical PEG-coated particles and show good stability of {sup 188}Re/{sup 99m}Tc-SSS labelling. (orig.)

  13. Study on radiolabeling of 1, 2, 3-triazole analogs with fac-[188Re(CO)3(H2O)3]+ via click chemistry

    Click chemistry was used to study on radiolabeling of 1, 2, 3-triazole analogs with. fac-[188Re(CO)3(H2O)3]+. CuSO4/L-sodium ascorbate was chosen as the catalyst system, three terminal alkynes were conjugated with two different azides respectively, and then the new prepared fac-[188Re(CO)3(H2O)3]+ was coordinated to the six triazoles. The results showed that the radiochemical yields (RCY) of the conjugation of fac-[188Re(CO)3]+ with six triazoles were over 90%, and the triazoles showed high stability in phosphate-buffered saline and new-born calf serum. The preliminary biological evaluation results showed that the new 188Re-labeling method via click chemistry could have general application in labeling bioactive molecules in high radiochemical yield and high specific activity for further SPECT research. (authors)

  14. Evaluation of 188Re-labeled PEGylated nanoliposome as a radionuclide therapeutic agent in an orthotopic glioma-bearing rat model

    Huang FYJ

    2015-01-01

    Full Text Available Feng-Yun J Huang,1 Te-Wei Lee,2 Chih-Hsien Chang,2 Liang-Cheng Chen,2 Wei-Hsin Hsu,2 Chien-Wen Chang,1 Jem-Mau Lo1 1Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan; 2Institute of Nuclear Energy Research, Longtan, Taiwan Purpose: In this study, the 188Re-labeled PEGylated nanoliposome (188Re-liposome was prepared and evaluated as a therapeutic agent for glioma.Materials and methods: The reporter cell line, F98luc was prepared via Lentivector expression kit system and used to set up the orthotopic glioma-bearing rat model for non-invasive bioluminescent imaging. The maximum tolerated dose applicable in Fischer344 rats was explored via body weight monitoring of the rats after single intravenous injection of 188Re-liposome with varying dosages before the treatment study. The OLINDA/EXM 1.1 software was utilized for estimating the radiation dosimetry. To assess the therapeutic efficacy, tumor-bearing rats were intravenously administered 188Re-liposome or normal saline followed by monitoring of the tumor growth and animal survival time. In addition, the histopathological examinations of tumors were conducted on the 188Re-liposome-treated rats.Results: By using bioluminescent imaging, the well-established reporter cell line (F98luc showed a high relationship between cell number and its bioluminescent intensity (R2=0.99 in vitro; furthermore, it could also provide clear tumor imaging for monitoring tumor growth in vivo. The maximum tolerated dose of 188Re-liposome in Fischer344 rats was estimated to be 333 MBq. According to the dosimetry results, higher equivalent doses were observed in spleen and kidneys while very less were in normal brain, red marrow, and thyroid. For therapeutic efficacy study, the progression of tumor growth in terms of tumor volume and/or tumor weight was significantly slower for the 188Re-liposome-treated group than the control group (P<0.05. As a result, the

  15. Radiosynthesis and evaluation of 188Re-c(RGDyK)-His as a novel radiotherapeutic agent for integrin αvβ3 targeting tumour

    The successes of noninvasive methods to visualize and quantify integrin αvβ3 expression in vivo have paved the way for radiolabeling anti-integrin therapy in clinic. Arginine-glycine-aspartice (RGD) peptide and related derivatives labeled with radionuclides for radio-therapy, which specifically targeting integrin αvβ3-positive tumors, could be used to treat these tumors. We have labeled c(RGDyK)-His, a RGD derivative, with 188Re and the radio-therapy efficiency has been evaluated in model nude mice. c(RGDyK)-His was labeled with 188Re by chelating with [188Re(CO)3(H2O)3]+ under a slightly basic condition. The in vitro specific binding affinity to U87 MG cell lines and the biodistribution of 188Re-c(RGDyK)-His in the animal tumor models was measured. The inhibitory effects of 188Re-c(RGDyK)-His were observed more than 1 month, and evaluated by microPET/CT imaging with 18F-FDG. Results of in vivo, cell uptake demonstrated 188Re-c(RGDyK)-His had a high specific binding affinity to receptor integrin αvβ3. In biodistribution experiment, 188Re-c(RGDyK)-His was accumulated in the tumor and cleared fast from the normal tissues. In radiotherapy study, tumor growth inhibition was significantly higher in the treatment groups than in the control groups. These studies showed that 188Re-c(RGDyK)-His could be effectively used for integrin αvβ3 targeting therapy. This may offer a potential therapeutic strategy for the treatment of integrin-positive tumors in clinic. (author)

  16. Therapeutic efficacy and microSPECT/CT imaging of {sup 188}Re-DXR-liposome in a C26 murine colon carcinoma solid tumor model

    Chang, Y.-J.; Chang, C.-H.; Yu, C.-Y.; Chang, T.-J.; Chen, L.-C. [Institute of Nuclear Energy Research, Taoyuan, Taiwan (China); Chen, M.-H. [National Health Research Institutes, Miaoli, Taiwan (China); Lee, T.-W. [Institute of Nuclear Energy Research, Taoyuan, Taiwan (China); Ting Gann [National Health Research Institutes, Miaoli, Taiwan (China)], E-mail: gann.ting@msa.hinet.net

    2010-01-15

    Nanocarriers can selectively target cancer sites and carry payloads, thereby improving diagnostic and therapeutic effectiveness and reducing toxicity. The objective of this study was to investigate the therapeutic efficacy of a new co-delivery radiochemotherapeutics of {sup 188}Re-N,N-bis (2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA)-labeled pegylated liposomal doxorubicin (DXR) ({sup 188}Re-DXR-liposome) in a C26 murine colon carcinoma solid tumor model. To evaluate the targeting and localization of {sup 188}Re-DXR-liposome in C26 murine tumor-bearing mice, biodistribution, microSPECT/CT imaging and pharmacokinetic studies were performed. The antitumor effect of {sup 188}Re-DXR-liposome was assessed by tumor growth inhibition, survival ratio and histopathological hematoxylin-eosin staining. The tumor target and localization of the nanoliposome delivery radiochemotherapeutics of {sup 188}Re-DXR-liposome were demonstrated in the biodistribution, pharmacokinetics and in vivo nuclear imaging studies. In the study on therapeutic efficacy, the tumor-bearing mice treated with bimodality radiochemotherapeutics of {sup 188}Re-DXR-liposome showed better mean tumor growth inhibition rate (MGI) and longer median survival time (MGI=0.048; 74 days) than those treated with radiotherapeutics of {sup 188}Re-liposome (MGI=0.134; 60 days) and chemotherapeutics of Lipo-Dox (MGI=0.413; 38 days). The synergistic tumor regression effect was observed with the combination index (CI) exceeding 1 (CI=1.145) for co-delivery radiochemotherapeutics of {sup 188}Re-DXR-liposome. Two (25%) of the mice treated with radiochemotherapeutics were completely cured after 120 days. The therapeutic efficacy of radiotherapeutics of {sup 188}Re-liposome and the synergistic effect of the combination radiochemotherapeutics of {sup 188}Re-DXR-liposome have been demonstrated in a C26 murine solid tumor animal model, which pointed to the potential benefit and promise of the co-delivery of

  17. Monte Carlo microdosimetry of {sup 188}Re- and {sup 131}I-labelled anti-CD20

    Torres-GarcIa, E [Coordinacion de Posgrado, Facultad de Medicina, Universidad Autonoma del Estado de Mexico, Paseo Tollocan S/N, Toluca, Estado de Mexico 50180 (Mexico); Garnica-Garza, H M [Coordinacion de Posgrado, Facultad de Medicina, Universidad Autonoma del Estado de Mexico, Paseo Tollocan S/N, Toluca, Estado de Mexico 50180 (Mexico); Ferro-Flores, G [Instituto Nacional de Investigaciones Nucleares, Carretera Mexico-Toluca, Ocoyoacac, Estado de Mexico 52750 (Mexico)

    2006-10-07

    The radiolabelled monoclonal antibody anti-CD20 has the property of binding to the CD20 antigen expressed on the cell surface of B-lymphocytes, thus making it a useful tool in the treatment of non-Hodgkin's lymphoma. In this work, the event-by-event Monte Carlo code NOREC is used to calculate the single-event distribution function f{sub 1}(z) in the cell nucleus using the beta spectra of the {sup 188}Re and {sup 131}I radionuclides. The simulated geometry consists of two concentric spheres representing the nucleus and the cell surface embedded in a semi-infinite water medium. An isotropic point source was placed on the cell surface to simulate the binding of the anti-CD20 labelled with either {sup 188}Re or {sup 131}I. The simulations were carried out for two combinations of cell surface and nucleus radii. A method was devised that allows one to calculate the contribution of betas of energy greater than 1 MeV, which cannot be simulated by the NOREC code, to the single-event distribution function. It is shown that disregarding this contribution leads to an overestimation of the frequency-mean specific energy of the order of 9-12%. In general, the antibody radiolabelled with {sup 131}I produces single-event distribution functions that yield higher frequency-mean specific energies. (note)

  18. An experimental study on the treatment of nude mice with liver carcinoma by intratumoral injection with 188Re rhenium sulfide suspension

    Objective: To prepare a [188Re] rhenium sulfide suspension and to evaluate its therapeutic effects on liver carcinoma by intratumoral injection. Methods: 30 nude mice bearing SMMC-7721 human liver carcinoma were used for the biodistribution study after intratumoral injection of [188Re] rhenium sulfide suspension or sodium [188Re] perrhenate solution. Another 30 tumor-bearing nude mice were divided into six groups, four groups of them were treated with a 0.1 mL [188Re] rhenium sulfide suspension at doses of 3.7, 7.4, 18.5, 29.6 MBq by a single intratumoral injection. For control studies, the remaining two groups were injected with nonradioactive rhenium sulfide suspension and Hanks' balanced salt solution, respectively. Every injection was repeated 6 days later. Results: The retention percentages of radioactivity (% ID) in tumors injected with [188Re] rhenium sulfide suspension were (90.96 +- 6.63)%, (86.09 +- 22.58)% and (87.62 +- 13.97)% at 1, 24 and 48 h, respectively, which were much higher than retention in normal organs evaluated. In the case of sodium 188Re-perrhenate solution, the % ID values were only (1.66 +- 0.35)%, (0.02 +- 0.01)% and (0.01 +- 0.01)%, respectively. Tumor inhibition ratios were as high as 89% when the peripheral portion of tumor (0.5 - 0.6 cm from center) absorbed an activity share of about 507.6 Gy . Conclusion: Intratumoral injection of [188Re] rhenium sulfide suspension results in significant tumor restraint and it is indicated that this is a highly potential approach to the treatment of hepatic carcinoma

  19. A Freeze-Dried Kit for the Preparation of (188)Re-HEDP for Bone Pain Palliation: Preparation and Preliminary Clinical Evaluation.

    Mallia, Madhava B; Shinto, Ajit Sugunan; Kameswaran, Mythili; Kamaleshwaran, Koramadai Karuppusamy; Kalarikal, Radhakrishnan; Aswathy, K K; Banerjee, Sharmila

    2016-05-01

    (188)Re-HEDP is an established radiopharmaceutical used for pain palliation in patients with osseous metastasis. Considering commercial availability of (188)W/(188)Re generator, the accessibility to a lyophilized kit would make preparation of this radiopharmaceutical feasible at the hospital radiopharmacy having access to a generator. A protocol for the preparation of a single-vial lyophilized hydroxyethane 1,1-diphosphonic acid (HEDP) kit was developed and its consistency was checked by preparing six batches. Each sterile lyophilized kit prepared as per the protocol contained 9 mg of HEDP, 3 mg of gentisic acid, and 4 mg of SnCl2.2H2O. Randomly selected kits from all six batches were subjected to thorough quality control tests that were passed by all batches. (188)Re-HEDP could be prepared by addition of 1 mL of freshly eluted Na(188)ReO4 (up to 3700 MBq) containing 1 μmol of carrier ReO4(-) (perrhenate) and heating at 100°C for 15 minutes. (188)Re-HEDP with >95% radiochemical purity could be consistently prepared using the lyophilized kits. Sterile (188)Re-HEDP prepared using the lyophilized kit was evaluated in patients with osseous metastasis. Post-therapy images of the patient were compared with (99m)Tc-MDP bone scan and found to be satisfactory. The bone-to-background as well as tumor-to-normal bone uptake ratio was found to be significant. All patients who received therapy reported significant pain relief within a week to 10 days post-administration of (188)Re-HEDP. PMID:27183437

  20. {sup 188}Re-HEDP combined with capecitabine in hormone-refractory prostate cancer patients with bone metastases: a phase I safety and toxicity study

    Lam, Marnix G.E.H. [University Medical Center Utrecht, Department of Nuclear Medicine, Utrecht (Netherlands); University Medical Center Utrecht, Department of Radiology and Nuclear Medicine, P.O. Box 85500, Utrecht (Netherlands); Bosma, Tjitske B.; Rijk, Peter P. van [University Medical Center Utrecht, Department of Nuclear Medicine, Utrecht (Netherlands); Zonnenberg, Bernard A. [UMC Utrecht, Department of Internal Medicine, Utrecht (Netherlands)

    2009-09-15

    {sup 188}Re-HEDP is indicated for the treatment of pain in patients with painful osteoblastic bone metastases, including hormone-refractory prostate cancer patients. Efficacy may be improved by adding chemotherapy to the treatment regimen as a radiation sensitizer. The combination of {sup 188}Re-HEDP and capecitabine (Xeloda registered) was tested in a clinical phase I study. Patients with hormone-refractory prostate cancer were treated with capecitabine for 14 days (oral twice daily in a dose escalation regimen with steps of 1/3 of 2,500 mg/m{sup 2} per day in cohorts of three to six patients, depending on toxicity). Two days later patients were treated with 37 MBq/kg {sup 188}Re-HEDP as an intravenous injection. Six hours after treatment post-therapy scintigraphy was performed. Urine was collected for 8 h post-injection. Follow-up was at least 8 weeks. The primary end-point was to establish the maximum tolerable dose (MTD) of capecitabine when combined with {sup 188}Re-HEDP. Secondary end-points included the effect of capecitabine on the biodistribution and pharmacokinetics of {sup 188}Re-HEDP. Three patients were treated in the first and second cohorts, each without unacceptable toxicity. One of six patients in the highest cohort experienced unacceptable toxicity (grade 4 thrombopaenia). The MTD proved to be the maximum dose of 2,500 mg/m{sup 2} per day capecitabine. No unexpected toxicity occurred. Capecitabine had no effect on uptake or excretion of {sup 188}Re-HEDP. Capecitabine may be safely used in combination with {sup 188}Re-HEDP in a dose of 2,500 mg/m{sup 2} per day and 37 MBq/kg, respectively. Efficacy will be further studied in a phase II study using these dosages. (orig.)

  1. Biodistribution and pharmacokinetics of 188Re-liposomes and their comparative therapeutic efficacy with 5-fluorouracil in C26 colonic peritoneal carcinomatosis mice

    Tsai CC

    2011-10-01

    Full Text Available Chia-Che Tsai1, Chih-Hsien Chang1, Liang-Cheng Chen1, Ya-Jen Chang1, Keng-Li Lan2, Yu-Hsien Wu1, Chin-Wei Hsu1, I-Hsiang Liu1, Chung-Li Ho1, Wan-Chi Lee1, Hsiao-Chiang Ni1, Tsui-Jung Chang1, Gann Ting3, Te-Wei Lee11Institute of Nuclear Energy Research, Taoyuan, 2Cancer Center, Taipei Veterans General Hospital, Taipei, 3National Health Research Institutes, Taipei, Taiwan, ROCBackground: Nanoliposomes are designed as carriers capable of packaging drugs through passive targeting tumor sites by enhanced permeability and retention (EPR effects. In the present study the biodistribution, pharmacokinetics, micro single-photon emission computed tomography (micro-SPECT/CT image, dosimetry, and therapeutic efficacy of 188Re-labeled nanoliposomes (188Re-liposomes in a C26 colonic peritoneal carcinomatosis mouse model were evaluated.Methods: Colon carcinoma peritoneal metastatic BALB/c mice were intravenously administered 188Re-liposomes. Biodistribution and micro-SPECT/CT imaging were performed to determine the drug profile and targeting efficiency of 188Re-liposomes. Pharmacokinetics study was described by a noncompartmental model. The OLINDA|EXM® computer program was used for the dosimetry evaluation. For therapeutic efficacy, the survival, tumor, and ascites inhibition of mice after treatment with 188Re-liposomes and 5-fluorouracil (5-FU, respectively, were evaluated and compared.Results: In biodistribution, the highest uptake of 188Re-liposomes in tumor tissues (7.91% ± 2.02% of the injected dose per gram of tissue [%ID/g] and a high tumor to muscle ratio (25.8 ± 6.1 were observed at 24 hours after intravenous administration. The pharmacokinetics of 188Re-liposomes showed high circulation time and high bioavailability (mean residence time [MRT] = 19.2 hours, area under the curve [AUC] = 820.4%ID/g*h. Micro-SPECT/CT imaging of 188Re-liposomes showed a high uptake and targeting in ascites, liver, spleen, and tumor. The results were correlated with

  2. Treatment of transplanted tumor of lung adenocarcinoma A549 transfected by human somatostatin receptor subtype 2 (hsstr2) gene with 188Re-RC-160

    Background and aim: Radionuclide-labeled somatostatin analogues selectively target somatostatin receptor (SSTR)-expressing tumors as a basis for diagnosis and treatment of these tumors. To those tumors without somatostatin receptor expressed, the hSSTR2 gene was transfected. Express of the hSSTR2 receptor was imaging and the radiotherapeutic effect was evaluated with 188Re-RC-160. Methods: The stable hSSTR2-expressing A549 cells (pcDNA3-hSSTR2 A549) and non-somatostatin receptor expressing A549 cells (pcDNA3 A549) were selected by western blot. Later, a corresponding animal tumor model was established. Expression of the hSSTR2 reporter was imaged using 188Re-RC-160 recognition. Tumors were evaluated for somatostatin receptor expression using immunohistochemistry. The distribution of 188Re-RC-160 in the animal tumor model was measured and the inhibitory effects of 188Re-RC-160 were evaluated by measurement of tumor growth and hematoxylin and eosin and TdT mediated dUTP nick end labeling (TUNEL) staining. Results: In vivo radioimaging revealed specific targeting of 188Re-RC-160 to tumors derived from pcDNA3- hSSTR2 A549 cells, compared to those from pcDNA3 A549 cells. pcDNA3- hSSTR2 A549 tumor growth inhibition was significantly higher in the single 7.4 MBq 188Re-RC-160 treatment group than in the 2x7.4 MBq rhenium-188, RC-160 group, control group, and pcDNA3 A549 tumors (P188Re-RC-160), induced significantly increased tumor-growth inhibition compare with single 7.4 MBq 188Re-RC-160 treatment (P188Re-RC-160 could be effectively used for targeting therapy the A549-derived tumors exogenously expressing hSSTR2, which will offers a potential therapeutic strategy for the treatment of somatostatin receptor-negative cancers.

  3. Internal Dosimetry in therapy with 90Y

    Introduction: 90Y has shown satisfactory results in the therapy of multiple oncological diseases. This radionuclide has been widely used in therapy of diseases such as NHL (Zevalin), TNE (90Y-DOTATOC), liver cancer, etc. Its safe and effective use presupposes the availability of accurate dosimetry methods and reproducible.El objective of this work is to standardize and optimize images use procedures that allow for dosimetric estimates braking during therapy of malignant diseases 90Y. Materials and Methods: To quantify the activity in absolute units from scans correction methods that consider the peculiarities of the bremsstrahlung of 90Y were proposed. acquisition parameters such as the selection of the collimator and the definition of energy windows as well as methods of scatter correction, attenuation, interactions of radiation with the collimator (septal penetration and degradation of information with distance) were considered and sensitivity or calibration factor was estimated. They were evaluated and calibrated parameters for dosimetry at the level of organ and estimates of distributions 3D dose, using experimental measurements with SPECT Mediso Nucline ™ Spirit DH-V system and simulations were performed using the Monte Carlo method, using the SIMIND v5 software .0. Results: The optimum position-energy window width and collimator to be used is determined from the relationship between total photons and primary photons (T / P), calculated with SIMIND. The results were favorable to employ HEGP collimator and energy window between 90-170kev. the sensitivity of the system for the selected collimator (HEGP for 90Y) was estimated. He was evaluated and determined the MTF order to correct dispersive plane images, the source-detector and interactions of radiation with the collimator distance, using filtering methods (Wiener filter), including empirical estimates of the SNR component. Similarly the procedure for the use of transmission maps obtained from standardized

  4. Production of 188-Re Sulphide Colloid for Knee Joints Arthritis Treatment and Acidity, Molar Ratio and Ultrasonic Time Optimization

    In this study, 188-Re sulphide colloid was synthesized as a radio synovectomy agent by reduction of sodium thiosulfate in the presence of perrhenate. The influences of the acidity, molar ratio and ultrasonic time on the colloid properties were investigated from 0.1 to 5 mol L-1; 5 to 70; and 10 to 60 min, respectively. The criteria for optimization of the influencing factors were the particle size and radiolabeling yield. Based on these factors the selected conditions were 1M HCl, thiosulfate to perrhenate molar ratio of 35 and 45 min for the ultrasonic time. The sizes of the particles were in the range of 1 to 5μm for more than 95% of the particles. The radionuclidic and radiochemical purity were found to be more than 99%. In addition, the synthesized colloid was stable for 5 days.

  5. Evaluation of safe use of 188Re-HEDP comparing urine data and whole body counting in gamma camera

    Cancer is the second more frequent cause of death, after cardiovascular disease, in developing countries. Most of adult patients with neoplasms will develop skeletal metastases that can lead to progressive pain. 188Re emits both beta particles suitable for therapy and a gamma ray (155 keV), adequate for diagnostic imaging in order to verify localization in the pain areas associated to metastatic process. The aim of this work was to correlate 188Re-HEDP dose estimations using biological samples and direct measures. All the patients had breast or prostate cancer, with bone metastases. Each patient received a tracer dose of 185 MBq of radiopharmaceutical. Urine samples were collected at 0-1, 1-2, 2-4 and, 4-6 hours post administration, and measured in dose calibrator. Whole body counts were acquired using a camera without collimator, window centered at 155 KeV, matrix 256 x 256, during 60 seconds. Data were obtained at 1 and 6 hours post administration with the patient in sitting position at 2 meter from the detector. Percentage of injected dose was calculated both for urine samples and image for each patient. The number of disintegrations was determined for organs in which higher concentration of activity was observed: those involved in the excretion, red marrow and the reminder of the body. Total doses were estimated using OLINDA/EXM software. Conclusions: Data showed that the organs chosen as more compromised during the tracer dose procedure received very low effective doses. A good correlation between calculations performed both for image and urine samples was obtained. Safety of the radiopharmaceutical was also verified using this method. (author)

  6. A YAP camera for the biodistribution of {sup 188}Re conjugated with Hyaluronic-Acid in 'in vivo' systems

    Antoccia, A. [Department of Biology, Roma3 University (Italy); INFN, Roma3 (Italy); Baldazzi, G. [Department of Physics, Bologna University (Italy); INFN, Bologna (Italy); Banzato, A. [Department of Oncology and Surgical Sciences, Padova University (Italy); Bello, M. [INFN, National Laboratories, Legnaro (Italy); Department of Physics, Padova University (Italy); Boccaccio, P. [INFN, National Laboratories, Legnaro (Italy); Bollini, D. [Department of Physics, Bologna University (Italy); INFN, Bologna (Italy); De Notaristefani, F. [INFN, Roma3 (Italy); Department of Electronic Engineering, Roma3 University and INFN (Italy); Mazzi, U. [Department of Pharmaceutical Sciences, Padova University (Italy); Alafort, L.M. [Department of Pharmaceutical Sciences, Padova University (Italy); Moschini, G. [INFN, National Laboratories, Legnaro (Italy); Department of Physics, Padova University (Italy); Navarria, F.L. [Department of Physics, Bologna University (Italy); INFN, Bologna (Italy); Pani, R. [Department of Experimental Medecine and Pathology, Roma1 University (Italy); INFN, Roma1 (Italy); Perrotta, A. [INFN, Bologna (Italy)]. E-mail: perrotta@bo.infn.it; Rosato, A. [Department of Oncology and Surgical Sciences, Padova University (Italy); Istituto Oncologico Veneto, Padova (Italy); Tanzarella, C. [Department of Biology, Roma3 University (Italy); Uzunov, N.M. [INFN, National Laboratories, Legnaro (Italy); Dept. Natural Sciences, Shumen Univ. (Bulgaria)

    2007-02-01

    The aim of the SCINTIRAD experiment is to determine the radio-response of {sup 188}Rhenium (Re) in in vitro cells and the biodistribution in different organs of in vivo mice, and subsequently to assess the therapeutic effect on liver tumours induced in mice. Both the {gamma}- and {beta}- emissions of {sup 188}Re have been exploited in the experiment. The in vivo biodistribution in mice was studied also with a {gamma}-camera using different parallel hole collimators. In the {sup 188}Re spectrum, while the 155 keV {gamma}-peak is useful for imaging, the photons emitted at larger energies and the {beta}-particles act as noise in the image reconstruction. The {gamma}-cameras previously used to image biodistributions obtained with {sup 99}Tc are, therefore, not optimized for use with {sup 188}Re. A new setup of the {gamma}-camera has been studied for {sup 188}Re: 66x66 YAP:Ce crystals (0.6x0.6x10 mm{sup 3}, 5 {mu}m optical insulation) guarantee a FOV of 40x40 mm{sup 2}, a Hamamatsu R2486 PSPMT, 3 in. diameter, converts their light into an electrical signal and allows reconstructing the spatial coordinates of the light spot; incoming photon directions are selected through a lead collimator with 1.5 mm diameter hexagonal holes, 0.18 mm septa, 40 mm thickness. Using this setup, results have been obtained both with {sup 99}Tc filled and {sup 188}Re filled capillaries and wells. The energy spectrum of the collected photons and the spatial resolutions obtainable with the {sup 188}Re source will be presented.

  7. 188Re-HEDP combined with capecitabine in hormone-refractory prostate cancer patients with bone metastases: a phase I safety and toxicity study

    Lam, Marnix G.E.H.; Bosma, Tjitske B.; Rijk, Peter P. van; Zonnenberg, Bernard A.

    2009-01-01

    Purpose 188Re-HEDP is indicated for the treatment of pain in patients with painful osteoblastic bone metastases, including hormone-refractory prostate cancer patients. Efficacy may be improved by adding chemotherapy to the treatment regimen as a radiation sensitizer. The combination of 188Re-HEDP and capecitabine (Xeloda®) was tested in a clinical phase I study. Methods Patients with hormone-refractory prostate cancer were treated with capecitabine for 14 days (oral twice daily in a dose esca...

  8. 2012 Rose Site 32P

    US Fish and Wildlife Service, Department of the Interior — Underwater Site 32P was established off Rose Atoll, American Samoa by Dr. James Maragos, U.S. Fish & Wildlife Service, on August 2, 2004. With a start point...

  9. 2004 Rose Site 32P

    US Fish and Wildlife Service, Department of the Interior — Underwater Site 32P was established off Rose Atoll, American Samoa by Dr. James Maragos, U.S. Fish & Wildlife Service, on August 2, 2004. With a start point...

  10. Labeling , in -Vitro Stability and Biological Distribution of 188 Re- Ethylenediamine- N,N,N,N,-tetrakis (Methylene Phosphonic) Acid complex

    Labeling of ethylenediamine-N,N,N,N-tetrakis (methylene phosphonic) acid (EDTMP) with rhenium -188 was investigated. Stannous chloride was used as a reducing agent for the reduction of 188 ReO4. Dependence of the yield of 188Re-EDTMP complex upon the concentration of EDTMP, tin (II) content, reaction time, amount of antioxidant, Ph, reaction temperature and adding of carrier was examined. The optimum condition that given high labeling yield of 188 Re-EDTMP complex (95.8% with carrier - free rhenium and 97% with carrier-added rhenium) was achieved using 40 mg EDTMP, 0.8 mg Sn(II),Ph=0.8, reaction temperature 100 degree and 5 min reaction time. the amount of carrier added equal to 200 μg KReO4 Furthermore, 188Re-EDTMP complex prepared at 100 degree is more stable than that prepared at 30 degree and the carrier added 188R-EDTMP complex is more stable than the no carrier added complex

  11. Three-dimensional personalized dosimetry for 188Re liver selective internal radiation therapy based on quantitative post-treatment SPECT studies

    Shcherbinin, S.; Grimes, J.; Bator, A.; Cwikla, J. B.; Celler, A.

    2014-01-01

    We demonstrate that accurate patient-specific distributions of microspheres labeled with 188Re and resulting absorbed doses can be obtained from single-photon emission computed tomography (SPECT) studies performed after 188Re selective internal radiation therapy when accurate correction methods are employed in image reconstruction. Our quantitative image reconstruction algorithm includes corrections for attenuation, resolution degradations and scatter as well as a window-based compensation for contamination. The procedure has been validated using four phantom experiments containing an 18 ml cylindrical source (82-93 MBq of 188Re activity) simulating a liver tumor. In addition, we applied our approach to post-therapy SPECT studies of ten patients with progressive primary or metastatic liver carcinomas. Our quantitative algorithm accurately (within 9%) recovered 188Re activity from four phantom experiments. In addition, for two patients that received three scans, deviations remained consistent between the measured and the reconstructed activities that were determined from studies with differing severity of the dead-time effect. The analysis of absorbed doses for patient studies allowed us to hypothesize that D90 (the minimum dose received by 90% of the tumor volume) may be a reliable metric relating therapy outcomes to the calculated doses. Among several considered metrics, only D90 showed statistically significant correlation with the overall survival.

  12. Technological line for production of carrier-free 188Re in the form of sterile, isotonic solution of sodium perrhenate (VII)

    Full text: Radiometric properties of 188Re create convenient condition for medical application of this radionuclide. A big interest has arisen concerning the use of 188Re for radioimmunotherapy, radionuclide synovectomy and bone pain palliation. This is due to the favorable characteristic of 188Re (T1/2 = 16,98 h), emission β- particles with an average energy of 764 keV and emission of 155 eV gamma photon (15%, γ-rays), which permits the in vivo biodistribution evaluation of 188Re-labeled ligands with gamma camera. Radionuclide 188Re is produced in results of 188W decay. Tungsten-188 is obtained by neutron activation of 186W according to nuclear reaction 186W (n,γ) → 187W (n,γ) → 188W. At the Radioisotope Centre Polatom the technology for production of sterile and isotonic solution of 188Re has been elaborated. High specific activity 188W is imported from RIAR, Russia with following specification; sodium tungstenate in sodium hydroxide solution, 188W specific activity 195 GBq/g, 187W to 188W activity ratio 0,23%, total gamma emitters to 188W activity ratio 0,3%, solvent concentration (sodium hydroxide) 0,24 mol/l and tungsten concentration 50 g/l. The solution of sodium tungstenate is processing in technological line consisting of five lead-shielded chambers in which following operations are carried out. 1. Unloading of active material 2. Filling of 188W solution on alumina column 3. Elution of 188Re in form sodium perrhenate 4. Concentration of eluate 5. Proportioning of 188Re solution to vials and its sterilization 6. Vials removal from technological line. Alumina used for filling the generator columns was first activated using 0,9% NaCl in 0,001M HCl and 32% HCl to obtain final pH of about 3. Tungsten 188W in the form of tungstenic acid was slowly loaded on the column (flow 0,1 ml/min). After 188W deposition the alumina column was washed with 0,9% NaCl to remove the unbound 188W. The adsorption capacity of alumina has been studied and the optimal

  13. Cellular metabolic responses of PET radiotracers to {sup 188}Re radiation in an MCF7 cell line containing dominant-negative mutant p53

    Cheon, Gi Jeong [Laboratory of Nuclear Medicine Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of) and Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of)]. E-mail: larry@kcch.re.kr; Chung, Hye-Kyung [Laboratory of Nuclear Medicine Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Choi, Jung-A [Laboratory of Radiation Experimental Therapeutics, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Lee, Su-Jae [Laboratory of Radiation Experimental Therapeutics, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Ahn, Soon-Hyuk [Laboratory of Nuclear Medicine Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Lee, Tae-Sup [Laboratory of Nuclear Medicine Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Choi, Chang Woon [Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Lim, Sang Moo [Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of)

    2007-05-15

    We investigated the relations between the cell uptakes of metabolic radiotracers and {beta}-radiation pretreatment using a dominant mutant p53 (p53mt) cell line to evaluate the effects of p53 genes on {sup 18}F labeled positron emission tomography (PET) radiotracer uptakes. Methods: pCMV-Neo-Bam (control), which contains a neo-resistance marker, and p53 dominant-negative mutant expression constructs were stably transfected into MCF7 cell line. Cells were plated in 24-well plates at 1.0x10{sup 5} cells for 18 h. Rhenium-188 ({sup 188}Re) (a beta emitter) was added to the medium (3.7, 18.5, 37 MBq) and incubated for 24 h. We performed gamma-counting to determine the cellular uptakes of 2-[{sup 18}F]fluoro-2-deoxy-D-glucose (FDG), o-(2-[{sup 18}F]fluoroethyl)-L-tyrosine (FET) and 2'-[{sup 18}F]fluoro-2'-deoxythymidine (FLT) (370 kBq, 60 min). Cell viabilities were determined by trypan blue staining and flow cytometry. Results: p53mt cells showed 1.5-2-fold higher FDG uptake than wild-type p53 cells in basal condition, and the difference of FDG uptake was greater after {sup 188}Re treatment (P<.01). FET uptake increased with {sup 188}Re dose without a significant difference between p53 statuses. p53mt cells showed lower FLT uptake than wild-type p53 cells in basal condition, and the difference of FLT uptake was greater after {sup 188}Re treatment. By cell viability testing and FACS analysis, p53mt cells showed lower viability and a larger apoptotic fraction (sub-G1) than wild-type p53 cells after {sup 188}Re treatment. Conclusion: We speculate that p53 dysfunction increases glucose and decreases thymidine metabolism in cancer cells and that this may be exaggerated by {sup 188}Re {beta}-radiation. Our findings suggest that FDG could reflect tumor viability and malignant potential after {sup 188}Re {beta}-radiation treatment, whereas FLT could be a more useful PET radiotracer for assessing therapeutic response to {beta}-radiation, especially in cancer cells

  14. Study of different absorbent materials for the preparation of generator systems of 99Mo - 99mTc and 188W-188Re

    Amongst some currently radioisotopes, 99mTc and 188Re present adequate decay properties for use in Nuclear Medicine. In the current times the most diagnosis examinations are performed with 99mTc and 188Re is one radioisotope of potential use in therapy techniques. The objective of this work consists of determining the capacity of some adsorbent materials for retention of molybdenum and tungsten, aiming the optimization of generator systems of 99Mo-99mTc and 188W-188Re with suitable characteristics for application in Nuclear Medicine. Known amounts, in mass, of molybdenum and tungsten were percolated through different chromatographic columns containing different commercial adsorbent materials such as: PZC (poly-zirconium compound), acid alumina and calcinated alumina used in the routine preparation of 99Mo-99mTc generators at IPEN. The tungsten (188W), as well the PZC used in this project, supplied by Russia and Japan, respectively, through the International Atomic Energy Agency (IAEA) and used without any previous preparation. Also trace amounts of 99Mo and 188W were added to the initial solutions and the generators were assembled. The 99Mo-99mTc generators were then eluted with known volumes of 0.9% NaCl solution every 24 hours whereas the 188W-188Re generators were eluted every 48 hours. The eluted samples were analyzed by Gamma Spectroscopy and later submitted to quality control evaluation. The results showed that the PZC presents superior retention capacity for Mo of 97.50mg Mo/gPZC, higher than in acid and calcinated alumina, however the elution efficiency at lower pHs is not so high. With regards to the experiments carried out with 188W and alumina, it was verified that the elution efficiency of 188Re was not reproducible and the retention capacity of W was 90.23mgW/gAl2O3 at pH 7. (author)

  15. Facile Synthesis of Histidine Derivatives for fac-[M(CO)3]+ precursor [M=99mTc, 188Re

    The technetium-99m(99mTc) is one of the most widely used radionuclides in nuclear medicine, because of its preferable properties(T1/2= 6.02 hr, Eγ= 140 keV). More than 85% of diagnostic scans were performed in hospitals worldwide. A variety of 99mTc-based radiopharmaceuticals have been developed for evaluating organ function and assessing disease status by imaging methods. The labeling of biologically active molecules with 99mTc is the most important research area. Although 99mTc complexes with a +5-oxidation state are commonly available recently, many researches have been focused on the 99mTc precursor with the +1-oxidation state [M(CO)3]+ due to its small size and ease in preparation. A variety of researches have revealed that histidine complexes with the fac-[M(CO)3] precursor show a good stability through in-vivo and in-vitro studies. In this study, we present a synthetic approach for the histidine derivatives as bifunctional chelating agent for the conjugation with biomolecules as well as for a labeling with the fac-[M(CO)3]+ precursor [M=99mTc, 186/188Re

  16. Therapeutic efficacy of 188Re-MN-16ET lipiodol in an animal model of hepatocellular carcinoma

    In our recent study, we developed a new radiopharmaceutical (rhenium-188 (Re-188) MN-16ET lipiodol) with encouraging results for the treatment of liver malignancy. In this study, we further evaluated the therapeutic efficacy of this radiopharmaceutical by measuring tumor response and survival times in rats with liver tumors after intra-hepatic arterial injection of Re-188 MN-16ET lipiodol. Twelve male rats bearing hepatic tumors were divided into three groups. Group 1 received an intra-hepatic arterial injection of 18.5 MBq Re-188 MN-16ET lipiodol; Group 2 received lipiodol and Group 3 received normal saline. Tumor size was measured by liver sonography before injection, at 2, 4, and 8 weeks after injection. Survival time and response rate were calculated. All rats showed good response and survived over 60 days in Group 1 while all rats showed poor response in Group 2 and Group 3 with only 25% of rats in Group 2 and none (0%) in Group 3 survived over 60 days. The p value was 0.0067 between Group 1 and Group 3; 0.04 between Group 1 and Group 2; and 0.034 between Group 2 and Group 3. Re-188 MN-16ET lipiodol has good potential for the treatment of hepatoma. (author)

  17. Local Development of 90Y/90Sr Generators and 90Y Radiopharmaceuticals in the Syrian Arab Republic. Chapter 11

    Radiopharmaceuticals have shown promise in the field of therapy in the last decades. The use of generator produced radionuclides, such as 90Y, has increased because of their unique properties. The focus of the work in this chapter has been the development of a 90Y generator and related radiopharmaceuticals. A 90Sr/90Y generator was developed based on the isolation of 90Y from 90Sr using Sr-Spec resin packed in three columns. The resulting 90Y solution was used for the preparation of therapeutic radiopharmaceuticals. In the 90Sr/90Y generator developed, a maximum of 200 mCi of 90Sr was loaded onto the first column and 90Y was eluted with 3M nitric acid. The middle two columns were used as purification barriers. The resulting eluate was evaporated and further purified by passing it through a cation exchange column for removal of trace elements. The final solution was concentrated and 90Y obtained in the chloride form. The yield of 90Y was ~90% with ≤10-6% 90Sr. The quality of the 90Y solution was tested in terms of radiochemical, radionuclidic and biological purities, which were found to be high. This reflected in obtaining high labelling efficiency and high quality of final radiopharmaceuticals, which included 90Y EDTMP, 90Y ferric hydroxide macroaggregates (FHMAs), 90Y DOTA-h-R3 antibody and 90Y DOTA rituximab. (author)

  18. Dosimetry and microdosimetry of 188 Re-anti-CD20 and 131 I-anti-CD20 for the treatment of No Hodgkin lymphomas

    The purpose of this investigation was to prepare 131I-anti-CD20 and 188Re-anti-CD20 and to estimate the radiation absorbed dose at macro- and micro- level during a NHL treatment. The work was divided in 4 general objectives: 1) preparation of 131I-anti-CD20 and 188Re-anti-CD20, 2) application in patients to obtain biokinetic parameters and estimate the organ absorbed doses 3) estimation of the cellular dosimetry using the MIRD methodology and the MCNP4C2 code and 4) estimation of the cellular microdosimetry using the NOREC code. 188Re-anti-CD20 was prepared by a direct labelling method using sodium tartrate as a weak ligand. To evaluate the biological recognition a comparative study of the in vitro binding of 188Re-anti-CD20, 125I-anti-CD20 (positive control) and 188Re-anti-CEA (negative control) to normal B Iymphocytes was performed. Biodistribution studies in normal mice were accomplished to assess the in vivo Re-anti-CD20 complex stability. The binding of ' Re-anti-CD20 to cells was in the same range as '251-anti-CD20 (>80%) considered as the positive control. 188Re-anti-CD20 and '3'1-anti-CD20 prepared were administered in patients diagnosed with B cell NHL at the Centro Medico Siglo XXI (IMSS). The protocol was approved by the hospital's Medical Ethics Committee. AJI patients signed a consent form after receiving detailed information on the aims of the study. N data were the input for the OLINDA/EXM software to calculate the radiation absorbed dose to organs and whole body. Dosimetric studies indicate that after administration of 6.4 GBq and 4.87 to 8.75 GBq of '3'1-anti-CD20 and 188Re-anti-CD20 respectively, the absorbed dose to total body would be 0.75 Gy which corresponds to the recommended dose for NHL therapies. The calculated organ absorbed doses indicate that 188Re-anti-CD20 may be used in radioimmunotherapy without the risk of toxicity to red marrow or healthy organs. The absorbed dose (D) into cellular nucleus was calculated by two different

  19. Country report: United Kingdom. Bifunctional bisphosphonate complexes with 99mTc and 188Re for the diagnosis and therapy of bone metastases

    1,1-Bisphosphonates (BPs) are a family of compounds extensively used in the management of disorders of bone metabolism.1 They accumulate in areas of high bone metabolism, such as bone metastases, and consequently have been receiving increasing attention as molecular imaging probes and pain palliation treatments.2 Imaging bone metastases with BPs using single photon emission computed tomography (SPECT) or planar scintigraphy is one of the most often-performed clinical imaging procedures. Beta-emitting analogues capable of producing a therapeutic effect have also been developed.3 In particular, the rhenium compounds 186/188Re-hydroxyethylidene-1,1-diphosphonate (186/188Re-HEDP) have shown promise as palliative agents for bone metastases in recent clinical trials.4 The radiochemicals consist of a complex of a BP (e.g. methylene diphosphonate, MDP) with gamma- (99mTc) or beta- (186/186Re) emitters

  20. Therapeutic effect of intratumoral injection of 188Re labeled stannic sulfur suspension in liver cancer. A comparative study with chemical agents in nude mice

    Objectives: Hepatoma is a common disease in some countries. The intervention therapy was used often for non-resectable tumor. The aim of our study was to compare the therapeutic effect of 188Re labeled stannic sulfur suspension to ethanol, acetic acid and the mixture of mitomycin and lipiodol for hepatoma in an animal model by intermittently injection. Methods: Forty-nine nude mice bearing hepatic cell carcinoma were divided into six groups. Group 1 (n=14) was intratumoral y injected with 0.1 ml saline. There were 5 experimental groups (group 2 to 6). Each group consisted of 7 mice. The mice in group 2 was intratumoral y injected with 18.5 MBq/0.1 ml 188Re labeled stannic sulfur suspension each, the mice in group 3 was injected intratumorally with 9.25 MBq/0.1 ml 188Re labeled stannic sulfur suspension each, group 4 was injected intratumorally with 0.1 ml ethanol, the mice in group 5 was injected with 0.1 ml 30% acetic acid and group 6 was injected intratumorally with 30 μg mitomycin in 0.1 ml lipiodol respectively. The mice were sacrificed 7 days post injection and the specimen were collected for pathological analysis. Results: The average tumor weight were 1.75±0.29 g (mean±S.D.), 0.26±0.03 g, 0.44±0.17 g, 1.38±0.25 g, 0.91±0.28 g, 1.38±0.28 g for group 1 to 6 respectively. Tumors in all experimental groups were significantly smaller than group 1 (control group, P88Re labeled stannic sulfur suspension injection had the smallest tumor weight among all the experimental groups (P188Re labeled stannic sulfur suspension shows better therapeutic effect. (authors)

  1. Development of pharmaceuticals with radioactive rhenium for cancer therapy. Production of {sup 186}Re and {sup 188}Re, synthesis of labeled compounds and their biodistributions

    NONE

    1998-03-01

    Production of the radioactive rhenium isotopes {sup 186}Re and {sup 188}Re, and synthesis of their labeled compounds have been studied together with the biodistributions of the compounds. This work was carried out by the Working Group on Radioactive Rhenium, consisting of researchers of JAERI and some universities, in the Subcommittee for Production and Radiolabeling under the Consultative Committee of Research on Radioisotopes. For {sup 186}Re, production methods by the {sup 185}Re(n,{gamma}){sup 186}Re reaction in a reactor and by the {sup 186}W(p,n){sup 186}Re reaction with an accelerator, which can produce nocarrier-added {sup 186}Re, have been established. For {sup 188}Re, a production method by the double neutron capture reaction of {sup 186}W, which produces a {sup 188}W/{sup 188}Re generator, has been established. For labeling of bisphosphonate, DMSA, DTPA, DADS, aminomethylenephosphonate and some monoclonal antibodies with the radioactive rhenium isotopes, the optimum conditions, including pH, the amounts of reagents and so on, have been determined for each compound. The biodistributions of each of the labeled compounds in mice have been also obtained. (author)

  2. Isostructural folate conjugates radiolabeled with the matched pair 99mTc/188Re: a potential strategy for diagnosis and therapy of folate receptor-positive tumors

    99mTc-technetium (99mTc) and 188Re-rhenium (188Re) represent an interesting pair of radionuclides for diagnosis and therapy. The aim of this study was to synthesize and characterize in vitro/in vivo the first 188Re-folate derivative [188Re(CO)3-picolylamine monoacetic acid 188Re-PAMA-folate (2)] for potential targeted radionuclide therapy of FR-positive tumors. The data were compared with those of the isostructural 99mTc-analog [99mTc-PAMA folate (1)] reported previously. Methods: In vitro stability of compound was tested in phosphate-buffered saline and human plasma. Cell binding experiments were performed with FR-positive human KB cells. Biodistribution was assessed in female nude mice, bearing KB tumor xenografts. Results: Cell binding experiments showed high and FR-specific uptake. In vivo, compound accumulated specifically in the FR-positive tumors with maximal values 4 h post injection (p.i.) [: 1.87±0.04 percent injected dose per gram of weight tissue (% ID/g) vs. : 2.33±0.36% ID/g]. Unfavorably high retention of radioactivity was found in FR-positive kidneys (12.04±0.62% ID/g; 4 h p.i.). Tumor-to-blood ratio of radioactivity (: 14.5±1.32, 4 h p.i.) was lower than for compound (58.0±12.2, 4 h p.i.), whereas tumor-to-kidney ratios were in the same range (: 0.15±0.01 vs. : 0.13±0.02, 4 h p.i.). Preadministration of the antifolate pemetrexed significantly improved the tumor-to-kidney ratio (: 1.59±0.30, 4 h p.i.). Conclusions: The isostructural radiofolates and displayed almost identical pharmacokinetic profiles and accumulated both specifically in FR-positive tumors. However, only the coapplication of the antifolate pemetrexed improved the biodistribution of the radiotracers in such ways that a potential therapeutic application of compound can be envisaged in the future

  3. 90Y of high purity for medical applications

    Several 90 Sr/90Y-generator systems have been developed and used to produce 90Y. The most important parameter of the 90Y to be assayed is 90Sr content. In addition, when labelling monoclonal antibodies for therapy trace metal quantities accompanying 90Y (Fe3+, Zn2+ , Cu2+ , ZrO2+ , etc.) are to be kept as low as possible in order to obtain high labelling efficiencies. Generally generators' lifetime is limited due to the 90Sr breakthrough which increases in eluates as a result of the radiolytic degradation of the resin used as support. In the study a described procedure for 90Y purification from metal contamination is modified in order to lower the amount of 90Sr present in eluates from generators. As a result a very low 90Sr content is always assured (90 Sr/90Y-6). (author)

  4. Synthesis and characterization of {sup 99m}Tc- and {sup 188}Re-complexes with a diamido-dihydroxymethylenephosphine-based bifunctional chelating agent (N{sub 2}P{sub 2}-BFCA)

    Kothari, K.K. E-mail: kanchan@apsara.barc.ernet.in; Gali, H.; Prabhu, K.R.; Pillarsetty, N.; Owen, N.K.; Katti, K.V.; Hoffman, T.J.; Volkert, W.A

    2002-01-01

    A diamido-dihydroxymethylenephosphine (N{sub 2}P{sub 2}) bifunction chelating agent (BFCA) was shown to form well-defined {sup 99m}Tc- and {sup 188}Re-chelate structures. The 4, 4-bis [bis-hydroxymethyl-phosphonyl-propylcarbonmoyl]-butyric acid bifunctional chelating agent (N{sub 2}P{sub 2}-BFCA) formed stable complexes with {sup 99m}Tc and {sup 188}Re in >95% yield with high radiochemical purity (RCP). The biodistribution of the {sup 99m}Tc- and {sup 188}Re-N{sub 2}P{sub 2}-BFCAs after intravenous injection studied in normal mice showed the activity was excreted primarily via renal-urinary pathway indicating their use for labeling peptides with {sup 99m}Tc and {sup 188}Re.

  5. A new 90Sr/90Y radioisotope generator

    A 90Sr/90Y MINIGENERATOR has been developed for use as an educational aid. It consists of ion exchange paper impregnated with Amberlite IR-120 resin on which 0.1 μCi of 90Sr is deposited and from which 90Y is eluted with a dilute solution of disodium ethylenediaminetetraacetic acid (EDTA). More than 95% of the 90Y is recovered in 2 ml of 0.003 M EDTA with radionuclide purity greater than 99.9%. The system does not change its characteristics even after 1000 elutions. Such an ion exchange system has not previously been reported for separation of 90Y from 90Sr. (author)

  6. Dosimetry and microdosimetry of {sup 188} Re-anti-CD20 and {sup 131} I-anti-CD20 for the treatment of No Hodgkin lymphomas; Dosimetria y microdosimetria del {sup 188} Re-anti-CD20 y {sup 131} I-anti-CD20 para el tratamiento de linfomas No Hodgkin

    Torres G, E

    2007-07-01

    The purpose of this investigation was to prepare {sup 131}I-anti-CD20 and {sup 188}Re-anti-CD20 and to estimate the radiation absorbed dose at macro- and micro- level during a NHL treatment. The work was divided in 4 general objectives: 1) preparation of {sup 131}I-anti-CD20 and {sup 188}Re-anti-CD20, 2) application in patients to obtain biokinetic parameters and estimate the organ absorbed doses 3) estimation of the cellular dosimetry using the MIRD methodology and the MCNP4C2 code and 4) estimation of the cellular microdosimetry using the NOREC code. {sup 188}Re-anti-CD20 was prepared by a direct labelling method using sodium tartrate as a weak ligand. To evaluate the biological recognition a comparative study of the in vitro binding of {sup 188}Re-anti-CD20, {sup 125}I-anti-CD20 (positive control) and {sup 188}Re-anti-CEA (negative control) to normal B Iymphocytes was performed. Biodistribution studies in normal mice were accomplished to assess the in vivo Re-anti-CD20 complex stability. The binding of ' Re-anti-CD20 to cells was in the same range as '251-anti-CD20 (>80%) considered as the positive control. {sup 188}Re-anti-CD20 and '3'1-anti-CD20 prepared were administered in patients diagnosed with B cell NHL at the Centro Medico Siglo XXI (IMSS). The protocol was approved by the hospital's Medical Ethics Committee. AJI patients signed a consent form after receiving detailed information on the aims of the study. N data were the input for the OLINDA/EXM software to calculate the radiation absorbed dose to organs and whole body. Dosimetric studies indicate that after administration of 6.4 GBq and 4.87 to 8.75 GBq of '3'1-anti-CD20 and {sup 188}Re-anti-CD20 respectively, the absorbed dose to total body would be 0.75 Gy which corresponds to the recommended dose for NHL therapies. The calculated organ absorbed doses indicate that {sup 188}Re-anti-CD20 may be used in radioimmunotherapy without the risk of toxicity to red marrow or

  7. 90Y and 105Rh labelled preparations: Potential therapeutic agents

    90Y and 105Rh formulations were studied with an aim to prepare therapeutic radiopharmaceuticals. 90Y obtained from a 90Sr-90Y generator as chloride was complexed with known ligands such as DTPA, EDTMP and DOTA as well as a few other phosphonate ligands. Particulates such as 90Y labelled ferric hydroxide macroaggregates (FHMA) and 105Rh-sulphur colloid were prepared and studied for their stability in buffers and human serum. The studies on the complexation of 90Y and the preparation of radiolabelled particulates are described. 90Y complexed nearly quantitatively with DTPA, DOTA and EDTMP under optimised conditions of reaction pH, temperature and ligand concentrations. Both 90Y-FHMA and 105Rh-S colloid could be prepared in high yields under optimised conditions. The labelled particulates were measuring 20-100 μm and 1-20 μm, respectively and were found to be very stable in buffers as well as human serum at 37 deg. C. The particulates have the potential for use as radiosynovectomy agents and for therapy of cancers such as hepatomas. (author)

  8. Steps toward high specific activity labeling of biomolecules for therapeutic application: preparation of precursor [(188)Re(H(2)O)(3)(CO)(3)](+) and synthesis of tailor-made bifunctional ligand systems.

    Schibli, Roger; Schwarzbach, Rolf; Alberto, Roger; Ortner, Kirstin; Schmalle, Helmut; Dumas, Cécile; Egli, André; Schubiger, P August

    2002-01-01

    Two kit preparations of the organometallic precursor [(188)Re(H(2)O)(3)(CO)(3)](+) in aqueous media are presented. Method A uses gaseous carbon monoxide and amine borane (BH(3).NH(3)) as the reducing agent. In method B CO(g) is replaced by K(2)[H(3)BCO(2)] that releases carbon monoxide during hydrolysis. Both procedures afford the desired precursor in yields >85% after 10 min at 60 degrees C. HPLC and TLC analyses revealed 7 +/- 3% of unreacted (188)ReO(4)(-) and 95% with [(188)Re(H(2)O)(3)(CO)(3)](+) under mild reaction conditions (PBS buffer, 60 degrees C, 60 min) at ligand concentrations between 5 x 10(-4) M and 5 x 10(-5) M. Thus, specific activities of 22-220 GBq pe micromol of ligand could be achieved. Incubation of the corresponding Re-188 complexes in human serum at 37 degrees C revealed stabilities between 80 +/- 4% and 45 +/- 10% at 24 h, respectively, and 63 +/- 3% and 34 +/- 3% at 48 h postincubation in human serum depending on the chelating system. Decomposition product was mainly (188)ReO(4)(-). The routine kit-preparation of the precursor [(188)Re(H(2)O)(3)(CO)(3)](+) in combination with tailor-made ligand systems enables the organometallic labeling of biomolecules with unprecedented high specific activities. PMID:12121130

  9. Development of activity standard for {sup 90}Y microspheres

    Mo, L. [Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234 (Australia) and Institute of Medical Physics, University of Sydney, NSW 2006 (Australia)]. E-mail: lmx@ansto.gov.au; Avci, B. [SIRTeX Medical Limited, Unit F6 Parkview, 16 Mars Road, Lane Cove, NSW 2066 (Australia); James, D. [SIRTeX Medical Limited, Unit F6 Parkview, 16 Mars Road, Lane Cove, NSW 2066 (Australia); Simpson, B. [CSIR National Metrology Laboratory, 15 Lower Hope Road, Rosebank, Cape Town 7700 (South Africa); Van Wyngaardt, W.M. [CSIR National Metrology Laboratory, 15 Lower Hope Road, Rosebank, Cape Town 7700 (South Africa); Cessna, J.T. [National Institute of Standards and Technology, Gaithersburg, MD 20899 (United States); Baldock, C. [Institute of Medical Physics, University of Sydney, NSW 2006 (Australia)

    2005-08-01

    {sup 90}Y microspheres are important therapeutic radiopharmaceuticals used in the treatment of liver cancer through a process known as selective internal radiation therapy. SIR-spheres[reg] is a radiopharmaceutical product that is comprised of {sup 90}Y microspheres suspended in sterile, pyrogen-free water for injection into patients. It is necessary to establish for the SIR-spheres[reg] production the capability of accurately measuring the activity of this product to a traceable national measurement standard. An activity standard for SIR-spheres[reg] was developed from a standard for {sup 90}Y solution, employing a highly quantifiable chemical digestion process. Calibration factors for the manufacturer's ionisation chambers were determined for 1 and 5 ml of the SIR-spheres[reg] product placed in Wheaton vials, for both 34% and 44% of {sup 90}Y microsphere concentration.

  10. Studies on the preparation of medical 90Y generator

    Based on the determination of the distribution coefficients of Sr and Y ions on cation exchange resin (732) and the column separation of 90Y from 90Sr, three 90Y generators with about 800 MBq 90Sr loaded were prepared and eluted with citric acid of 25 mmol·L-1 and pH 5.5 (G-1), ethylenediamine tetraacetic acid (EDTA) of 3 mmol·L-1 and pH 4.5 (G-2), and diethylenetriamine pentraacetric acid (DTPA) of 3 mmol·L-1 and pH 5.5 (G-3) respectively. The elution efficiencies of 90Y were greater than 90 per cent, and the corresponding breakthroughs (B) of 90Sr were less than 1 x 10-5, 6 x 10-7 and 3 x 10-7 respectively. G-1 has been used for two years to provide 90Y for labeling of antibodies, with no significant change of B. G-3 has been eluted for over one year and the mean B was (1.7 +- 0.5) x 10-7 (+-s, n = 29). The results show that as the eluent of 90Y generator, EDTA is better than citric acid, while DTPA is the best; and that generator eluted with either EDTA or DTPA can provides 90Y used in radioimmunotherapy of cancers

  11. The enzymatic preparation of [α-32P]nucleoside triphosphates, cyclic [32P]AMP, and cyclic [32P]GMP

    A method has been developed for the enzymatic preparation of α-32P-labelled ribo- and deoxyribonucleoside triphosphates, cyclic [32P]AMP, and cyclic [32P]GMP of high specific radioactivity and in high yield from 32Psub(i). The method also enables the preparation of [γ-32P]ATP, [γ-32P]GTP, [γ-32P]ITP, and [γ-32P]-dATP of very high specific activity and in high yield. (Auth.)

  12. 188Re-ZHER2:V2, a promising targeting against HER2-expressing tumors: in vitro and in vivo assessment

    Full text of publication follows. Aim: Rhenium-188 (T1/2 =17 h) is a promising radionuclide for therapy applications. This generator-produced high energy beta-emitter is suitable for eradication of bulky non-operable tumors. Low abundance 155 KeV photons permit SPECT imaging of biodistribution of Rhenium-188 labeled targeting agents during therapy for personalized dosimetry. Affibody molecules are small (7 kDa) non-immunoglobulin scaffold proteins with good tumor targeting properties and favorable kinetics. Optimization of the targeting properties of Technetium-99m and Rhenium-188 labeled anti-HER2 affibody molecules demonstrated that the variant with C-terminal glycyl-glycyl-glycyl-cysteine (-GGGC) chelating sequence (designated ZHER2:V2) has the best biodistribution profile in vivo and the lowest renal uptake of radioactivity. The aim of this study is to evaluate 188Re-ZHER2:V2 as a potential candidate for affibody-based radionuclide targeted therapy against HER2-expressing tumors. Methods: ZHER2:V2 was labeled with Rhenium-188 using gluconate-containing kit at pH 4.2. Binding specificity to HER2-expressing cells in vitro was evaluated. Targeting of HER2-over-expressing SKOV-3 ovarian carcinoma xenografts in NMRI nu/nu female mice was studied for a preliminary dosimetry assessment. Results: The labeling method provided labeling yields over 95%. The release of free 188Re was negligible after incubation in serum. Binding of 188Re-ZHER2:V2 to living SKOV-3 cells was HER2-mediated (KD = 13 pM). The biodistribution study showed a rapid blood clearance (1.2±0.1 %IA/g at 1 h p.i.). Bone uptake was 1.2±0.1 %IA/g at 1 h p.i. and remained below 0.15 %IA/g after 4 h p.i. The tumor uptake was 11±3, 10±1, 4±2 and 1.6±0.5 %IA/g at 1, 4, 24 and 48 h p.i., respectively. Pre-saturation of HER2 in xenografts by a pre-injection of a large excess of non-labeled affibody molecules reduced tumor uptake to 2±0.1 %IA/g at 4 h p.i., suggesting receptor specificity of the targeting

  13. 188Re- and 99mTc-MAG3 as prosthetic groups for labeling amines and peptides Approaches with pre- and postconjugate labeling

    Either radiolabeled Tc-99m- or Re-188-labeled MAG3-4-nitrophenylester or unlabeled Bz-MAG3-4-nitrophenylester was reacted with amines and peptides to follow a pre- or a postconjugate radiolabeling route, respectively. The model compounds were N'-t-butyloxycarbonyl-1,6-diaminohexane (DH-Boc) and a Lysprotected derivative of the somatostatin analog RC-160 (cyclic D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2). In the case of labeling DH-Boc, both the preconjugate labeling and the postconjugate labeling were found by using analytical HPLC to provide identical radiolabeled compounds regardless whether Re-188 or Tc-99m was used. The results are supported by infrared and mass-spectral data obtained from compounds synthesized using stable rhenium. The 188Re- or 99mTc-MAG3-RC-160 somatostatin analog were synthesized following the preconjugate labeling route and subsequent removal of the protecting group. Biodistributions of 188Re- and 99mTc-MAG3-RC-160 were evaluated in normal and tumor-bearing mice, and were similar to those of radioiodinated 131I-RC-160. All radiolabeled analogs of RC-160 were rapidly cleared from the blood and were excreted through the hepatobiliary system with very little normal organ uptake. The tumor uptake (PC-3, human prostate adenocarcinoma) of systemically administered Re-188-MAG3-RC160 was very low, and it reached only 0.28% injected dose/g (%IDg) at 24 h postinjection, similar to what was obtained with I-131-RC-160. Intratumor injections resulted in significant tumor retentions (9.3% ID/g at 24 h)

  14. The remaining percentage of 32P after burning of sulphur tablet containing 32P

    Three types of sulphur tablet containing 32P are made artificially. The remaining percentage of 32P after burning of three types of sulphur tablets containing 32P is 98.1 ± 1.3% for 1st and 2nd types and 97.2 ± 2.8% for 3rd type

  15. 90 Y-ibritumomab tiuxetan: a nearly forgotten opportunityr.

    Mondello, Patrizia; Cuzzocrea, Salvatore; Navarra, Michele; Mian, Michael

    2016-02-16

    Y-ibritumomab tiuxetan (90Y-IT) combines the benefits of a monoclonal antibody with the efficacy of radiation in the treatment of B-cell non-Hodgkin lymphoma (NHL), a remarkably radiosensitive hematologic malignancy. 90Y-IT activity has been well established in the indolent setting, being approved in front-line treatment of follicular lymphoma (FL) patients as well as salvage therapy. However, no advantage in OS was observed with respect to standard treatment. Promising data are available also for aggressive B-cell lymphoma. In particular, the addition of RIT to short-course first line chemotherapy enables reduction of chemotherapy while maintaining cure rates in elderly, untreated diffuse large B-cell lymphoma (DLBCL) patients. Furthermore, 90Y-IT improves response rate and outcomes of relapsed/refractory DLBCL patients, eligible and ineligible for autologous stem cell transplantation (ASCT). Clinical results have shown a role of 90Y-IT even in mantle cell lymphoma (MCL). RIT might improve responses and treat minimal residual disease when used as consolidation after first-line chemotherapy in MCL. Moreover, 90Y-IT has demonstrated its efficacy in combination with high-dose chemotherapies as conditioning regimen for ASCT, with evidence suggesting the ability to overcome chemotherapy resistance. Herein, we review the available evidence for this approved drug and examine the recently published and ongoing trials for potential novel indication in aggressive B-cell NHL. PMID:26657116

  16. Investigation of plasma stealth excited by 90Sr/90Y

    Background: Plasma stealth is one of the most important branches of the electromagnetic stealth technology. β-ray could ionize the air and excite the plasma. Under certain conditions, the plasma has stealth effect to the radar wave. Purpose: The aim is mainly to investigate the plasma stealth excited by 90Sr/90Y. Methods: We calculated the density distribution of the plasma excited by 90Sr/90Y with different radioactivity through configuring the weighting factor based on the decay energy spectrum of 90Sr/90Y with the electron diffusion and recombination in the air taken into consideration, and obtained the reflectivity of the plasma that was excited by infinite metal plate coated with 90Sr/90Y to electromagnetic waves with different incident angles and frequencies using the WKB (Wentzel-Kramers-Brillouin) method. Results: The reflectivity of the plasma with the radioactivity being 3.7x1010Bq·cm-2 and 3.7x1011Bq·cm-2 to the vertically incident electromagnetic wave of 1.5 GHz could reach -2.2 dB and -7.45 dB respectively. Conclusion: In the range of 1-100 GHz, the reflectivity increases monotonically with the frequency, while decreases monotonically with the increase of incident angle. The stealth effect of the plasma excited by 90Sr/90Y with a certain radioactivity is of significance. (authors)

  17. Calibration of dermatological applicators of 90 Sr+90 Y

    90 Sr+90 Y dermatological applicators are widely used in the treatment of skin lesions. Despite calibrated by the manufacturers, these sources must be re-calibrated periodically by standard laboratories. Articles published by different authors show the discrepancies between manufacturers and standard laboratories calibrations of 90 Sr+90 Y applicators. Ionization chambers with variable volume, named extrapolation chambers, are utilized for the calibration of such sources. An extrapolation chamber was developed at IPEN for the calibration of 90 Sr+90 Y dermatological applicators. This chamber shows a good performance in the detection of beta particles. The aim of this work is to establish and to apply a routine calibration procedure to a dermatological applicator, based on former work developed in this institution. (author)

  18. 90Y Production and Its Biodistribution in Mice

    Yttrium - 90 is radioisotope emitting pure β with maximum energy of 2.27 MeV while its average β energy is 0.93 MeV. 90Y radioisotope was produced utilizing G.A Siwabessy reactor employing thermal neutron capture process. In nuclear medicine this radioisotope is utilized for bone mettastase palliative and curative therapies. Parameters in this research were the weight of natural Y2O3 target, irradiation time in the reactor, radiochemical purity and specific activity. The end product of the process is YCl3, in saline solution. Then sterility of the 90Y radioisotope so produced is tested and its biodistribution analysis results in mice organs show that the percentage of this radioisotope in the liver is much higher than the ones in heart, kidneys, lung and intestine. Therefore it is concluded that 90Y radioisotope in the form of YCl3 can be utilized as a radiopharmaceutical in nuclear medicine. (author)

  19. 90 Y-ibritumomab tiuxetan: a nearly forgotten opportunity

    Mondello, Patrizia; Cuzzocrea, Salvatore; Navarra, Michele; Mian, Michael

    2015-01-01

    Y-ibritumomab tiuxetan (90Y-IT) combines the benefits of a monoclonal antibody with the efficacy of radiation in the treatment of B-cell non-Hodgkin lymphoma (NHL), a remarkably radiosensitive hematologic malignancy. 90Y-IT activity has been well established in the indolent setting, being approved in front-line treatment of follicular lymphoma (FL) patients as well as salvage therapy. However, no advantage in OS was observed with respect to standard treatment. Promising data are available als...

  20. Preparation & in vitro evaluation of 90 Y-DOTA-rituximab

    Mythili Kameswaran

    2016-01-01

    Full Text Available Background & objectives: Radioimmunotherapy is extensively being used for the treatment of non-Hodgkin′s lymphoma (NHL. Use of rituximab, a chimeric anti-CD20 antibody directed against the CD20 antigen in combination with suitable beta emitters is expected to result in good treatment response by its cross-fire and bystander effects. The present work involves the conjugation of p-isothiocyanatobenzyl DOTA (p-SCN-Bn-DOTA to rituximab, its radiolabelling with [90] Y and in vitro and in vivo evaluation to determine its potential as a radioimmunotherapeutic agent. Methods: Rituximab was conjugated with p-SCN-Bn-DOTA at 1:1 antibody: DOTA molar ratio. The number of DOTA molecules linked to one molecule of rituximab was determined by radioassay and spectroscopic assay. Radiolabelling of rituximab with 90 Y was carried out and its in vitro stability was evaluated. In vitro cell binding studies were carried out in Raji cells expressing CD20 antigen. Biodistribution studies were carried out in normal Swiss mice. Results: Using both radioassay and spectroscopic method, it was determined that about five molecules of DOTA were linked to rituximab. Radiolabelling of the rituximab conjugate with [90] Y and subsequent purification on PD-10 column gave a product with radiochemical purity (RCP > 98 per cent which was retained at > 90 per cent up to 72 h when stored at 37°C. In vitro cell binding experiments of 90 Y-DOTA-rituximab with Raji cells exhibited specific binding of 20.7 ± 0.1 per cent with [90] Y-DOTA-rituximab which reduced to 15.5 ± 0.2 per cent when incubated with cold rituximab. The equilibrium constant K d for 90 Y-DOTA-Rituximab was determined to be 3.38 nM. Radiolabelled antibody showed clearance via hepatobiliary and renal routes and activity in tibia was found to be quite low indicating in vivo stability of [90] Y-DOTA-rituximab. Interpretation & conclusions: p-SCN-Bn-DOTA was conjugated with rituximab and radiolabelling with 90 Y was

  1. Preclinical Evaluation of 90Y Labelled Rituximab and ERIC-1: Two Antibodies for Tumour Therapy. Chapter 5

    The project described in this chapter focuses on harnessing the great potential of radionuclide therapy, using various vehicles to transport radionuclides into tumour tissues. The main aim of the project was to make specific vehicle molecules whose tumour affinity and suitability for radioactive coupling have been proven through laboratory trials on animals and cell cultures at the Department of Nuclear Medicine, University of Cologne, Germany, and to label them with 90Y. The vectors to transport radionuclides into tumour tissue for treatment were antibodies against lymphomas and neuroblastomas. Tumour pretargeting has shown clear advantages over the direct application of labelled antibodies with regard to tumour to background ratios. The pretargeting strategy would be first evaluated on cell cultures and the results then transferred to in vivo experiments on tumour bearing mice. Briefly, the first component of a three step pretargeting strategy would consist of the biotinylated antibody. This would include the protocol for determination of the number of biotin molecules per antibody. Using this technique, a stock of biotinylated antibody in lyophilized form can be built up, ready for further experiments. In the second step, commercially available avidin streptavidin would be used. The third and final step is the binding of radiolabelled (188Re, 90Y) biotin to the tumour cells through the avidin antibody bridge, after administration of a clearing agent. Initial evaluations of the potential radiopharmaceuticals have been carried out by in vitro experiments on cell lines expressing the corresponding antigen. The work done so far for the three step pretargeting method can be summarized as follows: —— Yttrium-90 labelling of biotin DOTA; —— Coupling of biotinylated rituximab to CD20 positive Raji cells; —— Successful labelling of cells conjugated with a complex of biotinylated antibody and avidin with 90Y DOTA biotin; —— First animal experiments with

  2. Reduction of skeletal accumulation of radioactivity by co-injection of DTPA in [90Y-DOTA0,Tyr3]octreotide solutions containing free 90Y3+

    Peptide receptor-targeted radionuclide therapy is nowadays being performed with radiolabeled DOTA-conjugated peptides, such as [90Y-DOTA0,Tyr3]octreotide (also known as OctreoTher[reg ] or 90Y-DOTATOC). The incorporation of 90Y3+ is typically ≥99%, however, since a total patient dose can be as high as 26 GBq or 700 mCi the amount of free 90Y3+ (=non-DOTA-incorporated) can be substantial. Free 90Y3+ accumulates in bone with undesired radiation of bone marrow as a consequence. 90Y-DTPA is excreted rapidly via the kidneys. Incorporation of free 90Y3+ into 90Y-DTPA might prevent this fraction from being accumulated into bone, therefore we have investigated: the biodistribution in rats of 90YCl3, [90Y-DOTA0,Tyr3]octreotide, and 90Y-DTPA; possibilities to complex 10% of free 90Y3+ in a [90Y-DOTA0,Tyr3]octreotide containing solution into 90Y-DTPA prior to intravenous injection; and effects of 10% free 90Y3+ in [90Y-DOTA0,Tyr3]octreotide solution, in the presence and in the absence of excess DTPA, on the biodistribution of in rats. The following results are presented: 90YCl3 showed high skeletal uptake (i.e., 1% ID (injected dose) per gram femur, with main localization in the epiphyseal plates) and a 24 h total body retention of 74% ID; 90Y-DTPA had rapid renal clearance, and 24 h total body retention of 90Y3+ in [90Y-DOTA0,Tyr3]octreotide solution could rapidly be incorporated into 90Y-DTPA at room temperature; and accumulation of 90Y3+ in femur, blood, and liver was related to the amount of free 90Y3+, whereas these accumulations could be prevented by the addition of DTPA. In conclusion, the addition of excess DTPA to [90Y-DOTA0,Tyr3]octreotide with incomplete 90Y-incorporation is recommended

  3. SNO+ scintillator cocktail studies using an ${}^{90}$Y source

    Arushanova, Evelina

    2016-01-01

    We present the design of ${}^{90}$Y calibration source and its manufacturing procedure, that has been implemented in the University of Sussex radioactive laboratory. The radioactive source was first tested at the University of Sussex using a small scintillator cocktail sample. Further measurements were performed at the University of Pennsylvania using a larger volume of the scintillator cocktail. The results of both studies are presented and discussed.

  4. Preparation & in vitro evaluation of 90Y-DOTA-rituximab

    Mythili Kameswaran; Usha Pandey; Ashutosh Dash; Grace Samuel; Meera Venkatesh

    2016-01-01

    Background & objectives: Radioimmunotherapy is extensively being used for the treatment of non-Hodgkin′s lymphoma (NHL). Use of rituximab, a chimeric anti-CD20 antibody directed against the CD20 antigen in combination with suitable beta emitters is expected to result in good treatment response by its cross-fire and bystander effects. The present work involves the conjugation of p-isothiocyanatobenzyl DOTA (p-SCN-Bn-DOTA) to rituximab, its radiolabelling with [90] Y and in vitro and in vivo ev...

  5. Preparation & in vitro evaluation of 90 Y-DOTA-rituximab

    Mythili Kameswaran; Usha Pandey; Ashutosh Dash; Grace Samuel; Meera Venkatesh

    2016-01-01

    Background & objectives: Radioimmunotherapy is extensively being used for the treatment of non-Hodgkin′s lymphoma (NHL). Use of rituximab, a chimeric anti-CD20 antibody directed against the CD20 antigen in combination with suitable beta emitters is expected to result in good treatment response by its cross-fire and bystander effects. The present work involves the conjugation of p-isothiocyanatobenzyl DOTA (p-SCN-Bn-DOTA) to rituximab, its radiolabelling with [90] Y and in vitro and in vivo ev...

  6. Development of [90Y]DOTA-conjugated bisphosphonate for treatment of painful bone metastases

    Introduction: Based on the concept of bifunctional radiopharmaceuticals, we have previously developed 186Re-complex-conjugated bisphosphonate analogs for palliation of painful bone metastases and have demonstrated the utility of these compounds. By applying a similar concept, we hypothesized that a bone-specific directed 90Y-labeled radiopharmaceutical could be developed. Methods: In this study, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was chosen as the chelating site, and DOTA was conjugated with 4-amino-1-hydroxybutylidene-1,1-bisphosphonate. [90Y]DOTA-complex-conjugated bisphosphonate ([90Y]DOTA-HBP) was prepared by coordination with 90Y, and its biodistribution was studied in comparison to [90Y]citrate. Results: In biodistribution experiments, [90Y]DOTA-HBP and [90Y]citrate rapidly accumulated and resided in the bone. Although [90Y]citrate showed a higher level of accumulation in the bone than [90Y]DOTA-HBP, the clearances of [90Y]DOTA-HBP from the blood and from almost all soft tissues were much faster than those of [90Y]citrate. As a result, the estimated absorbed dose ratios of soft tissues to osteogenic cells (target organ) of [90Y]DOTA-HBP were lower than those of [90Y]citrate. Conclusions: [90Y]DOTA-HBP showed superior biodistribution characteristics as a bone-seeking agent and led to a decrease in the level of unnecessary radiation compared to [90Y]citrate. Since the DOTA ligand forms a stable complex not only with 90Y but also with lutetium (177Lu), indium (111In), gallium (67/68Ga), gadolinium (Gd) and so on, complexes of DOTA-conjugated bisphosphonate with various metals could be useful as agents for palliation of metastatic bone pain, bone scintigraphy and magnetic resonance imaging

  7. Calibration of two 90Sr+90Y dermatological applicators

    The 90Sr+90Y applicators need to be periodically calibrated, but in Brazil the service it not offered yet. The recommended method for the calibration of this kind of applicators is the use of extrapolation chambers. An alternative method for the calibration of clinical applicators is the use of thermoluminescent dosimeters. A dosimetric method of these applicators was already developed at Instituto de Pesquisas Energeticas e Nucleares (IPEN) and several types of thermoluminescent dosimeters were studied in previous works. The aim of this work was the application of this method to calibrate two dermatological applicators. Thin CaSO4:Dy pellets, with and without 10% of graphite were utilized. The reproducibility of these pellets was studied, and calibration curves were obtained using a standard applicator calibrated at the National Institute of Standards and Technology (NIST), USA. Both applicators showed similar results. The TL materials tested showed usefulness for dosimetry and calibration of this kind of applicators. (author)

  8. Calculus of spatial distribution of absorbed dose to cellular level by Monte Carlo simulation for a radio-labelled peptide with 188Re and with nuclear internalization : preliminary results

    The 188Re is a radionuclide of radiation gamma emitter, useful in obtaining of gamma-graphic images, but it is also emitter of beta radiations and Auger electrons. A bio-molecule directed to a specific receptor of a cancer cell labeled with a emitter radionuclide of beta particles and Auger electrons, as the 188Re-Tat-Bombesin, it has the potential to be used in radiotherapy of molecular targets for its capacity to penetrate to cellular nucleus. In this system, the radiation dose is distributed in way located at microscopic levels in sub cellular specific places, where Auger emissions contributes of significant way in absorbed dose. The cellular dosimetry is realized in most of cases, using analytic or semi analytical methods, for example the cellular MIRD methodology. However, it is required to complement these calculations simulating the electrons transport and considering experimental bio kinetics data. Therefore, in this work preliminary results are presented of dosimetric calculation to sub cellular level for 188Re-Tat-Bombesin by Monte Carlo simulation, using the 2008 version of PENELOPE: PENEASY code. The spatial distribution of absorbed dose in membrane, cytoplasm and nucleus, was calculated with geometry of a cell of 10 μm of diameter, a nucleus of 2 μm of ratio and membrane of 0.2 μm of thickness, considering elementary constitution for each cellular compartment proposal in literature. The total number of disintegrations at sub cellular level was evaluated integrating the activity in function of time starting from experimental bio kinetics data in mamma cancer cells MDA-MB231. The preliminary results show that 46.4% of total disintegrations for unit of captured activity by cell occurs in nucleus, 38.4% in membrane and 15.2% in cytoplasm. The due absorbed dose to Auger electrons for 1 Bq of 188Re located in cellular membrane were respectively of 1.32E-1 and 1.43E-1 Gy in cytoplasm and nucleus. (Author)

  9. Radiochemistry, pre-clinical studies and first clinical investigation of 90Y-labeled hydroxyapatite (HA) particles prepared utilizing 90Y produced by (n,γ) route

    Introduction: The scope of using no carrier added (NCA) 90Y [T1/2 = 64.1 h, Eβ(max) = 2.28 MeV] obtained from 90Sr/90Y generator in radiation synovectomy (RSV) is widely accepted. In the present study, the prospect of using 90Y produced by (n,γ) route in a medium flux research reactor for use in RSV was explored. Methods: Yttrium-90 was produced by thermal neutron irradiation of Y2O3 target at a neutron flux of ~ 1 × 1014 n/cm2.s for 14 d. The influence of various experimental parameters were systematically investigated and optimized to arrive at the most favorable conditions for the formulation of 90Y labeled hydroxyapatite (HA) using HA particles of 1–10 μm size range. An optimized kit formulation strategy was developed for convenient one-step compounding of 90Y-HA, which is easily adaptable at hospital radiopharmacy. The pre-clinical biological evaluation of 90Y-HA particles was studied by carrying out biodistribution and bioluminiscence imaging studies in Wistar rats. The first clinical investigation using the radiolabeled preparation was performed on a patient suffering from chronic arthritis in knee joint by administering 185 MBq 90Y-HA formulated at the hospital radiopharmacy deploying the proposed strategy. Results: Yttrium-90 was produced with a specific activity of 851 ± 111 MBq/mg and radionuclidic purity of 99.95 ± 0.02%. 90Y-labeled HA particles (185 ± 10 MBq doses) were formulated in high radiochemical purity (> 99%) and excellent in vitro stability. The preparation showed promising results in pre-clinical studies carried out in Wistar rats. The preliminary results of the first clinical investigation of 90Y-HA preparation in a patient with rheumatoid arthritis in knee joints demonstrated the effectiveness of the formulation prepared using 90Y produced via (n,γ) route in the management of the disease. Conclusion: The studies revealed that effective utilization of 90Y produced via (n,γ) route in a medium flux research reactor coupled with the

  10. Research on extracted 90Y with P204 in lipiodol for liver cancer

    Research on extracted 90Y with di(2-ethylhexyl) orthophosphoric acid (P204) in lipiodol for liver cancer was made to evaluate the stability of extracted 90Y with P204 in lipiodol (90Y-P204-lipiodol) in serum of newly-born cattle and human's blood. At first, P204 (extractant) was dissolved in lipiodol (organic phase). Secondly, 90Y was extracted to organic phase after adding 90Y solution into test tube with P204 and lipiodol in it. The extracting efficiency with 0.01 mol/l P204 could reach 99.4%. The stability of 90Y-P204-lipiodol has been experimented in physiological saline solution as preparation for further stability experiment. The result indicated that the extracted 90Y lost 0.02%-0.36% in physiological saline solution. The results of further stability experiment showed that loss efficiencies of extracted 90Y after adding newly-born cattle serum 1 hour, 1 day, 3 and 7 days are 3.38%, 3.12%, 4.29% and 6.62%, respectively, and loss efficiencies of extracted 90Y after adding human's blood 1 hour, 1 day, 3 and 7 days are 2.55%, 5.91%, 7.88% and 5.63%, respectively. Our data also indicated that 90Y is the most possible radioisotope for being extracted with P204 in lipiodol to treat hepatocellular carcinoma, particularly in cases of unresectable liver tumors, since 90Y is available from several commercial sources in clinical quality. We conclude that the stability of 90Y-P204-lipiodol tested with newly-born cattle serum and human's blood attained great results. 90Y-P204-lipiodol is a kind of potential and exciting pharmaceutical in interventional therapy for liver cancer and we can carry on the further animal test and clinical trial. (author)

  11. Spring mobilization of storage /sup 32/P in gingko trees

    Shim, K.K. (City Univ. of Seoul, Korea); Chung, K.H.; Kwon, S.H.

    1978-01-01

    The labelled phosphorus was supplied to the roots of 1-year-old gingko (Gingko biloba L.) trees during dormant period in the glass house and the mobilization of stored /sup 32/P determined in the following early growing season. /sup 32/P was detected in all growing tissues, the level of radioactivity being greatest in the root tissues over the 4-week sampling period. At dormant period, only 0.44% of /sup 32/P was found in storage tissues although the accumulation of /sup 32/P occurred especially in root tissues. During early growing season, /sup 32/P was transported from root tissues to new growing tissues. Eight percent of the initial /sup 32/P in storage tissues was transported to new growing tissues. During the period, the /sup 32/P in the bud tissues increased about 12 fold.

  12. Spring mobilization of storage 32P in gingko trees

    The labelled phosphorus was supplied to the roots of 1-year-old gingko (Gingko biloba L.) trees during dormant period in the glass house and the mobilization of stored 32P determined in the following early growing season. 32P was detected in all growing tissues, the level of radioactivity being greatest in the root tissues over the 4-week sampling period. At dormant period, only 0.44% of 32P was found in storage tissues (bark, wood and bud) although the accumulation of 32P occurred especially in root tissues. During early growing season, 32P was transported from root tissues to new growing tissues (buds). Eight percent of the initial 32P in storage tissues was transported to new growing tissues. During this period, the 32P in the bud tissues increased about 12 fold. (author)

  13. Experimental study on the radio injury action of 90Y labelled resin

    90Y generator was made by absorption 90Sr-90Y equilibrium system to Dowex 50 resin. 90Y was obtained by elution with sodium citrate buffer solution. The 90Y was mixed with Bio-Rex 70 resin, high binding rate were achieved when the pH value was more than eight and the mixing duration was 4 h. 90Y labelled resin was injected through hepatic artery catheter into the right lower lobe of liver in dog. The total blood concentration of 90Y was estimated to be 1% of total dose administered. After 2 weeks, X-CT showed that the administered liver lobe observed liquefied necrosis and liver atrophy grossly, also liver cell die away extensively in pathological sections. These preliminary findings suggested that with selective administration of hepatic artery catheterization, radiolabelled resin was an effective and safe radioinjury reagent, and can be used for tumor radiotherapy

  14. Radiopharmaceutical management of 90Y/111In labeled antibodies. Shielding and quatification during preparation and administration

    The combined application of potent β-emitting isotopes for therapy with γ-emitting isotopes for scintigraphy requires a profound regimen concerning team member safety and radionuclide quantification. We have developed materials and methods for a proper and easy manipulation of 90Y during preparation and administration of 90Y/111In pharmaceuticals used for radioimmunotherapy. The efficacy of the shielding measures is documented. Protocols for the calibration of γ-dose calibrators with respect to 90Y are extended to the assessment of quench-corrected liquid scintillation counting of 90Y. The contribution of 90Y backscatter to 111In counting is quantified. Newly developed shielding equipment allows an adequate administration of relatively large volumes (100 ml) of 90Y/111In labeled pharmaceuticals to patients. The procedures described combine pharmaceutical (Good Manufacturing Practice) and radiation safety requirements with an accurate logging of relevant data. (author)

  15. Liver radioembolization with {sup 90}Y microspheres. 2. ed.

    Bilbao, Jose Ignacio [Clinica Universidad de Navarra, Pamplona (Spain). Dept. de Radiologia; Reiser, Maximilian F. (ed.) [Universitaetsklinikum Muenchen Klinikum Grosshadern, Muenchen (Germany). Inst. fuer Klinische Radiologie

    2014-07-01

    New, up-to-date edition of the only book devoted specifically to the subject. Key basic information on how to use the procedure successfully in clinical practice. Detailed information on candidate selection, vascular anatomy, dosimetry, and treatment evaluation. Thorough summary of published results. This is the second edition of a very well received book devoted specifically to the treatment of liver tumors by radioembolization with {sup 90}Y microspheres. The success of the first edition was based on the provision of all the fundamental information required for successful use of this therapeutic modality in clinical practice. The new edition has been fully updated to cover the most recent advances and includes additional chapters on regulations and emerging trends. Detailed information is provided on the full range of relevant topics, including hepatic vascular anatomy (including variants), dosimetry, assessment of tumor response, and the results achieved using radioembolization alone and in combination with other treatments in patients with primary or metastatic disease. Complications and side-effects are also fully discussed. This book will prove immensely valuable for both beginners and practitioners.

  16. 90Y-preparation and some preliminary results on labelling of radiopharmaceuticals

    The production of 90Y by 90Sr-90Y generator was studied. 90Sr was adsorbed at a column with Aminex A-5 resin. The daughter radionuclide 90Y was eluted with 0.7 M α-hydroxyisobutyrate (α-HIB, pH5.4). Radionuclidic, radiochemical and chemical purities were >98% and yield >85%. After converting into chloride form 90YCl3-solution (pH:1) was used for preparing injectable yttrium citrate and labelling some other radiopharmaceuticals such as antibody or methylene diphosphonate (MDP). Furthermore, a fast ITLC-method for determination the content of 90Sr in 90Y-eluate was developed. (author)

  17. Hanford isotope project strategic business analysis yttrium-90 (Y-90)

    The purpose of this analysis is to address the short-term direction for the Hanford yttrium-90 (Y-90) project. Hanford is the sole DOE producer of Y-90, and is the largest repository for its source in this country. The production of Y-90 is part of the DOE Isotope Production and Distribution (IP and D) mission. The Y-90 is ''milked'' from strontium-90 (Sr-90), a byproduct of the previous Hanford missions. The use of Sr-90 to produce Y-90 could help reduce the amount of waste material processed and the related costs incurred by the clean-up mission, while providing medical and economic benefits. The cost of producing Y-90 is being subsidized by DOE-IP and D due to its use for research, and resultant low production level. It is possible that the sales of Y-90 could produce full cost recovery within two to three years, at two curies per week. Preliminary projections place the demand at between 20,000 and 50,000 curies per year within the next ten years, assuming FDA approval of one or more of the current therapies now in clinical trials. This level of production would incentivize private firms to commercialize the operation, and allow the government to recover some of its sunk costs. There are a number of potential barriers to the success of the Y-90 project, outside the control of the Hanford Site. The key issues include: efficacy, Food and Drug Administration (FDA) approval and medical community acceptance. There are at least three other sources for Y-90 available to the US users, but they appear to have limited resources to produce the isotope. Several companies have communicated interest in entering into agreements with Hanford for the processing and distribution of Y-90, including some of the major pharmaceutical firms in this country

  18. Hanford isotope project strategic business analysis yttrium-90 (Y-90)

    NONE

    1995-10-01

    The purpose of this analysis is to address the short-term direction for the Hanford yttrium-90 (Y-90) project. Hanford is the sole DOE producer of Y-90, and is the largest repository for its source in this country. The production of Y-90 is part of the DOE Isotope Production and Distribution (IP and D) mission. The Y-90 is ``milked`` from strontium-90 (Sr-90), a byproduct of the previous Hanford missions. The use of Sr-90 to produce Y-90 could help reduce the amount of waste material processed and the related costs incurred by the clean-up mission, while providing medical and economic benefits. The cost of producing Y-90 is being subsidized by DOE-IP and D due to its use for research, and resultant low production level. It is possible that the sales of Y-90 could produce full cost recovery within two to three years, at two curies per week. Preliminary projections place the demand at between 20,000 and 50,000 curies per year within the next ten years, assuming FDA approval of one or more of the current therapies now in clinical trials. This level of production would incentivize private firms to commercialize the operation, and allow the government to recover some of its sunk costs. There are a number of potential barriers to the success of the Y-90 project, outside the control of the Hanford Site. The key issues include: efficacy, Food and Drug Administration (FDA) approval and medical community acceptance. There are at least three other sources for Y-90 available to the US users, but they appear to have limited resources to produce the isotope. Several companies have communicated interest in entering into agreements with Hanford for the processing and distribution of Y-90, including some of the major pharmaceutical firms in this country.

  19. Clinical results of radionuclide therapy of neuroendocrine tumours with 90Y-DOTATATE and tandem 90Y/177Lu-DOTATATE: which is a better therapy option?

    Peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues is a treatment option for patients with disseminated neuroendocrine tumours (NET). A combination treatment using the high-energy 90Y beta emitter for larger lesions and the lower energy 177Lu for smaller lesions has been postulated in the literature.The aim of the study was to evaluate combined 90Y/177Lu-DOTATATE therapy in comparison to 90Y-DOTATATE alone. Fifty patients with disseminated NET were included in the study prospectively and divided into two groups: group A (n = 25) was treated with 90Y-DOTATATE, whereas group B (n = 25) received the 1:1 90Y/177Lu-DOTATATE. The administered activity was based on 3.7 GBq/m2 body surface area in three to five cycles, with amino acid infusion for nephroprotection. The median overall survival time in group A was 26.2 months while in group B median survival was not reached. Overall survival was significantly higher in group B (p = 0.027). Median event-free survival time in group A was 21.4 months and in group B 29.4 months (p > 0.1). At the 12-month follow-up, comparison of group A vs group B showed stable disease (SD) in 13 vs 16 patients, disease regression (RD) in 5 vs 3 patients and disease progression (PD) in 3 vs 4 patients; 4 and 2 patients died, respectively. The 24-month follow-up results were SD in nine vs ten patients, RD in one patient vs none and PD in four patients in both groups; three and four patients died, respectively. Side effects were rare and mild. The results indicate that therapy with tandem radioisotopes (90Y/177Lu-DOTATATE) provides longer overall survival than with a single radioisotope (90Y-DOTATATE) and the safety of both methods is comparable. (orig.)

  20. Separation of carrier-free 90Y from 90Sr by ion exchange chromatography

    Separation of carrier free 90Y from fission product 90Sr by column chromatography was investigated using composite inorganic ion exchanger poly antimonic acid (PAA), which was developed in house. The optimum conditions of separation were obtained by studying the distribution coefficients for 90Y from different acid solutions (HNO3, HCl and H2SO4) in concentration range of 0.001 - 3 M on the sorbent. The results indicated that after loading 90S/90Y equilibrium solution, pure carrier free 90Y was obtained from the column using 1 M HNO3 solutions as eluent. The radiochemical purity of the separated 90Y was confirmed by studying its decay curve. (author)

  1. Development of the new distillation method for 32P production

    32P as a pure β-ray emitter is widely used in nuclear medicine, genetic engineering, biological research, etc. The production process of 32P is mainly based on sulfur distillation after natural 32S(n,p)32P reaction. In this study, a new distillation process for 32P production has been developed and applied for production of 32P. Distillation and condensation of sulfur in the capsule occurred at about 180 .deg. C under 0.1 torr pressure and the distillation rate of sulfur dependened on the temperature of distillation zone. In the typical case, it took 1.5 - 2 hours for the complete distillation of 1 g of sulfur under 0.1 torr pressure and the recovery yield of sulfur was near 100%. Sulfur target in the evacuated capsule was irradiated for 72 hours in HANARO reactor and the fast neutron flux of irradiation hole was 2.8x1014 n/cm2·sec. The irradiated target was distilled at 220 .deg. C and then leached out 32P residue on the capsule surface. The yield of 32P was 8 mCi per 1g of natural sulfur and the qulity analysis of the final product was carried out for radionuclidic purity, radiochemical purity and solid residue. It is expected that the developed process can be useful for production of around 100 mCi 32P and also can be applied to produce 33P using enriched 33S targets

  2. Development of {sup 90}Sr-{sup 90}Y generators; Desenvolvimento de geradores de {sup 90}Sr-{sup 90}Y

    Barrio, Graciela, E-mail: gracielabarrio@gmail.co [Pontificia Univ. Catolica de Sao Paulo (PUC-SP), SP (Brazil). Dept. de Fisica; Osso Junior, Joao Alberto, E-mail: jaossoj@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2007-07-01

    Yttrium-90 is a radioisotope of great interest in the field of Nuclear Medicine. It is considered one of the most important and most used radionuclides for radioimmunotherapeutical applications, especially promising for the treatment of certain types of cancer. Another important application of {sup 90}Y is radio synovectomy. This radionuclide has a half-life of 64 hours, emits long range beta particles (maximum energy of 2.3 MeV) and decays, without intermediate nuclides, to a stable daughter. {sup 90}Y may be obtained carrier-free, generated by the decay of its parent {sup 90}Sr (half-life=28 years). {sup 90}Sr is a product from uranium fission, and due to its long half-life, can be indefinitely used, which is certainly advantageous. It is present in great amounts, and needs to be processed and purified in order to be used as raw material for the generators. Generators of {sup 90}Sr-{sup 90}Y may thus be used during various months, due to {sup 90}Sr long half-life. Several methods for the separation of {sup 90}Y from {sup 90}Sr by solvent extraction and ion exchange have been reported in literature. Thanks to its simplicity, ion exchange techniques have been more commonly used for this generator system. The main objective of this work was to develop a methodology for the preparation of {sup 90}Sr-{sup 90}Y generators, using cationic exchange resins. In such method, {sup 90}Sr is strongly adsorbed in the resin and {sup 90}Y is eluted by a 0.003 M EDTA solution. According to the quality control carried out, results showed that elution yields are greater than 65%, thus confirming the efficiency of the separation method used.

  3. External Beam Radiotherapy Followed by 90Y Ibritumomab Tiuxetan in Relapsed or Refractory Bulky Follicular Lymphoma

    Purpose: We combined external beam radiotherapy (EBRT) with yttrium-90 ibritumomab tiuxetan (90Y-IT) in an attempt to improve therapeutic response in patients with relapsed or refractory bulky follicular lymphoma (RRBFL). Methods and Materials: Between February 2006 and September 2007, 11 patients with RRBFL were treated with EBRT followed by 90Y-IT. Bulky disease (BD) was defined as >5 cm. EBRT was delivered to BD as 2,400 cGy in eight fractions using computed tomography (CT)-based planning. BD was contoured as the gross tumor volume. A planning margin of 1 to 2 cm was added depending on anatomical location. After recovery of complete blood counts (CBC), 90Y-IT was administered at a dose of 0.3 or 0.4 mCi/kg depending on platelet counts. Hematologic toxicity was monitored through weekly CBC. Response was measured by positron emission tomography/CT or CT 3-4 months after 90Y-IT. Results: Only 2 patients required prolonged breaks between EBRT and 90Y-IT. The median time after 90Y-IT for platelets to recover to >100,000/ml was 55 days (range, 41-128 days). Platelet counts for 1 patient, who had received 4 previous chemotherapy regimens, never reached 100,000/ml. The complete and overall responses to combined therapy as measured 3-4 months after 90Y-IT were 64%. No patients relapsed within the EBRT field. With a median follow-up of 36.1 months, 6 patients have relapsed, 2 of whom have died. Median progression-free survival was 17.5 months. Conclusions: In contrast to prior failure analysis data for RRBFL patients treated with 90Y-IT alone, a brief course of EBRT prevented relapse in sites of BD. EBRT used to pretreat bulky sites may improve clinical outcomes and potentially extend survival when combined with 90Y-IT.

  4. Therapy with {sup 90}Y microspheres: radiation protection in new medical therapies; Terapia con microesferas de {sup 90}Y: proteccion radiologica en nuevas terapias medicas

    Rojo, Ana; Puerta, Nancy, E-mail: arojo@arn.gob.ar [Autoridad Regulatoria Nuclear (ARN), Buenos Aires (Argentina)

    2013-07-01

    Primary liver cancer is one of the most frequent in the world and with a low cure rate. Radioembolization using 90y spheres is a promising treatment of this pathology and involves the percutaneous vascular application of radioisotope-labeled the order of Micron size particles. The advantages of this technique include the permit administered high doses of radiation to small volumes with low relative toxicity, offer the possibility of treating all the liver including microscopic tumors, and finally, the feasibility of combined with other therapies. Radiation protection in new medical therapies requires justification and optimization, as requirements for their implementation. The application of the principle of optimization in the context of the protection of the patient must be the minimum that it can be reasonably reached compatible with the required doses of treatment dose to healthy tissue. With {sup 90}Y microspheres therapy this optimization applies to the activity of 90y which is administered to the patient, and estimation methods are postulated. in this work are analyzed comparatively these methods, described the early physicists, equations and the limitations of each. Finally, it is concluded that the optimal method to be implemented for the evaluation of the activity of {sup 90}Y manage must be based in a voxel dosimetric model specific for each patient, however, the partitional method may be a good alternative if you don't have the tools to apply the method.

  5. Enrichment and determination of small amounts of 90Sr/90Y in water samples

    Small amounts of 90Sr/90Y can be concentrated from large volumes of surface water (100 l) by precipitation of the phosphates, using bentonite as adsorber matrix. In the case of samples containing no or nearly no suspended matter (tap water, ground water, sea water), the daughter 90Y can be extracted directly by using filter beds impregnated with HDEHP. The applicability of both techniques is demonstrated under realistic conditions. (orig.) 891 HP/orig. 892 MKO

  6. An adapted purification procedure to improve the quality of {sup 90}Y for clinical use

    Xiques Castillo, A.; Olive, K. Isaac; Casanova Gonzalez, E.; Beckford, D.; Leyva Montana, R.; Olive Alvare, E. [Centro dc Isotopos (CENTIS), La Habana (Cuba); Montero Alvarez, A. [Centro de Aplicaciones Tecnologicas y Desarrollo Nuclear, La Habana (Cuba)

    2009-07-01

    There is an increasing interest for {sup 90}Y for radionuclide therapy. However, radioimmunotherapy, one of the most important applications for {sup 90}Y, demands a very high purity product. Obtaining a high quality {sup 90}Y is difficult not only because of the complex and time consuming production schemes but also because of the quality control which has challenging tasks like the determination of {sup 90}Sr at very low concentrations. The present paper investigates a reported purification procedure for the removal of stable metal trace contaminants from an {sup 90}Y solution, seeking for its potential use in the elimination of the radioactive contaminant {sup 90}Sr and its fast determination. For this purpose a washing step with HNO{sub 3} acid is introduced to elute {sup 90}Sr, the order of each acid solution is rearranged to reduce the potential contaminants present in acids and the size of the column is reduced to further optimize the procedure. As a result, an improved purification method is obtained, which allows the removal of both trace metal contaminants and {sup 90}Sr from an {sup 90}Y solution and the measurement of {sup 90}Sr/{sup 90}Y ratios of the order of 10{sup -7}, which are well below the established pharmacopeia limit of 2 x 10{sup -5}. (orig.)

  7. 32P-postlabelling methods for cyclic DNA adducts.

    Watson, W P; Crane, A E; Steiner, S

    1993-01-01

    32P-Postlabelling procedures coupled with HPLC have been developed to detect and measure a range of cyclic DNA adducts formed by bifunctional genotoxic agents. The methods are based on reverse-phase HPLC, particularly column-switching HPLC, to enrich adduct 3'-monophosphates before labelling. Following 3'-dephosphorylation of the 3'5'-[5'-32P]bisphosphates with nuclease P1, the resulting 5'-[32P]monophosphate adducts are resolved, identified and characterized by co-chromatography with synthetic reference standards. The procedures have been applied to a number of cyclic adducts including those formed by chloroacetaldehyde, glycidaldehyde and malonaldehyde. In general, labelling efficiencies measured as chromatographed 5'-[32P]monophosphates were in the range 30-40%. However, the values for the malonaldehyde deoxyguanosine adduct were much lower. The techniques have been applied to studies on the formation of DNA adducts in the skin of male C3H mice treated cutaneously with glycidaldehyde. The HPLC-32P-postlabelling analysis of epidermal DNA hydrolysates indicated that a single major cyclic adduct was formed by reaction with deoxyadenosine residues in mouse skin DNA. The adduct was identified as a hydroxymethyl ethenodeoxyadenosine adduct by comparison with a synthetic standard. This adduct was highly fluorescent and it was possible to make quantitative comparisons of the amounts of adduct determined by either HPLC-32P-postlabelling or HPLC-fluorescence detection. PMID:8225493

  8. Separation of carrier free 90Y from 90Y -90Sr using membrane technique employing novel Calix(4)arene-diglycolamides

    90Y is one of the important radionuclides being used in targeted therapy for bone pain palliation due to its high energy β particle (β-max = 2.2MeV) and short half life (t1/2 = 64.1 hrs). The source of 90Y is either neutron activation of 89Yin reactors or separation of the daughter product of 90Sr through a suitable separation method. The neutron activation method can have large amounts of carrier in the product while the daughter product of 90Sr can be considered as carrier free tracer. There are several methods which have been used for the separation of carrier-free 90Y from 90Sr. Out of those, solvent extraction methods using diglycolamide (DGA) extractants have yielded promising results. Our recent studies with multiple DGA-functionalized ligands have indicated these to be highly efficient ligands. Thus, it was of interest to investigate the Y(III) - Sr(II) separation using these ligands. Furthermore, reports on liquid membrane based separation methods have been scarce. In the present study, we have investigated the relative transport behaviour of Y(III) and Sr(II) using flat sheet supported liquid membranes containing several DGA functionalized Calix(4)arene (hereafter termed as C4DGA) ligands with separation possibilities relevant for pharmaceutical applications. The transport studies involved feed solutions containing Y(III) or Sr(II) at 3 M HNO3 and EDTA or DOTA as the complexing agent in the receiver compartment. Highest transport rate of Y(III) was observed with L-III (>98% in 6 h) with 0.01 M EDTA as the strip solution. Transport of Sr(II) was negligible in all cases. Separation of carrier free 90Y was carried out from 90Y-90Sr mixture using L-I at 3 M HNO3 feed and EDTA and DOTA solution as receiver phase. Purity of product was measured by half life measurements. 90Y was transported into the receiver compartment with undetected Sr transport up to 120 minutes, beyond which the product was found to be slightly contaminated. The ease of method, one step

  9. Standardization of 90Sr+ 90Y by Means of a Chemical Separation

    Precipitation of strontium in a 90Sr + 90Y solution by fuming nitric acid offers an opportunity of preparing sources in which, at first, one of the two activities is much weaker than the other. If the initially weaker activity is known, the other can be calculated from the count rates measured at two suitably chosen times. A procedure is developed which quantitatively connects the specific activity of the mother solution with that of the solution dispensed onto the source mounts. The main difficulty is encountered in determining the initial 90Y activity of the 90Sr-enriched sources. Since a high degree of separation can hardly be achieved in a single precipitation, the 90Y content of the supernate has to be determined as well. If the 90Y is distributed uniformly after the precipitation, the corresponding 90Y activity retained by the precipitate can be calculated easily. Yet the 90Y concentration sometimes deviated significantly from uniformity. A way of partially circumventing this difficulty is pointed out. Exact formulae are derived expressing the activities in terms of the count rates observed at different times. A full account of the various sources of error is given; the spread of the results obtained is compatible with that expected. The specific activity of the mother solution is calculated with 15 sources prepared from four independent precipitations. The mother solution had already been calibrated by 24 laboratories taking part in an international comparison organized by the Bipm in 1964. The agreement is well within the limits of error. Although the separation method described here is too laborious to be used in routine work, it merits some attention as an independent method of standardizing a pure β-emitter by β-counting alone, without using any extrapolation. The accuracy reached compares favourably with that of currently used methods. The separation method may be superior to others when a 90Sr + 90Y solution with a high carrier content is to be

  10. Radioimmunotherapy with 90Y-labeled monoclonal antibodies in a nude mouse ovarian cancer model

    Tumor stroma contains much fibrin, and so monoclonal antifibrin antibody can accumulate in tumors. We treated nude mice bearing human ovarian carcinoma xenografts with 90Y-labeled monoclonal antifibrin antibody Fab fragments administered intratumorally. The survival time vs. a control group was significantly prolonged and tumor growth rate was decreased. Another group of animals was treated with 90Y-labeled OC 125-monoclonal antibody; these mice received the antibodies intratumorally, intraperitoneally or intravenously. The survival time was longest in the intratumorally treated group. There was no significant difference in survival between 90Y-labeled OC 125 and antifibrin in the intratumorally treated animal groups. The tissue activity distribution studies revealed that bone marrow is the critical organ. Intratumorally injected monoclonal 90Y-antifibrin antibodies were retained at least 36 h (up to 50% of injected activity per gram tumor tissue) in the xenograft after one treatment, causing cell death. Beta-camera imaging and immunohistochemistry were performed for studies of the correlation between 90Y activity and fibrin distribution in tumor specimens. These results were in concordance. In conclusion, intratumoral administration seems suitable for radioimmunotherapy, with an antibody that targets stromal structures. The accumulation can be successfully monitored by a beta-camera. (orig.)

  11. Experimental study on 32P uptake in vivo

    Disturbances in the development of the teeth which were caused by internal irradiation of 32P were studied using rats of Wister strain about one month old. The experiment with a dose of 7 μc/g of 32P showed that 4 of 30 rats died within 90 days of observation. The experiment with a dose of 10 μc/g of 32P showed that none of the rats survived longer than 18 days. Correlationship was found among increase and decrease of the body weight, myelogram of the femoral bone, and ability of the tooth development. The disturbances showed a peak about 20 days after the administration of 32P and then subsided. As regards the relationship between the mechanisms of tooth formation and tooth eruption, reformation of the dentine was noted but no recovery of tooth eruption was noted 30 days after 32P-administration. Some recovery from disturbance of the tooth formation could be observed after 30 days of the administration of 32P. 90 days after the administration, dentin formation could still be noted in the apical part, while germ cells of the tooth had been destroyed completely and peridental tissues had also been destroyed remarkably. Persistent osteoid dentin, characteristic of disturbance of the incisor due to internal irradiation, proliferated in a shape of a belt along the dentin blastocytes in the labial side, gradually infiltrating into the center of the dental pulp. The osteoid dentin proliferated in a shape of lump in the dental germ of the lingual side. In the experiments with 7 μc/g, there was left a possibility of maintaining vital power of rats judging from their weights and myelogram of the femoral bone, while the dose had destructive effects on the incisors. This was substantiated by the fact that the absorbed dose of the incisor was highest among those of the hard tissues. (Ueda, J.)

  12. Use of 32P in aluminum sensibility tests with bean

    Four greenhouse experiments were conducted to study the possibility of using 32P in aluminium tolerance tests of bean (Phaseolus vulgaris L.). The cultivars were previously classified according to dry matter yield date by regression analysis as aluminium tolerant (C20-Mulatinho Paulista; C26-Ricobaio 1014 and C33-Roxo 750) and aluminium sensitive (C17-Jamapa; C28-Rio Tibagi and C34-Tambo). Chopped roots from plant grown in a complete nutrient solution during 30 days and submerged in another solution containing aluminium showed to be a reliable indicator of 32P absorption efficiency to aluminium tolerant and sensitive cultivars. (M.A.C.)

  13. Calibration of the 90Sr+90Y ophthalmic and dermatological applicators with an extrapolation ionization minichamber

    90Sr+90Y clinical applicators are used for brachytherapy in Brazilian clinics even though they are not manufactured anymore. Such sources must be calibrated periodically, and one of the calibration methods in use is ionometry with extrapolation ionization chambers. 90Sr+90Y clinical applicators were calibrated using an extrapolation minichamber developed at the Calibration Laboratory at IPEN. The obtained results agree satisfactorily with the data provided in calibration certificates of the sources. - Highlights: • 90Sr+90Y clinical applicators were calibrated using a mini-extrapolation chamber. • An extrapolation curve was obtained for each applicator during its calibration. • The results were compared with those provided by the calibration certificates. • All results of the dermatological applicators presented lower differences than 5%

  14. Fast determination of 90Sr/90Y activity in milk by Cherenkov counting

    Cherenkov counting of the 90Sr/90Y pure beta emitters is an attractive method for 90Sr activity determination, but the color quenching effect may be significant, especially for strongly colored or semi-opaque media. A quench correction method based on the external source of some liquid scintillation systems (named ESAR – external source area ratio) was proposed and checked for aqueous solutions and was proved to be effective also for urine samples. In the present work, the application of the ESAR method for fast determination of 90Sr/90Y activity in milk samples is described. - Highlights: • A new color quenching correction method (ESAR) for Cherenkov counting was tested. • It uses the spectrum of the 152Eu outer source of a Quantulus 1220TM system. • The method was applied for fast 90Sr/90Y determination in milk. • The method works for a great variety of milk products from different animals, with different fat contents

  15. Determination of 90Sr–90Y activity in urine samples by using Cherenkov counting

    Cherenkov counting of the 90Sr–90Y pure beta emitters in aqueous samples is an attractive method; but color quenching correction is needed, this being especially significant for urine which is characterized by a strong coloration. A quench correction method based on the external source of some liquid scintillation systems (named ESAR—External Source Area Ratio) was proposed for aqueous solutions. In the present work, the application of the ESAR method for determination of 90Sr–90Y in human urine samples is described. - Highlights: ► A new color quenching correction method (ESAR) was tested for Cherenkov counting. ► It uses the spectrum of the 152Eu outer source of a Quantulus 1220™ system. ► The method was applied for 90Sr–90Y determination in urine samples. ► Results within the range of 11.5% from target values were obtained in blind tests of urine samples

  16. Modeling of biodistribution of 90 Y-DOTA-hR3 by using artificial intelligence techniques

    In this work the biodistribution of radioimmunoconjugate 90Y-DOTA-hR3 was modeled by using an artificial neural network. In vivo stability of 90Y-DOTA-hR3 was determined in healthy male Wistar rats at 4, 24 and 48 hours, in different organs. A model describing the relationship between, by one hand, the incorporated dose and, by the other hand, organ and time was developed by using a multilayer perceptron neural network. Adjusted model was analyzed by several statistical tests. Outcomes shown that proposed neural model describes the relationship between the studied variables in a proper way. (Author)

  17. Preliminary therapeutic treatment of 90Y-EDTMP for the bone metastatic pain

    To relieve bony pain due to disseminated bone metastases, 72 patients were treated with 90Y-EDTMP with dosage of 7.4-9.25 mBq/kg in 122 times. 53 patients were followed, among them 13 had significant pain relief, 28 effective, the overall effective ratio was 77.4%(41/53). In 17 patients transient decreasing of the peripheral blood cell occurred, and 7 patients had reactive pain aggravation in short duration. No irreversible bone marrow depression and liver function injury was found. It was considered 90Y-EDTMP is an easy, less side effect and effective method for the relief of bone metastatic pain

  18. The somatostatin receptor-targeted radiotherapeutic [90Y-DOTA-dPhe1,Tyr3]octreotide (90Y-SMT 487) eradicates experimental rat pancreatic CA 20948 tumours

    Somatostatin receptor-expressing tumours are potential targets for therapy with radiolabelled somatostatin analogues. We have synthesized a number of such analogues in the past and identified [DOTA-dPhe1, Tyr3]octreotide (SMT 487) as the most promising candidate molecule because of its advantageous properties in cellular and in vivo tumour models. In the current paper we describe the radiotherapeutic effect of yttrium-90 labelled SMT 487 in Lewis rats bearing the somatostatin receptor-positive rat pancreatic tumour CA 20948. SMT 487 binds with nanomolar affinity to both the human and the rat somatostatin receptor subtype 2 (sst2) (human sst2 IC50=0.9 nM, rat sst2 IC50=0.5 nM). In vivo, 90Y-SMT 487 distributed rapidly to the sst2 expressing CA 20948 rat pancreatic tumour, with a tumour-to-blood ratio of 49.15 at 24 h post injection. A single intravenous administration of 10 mCi/kg 90Y-SMT 487 resulted in a complete remission of the tumours in five out of seven CA 20948 tumour-bearing Lewis rats. No regrowth of the tumours occurred 8 months post injection. Control animals that were treated with 30 μg/kg of unlabelled SMT 487 had to be sacrificed 10 days post injection due to excessive growth or necrotic areas on the tumour surface. Upon re-inoculation of tumour cells into those rats that had shown complete remission, the tumours disappeared after 3-4 weeks of moderate growth without any further treatment. The present study shows for the first time the curative potential of 90Y-SMT 487-based radiotherapy for somatostatin receptor-expressing tumours. Clinical phase I studies with yttrium-labelled SMT 487 have started in September 1997. (orig.)

  19. Development of a 90Sr/90Y electrochemical generator in Brazil

    Yttrium-90 based radiopharmaceuticals for therapy are nowadays a powerful tool for cancer treatment. Among their main applications are radioimmunotherapy and radiosynoviortesis. In order to make this radioisotope widely available for research and application, it is necessary an in-house production with the help of a suitable generator. The electrochemical generator is a proper solution because there are no significant effects of the radiation on the generator itself. One of the main advantages of this method is that, by appropriately adjusting the volume of the solution used for final dissolution, 90Y could be obtained at high radioactivity concentrations. The aim of this work is to show the preliminary results coming from the development of a 90Sr/90Y electrochemical generator at IPEN-CNEN/SP. In this generator, on applying a suitable electric potential, 90Y can be selectively deposited at the cathode from a mixture of 90Sr and 90Y. The experiments were performed using a simple electrochemical device, with two Platinum electrodes acting as cathode and anode. Several parameters were varied, such as time and current of the electrodeposition, pH of the solution and cation concentration. After that the experiments were performed using the following gamma emitting radiotracers: 88Y and 85Sr which were prepared irradiating Y oxide and Sr nitrate at the IEA-R1m Nuclear Reactor, respectively. The results so far showed that Sr is not electroplated in any condition and that up to 40% of Y can be selectively electroplated. (author)

  20. Therapy with 90Y microspheres: radiation protection in new medical therapies

    Primary liver cancer is one of the most frequent in the world and with a low cure rate. Radioembolization using 90y spheres is a promising treatment of this pathology and involves the percutaneous vascular application of radioisotope-labeled the order of Micron size particles. The advantages of this technique include the permit administered high doses of radiation to small volumes with low relative toxicity, offer the possibility of treating all the liver including microscopic tumors, and finally, the feasibility of combined with other therapies. Radiation protection in new medical therapies requires justification and optimization, as requirements for their implementation. The application of the principle of optimization in the context of the protection of the patient must be the minimum that it can be reasonably reached compatible with the required doses of treatment dose to healthy tissue. With 90Y microspheres therapy this optimization applies to the activity of 90y which is administered to the patient, and estimation methods are postulated. in this work are analyzed comparatively these methods, described the early physicists, equations and the limitations of each. Finally, it is concluded that the optimal method to be implemented for the evaluation of the activity of 90Y manage must be based in a voxel dosimetric model specific for each patient, however, the partitional method may be a good alternative if you don't have the tools to apply the method

  1. Surface dose rate measurement of 90Sr/90Y ophthalmic applicator: a comparative study

    Removable ophthalmic plaques are used in treatment of malignant melanoma of the uvea, post-operative irradiation in treatment of pterygium and other superficial lesions. 90Sr/90Y ophthalmic applicator uses 90Y(T1/2 64 hours) present in secular equilibrium with its parent 90Sr(T1/2 = 28 years). Filters (AI, Stainless Steel) in the front surface flatten the energy spectrum, absorb most of the low energy beta particles from 90Sr (0.54 MeV) and also permits the high-energy beta from 90Y (2.27 MeV) to enter the eye. Different methods have been used to quantify surface dose rate of ophthalmic applicators. Surface dose rate representing the applicator characteristic allows a convenient way for evaluation and correlation of results using different procedures. Experiments were performed to measure the surface dose rate of 90Sr/90Y planar ophthalmic applicator (Tracerlab, U.S.A.) by the reference method using extrapolation chamber and the GAFChromic MD-55 films

  2. Synthesis and biological property evaluation of 90Y radiolabeled glycosylated somatostatin

    Natural somatostatin (SMS), dextran-70 (Dx70) and a bifunctional chelator 2-methyl-6-(p-amidobenzyl) -diethylenetriaminepentaacetic acid (1B4M-DTPA) were used to synthesize a novel somatostatin-dextran-DTPA (SMS-Dx70-DTPA) conjugate and radiolabeled with 9OY. An in vitro somatostatin receptor competition binding study was carded out by using 125I-Tyr3-Octreotide as a radioligand to measure the IC50 value of SMS-Dx70-DTPA. Biodistribution and blood half-life of 90Y-DTPA-Dx70-SMS were investigated in normal rats. The results show that SMS-Dx70-DTPA has a high receptor binding affinity to somatostatin receptor subtype 2, with the IC50 value being in the same range as somatostatin. The blood half-life of 90Y-DTPA-Dx70-SMS in normal rats was 6.39h post-injection. Digestion and excretion of 90Y-DTPA-Dx70-SMS was mainly through the hepatobiliary and kidney systems. Increased uptake was seen in the adrenals and pancreas, and it kept almost constant during 24h. Therefore 90Y-DTPA-Dx70-SMS has targeting properties towards somatostatin receptor positive organs and it may become a promising therapeutic agent candidate for somatostatin receptor positive tumors. (authors)

  3. Uncertainties in measurement of 90Y and 177Lu activities in an ionisation chamber

    Full text of publication follows. Accurate measurement of administered activity is essential in radionuclide therapy. However, this can be difficult to perform using a standard ionisation chamber, particularly with beta emitting radionuclides where measurements are greatly affected by the type of container (e.g. glass vial vs plastic syringe) in which the activity is contained, as well as the shape and volume of the sample. Methods: All measurements were taken with one of two ionisation chambers of the same model (Capintec CRC-15R). Shipments were received from two different suppliers of 90Y (Polatom; Eckert-Ziegler-EZ) and two suppliers of 177Lu (ITG Munich; Advanced Accelerator Applications-AAA). The quantities of 90Y varied from 2.5-7.4 GBq and of 177Lu from 3.3-8.4 GBq. The calibration factors used to make measurements in the glass vials supplied were 62*10 for 90Y and 450*10 for 177Lu. A reference sample of 177Lu was sent to the UK National Physical Laboratory, Teddington, for absolute calibration. Results: Compared to the manufacturer's calibration, the activities received were (88±23%) for Polatom 90Y (n=7), (103±5%) for EZ 90Y (n=56), (94±2%) for ITG 177Lu (n=93) and (112±5%) for AAA 177Lu (n=14). The large variation in measurements on Polatom 90Y was due to one shipment at 36%; without that value the mean was (96±4%) (n=6). With AAA 177Lu there was a step change during the process with the initial shipments reading significantly higher than the later ones: (115±1%) (n=10) vs (105±4%) (n=4). With 90Y a different calibration factor was required for doses drawn into syringes (49*10), whereas with 177Lu the same value could be used; this is presumably due to the contribution of the gamma emissions of 177Lu. Cross calibration with the national metrology institute showed that our measurements were within about 1% of the accepted value for 177Lu. Conclusions: Accurate measurement of beta emitters used in radionuclide therapy requires careful attention

  4. Change in total lesion glycolysis and clinical outcome after 90Y radioembolization in intrahepatic cholangiocarcinoma

    Introduction: Our aim was to assess the prognostic value of post-treatment decrease in total lesion glycolysis (ΔTLG) assessed by 2-[18 F]-fluorodeoxyglucose ([18 F] FDG) PET-CT performed 6 weeks after 90Y radioembolization (90Y RE) in patients affected by intrahepatic cholangiocarcinoma (ICC). Methods: A total of 18 patients were accepted into our department for 90Y RE. Before the procedure, all patients underwent [18 F] FDG PET-CT, and total lesion glycolysis was calculated. Six weeks after 90Y administration, PET scan was performed, and ΔTLG was determined. Patients underwent follow up by imaging and laboratory at quarterly intervals until death or for at least 24 months from 90Y RE. Furthermore, subjects were divided in 2 groups (group 1: 6 weeks ΔTLG > 50%, group 2: ΔTLG < 50%). Kaplan–Meier method was used to achieve time to progression (TTP) and overall survival (OS) curves for each group. TTP and OS curves were compared to demonstrate eventual relevant differences between the 2 groups. Results: Seventeen patients underwent 90Y RE, and one subject was considered ineligible. According to PET Response Criteria in Solid Tumors, partial response was found in 14 patients (82.4%), stable disease in 3 (17.6%). No patient showed complete metabolic response. The mean OS for all patients was 64.5 ± 5.0 weeks. Subjects with a ΔTLG > 50% and ΔTLG < 50% had a mean OS of 79.6 ± 3.6 and 43.1 ± 2.0 weeks, respectively (p < 0.001). TTP resulted of 28.9 ± 3.8 weeks for the whole cohort. Patients with ΔTLG > 50% had a significantly longer TTP (mean 36.9 ± 3.6 weeks) than those with ΔTLG < 50% (mean 13.7 ± 1.7 weeks, p = 0.001). Conclusion: Our results indicate that 90Y RE can be an effective and safe therapy for ICC. ΔTLG calculated on post-treatment [18 F] FDG PET-CT agrees with patients' final outcome

  5. A dosimetry evaluation of 90y-stent implantation in intracoronary radiation treatment

    Karimian Alireza

    2013-01-01

    Full Text Available Ionizing particles have been used for the treatment of atherosclerosis. Internal irradiation is commonly carried out by means of several methods (catheter-based systems, radioactive stents or balloons to reduce the probability of restenosis. 90Y, due to some of its characteristics, is an appropriate radioisotope for intravascular brachytherapy. However, since there are some critical tissues in the vicinity of the heart like the breast and lymph nodes, it is necessary to perform a dosimetry calculation around the artery under radiotherapy to justify the treatment method. In this study, a 3-D dose distribution was obtained for the coronary vessel and its surrounding tissues for a standard 90Y stent in a MCNPX program. The results were compared with other investigations on restenosis prevention using 90Y-coated stents. The calculations represented a 28-day cumulative dose between 1230 cGy and 2400 cGy at 0.1 mm from the stent surface, while this quantity was about 23.8 cGy at 8.5 mm from the stent surface. An assessment of the dose equivalent and effective dose was also performed at r = 8.5 mm for the mentioned surrounding tissues which may be located in the area, based on the latest changes in ICRP recommendations. Additionally, the dose equivalent calculated within the treatment period for these organs was compared with published dosimetry data for 90Sr/90Y seed sources in order to evaluate radiation protection concerns about these two radiotherapy methods. It has been found that, depending on stent parameters, 90Y stent implantation might increase the unfavorable side effects for the patient, but to a much lesser degree than the other methods.

  6. Posttherapy radiation safety considerations in radiomicrosphere treatment with 90Y-microspheres.

    Gulec, Seza A; Siegel, Jeffry A

    2007-12-01

    Radiomicrosphere treatment involves the intrahepatic arterial administration of (90)Y-resin or (90)Y-glass microspheres. The microspheres are biocompatible, but not biodegradable, and little to no (90)Y leaches from the microspheres. Without any bioelimination, the beta-dose delivery is generally confined to the liver. Although U.S. Nuclear Regulatory Commission requirements permit patients treated with these microspheres to be released without the need for dose determination or patient instructions, there are important radiation safety issues that need scientific clarification. We carefully evaluated the radiation exposure mechanisms, including the bremsstrahlung radiation doses to others, for a variety of lifestyle behaviors. Dose estimates were also made for several practical and theoretic situations involving the patient's gonads, an embryo or fetus, and a nursing infant. For the infant, we evaluated the potential beta-dose that might be introduced via breast milk ingestion. The bremsstrahlung component of the decay scheme of the pure beta-emitter (90)Y has traditionally been ignored in internal and external dose calculations. Because the production of in vivo bremsstrahlung with the high-energy pure beta-particle-emitting radionuclides used for therapeutic purposes is sufficient to permit external detection and imaging, we believe that the contribution of such radiation should be considered with regard to patient release; we therefore chose to evaluate this potential external radiation hazard. In all cases, the estimated doses were very small, indicating that no patient restrictions are required for radiation safety purposes after the release of a patient who has been treated with (90)Y-microspheres. PMID:18006608

  7. Preparation and quality control and biodistribution studies of [90Y]-DOTA-cetuximab for radioimmunotherapy

    Yttrium-90 is a useful radionuclide for radioimmunotherapy (RIT) and the anti-epidermal growth factor receptor (anti-EGFR) antibody cetuximab is clinicsally approved for the treatment of EGFR-expressing metastatic colorectal cancer and advanced head and neck cancer. Thus in this work radiolabeling of monoclonal anti-EGFR with 90Y for radioimmunotherapy (RIT) is targeted. Cetuximab was successively labeled with [90Y] chloride (74 MBq) 2 mCi after conjugation with macrocyclics bifunctional chelating agent, 1,4,7,10-tetraazacyclododecane-N,N',N',N'-tetraacetic acid mono-(N-hydroxysuccinimidyl) ester (DOTA-NHS), purified and concentrated by centrifugation using an Amicon Ultra-15 filter (Millipore, MWCo, 30000). 90Y chloride was obtained by 90Sr/90Y generator. Radiolabeling was completed in 2 h by the addition of DOTA-cetuximab conjugate at 42 °C. The stability of radiolabeled was studied in human serum. Biodistribution studies in normal rats were carried out to determine the radioimmunoconjugate distribution up to 96 h. Radiochemical purity of 92 % (using ITLC) was obtained for final radioimmunoconjugate (Specific activity = 0.55 GBq/mg). Stability of radiolabeled protein in presence of human serum was tested at 37 °C for up to 24 h. Biodistribution studies demonstrated the highest ID/g % in the blood (2.62 ± 0.005 at 24 h) and the liver (2.19 ± 0.001). This study demonstrated that 90Y-DOTA-cetuximab is a potential compound for the treatment of EGFR-expressing cancers. (author)

  8. Leaf absorption of 32P in the pumpkin

    The author presents a method to study the influence of various factors of the absorption of 32P applied under the form of phosphates by a plant cultivated in conditions ensuring a normal development. Experiments provided indications on leaf absorption and 32P transport by pumpkin leaves: phosphor 32 is absorbed and then quickly transported into the different organs of the plant (24 hours after treatment, it is present in aerial and underground parts), the quantity of absorbed phosphor increases with phosphor concentration in the applied solution, atmosphere humidity is an important factor for phosphor penetration into the leaves, plants absorb phosphor in darkness as well as in light, and the absorption of phosphor is not modified when applied with low glucose concentrations

  9. MO-G-17A-06: Kernel Based Dosimetry for 90Y Microsphere Liver Therapy Using 90Y Bremsstrahlung SPECT/CT

    Mikell, J; Siman, W; Kappadath, S [The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX (United States); University of Texas MD Anderson Cancer Center, Houston, TX (United States); Mahvash, A [University of Texas MD Anderson Cancer Center, Houston, TX (United States); Mourtada, F [Christiana Care Hospital, Newark, DE (United States)

    2014-06-15

    Purpose: 90Y microsphere therapy in liver presents a situation where beta transport is dominant and the tissue is relatively homogenous. We compare voxel-based absorbed doses from a 90Y kernel to Monte Carlo (MC) using quantitative 90Y bremsstrahlung SPECT/CT as source distribution. Methods: Liver, normal liver, and tumors were delineated by an interventional radiologist using contrast-enhanced CT registered with 90Y SPECT/CT scans for 14 therapies. Right lung was segmented via region growing. The kernel was generated with 1.04 g/cc soft tissue for 4.8 mm voxel matching the SPECT. MC simulation materials included air, lung, soft tissue, and bone with varying densities. We report percent difference between kernel and MC (%Δ(K,MC)) for mean absorbed dose, D70, and V20Gy in total liver, normal liver, tumors, and right lung. We also report %Δ(K,MC) for heterogeneity metrics: coefficient of variation (COV) and D10/D90. The impact of spatial resolution (0, 10, 20 mm FWHM) and lung shunt fraction (LSF) (1,5,10,20%) on the accuracy of MC and kernel doses near the liver-lung interface was modeled in 1D. We report the distance from the interface where errors become <10% of unblurred MC as d10(side of interface, dose calculation, FWHM blurring, LSF). Results: The %Δ(K,MC) for mean, D70, and V20Gy in tumor and liver was <7% while right lung differences varied from 60–90%. The %Δ(K,MC) for COV was <4.8% for tumor and liver and <54% for the right lung. The %Δ(K,MC) for D10/D90 was <5% for 22/23 tumors. d10(liver,MC,10,1–20) awere <9mm and d10(liver,MC,20,1–20) awere <15mm; both agreed within 3mm to the kernel. d10(lung,MC,10,20), d10(lung,MC,10,1), d10(lung,MC,20,20), and d10(lung,MC,20,1) awere 6, 25, 15, and 34mm, respectively. Kernel calculations on blurred distributions in lung had errors > 10%. Conclusions: Liver and tumor voxel doses with 90Y kernel and MC agree within 7%. Large differences exist between the two methods in right lung. Research reported in this

  10. Some preliminary results on labelling of 1-hydroxyethylene-diphosphonic acid (HEDPA) with 90Y

    The interest for radiopharmaceuticals for direct management of serious illness and specially cancer and rheumatism has increased during the last decade. Such radioisotopes as 89Sr, 186Re, 153Sm, 90Y and 166Ho are now used routinely in the practice of medical clinics. The tendency is to concentrate the studies in designing radioparmaceuticals that fulfill these important requirements: a) realize a high absorbing dose in malign cells in the shortest time and b) not damage the healthy cells. Radioisotopes that emit α and β particles generally fulfill these requests. 90Y is one of the radioisotopes of the choice. 90Y has a LET useful for therapy. Eβmax = 2.3 MeV, T1/2=64.1 h with no gamma emissions. 90Y is produced from the homemade 90Sr-90Y generator. 90Sr was fixed in Aminex-5 ion-exchange resin of Bio-Rad Company. The 90Sr-90Y generator consist of three chromatographic columns, the first was loaded 90Sr, the second is for safety reason, with aim to fix breakthrough of 90Sr from first column and the third column transforming 90Y from organic complex form (α-hydroxyisobutyrate) in inorganic (cationic) form. The solution of 90Y produced is of high purity and useful for labeling sensitive molecules. This 90Y solution is used for labeling 1-hydroxyethylenediphosphonic acid (HEDPA). The structural formula of HEDPA is given. Following reaction home makes HEDPA: PCl3 + CH3COOH → HEDPA The aim of the work was to study the conditions of labeling, investigate yield of labeling, and the stability of constitute complex. 1. Initially the capability of complexion of HEDPA with 90Y was studied. For this purpose it is used HPLC method to check formation of HEDPA-Y complex. It is mixed 1 ml of HEDPA solution (concentration 1mg/ml) with 0.1 ml solution of YCl3 at pH∼5 (concentration 0.1mg/ml). It is compared RT of pure HEDPA with potentially formed complex. The reaction mixture has been studied by using HPLC system of KNUER Company and NucleosilmC18 5μm, as a column. As elute

  11. Using Cherenkov Counting For Fast Determination of 90Sr/90Y Activity in Milk

    90Sr is one of the main long-lived fission products, and it is transferred into human body primarily by food, with milk being a substantial contributor. Due to its biochemical similarity to calcium, most strontium is efficiently incorporated into bone tissues. 90Sr is characterized by a long physical half life (28.8 y) and decays by beta particles with an Emax of 0.546 MeV to 90Y. This daughter isotope has a half life of 64 h and decays into 90Zr by beta particles with an Emax of 2.284 MeV. The milk components produce a high turbidity and light attenuation, causing a significant decrease of the counting efficiency in liquid scintillation counting (LSC) systems, mostly used for beta emitters detection. Most methods proposed in the past are time-consuming, as they are based on several stages of chemical and physical treatments, including precipitation, ashing, ion exchange and extraction (Wikins et al., 1984, Porter et al, 1961, Kimura et al., 1979). When measuring 90Sr/90Y activity by Cherenkov counting, most of the Cherenkov radiation is produced by 90Y (about 98.6%), due to the much higher energy of its beta particles relative to these from 90Sr. The counting efficiency varies strongly with color quenching, at a greater extent than in standard liquid scintillation counting (L'Annunziata, 2012), and therefore the quench correction is critical. The ‘‘external source area ratio’’ (ESAR) quench correction method was applied to measure 90Sr/90Y activities in aqueous samples with a wide range of quenching levels (Tsroya et al., 2009). This method was proved to be superior to all other quench correction methods (Tsroya et al., 2012) and is applicable also for determination of 90Sr/90Y in human urine (Tsroya et al., 2013). In the present work the applicability of the ESAR method to measurement of 90Sr/90Y activities in milk and some of its products was investigated

  12. Disproof of solar influence on the decay rates of 90Sr/90 Y

    Kossert, Karsten; Nähle, Ole J.

    2015-09-01

    A custom-built liquid scintillation counter was used for long-term measurements of 90Sr/90 Y sources. The detector system is equipped with an automated sample changer and three photomultiplier tubes, which makes the application of the triple-to-double coincidence ratio (TDCR) method possible. After decay correction, the measured decay rates were found to be stable and no annual oscillation could be observed. Thus, the findings of this work are in strong contradiction to those of Parkhomov (2011) who reported on annual oscillations when measuring 90Sr/90 Y with a Geiger-Müller counter. Sturrock et al. (2012) carried out a more detailed analysis of the experimental data from Parkhomov and claimed to have found correlations between the decay rates and processes inside the Sun. These findings are questionable, since they are based on inappropriate experimental data as is demonstrated in this work. A frequency analysis of our activity data does not show any significant periodicity.

  13. Disproof of solar influence on the decay rates of 90Sr/90Y

    Kossert, Karsten

    2014-01-01

    A custom-built liquid scintillation counter was used for long-term measurements of 90Sr/90Y sources. The detector system is equipped with an automated sample changer and three photomultiplier tubes, which makes the application of the triple-to-double coincidence ratio (TDCR) method possible. After decay correction, the measured decay rates were found to be stable and no annual oscillation could be observed. Thus, the findings of this work are in strong contradiction to those of Parkhomov [1] who reported on annual oscillations when measuring 90Sr/90Y with a Geiger-M\\"uller counter. Sturrock et al. [2] carried out a more detailed analysis of the experimental data from Parkhomov and claimed to have found correlations between the decay rates and processes inside the Sun. These findings are questionable, since they are based on inappropriate experimental data as is demonstrated in this work. A frequency analysis of our activity data does not show any significant periodicity.

  14. Receptor-mediated radiotherapy with 90Y-DOTA-D-Phe1-Tyr3-octreotide

    A newly developed somatostatin radioligand, DOTA-[D-Phe1-Tyr3]-octreotide (DOTATOC), has been synthesised for therapeutic purposes, because of its stable and easy labelling with yttrium-90. The aim of this study was to determine the dosage, safety profile and therapeutic efficacy of 90Y-DOTATOC in patients with cancers expressing somatostatin receptors. We recruited 30 patients with histologically confirmed cancer. The main inclusion criterion was the presence of somatostatin receptors as documented by 111In-DOTATOC scintigraphy. 90Y-DOTATOC was injected intravenously using a horizontal protocol: patients received equivalent-activity doses in each of three cycles over 6 months. The first six patients received 1.11 GBq per cycle and the four successive groups of six patients received doses increasing in 0.37-GBq steps. Toxicity was evaluated according to WHO criteria. No patient had acute or delayed adverse reactions up to 2.59 GBq 90Y-DOTATOC per cycle (total 7.77 GBq). After a total dose of 3.33 GBq, one patient developed grade II renal toxicity 6 months later. The maximum tolerated dose per cycle has not yet been reached, although transient lymphocytopenia has been observed. Total injectable activity is limited by the fact that the maximum dose tolerated by the kidneys has been estimated at 20-25 Gy. Complete or partial tumour mass reduction occurred in 23% of patients; 64% had stable and 13% progressive disease. It is concluded that high activities of 90Y-DOTATOC can be administered with a low risk of myelotoxicity, although the cumulative radiation dose to the kidneys is a limiting factor and requires careful evaluation. Objective therapeutic responses have been observed. (orig.)

  15. Efficiency calibration of a liquid scintillation counter for 90Y Cherenkov counting

    In this paper a complete and self-consistent method for 90Sr determination in environmental samples is presented. It is based on the Cherenkov counting of 90Y with a conventional liquid scintillation counter. The effects of color quenching on the counting efficiency and background are carefully studied. A working curve is presented which allows to quantify the correction in the counting efficiency depending on the color quenching strength. (orig.)

  16. Pathologic response and microdosimetry of 90Y microspheres in man: Review of four explanted whole livers

    Introduction: Radioactive microsphere 90Y therapy is increasingly used for primary and metastatic solid tumors in the liver. We present an analysis of 4 explanted livers previously treated with 90Y microsphere agents (glass or resin). One tumor nodule was analyzed with submillimeter three-dimensional microdosimetry. Methods and materials: Four patients received hepatic artery delivery of 90Y microspheres for unresectable hepatocellular and colon cancers. Whole livers were explanted as part of lifesaving cadaveric transplant in 2 patients with hepatoma. These patients had received glass microspheres as a procedural bridge to transplant. Autopsy was performed on 2 patients with colon cancer who died of progressive metastatic disease and who had been treated with resin microspheres. Complete pathologic review was performed on each whole liver, including estimation of the response of the tumor to therapy, distribution of microspheres in the tumor and normal liver tissues, and normal-tissue radiation response. A biopsy taken from the edge of a tumor nodule was sectioned serially for three-dimensional radiation dosimetry analyses. Three-dimensional microsphere coordinates within the biopsy specimen were used to calculate dosage using a three-dimensional dose kernel. Isodose coverage of tumor and normal liver areas and total dose delivered were determined. Results: Preferential and heterogeneous deposition of microspheres was noted at the edge of tumor nodules compared with the center portion of the tumor or normal liver parenchyma. Both glass and resin microspheres delivered high cumulative doses to the tumor, which varied from 100 Gy to more than 3000 Gy. No veno-occlusive disease or widespread radiation hepatitis was seen. Conclusion: Microsphere (90Y) therapy delivers high numbers of spheres with resulting high total doses of radiation, preferentially in the periphery of tumors. Normal liver parenchyma showed little radiation effect away from the tumors. Heterogeneous

  17. Studying on process for labeling of EDTMP with 90Y using for bone pain palliation

    This Study describes the method for preparation of labelling compound Ethylene diamine tetramethylene phosphonic acid (EDTMP) with 90Y. Malignant cancer is one of the most important resulting in human death. Bone metastases in nearly 25% of all cancer patients; so it is useful to develop radiopharmaceuticals for the treatment of bone cancer. Yttrium-90 is high energy (2.3 MeV) beta emitter required with a physical haft life of 2.7 days which has limited bone-seeking properties. Its physical properties make it ideal for therapeutic application, the most energetic beta emission being able to penetrate to 1 cm from the site of deposition in soft tissue with an average range of approximately 4 mm. Theoretically, therefore, it can penetrate all marrow spaces in normal trabecular bone and conceivably even to the centre of large tumours where bone destruction may be extensive. Specific deposition of 90Y into the skeleton demands its delivery in a chemical form with affinity for bone mineral alone. Compounds with these properties are the phosphonate analogues of polyaminocarboxylic acids, and one in particular EDTMP (ethylen diamine tetra methylene phosphonate) has already been used to target 153Sm to bone mineral with success. Because of chemical similarities between 90Y and the rare earths, EDTMP should form stable complexes with 90Y and carry it specifically to the bone with comparable efficiency. Skeletal uptake of -emitting radionuclides may be used for bone pain palliation or myeloablation. The physical characteristics of the β- particles required for the two conditions are, however, different, that is, higher energies are favorable for destruction of bone marrow. (author)

  18. Development of a {sup 90}Sr/{sup 90}Y electrochemical generator in Brazil

    Barrio, Graciela; Osso Junior, Joao A., E-mail: gracielabarrio@usp.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2009-07-01

    Yttrium-90 based radiopharmaceuticals for therapy are nowadays a powerful tool for cancer treatment. Among their main applications are radioimmunotherapy and radiosynoviortesis. In order to make this radioisotope widely available for research and application, it is necessary an in-house production with the help of a suitable generator. The electrochemical generator is a proper solution because there are no significant effects of the radiation on the generator itself. One of the main advantages of this method is that, by appropriately adjusting the volume of the solution used for final dissolution, {sup 90}Y could be obtained at high radioactivity concentrations. The aim of this work is to show the preliminary results coming from the development of a {sup 90}Sr/{sup 90}Y electrochemical generator at IPEN-CNEN/SP. In this generator, on applying a suitable electric potential, {sup 90}Y can be selectively deposited at the cathode from a mixture of {sup 90}Sr and {sup 90}Y. The experiments were performed using a simple electrochemical device, with two Platinum electrodes acting as cathode and anode. Several parameters were varied, such as time and current of the electrodeposition, pH of the solution and cation concentration. After that the experiments were performed using the following gamma emitting radiotracers: {sup 88}Y and {sup 85}Sr which were prepared irradiating Y oxide and Sr nitrate at the IEA-R1m Nuclear Reactor, respectively. The results so far showed that Sr is not electroplated in any condition and that up to 40% of Y can be selectively electroplated. (author)

  19. Toxicity of inhaled 90Y in fused clay particles in beagle dogs. VI

    Studies on the metabolism, dosimetry, and effects of inhaled 90Y in fused clay in the Beagle dog are being continued to assess the consequences of inhalation of an energetic beta emitter that has a short effective half-life in the lung. A radiation dose pattern study in which 12 dogs were sacrificed in pairs at 0, 2, 4, 6, 8, and 12 days post-inhalation exposure has been completed. A longevity study in which 89 dogs have been exposed to 90Y fused clay with initial lung burdens ranging from 80 to 5200 μCi/kg body weight and 12 control dogs were exposed to stable yttrium in fused clay is in progress. The 90Y was retained in lung with a half-life similar to its physical half-life (64 hours) and with only small quantities translocated to tracheobronchial lymph nodes, skeleton, and liver. The infinite radiation doses to lung, tracheobronchial lymph nodes, skeleton, and liver for an initial lung burden of 100 μCi 90Y/kg of body weight were estimated to be 1600, 170, 0.54, and 0.38 rads, respectively. Thirty-eight of 39 dogs with doses to lung from 9300 to 70,000 rads have died at 7.5 to 903 days post-exposure. The one surviving dog in this dose range has radiographic evidence of pulmonary fibrosis at 1316 days post-exposure. All the dogs that died had radiation pneumonitis. The dog that died at 903 days post-exposure with a dose to lung of 11,000 rads also had 2 small pulmonary adenomas. Fifty exposed dogs with doses to lung of 1300 to 7900 rads are surviving with no significant abnormalities at 1278 to 1834 days post-exposure and will be studied for the remainder of their lifespan. (U.S.)

  20. Beta radiation exposure of staff during and after therapies with 90Y-labelled substances

    Radio-immuno-therapies (RITs) and peptide receptor radio-therapies (PRRTs) with 90Y-labelled compounds offer promising prospects for tumor treatment in nuclear medicine. However, when preparing and performing these therapies, which require manipulations of high activities of 90Y (>1 GBq), technicians and physicians may receive high exposures, mainly to the skin of the hands. Even non-occupationally exposed persons, such as caregivers and family members, receive external exposures in the initial period after therapy, arising from the 90Y in the patient. The local skin doses of the individual staff members, measured during RITs and PRRTs with thermoluminescence detectors fixed with tapes to the fingers, vary considerably. The exposure of staff can exceed the annual permissible dose limit of 500 mSv if radiation protection standards are low. Thus, adequate safety measures are needed. Measurements of the dose rate around patients, made using survey meters with sufficient response to beta particles, indicate that the exposure of caregivers and family members is considerably higher than previously assumed, and was dominated by primary beta radiation instead of Bremsstrahlung. Nevertheless, under normal circumstances, the annual dose limits for the public (effective dose: 1 mSv, skin dose: 50 mSv) will be complied with. (authors)

  1. Development of radioinmunoconjugate 90Y-DOTA-nimotuzumab-Fab for therapy of EGFR over expressing tumors

    Many monoclonal antibodies conjugated with 1,4,7,10-tetraaza cyclododecane-N, N', N'', N'''-tetraacetic acid (DOTA) and radiolabeled with 90Y, have been used for radioimmunotherapy. As know IgG molecules are heavy proteins with a molecular weight of approximately 150 kDa. Accordingly, intact IgG antibodies may have significant slow kinetics biodistribution and severely limited properties of tissue penetration. Antibody fragments labeled with radio metals could be promising radiopharmaceuticals for imaging and non-invasive therapy due to its high affinity to the tumor, the lack of effector function and rapid pharmacokinetic. In this work, the nimotuzumab Fab fragment was obtained by cleavage with papain in molar excess. After separating the reaction mixture in three steps using affinity, size exclusion and ion exchange chromatography; the Fab fragment showed high values of purity, integrity and identity. The Fab fragment was derivatized with DOTA and labeled with 90Y. The radioimmunoconjugate with high radiochemical yield was assessed by in vitro stability with an excess of 50mM DTPA. The development of 90Y-DOTA-Nimotuzumab-Fab radioimmunoconjugate allows to count on as a potential agent for radioimmunotherapy. (Author)

  2. Effective chelators for 90Y and 212Bi radioimmunotherapy of cancer

    Advances in synthesis and evaluation of monoclonal antibody (mAb)-ligand bioconjugates are required to further use of 90Y, 212Bi labeled mAb in cancer therapy. The authors have used ligand 1B4M-DTPA for preparation of 90Y-mAb-anti-TAC for an ongoing clinical trial of treatment of adult T-cell leukemia. Good results have been obtained in that of 10 evaluable patients, two are in complete remission 1 yr after initiation of therapy and six experienced partial remissions. Radiochemical dose was limited by marrow suppression, leading the authors to suspect that some 90Y was reaching bone. For this reason, they have prepared ultra-pure 88Y and thereafter 88Y-mAb conjugates with bifunctional DOTA and CHX-DTPA ligands which they have measured to be thermodynamically stronger for yttrium than the 1B4M ligand. The CHX ligand has also been useful for 212Bi-leukemia therapy in mice

  3. Patients' subjective assessment and clinical effect analysis of 90Sr-90Y brachytherapy to keloids

    From September 2005 to November 2009, 107 cases of keloids were treated by using 90Sr-90Y brachytherapy (25 Gy in 5 daily 5-Gy fractions, for 1-3 courses). No keloids were thicker than 6 mm. Questionnaires were developed to find assessment of the patients 12 months after the treatment. And χ2-test was used to tell the results differences according to the gender and recurrences. The radiation side effects were also recorded. The results showed that 65% patients considered the therapeutic outcome to be excellent or good, and 71% patients considered the cosmetic outcome to be excellent or good. Patients with keloids on ear or perineal were greatly satisfied with the outcome (both the therapeutic and cosmetic outcomes were 100%). The patients' assessment had no significant difference in gender. And patients without recurrence enjoyed the relief from former keloid-caused symptoms compared to the patients with recurrence (P0.05). The radiation side effects include telangiectasias (24%), hyperpigmentation (43%) and depigmentation (33%), but none of them was wild. No patients were found to get systemic adverse reactions. 90Sr-90Y brachytherapy is a good method to treat patients with keloides of less than 6 mm in thickness. The therapeutic and cosmetic outcomes are acceptable, and 90Sr-90Y brachytherapy is a good choose for the patients who cannot tolerate the pain of operations or injections.(authors)

  4. Peptide receptor radionuclide therapy with 90Y-DOTATOC in recurrent meningioma

    Meningiomas are generally benign and in most cases surgery is curative. However, for high-grade histotypes or partially resected tumours, recurrence is fairly common. External beam radiation therapy (EBRT) is usually given in such cases but is not always effective. We assessed peptide receptor radionuclide therapy (PRRT) using 90Y-DOTATOC in a group of patients with meningioma recurring after standard treatments in all of whom somatostatin receptors were strongly expressed on meningioma cell surfaces. Twenty-nine patients with scintigraphically proven somatostatin subtype 2 receptor-positive meningiomas were enrolled: 14 had benign (grade I), 9 had atypical (grade II) and 6 had malignant (grade III) disease. Patients received intravenous 90Y-DOTATOC for 2-6 cycles for a cumulative dose in the range of 5-15 GBq. Clinical and neuroradiological evaluations were performed at baseline, during and after PRRT. The treatment was well tolerated in all patients. MRI 3 months after treatment completion showed disease stabilization in 19 of 29 patients (66%) and progressive disease in the remaining 10 (34%). Better results were obtained in patients with grade I meningioma than in those with grade II-III, with median time to progression (from beginning PRRT) of 61 months in the low-grade group and 13 months in the high-grade group. PRRT with 90Y-DOTATOC can interfere with the growth of meningiomas. The adjuvant role of this treatment, soon after surgery, especially in atypical and malignant histotypes, deserves further investigation. (orig.)

  5. Peptide receptor radionuclide therapy with {sup 90}Y-DOTATOC in recurrent meningioma

    Bartolomei, Mirco; Bodei, Lisa; De Cicco, Concetta; Grana, Chiara Maria; Baio, Silvia Melania; Arico, Demetrio; Paganelli, Giovanni [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); Cremonesi, Marta [European Institute of Oncology, Division of Medical Physics, Milan (Italy); Botteri, Edoardo [European Institute of Oncology, Division of Epidemiology and Biostatistics, Milan (Italy); Sansovini, Maddalena [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.), Radiometabolic Medicine Division, Meldola (Italy)

    2009-09-15

    Meningiomas are generally benign and in most cases surgery is curative. However, for high-grade histotypes or partially resected tumours, recurrence is fairly common. External beam radiation therapy (EBRT) is usually given in such cases but is not always effective. We assessed peptide receptor radionuclide therapy (PRRT) using {sup 90}Y-DOTATOC in a group of patients with meningioma recurring after standard treatments in all of whom somatostatin receptors were strongly expressed on meningioma cell surfaces. Twenty-nine patients with scintigraphically proven somatostatin subtype 2 receptor-positive meningiomas were enrolled: 14 had benign (grade I), 9 had atypical (grade II) and 6 had malignant (grade III) disease. Patients received intravenous {sup 90}Y-DOTATOC for 2-6 cycles for a cumulative dose in the range of 5-15 GBq. Clinical and neuroradiological evaluations were performed at baseline, during and after PRRT. The treatment was well tolerated in all patients. MRI 3 months after treatment completion showed disease stabilization in 19 of 29 patients (66%) and progressive disease in the remaining 10 (34%). Better results were obtained in patients with grade I meningioma than in those with grade II-III, with median time to progression (from beginning PRRT) of 61 months in the low-grade group and 13 months in the high-grade group. PRRT with {sup 90}Y-DOTATOC can interfere with the growth of meningiomas. The adjuvant role of this treatment, soon after surgery, especially in atypical and malignant histotypes, deserves further investigation. (orig.)

  6. Effect of inhaled 90Y in fused clay particles on the gastrointestinal tract of beagle dogs

    Ten Beagle dogs were exposed by inhalation to aerosols of 90Y in fused clay particles to study the radiation dose to the gastrointestinal (GI) tract and effects resulting from clearance of the upper respiratory tract after the deposition of high initial body burdens of inhaled 90Y. Focal colonic lesions were found in 2 dogs, 8 and 12 days after inhalation of 90Y which resulted in transient GI burdens (GIB) of 18 and 34 mCi. Similar, but less severe, lesions were found in 2 dogs sacrificed 27 days after exposure with GIBs of 18 and 32 mCi. No GI lesions were found in 6 dogs with GIBs of 9 to 18 mCi. Two of the 10 dogs had thermoluminescent dosimeters surgically implanted in the GI tract lumen and submucosa. Highest radiation doses were measured in the colon. One dog, with measured doses to the colon of 3200 to 5700 rads, had focal colitis when sacrificed 8 days after exposure. The other dog, with doses to colon of 1000 to 2800 rads had no GI lesions at sacrifice 8 days after exposure. Although focal colitis was found, no dogs died due primarily to GI injury. Other significant findings were nasal dermatitis and radiation pneumonitis. The latter was more severe and life threatening than the GI injury. (U.S.)

  7. Decomposition and excretion of 32P-naled in milk

    The 32P-labelled organophosphorus insecticide naled is decomposed in milk in vitro at 5 0C with a half-life of 35 h with dichlorvos as a metabolite, that is also formed at short time heating and UV-irradiation. The recovery in milk powder is 25% (naled + dichlorvos) of the initial concentration. Following spray application of 0.05 mg naled/kg body mass to 2 lactating cows, 5 - 8 ppb of naled and 7 - 9 ppb of dichlorvos were found in the milk 5 h after application, not exceeding the tolerance level of 0.02 mg/kg according to regulations in the GDR. (author)

  8. Utilization of a novel electrochemical {sup 90}Sr/{sup 90}Y generator for the preparation of {sup 90}Y-labeled RGD peptide dimer in clinically relevant dose

    Chakraborty, Sudipta; Chakravarty, Rubel; Pillai, Maroor Raghavan Ambikalmajan; Dash, Ashutosh [Bhabha Atomic Research Centre, Mumbai (India). Radiopharmaceuticals Div.; Sarma, Haladhar Dev [Bhabha Atomic Research Centre, Mumbai (India). Radiation Biology and Health Sciences Div.

    2014-09-01

    The work reported in this paper provides a systematic study towards the development of an optimized strategy for preparation of a clinically relevant dose of {sup 90}Y-labeled dimeric RGD peptide derivative, DOTA-E[c(RGDfK)]{sub 2} [DOTA-(RGD){sub 2}] for in vivo targeted therapy utilizing {sup 90}Y obtained from a novel electrochemical {sup 90}Sr/{sup 90}Y generator. The performance of the generator was evaluated to ensure its suitability for providing {sup 90}Y in adequate quantity and purity required for formulation of clinically relevant dose for PRRT. {sup 90}Y-DOTA-(RGD){sub 2} was synthesized in high yield (86.2 ± 2.5%) and radiochemical purity (98.4 ± 0.5%) using clinically relevant dose (∝ 3.8 GBq) of {sup 90}Y. In vitro stability studies revealed that the radiolabeled conjugate retained its radiochemical purity in normal saline and human serum. Preliminary biodistribution studies carried out in C57/BL6 mice bearing melanoma tumors showed that the preparation exhibited significant tumor uptake (5.30 ± 0.78% of injected activity at 30 min post-injection) with good tumor to background ratio. The optimized radiolabeling protocol seems to be an attractive strategy which is largely viewed as a springboard to realize scope of developing {sup 90}Y labeled cyclic RGD peptides for targeted therapy of tumors over-expressing integrin-α{sub ν}β{sub 3} receptors. (orig.)

  9. Investigation of pharmaceuticals and medical devices containing 90Y extracted from high radioactive liquid waste in spent-fuel reprocessing

    Pharmaceuticals and medical devices containing radioactive 90Y are realized, approved and placed on the international market where three products are available in Europe and the United States, and one product in Japan. These products are used not for diagnosis but for treatment by internal irradiation. It was estimated from the deliberative report of the approval in Japan that 90Y was extracted in Europe from high radioactive liquid waste (HALW) yielded in spent-fuel reprocessing. In this report, products placed on the market and physical properties were reviewed, reasons of the realization and conditions to realize succeeding products were estimated, extraction method was compared with other methods, technical subjects, and relevant regulations were investigated. Although a medical device containing radioactive 90Y has been studied in Japan and one pharmaceutical product was approved, a breakthrough would be necessary to put 90Y utilization beyond alternative treatments. The breakthrough would become be promising; for example, if conventional treatments could be supported by technical development to deliver 90Y more sharply to the target with shorter serum half-life. Extraction of 90Y nuclide from HALW has advantages over thermal neutron irradiation of natural nuclide, a system is envisioned where 90Sr as a parent nuclide is separated in the reprocessing then transported to and stored in a factory of radiopharmaceuticals followed by 90Y extraction on demand. (author)

  10. Therapeutic trials to control metastatic cancer with 90Y-DOTA-Lanreotide

    As Somatostatin-analogue-scintigraphy using 111In labelled ligands could demonstrate a high density of somatostatin-receptors in a variety of cancer types, we tried to use 90Y-DOTA-Lanreotide (= 'MAURITIUS') for therapy in patients with rapidly progressing metastatic disease in whom no other therapy had been effective after uptake of the molecule in metastases was assessed by scanning (including SPECT) with 184 MBq 111In-DOTA-Lanreotide. Fifteen patients were treated so far (carcinoid tumours 8, thyroid cancer 5, oesophagus cancer 1, colon/prostate cancer 1) after dosimetry including estimates of radiation dose to tumour, whole body, marrow, urinary tract and liver. According to these data they received 740-1590 MBq 90Y-Lanreotide at intervals of 2-6 weeks up to 6 times which gave 10-18 Gy to the tumour. Follow-up for up to 12 months showed complete/partial remissions in 2/15, stable disease in 6/15 and no effect in 6/15. A comparison of scan data between 111In-Octreotide and 111In-Lanreotide showed that binding of both tracers was different in 7/17 patients, showing either better Octreotide-uptake or better Lanreotide-uptake. Side effects were only transient thrombocytopenia (5/15) and moderate leukopenia (6/15). Obviously, even with low doses of 90Y-Lanreotide some improvement in the management of patients with cancer types expressing somatostatin receptors can be achieved when rapid progression of metastases occurs. Modifications of the therapy protocol could perhaps improve our preliminary results. (author)