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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. 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.

  10. 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

  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. 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

  2. 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)

  3. 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

  4. 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

  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. 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)

  17. 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

  18. 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)

  19. 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

  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. 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)

  8. 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)

  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. 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

  19. 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

  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. 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.

  4. 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

  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. 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

  12. 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.

  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. 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)

  16. 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

  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. 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

  19. 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

  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. 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

  12. 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.)

  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. 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)

  18. 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)

  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)

    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.

  18. 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

  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. 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)

  2. 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

  3. 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

  4. 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

  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. 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)

  7. 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

  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. 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

  15. 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)

  16. 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)

  17. 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.)

  18. 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.)

  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. 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)

  1. 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.)

  2. 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.)

  3. 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)

  4. 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

  5. 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.)

  6. 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)

  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)

  11. Assessment of the best N3− donors in preparation of [M(N)(PNP)]-based (M = 99mTc-; 188Re) target-specific radiopharmaceuticals: Comparison among succinic dihydrazide (SDH), N-methyl-S-methyl dithiocarbazate (HDTCZ) and PEGylated N-methyl-S-methyl dithiocarbazate (HO2C-PEG600-DTCZ)

    Succinic dihydrazide (SDH), N-methyl-S-methyl dithiocarbazate (HDTCZ) and PEGylated N-methyl-S-methyl dithiocarbazate (HO2C-PEG600-DTCZ) are nitrido nitrogen atom donors employed for the preparation of nitride [M(N)]‐complexes (M = 99mTc and 188Re). This study aims to compare the capability and the efficiency of these three N3− group donors, in the preparation of [M(N)PNP]-based target-specific compounds (M = 99mTc, 188Re; PNP = aminodiphosphine). For this purpose, three different kit formulations (SDH kit; HO2C-PEG600-DTCZ kit; HDTCZ kit) were assembled and used in the preparation of [M(N)(cys ∼)(PNP3)]0/+ complexes (cys ∼ = cysteine derivate ligands). For each formulation, the radiochemical yield (RCY) of the [M(N)(∼ cys)(PNP3)] compounds, was determined by HPLC. The deviation of the percentage of RCY, due to changes in concentration of the N3− donors and of the exchanging ligand, was determined. For 99mTc, data clearly show that HDTCZ is the most efficient donor of N3−; however, SDH is the most suitable nitrido nitrogen atom donor for the preparation of [99mTc(N)(PNP)]-based target-specific agents with high specific activity. When HO2C-PEG600-DTCZ or HDTCZ are used in N3− donation, high amounts of the exchanging ligand (10−4 M) were required for the formation of the final complex in acceptable yield. The possibility to use microgram amounts of HDTCZ also in [188Re(N)] preparation (0.050 mg) reduces its ability to compete in ligand exchange reactions, minimizing the quantity of chelators required to obtain the final complex in high yield. This finding can be exploit for increasing the radiolabeling efficiency in [188Re(N)]-radiopharmaceutical preparations compared to the previously reported HDTCZ-based procedure, notwithstanding a purification process could be necessary to improve the specific activity of the complexes

  12. Essential thrombocythemia treated with oral sup(32)P

    A 65-year old man was admitted due to protracted gum bleeding after dental surgery. The peripheral blood smear showed thrombocytosis(1,160,000/mm3) with bizarre, giant platelets. The paltelet adhesiveness revealed 28% (normal control 31-85%) by Salzman method and the platelet aggregation revealed moderately delayed response to collagen, but normal responsiveness to A.D,P, and no responsiveness to epinephrine, the spleen scan(sup(99m)Tc-NaTcO4) showed the finding of splenic infraction. The gum bleeding ceased after transfusion of 8 units of platelet rich plasma, and he was treated with oral sup(32)P(2.5mCi/m2) under the diagnosis of essential thrombocythemia. The platelet count returned toward normal 2 months after treatment, and he was in good healthy condition. (Author)

  13. [Disintegration and elimination of 32P-naled in milk].

    Dedek, W; Scheybal, A; Gabrio, T; Kirst, E

    1981-01-01

    The organophosphorus insecticide naled (O,O-dimethyl-O,O-(1,2-dibromo-2,2-dichloroethyl)-phosphate, labeled by 32P] is degraded in milk in vitro at 5 degrees C 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 p.a., not exceeding the given tolerance level of 0,02 mg/kg in the German Democratic Republic. PMID:7290169

  14. Quantifying 32P-labeled and unlabeled nucleic acids

    Recombinant DNA technology depends on detection methods for nucleic acids compatible with amounts ranging from picograms to grams and from tenths of a microliter to liters. In practical terms there are three basic techniques: (1) absorbance methods suitable for a minimum concentration of micrograms per milliliter, (2) fluorescence methods capable of detecting nanograms of DNA and micrograms of RNA, and (3) methods based on the detection of 32P. Because of the overwhelming importance in molecular biology of the third group, this chapter will stress exquisitely sensitive methods for measuring radioactivity in very small volumes. An illustration in which an enzyme-catalyzed reaction performed in 20 μl is monitored by consuming less than 2% of the total volume will be presented

  15. Phosphate fertilizer studies using 32P dilution technique

    Agronomic effectiveness of highly soluble phosphate fertilizers for annual crop production is well known and documented. In recent years considerable research effort has been focused on search for alternative means of cheaper forms of P fertilizers to fill the needs of poor farmers, who has limited capital availability for purchase of fertilizers. Since some countries in the world have naturally occurring phosphate rocks (PR), the most appealing alternative is for direct application of PR. The low capital and energy inputs required to prepare these PR for use makes it the cheapest mineral P fertilizers possible. Thailand, Sri Lanka, Indonesia and Vietnam are some countries in the Asian region blessed with natural PR. Coupled with the inherently acidic and P deficient soils found in this region, research on direct application of these PR for crop production is indeed timely. Studies done in the temperate regions on direct application of PR have concluded that PR are not suitable for use in intensive agricultural system, because PR cannot maintain a sufficiently high P concentration in the soil solution for high crop yields. Research in direct application of PR to acidic soils of the Asian region have proven otherwise. The use of radioactive 32P isotope has helped in quantification of the amounts of P from the PR tested being utilized by the crop, and its distribution in the plant can also be monitored. In Malaysia, highly reactive North Carolina phosphate rock has been found to be as effective as triple superphosphate, where a total of about 18% of the P fertilizer applied was utilized by three consecutive crops of sweet corn grown under field conditions. Initial glasshouse screening of efficacy of PR can also be determined by the use of the 32P isotope. (author). 16 refs, 6 figs, 6 tabs

  16. Development of Therapeutic Radiopharmaceuticals Based on 90Y Biotin. Chapter 7

    The preparation of a biotin derivative labelled with 90Y to be employed as a breast cancer therapeutic radiopharmaceutical in the application of the new IART approach is described in this chapter. The effects of pH on the labelling yield and in vitro affinity for avidin of the resulting radiolabelled conjugate are evaluated. Radiolabelling was performed using a manual and an automated procedure, and radiation exposure was measured for each operational condition. Microbiological tests were conducted on each final batch after decay of activity. Results obtained from a first clinical study are also described. (author)

  17. Characterization of tumor dose heterogeneity for 90Y microsphere therapies using voxel- based dosimetry

    Justin Mikell

    2014-03-01

    Full Text Available Purpose: Dosimetry for 90Y microsphere therapies (YMT with Standard (SM and Partition (PM models provide only uniform dose estimates to tumor and liver. Our objective is to calculate tumor dose heterogeneity, known to effect response, using voxel-based dosimetry and investigate the limitations of SM and PM.Methods: Voxel-based dosimetry was performed on 17 YMT patients using Monte Carlo DOSXYZnrc. 90Y activity and tissue/density distributions were based on quantitative 90Y bremsstrahlung SPECT/CT. Tumors (n=31, liver, and treatment lobe/segments were segmented on diagnostic CT or MR. Dose volume histograms (DVH were created for tumors and normal liver. Bland-Altman analysis compared voxel-based mean absorbed doses to tumor and liver with SM and PM. Tumor and normal liver absorbed dose heterogeneity were investigated through metrics: integral uniformity (IU, D10/D90, COV. Correlations of heterogeneity with voxel-based mean doses and volumes were evaluated.Results: Heterogeneity metrics (mean ± 1σ for tumor dose were COV = 0.48 ± 0.28, D10/D90 = 4.7 ± 3.9, and IU = 0.8 ± 0.18. Heterogeneity metrics correlated with tumor volume (r > 0.58 but not tumor mean doses (r < 0.20. Voxel-based tumor mean doses correlated with PM (r = 0.84 but not SM (r = 0.08. Both yielded poor limits of agreement with of 83 ± 174 and -28 ± 181 Gy, respectively. Normal liver heterogeneity metrics (mean ± 1σ were COV = 0.83 ± 0.29, D10/D90 = 12 ± 15, and IU = 0.97 ± 0.03. Only D10/D90 (r = 0.49 correlated with mean normal liver absorbed dose. Voxel-based normal liver/lobe mean doses correlated with PM (r = 0.96, but had poor limits of agreement (26 ± 29 Gy.Conclusion: Tumor doses have high levels of heterogeneity that increase with volume but are independent of dose. Voxel-based DVH and dose heterogeneity metrics will promote accurate characterization of tumor response following YMT.--------------------------------------Cite this article as: Mikell J, Mourtada F

  18. Peptide receptor radionuclide targeting of neuroendoctrine tumours with 111In/90Y-DOTATOC

    Full text: Peptide receptors are overexpressed in several human cancers, such as somatostatine receptor (SSR) in most of neuroendocrine tumours, allowing the design of radiopharmaceuticals based on peptide receptor radionuclide target for diagnostic image studies and therapeutic treatment by substituting a gamma emitter radionuclide, as 111In, by a pure beta emitter, like 90Y. Because the extremely short plasma half life of Somatostatine itself, interest has been focused on radiolabeling somatostatine receptor analogues. Tyr3-Octreotide (TOC), a somastostatine analogue conjugated to the strong chelator 1,4,7,10- tetraazacyclododecane-N,N',N'',N'''tetraacetic acid (DOTA), is commercially available as DOTATOC from Pichem and can be radiolabeled with trivalent radiometals such as 111In and 90Y, which form stable complex with DOTA. Both 111InCl3 and 90YCl3 are commercially available from MDS Nordion. 111In and 90Y-DOTATOC could be similarly prepared using gentisic buffer (pH 5.05) and mixed with a saline solution of DOTATOC 2μg/μl, in order to have finally a ratio of 10-15 μg of DOTATOC / mCi of 111InCl3 and 1 - 1.5 μg of DOTATOC / mCi of 90YCl3. The reaction vial must be heated for 25 - 30 min, in a water bath at 90 deg. C. Chemical purity of DOTATOC must be analysed by HPLC and radiochemical purity could be determined by liquid chromatography using Sep-Pak C18 Cartridge, activated with methanol and conditioned with acetate buffer (pH 5.5). The chemical purity of the of the peptide is the determining factor for choosing (DOTATOC μg/mCi of radionuclide) that must be used in order to obtain the radiochemical purity recommended for diagnostic and therapeutic purpose. The Radiochemical purity obtained for both radiopharmaceuticals labelled using this methods was over 98% for 111In-DOTATOC and over 99% for 90Y-DOTATOC. To date, over 35 patients have been treated and all of them had positive SSR demonstrated by 111In-DOTATOC scintigraphic image. This valuable diagnosis

  19. 90Y-DOTA-CHS Microspheres for Live Radio microsphere Therapy: Preliminary In Vivo Lung Radiochemical Stability Studies

    Chitosan (CHS) is used to prepare microspheres of 31 ± 8 µm size. Surface modification with p-SCN-Bn-DOTA was performed. A maximum 90Y capacity was found to be 12.1 ± 4.4 µCi/particle. The best obtained labeling yield was 87.7 ± 0.6%. More than 90% in vitro stability was found. Particle in vitro degradation half-life in PBS was found to be greater than 21 days. In vivo studies with 90Y-DOTA-CHS showed more than 95% of the injected activity (decay corrected) in the lungs 24 hours after tail vein administration. 90Y-DOTA-CHS in vivo label stability was superior to resin microspheres. The addition of p-SCN-Bn-DOTA served as a radioprotectant for bone marrow as the 5% 90Y released, during the first 24 hours, was quickly eliminated via urine.

  20. PET optimization for improved assessment and accurate quantification of {sup 90}Y-microsphere biodistribution after radioembolization

    Martí-Climent, Josep M., E-mail: jmmartic@unav.es; Prieto, Elena; Elosúa, César; Rodríguez-Fraile, Macarena; Domínguez-Prado, Inés; Vigil, Carmen; García-Velloso, María J.; Arbizu, Javier; Peñuelas, Iván; Richter, José A. [Nuclear Medicine Department, Clínica Universidad de Navarra, 36, Pío XII Avenue, 31008 Pamplona (Spain)

    2014-09-15

    Purpose: {sup 90}Y-microspheres are widely used for the radioembolization of metastatic liver cancer or hepatocellular carcinoma and there is a growing interest for imaging {sup 90}Y-microspheres with PET. The aim of this study is to evaluate the performance of a current generation PET/CT scanner for {sup 90}Y imaging and to optimize the PET protocol to improve the assessment and the quantification of {sup 90}Y-microsphere biodistribution after radioembolization. Methods: Data were acquired on a Biograph mCT-TrueV scanner with time of flight (TOF) and point spread function (PSF) modeling. Spatial resolution was measured with a{sup 90}Y point source. Sensitivity was evaluated using the NEMA 70 cm line source filled with {sup 90}Y. To evaluate the count rate performance, {sup 90}Y vials with activity ranging from 3.64 to 0.035 GBq were measured in the center of the field of view (CFOV). The energy spectrum was evaluated. Image quality with different reconstructions was studied using the Jaszczak phantom containing six hollow spheres (diameters: 31.3, 28.1, 21.8, 16.1, 13.3, and 10.5 mm), filled with a 207 kBq/ml {sup 90}Y concentration and a 5:1 sphere-to-background ratio. Acquisition time was adjusted to simulate the quality of a realistic clinical PET acquisition of a patient treated with SIR-Spheres{sup ®}. The developed methodology was applied to ten patients after SIR-Spheres{sup ®} treatment acquiring a 10 min per bed PET. Results: The energy spectrum showed the{sup 90}Y bremsstrahlung radiation. The {sup 90}Y transverse resolution, with filtered backprojection reconstruction, was 4.5 mm in the CFOV and degraded to 5.0 mm at 10 cm off-axis. {sup 90}Y absolute sensitivity was 0.40 kcps/MBq in the center of the field of view. Tendency of true and random rates as a function of the {sup 90}Y activity could be accurately described using linear and quadratic models, respectively. Phantom studies demonstrated that, due to low count statistics in {sup 90}Y PET

  1. SPECT using bremsstrahlung to quantify 90Y uptake in Baker's cysts: Its application in radiation synovectomy of the knee

    The use of SPECT with bremsstrahlung radiation has been investigated in studies on patients undergoing 90Y therapy for persistent synovitis of the knee. In particular, its value in the estimation of 90Y uptake into Baker's cysts was assessed and, to this end, realistic 'knee phantoms' were employed in order to calibrate for cysts of different size. Problems associated with the measurement of the extensive bremsstrahlung spectrum and the estimation of cyst volume have been discussed. It is shown that, although the apparent volume of a cyst is markedly dependent on the chosen count rate threshold, volumes greater than about 30 ml can be estimated with reasonable accuracy using a threshold of 50%. The uptake of 90Y in cysts, measured on 3 occasions within the first 2 days in 10 patients, showed wide variation (0%-40%) between patients and was poorly related to the size of cysts on arthrograms and to the clinical response to therapy. In these studies, the ability to analyse SPECT slices provided a distinct advantage over planar imaging for discriminating between 90Y uptake in cysts and adjacent sites. Retention of 90Y in the total knee was also widely variable, with losses of 2%-38% observed 2 days after injection which, in general, were not fully accounted for by uptake in liver or lymph nodes. The changing distribution of 90Y colloid in the knee during the first two days, as observed in some patients, might explain part of the discrepancy. (orig.)

  2. Retention profile and selective separation of 90Y from 89Sr using zirconium-vanadate gel packed column

    A low cost and selective method has been developed for the separation of trace concentrations of 90Y3+ from its parent 89Sr2+. The proposed procedure is based upon complete retention of 90Y3+ onto zirconium-vanadate (Zr-V) gel ion exchanger packed column from aqueous solutions containing HCl (1.0 x 10-5 mol dm-3). Under these conditions, 89Sr2+ species were not retained onto Zr-V sorbent. The retained 90Y3+ species were then recovered with HCl. The performance of Zr-V sorbent packed column was determined via the height equivalent to the theoretical plates (HETP) and the number of plates (N). Validation of the developed method was checked by calculating the radionuclidic purity in terms of purification factor (Pf = A/A0) and radiochemical purity of the eluted 90Y from the column. Zr-V sorbent packed column offers unique advantages of retention and quantitative separation of 90Y from retention over conventional solid sorbents in rapid and effective separation of trace concentration of 90Y3+ from 89Sr2+ in their aqueous equilibrium media. (author)

  3. Production of large quantities of 90Y by ion-exchange chromatography using an organic resin and a chelating agent

    The performance of a system composed of an organic cation exchanger (Dowex 50Wx8) and a chelating agent (EDTA) previously described for the successful production of 90Y via a 90Sr/90Y generator is assessed under dynamic conditions. In an attempt to overcome the established limitation of ion-exchange resins for the separation of subcurie quantities of activity, 90Y is repeatedly isolated from an 11.8-GBq (320 mCi) 90Sr cow using a three-column tandem arrangement. The high recovery and radionuclidic purity obtained for 90Y and the parameters of the separation (time, eluant concentration, pH and flow rate range) strongly suggest that Ci quantities of 90Y can be handled satisfactorily by the ion-exchange method. No replacement or treatment of the cow, low waste generation and 90Sr losses less than 0.1% after each run were observed during the present study which, in combination with the low cost of this resin, may result in an attractive alternate method for the production of large quantities of 90Y.

  4. Effect of pulmonary irradiation from inhaled 90Y on immunity to Listeria monocytogenes in mice

    The immunological response of mice subjected to irradiation from particles deposited in the lungs and challenged with Listeria monocytogenes was investigated. Mice, exposed by inhalation to 90Y (a beta-emitting radionuclide) in relatively insoluble fused aluminosilicate particles, were immunized with L. monocytogenes either before or after exposure. Two additional groups of mice were either immunized or irradiated only. A group of control mice received no irradiation or immunization. The beta radiation dose absorbed by the lungs of each mouse at time of challenge averaged 10,000 rads. Fourteen days after immunization, all mice were challenged with 2 LD50 doses of L. monocytogenes via the respiratory route. Survival of all immunized mice either with or without exposure to 90Y varied from 90 to 100% as compared to 10 to 20% for the mice irradiated only and for control mice through 14 days after challenge. Pulmonary clearance of inhaled L. monocytogenes during the first 4 hr after challenge was suppressed in the mice irradiated only but not in those immunized only, or in the immunized and irradiated groups, and control mice. There appeared to be a suppression of proliferation of L. monocytogenes in lungs and spleen in the immunized groups 72 hr after challenge, whereas the lungs and spleens of the mice irradiated only and the control mice had extensive bacterial invasion. It was concluded that the 10,000 rads of beta radiation absorbed by the lungs did not suppress the immune mechanisms of the immunized mice

  5. Thermoluminescent dosimetry of beta radiations of 90 Sr/ 90 Y using amorphous ZrO2

    In this work the results of studying the thermoluminescent properties (Tl) of the zirconium oxide in its amorphous state (ZrO2-a) before beta radiations of 90 Sr/ 90 Y are presented. The amorphous powders of the zirconium oxide were synthesized by means of the sol-gel technique. The sol-gel process using alkoxides like precursors, is an efficient method to prepare a matrix of zirconium oxide by hydrolysis - condensation of the precursor to form chains of Zr-H3 and Zr-O2. One of the advantages of this technique is the obtention of gels at low temperatures with very high purity and homogeneity. The powders were characterized by means of thermal analysis and by X-ray diffraction. The powders of ZrO2-a, previously irradiated with beta particles of 90 Sr/90 Y, presented a thermoluminescent curve with two peaks at 150 and 257 C. The dissipation of the information of the one ZrO2-a was of 40% the first 2 hours remaining constant the information for the following 30 days. The reproducibility of the information was of ± 2.5% in standard deviation. The studied characteristics allow to propose to the amorphous zirconium oxide as thermoluminescent dosemeter for the detection of beta radiation. (Author)

  6. Development of a dosimetric system for 90Sr + 90Y betatherapy applicators

    The 90Sr+90Y applicators, used in betatherapy for prevention of keloids and pterigium, are imported and many times their dosimetric features are shown only in an illustrated form by the manufacturers. The exhaustive routine of the medical physicists in the clinic do not make possible the accomplishment of procedures for the confirmation of these parameters. This work presents the development of a methodology for the dosimetry of 90Sr+90Y betatherapy applicators. The Monte Carlo code MCNP5 was used for the simulation of the percentage depth dose curves and dose distribution profiles produced by these applicators. The experimental measurements of the radial and axial radiation attenuation, have been done with a mini-extrapolation chamber, thermoluminescent dosimeters and radiographic films. The experimental results have been compared with the simulated values. Both percentage depth dose curves and the radial dose profiles, the theoretical and the experimental ones, have presented good agreement, which may validate the use of the MCNP5 for these simulations, confirming the viability of the usage of this method in procedures of beta emitter sources dosimetry. (author)

  7. Absorption and scattering of 90Sr/90Y beta particles transmitted through aluminium and plastic filters

    Absorption and scattering of 90Sr/90Y beta particles transmitted through aluminium and plastic filters have been studied. From measurements of the ionisation current by the extrapolation chamber, it was shown that a build-up in absorbed dose rate occurred over the first 0.1 mm of aluminium thickness before attenuation started to dominate. This build-up thickness corresponded to a δ particle energy of 150 keV. The attenuation at large thicknesses followed an exponential function which predicted a half-value thickness of ∼ 112mg.cm-2 and a range (99% attenuation) of ∼1000 mg.cm-2. Angular distributions of the absorbed dose rate for 90Sr/90Y beta particles transmitted through aluminium and plastic filters have also been measured. These distributions followed the multiple scattering Gaussian curves for small projected angles and the single scattering tails for large projected angles. The mean square angle of the Gaussian distribution was approximately a linear function of the filter thickness. The peak height, however, dropped rapidly with increasing filter thickness at small thicknesses but slowly at large thicknesses. Both the mean square angle and the peak height were slightly dependent on the filter material. (Author)

  8. Depth dose curves from 90Sr+90Y clinical applicators using the thermoluminescent technique

    The 90Sr+90Y beta-ray sources widely used in brachytherapy applications were developed in the 1950's. Many of these sources, called clinical applicators, are still routinely used in several Brazilian radiotherapy clinics for the treatment of superficial lesions in the skin and eyes, although they are not commercialized anymore. These applicators have to be periodically calibrated, according to international recommendations, because these sources have to be very well specified in order to reach the traceability of calibration standards. In the case of beta-ray sources, the recommended quantity is the absorbed dose rate in water at a reference distance from the source. Moreover, there are other important quantities, as the depth dose curves and the source uniformity for beta-ray plaque sources. In this work, depth dose curves were obtained and studied of five dermatological applicators, using thin thermoluminescent dosimeters of CaSO4:Dy and phantoms of PMMA with different thicknesses (between 1.0 mm and 5.0 mm) positioned between each applicator and the TL pellets. The depth dose curves obtained presented the expected attenuation response in PMMA, and the results were compared with data obtained for a 90Sr+90Y standard source reported by the IAEA, and they were considered satisfactory. (author)

  9. A prototype of an extrapolation chamber for beta radiation beams of 90Sr+90Y

    Extrapolation chamber is the only primary standard dosimeter for beta radiation. With the aim to test new configurations and materials using easily-available and low-cost materials and fulfill the need of a chamber for scientific metrological purposes, in this paper the prototype of an extrapolation chamber has been built and its performance has been investigated in the beta radiation field of 90Sr+90Y. The main differences between the chamber and commercially available chambers are the geometry, constituent material and configuration. The obtained results were compared with those of the calibration certificate of the source and an agreement within 4 % was verified. The depth-dose curve was also obtained and compared with the curve published in ISO 6980, showing a good agreement. Moreover, Monte Carlo simulation was undertaken using MCNP4C code and the relative difference of 0.3 % was observed compared to the experiment. All of the results proved the suitability of the chamber in the beta radiation field of 90Sr+90Y. (author)

  10. Fractionation of applied 32P labeled TSP in calcareous soils

    Calcareous dark brown red soil (calcixerollic xerochrept) from northern Syria was used in a pot experiment to study the fate of triple super phosphate fertilizer (TSP) with and without a crop (Local durum wheat (Triticum turgidum L. group durum (Desf)) c v. Bohouth). The soil received 17μg P/g soil of 32 P labeled TSP, and samples were collected from soils and plants at successive dates. Soil inorganic P was ≅94% of total soil P, with only 50-80% being soluble. Calcium phosphate compounds were the dominant fraction (≤68%) of the soluble inorganic soil P followed by occluded iron phosphate (≤48%) and all other fractions were ≤9%. Isotopic measurements showed that ≅ 50% of fertilizer P was nonexchangeable within 2 days, and TSP values in each fraction of soil inorganic P fluctuated in relatively similar proportions to the concentrations of fractions in soil. Available P (soil and TSP) in cropped soil was more than that in the uncropped soil, and plants had no effect on the distribution of P from fertilizer amongst the different P fractions. (author)

  11. An overview of DNA fingerprinting with 32P nucleotides

    The DNA probes radiolabeled with 32P, a primary tool employed by researchers in the life sciences for > 20 yr, are used by private companies, state-run laboratories, and the FBI to generate autoradiographs displaying the unique banding patterns that constitute the DNA fingerprint. The ability to identify an individual or animal from a biological sample has profound implications. Unidentified bodies, unrecognizable remains, and missing children can be tested and the DNA fingerprint compared to those of family members for positive identification. Paternity can be established before a child's birth. Immigration disputes can easily be resolved. Other uses include pedigree determination and testing for cell-line cross-contamination. Using a DNA fingerprint to determine the guilt or innocence of an individual allegedly involved in a violent crime is very controversial and has great legal and moral implications for society. Forensic laboratories have been challenged to ensure a level of quality control and quality assurance consistent with the weight given to these tests when used as evidence in a court of law

  12. An overview of DNA fingerprinting with sup 32 P nucleotides

    Pappas, G.G.

    1992-01-01

    The DNA probes radiolabeled with {sup 32}P, a primary tool employed by researchers in the life sciences for > 20 yr, are used by private companies, state-run laboratories, and the FBI to generate autoradiographs displaying the unique banding patterns that constitute the DNA fingerprint. The ability to identify an individual or animal from a biological sample has profound implications. Unidentified bodies, unrecognizable remains, and missing children can be tested and the DNA fingerprint compared to those of family members for positive identification. Paternity can be established before a child's birth. Immigration disputes can easily be resolved. Other uses include pedigree determination and testing for cell-line cross-contamination. Using a DNA fingerprint to determine the guilt or innocence of an individual allegedly involved in a violent crime is very controversial and has great legal and moral implications for society. Forensic laboratories have been challenged to ensure a level of quality control and quality assurance consistent with the weight given to these tests when used as evidence in a court of law.

  13. Somatostatin-based radiopeptide therapy with [177Lu-DOTA]-TOC versus [90Y-DOTA]-TOC in neuroendocrine tumours

    Somatostatin-based radiopeptide treatment is generally performed using the β-emitting radionuclides 90Y or 177Lu. The present study aimed at comparing benefits and harms of both therapeutic approaches. In a comparative cohort study, patients with advanced neuroendocrine tumours underwent repeated cycles of [90Y-DOTA]-TOC or [177Lu-DOTA]-TOC until progression of disease or permanent adverse events. Multivariable Cox regression and competing risks regression were employed to examine predictors of survival and adverse events for both treatment groups. Overall, 910 patients underwent 1,804 cycles of [90Y-DOTA]-TOC and 141 patients underwent 259 cycles of [177Lu-DOTA]-TOC. The median survival after [177Lu-DOTA]-TOC and after [90Y-DOTA]-TOC was comparable (45.5 months versus 35.9 months, hazard ratio 0.91, 95 % confidence interval 0.63-1.30, p = 0.49). Subgroup analyses revealed a significantly longer survival for [177Lu-DOTA]-TOC over [90Y-DOTA]-TOC in patients with low tumour uptake, solitary lesions and extra-hepatic lesions. The rate of severe transient haematotoxicities was lower after [177Lu-DOTA]-TOC treatment (1.4 vs 10.1 %, p = 0.001), while the rate of severe permanent renal toxicities was similar in both treatment groups (9.2 vs 7.8 %, p = 0.32). The present results revealed no difference in median overall survival after [177Lu-DOTA]-TOC and [90Y-DOTA]-TOC. Furthermore, [177Lu-DOTA]-TOC was less haematotoxic than [90Y-DOTA]-TOC. (orig.)

  14. Occupational radiation exposure of medical staff performing 90Y-loaded microsphere radioembolization

    Radioembolization of liver cancer with 90Y-loaded microspheres is increasingly used but data regarding hospital staff exposure are scarce. We evaluated the radiation exposure of medical staff while preparing and injecting 90Y-loaded glass and resin microspheres especially in view of the increasing use of these products. Exposure of the chest and finger of the radiopharmacist, nuclear medicine physician and interventional radiologist during preparation and injection of 78 glass microsphere preparations and 16 resin microsphere preparations was monitored. Electronic dosimeters were used to measure chest exposure and ring dosimeters were used to measure finger exposure. Chest exposure was very low for both products used (<10 μSv from preparation and injection). In our experience, finger exposure was significantly lower than the annual limit of 500 mSv for both products. With glass microspheres, the mean finger exposure was 13.7 ± 5.2 μSv/GBq for the radiopharmacist, and initially 17.9 ± 5.4 μSv/GBq for the nuclear medicine physician reducing to 13.97 ± 7.9 μSv/GBq with increasing experience. With resin microspheres, finger exposure was more significant: mean finger exposure for the radiopharmacist was 295.1 ± 271.9 μSv/GBq but with a reduction with increasing experience to 97.5 ± 35.2 μSv/GBq for the six most recent dose preparations. For administration of resin microspheres, the greatest mean finger exposure for the nuclear medicine physician (the most exposed operator) was 235.5 ± 156 μSv/GBq. Medical staff performing 90Y-loaded microsphere radioembolization procedures are exposed to safe levels of radiation. Exposure is lower than that from treatments using 131I-lipiodol. The lowest finger exposure is from glass microspheres. With resin microspheres finger exposure is acceptable but could be optimized in accordance with the ALARA principle, and especially in view of the increasing use of radioembolization. (orig.)

  15. Occupational radiation exposure of medical staff performing {sup 90}Y-loaded microsphere radioembolization

    Laffont, Sophie; Ardisson, Valerie; Lenoir, Laurence [Cancer Institute, Centre Eugene Marquis, Department of Nuclear Medicine, Rennes (France); Rolland, Yan; Rohou, Tanguy [Cancer Institute, Centre Eugene Marquis, Department of Interventional Radiology, Rennes (France); Edeline, Julien [University of Rennes 1, Rennes (France); Comprehensive Cancer Center, Institute Eugene Marquis, Department of Medical Oncology, Rennes (France); INSERM, U-991, Liver Metabolisms and Cancer, Rennes (France); Pracht, Marc; Sourd, Samuel Le [Comprehensive Cancer Center, Institute Eugene Marquis, Department of Medical Oncology, Rennes (France); Lepareur, Nicolas [Cancer Institute, Centre Eugene Marquis, Department of Nuclear Medicine, Rennes (France); INSERM, U-991, Liver Metabolisms and Cancer, Rennes (France); Garin, Etienne [Cancer Institute, Centre Eugene Marquis, Department of Nuclear Medicine, Rennes (France); University of Rennes 1, Rennes (France); INSERM, U-991, Liver Metabolisms and Cancer, Rennes (France)

    2016-05-15

    Radioembolization of liver cancer with {sup 90}Y-loaded microspheres is increasingly used but data regarding hospital staff exposure are scarce. We evaluated the radiation exposure of medical staff while preparing and injecting {sup 90}Y-loaded glass and resin microspheres especially in view of the increasing use of these products. Exposure of the chest and finger of the radiopharmacist, nuclear medicine physician and interventional radiologist during preparation and injection of 78 glass microsphere preparations and 16 resin microsphere preparations was monitored. Electronic dosimeters were used to measure chest exposure and ring dosimeters were used to measure finger exposure. Chest exposure was very low for both products used (<10 μSv from preparation and injection). In our experience, finger exposure was significantly lower than the annual limit of 500 mSv for both products. With glass microspheres, the mean finger exposure was 13.7 ± 5.2 μSv/GBq for the radiopharmacist, and initially 17.9 ± 5.4 μSv/GBq for the nuclear medicine physician reducing to 13.97 ± 7.9 μSv/GBq with increasing experience. With resin microspheres, finger exposure was more significant: mean finger exposure for the radiopharmacist was 295.1 ± 271.9 μSv/GBq but with a reduction with increasing experience to 97.5 ± 35.2 μSv/GBq for the six most recent dose preparations. For administration of resin microspheres, the greatest mean finger exposure for the nuclear medicine physician (the most exposed operator) was 235.5 ± 156 μSv/GBq. Medical staff performing {sup 90}Y-loaded microsphere radioembolization procedures are exposed to safe levels of radiation. Exposure is lower than that from treatments using {sup 131}I-lipiodol. The lowest finger exposure is from glass microspheres. With resin microspheres finger exposure is acceptable but could be optimized in accordance with the ALARA principle, and especially in view of the increasing use of radioembolization. (orig.)

  16. Labeling an anti-CD20 monoclonal antibody with 90Y

    Lymphomas are among the 10 leading causes of death, both in Cuba and in the world, with an increasing incidence in recent years. Follicular lymphoma low-grade (indolent) is one of the most common in the Western world, representing 1/3 of all non-Hodgkin lymphomas (NHL). More than 90% of patients present with disseminated disease at diagnosis and generally have a slow evolution and good response to conventional treatment; but radically changed its forecast to relapse, resistance to therapeutic and histologic transformation can occur. The monoclonal antibody therapy has been a promising therapeutic. In this respect CD20 antigen it has been considered one of the most attractive targets in the therapy of follicular B cell lymphoma This is expressed in more than 90% of cases, while not present in stem cells and lines progenitors. Despite the success of immunotherapy, the relapse rate is still considerable. In order to increase the cytotoxic potential of immunotherapy, marked with beta emitting radionuclides alpha particles or monoclonal antibodies are used today. Despite encouraging results in patients with non-Hodgkin lymphomas refractory to other treatments, the extremely high costs of these commercial radiopharmaceuticals have greatly limited its application, even in the first world. A sustainable alternative is the marking of other anti-CD20 monoclonal antibodies, so researchers from several countries have concentrated their efforts on rituximaby other similar antibodies labeled with therapeutic radionuclides, as a possible cost-effectively to more problem. Today in Cuba it has an electrolytic generator 90Sr-90Y Isotope Center, which ensures the availability of the radionuclide. In addition, the chimeric MAb rituximab is applied as part of the therapy of NHL in its health system and, recently, the Center for Molecular Immunology has obtained a chimeric monoclonal anti-CD20 antibody biosimilar rituximab, which is in phase clinical trial; which opens prospects for the

  17. Increased [32P]-phosphorylation of tryptic peptides of erythrocyte spectrin in Duchenne muscular dystrophy

    Increased [32P]-incorporation in tryptic peptides of the erythrocyte membrane protein spectrin Band 2 in Duchenne muscular dystrophy (DMD) was studied in a consecutive series of 10 matched DMD/control pairs. Spectrin was [32P]-phosphorylated by cyclic AMP-independent endogenous membrane protein kinase in the presence of [gamma-32P]ATP. [32P]-labeled spectrin was isolated, purified, and subjected to tryptic cleavage with excess trypsin. The resulting peptides were separated on a high-resolution 5%/15% stacking SDS--polyacrylamide gel electrophoresis system. Liquid scintillation counting was performed on sequential slices of unstained gels. A broad [32P]-labeled band containing a number of [32P]-polypeptides was found to be more highly [32P]-phosphorylated in DMD patients than in their matched controls. This band migrated with an apparent molecular mass of 4.8-5.2 kilodaltons and contained approximately 55% of total [32P] radioactivity covalently bound to spectrin peptides. These data demonstrated an increased [32P]-phosphorylation of an identifiable tryptic peptide fraction in DMD that is consistent with previous reports of increased spectrin Band 2 [32P]-phosphorylation in DMD

  18. Hemangiomas of infancy: results of 90Y interstitial therapy: a retrospctive study

    The results of therapy have been analyzed in 99 infants with rapidly progressive hemangiomas, who were treated with interstitial beta radiation, using 90Y needles. Seventy two per cent of the treated lesions regressed completely, and 94% achieved a good or average cosmetic result when evaluated two years or more following treatment. Complications possibly related to the therapy occurred in only 4 of 123 interstitial implant procedures (3%). There has been no occurrence of radiation-induced neoplasm. Beta interstitial therapy is effective in initiating regression of large progressive infantile hemangiomas, providing excellent cosmetic results and an acceptably low complication rate. Such therapy may be useful in selected patients in whom large or rapidly progressive lesions are located in critical sites and cause funcitonal problems

  19. Characterization of an extrapolation chamber in a 90Sr/90Y beta radiation field

    The extrapolation chamber is a parallel plate chamber and variable volume based on the Bragg-Gray theory. It determines in absolute mode, with high accuracy the dose absorbed by the extrapolation of the ionization current measured for a null distance between the electrodes. This camera is used for dosimetry of external beta rays for radiation protection. This paper presents the characterization of an extrapolation chamber in a 90Sr/90Y beta radiation field. The absorbed dose rate to tissue at a depth of 0.07 mm was calculated and is (0.13206±0.0028) μGy. The extrapolation chamber null depth was determined and its value is 60 μm. The influence of temperature, pressure and humidity on the value of the corrected current was also evaluated. Temperature is the parameter that has more influence on this value and the influence of pressure and the humidity is not very significant. Extrapolation curves were obtained. (Author)

  20. Treatment of neuroendocrine tumors (NETs) expressing SMT 90Y and 177Lu

    Neuroendocrine tumors (NETs) are a relatively rare and extremely heterogeneous group, essentially characterized by a different metabolism and endocrine histologically pattern. NETs are a challenge for physicians not only for diagnosis but also for early treatment. In addition to this, QT or RT treatments that require a high rate of cell proliferation to be effective, they are not in these tumors as slow growth. The primary treatment of NETs is surgery, either with a curative intent or tumor shrinkage. Peptide Receptors Radiotherapy (RTPR) consists of the administration for therapeutic purposes of Radiolabeled Synthetic Peptides that bind specifically and with high affinity to receptors of tumor cells. The RTPR of TNE with SMT analogues is effective for handling or metastizados inoperable patients. The Conference gives an accurate picture of the treatment of these tumors both 90Y as 177Lu. (author)

  1. Radioembolisation with 90Y-microspheres: dosimetric and radiobiological investigation for multi-cycle treatment

    Radioembolisation with 90Y-microspheres is a new locoregional treatment of hepatic lesions, usually applied as single cycle. Multi-cycle treatments might be considered as a strategy to improve the risk-benefit balance. With the aim to derive suitable information for patient tailored therapy, available patients' dosimetric data were reviewed according to the linear-quadratic model and converted into biological effective dose (BED) values. Single vs. multi-cycle approaches were compared through radiobiological perspective. Twenty patients with metastatic lesions underwent radioembolisation. The 90Y-administered activity (AA) was established in order to respect a precautionary limit dose (40 Gy) for the non-tumoral liver (NTL). BED was calculated setting α/β 2.5 Gy (NTL), 10 Gy (tumours); T1/2,eff = T1/2,phys = 64.2 h; T1/2,rep = 2.5 h (NTL), 1.5 h (tumours). The BED to NTL was considered as a constraint for multi-cycle approach. The AA for two cycles and the percent variations of AA, tumour dose, BED were estimated. In one-cycle, for a prescribed BED to NTL of 64 Gy (NTL dose = 40 Gy), AA was 1.7 (0.9-3.2) GBq, tumour dose was 130 (65-235) Gy, and tumour BED was 170 (75-360) Gy. Considering two cycles, ∝15% increase was found for AA and dose to NTL, with unvaried BED for NTL. Tumour dose increase was 20 (10-35) Gy; tumour BED increase was 10 (3-11) Gy. In different protocols allowing 80 Gy to NTL, the BED sparing estimated was ∝50 Gy (two cycles) and 65 Gy (three cycles). From a radiobiological perspective, multi-cycle treatments would allow administering higher activities with increased tumour irradiation and preserved radiation effects on NTL. Trials comparing single vs. multiple cycles are suggested. (orig.)

  2. Individual voxelwise dosimetry of targeted 90Y-labelled substance P radiotherapy for malignant gliomas

    Substance P is the main ligand of neurokinin type 1 (NK-1) receptors, which are consistently overexpressed in malignant gliomas. The peptidic vector 111In/90Y-DOTAGA-substance P binds to these receptors and can be used for local treatment of brain tumours. Dosimetry for this interstitial brachytherapy has mainly been done using geometrical models; however, they often do not faithfully reproduce the in vivo biodistribution of radiopharmaceuticals, which is indispensable to correlate the deposited energy with clinical response. The aim of this study was to establish a reproducible dosimetry protocol for intratumoural radiopeptide therapy. For test and therapeutic injections, 2 MBq of 111In-substance P and 370-3,330 MBq of 90Y-substance P, respectively, were applied in 12 patients with malignant gliomas. Over a period of 24 h, serial SPECT scans were performed on a dual-head SPECT camera. The scans were acquired in a double-energy window technique together with 99mTc-ECD in order to co-register the dose distributions with a separately acquired, contrast-enhanced CT scan. Quantitative voxelwise dose distribution maps (in Gy/GBq) were computed from these data using a mono-exponential decay approach. Pre- and post-therapeutic values were compared. Agreement between pre- and post-therapeutic dosimetry was very good and delivered absolute dose values in Gy per injected GBq. In all patients, the pretherapeutic test injection together with the CT overlay technique could predict the precise localisation of dose deposition in an anatomical context. This protocol allows a precise pretherapeutic computation of the expected three-dimensional dose distribution and is clearly superior to the previously used dosimetry based on planar scintigraphic images. It has become an indispensable tool for planning intratumoural radiopeptide therapy in glioma patients. (orig.)

  3. Calibration and validation of a quality assurance system for 90Sr/90Y radiation source trains

    A quality assurance system (OPTIDOS, PTW-Freiburg) developed for dose rate verification of 90Sr/90Y radiation source trains (RSTs) was calibrated and validated. These source trains are used in the 5-F-BetaCathTM system (Novoste Corp.) for the treatment of endovascular diseases. The calibration factor of the OPTIDOS system was obtained empirically and is valid for 90Sr/90Y dose rate measurements at the specification point which is located at 2 mm distance from the source axis. A total of 187 OPTIDOS dose rate verifications of the 5-F-BetaCathTM system were performed in different hospitals. The histogram of the deviation between the manufacturer's dose rate specification and the dose rate measured using the OPTIDOS dosimetry system is Gaussian shaped with ±3% relative width and a mean shift of about +2% with respect to the corresponding dose rate specification. Additionally, 128 OPTIDOS dose rate verifications of the new jacketed RST (3.5-F-BetaCathTM, Novoste Corp.) were performed using the same calibration factor as derived for the 5-F-BetaCathTM system. Distribution of the deviation between the certified and the measured dose rate is nearly identical in comparison to the histogram of the 5-F-BetaCathTM system. The mean value of the deviations is shifted by -1.5% with respect to the certified dose rate. In order to compare the results of the calibrated OPTIDOS dosimetry system with a standard measuring method, separate dose rate measurements were performed using electron accelerator calibrated radiochromic films in which calibration is traceable to PTB (Physikalisch Technische Bundesanstalt, Germany). Deviation between both the methods is less than 3.1%. These results confirm that the calibrated OPTIDOS dosimetry system can be considered suitable for quality assurance of both types of RST used in the BetaCathTM systems

  4. Comparative efficacy of 177Lu and 90Y for Anti-CD20 Pretargeted Radioimmunotherapy in Murine Lymphoma Xenograft Models

    Purpose Pretargeted radioimmunotherapy (PRIT) is a multi-step method of selectively delivering high doses of radiotherapy to tumor cells while minimizing exposure to surrounding tissues. Yttrium-90 (90Y) and lutetium-177 (177Lu) are two of the most promising beta-particle emitting radionuclides used for radioimmunotherapy, which despite having similar chemistries differ distinctly in terms of radiophysical features. These differences may have important consequences for the absorbed dose to tumors and normal organs. Whereas 90Y has been successfully applied in a number of preclinical and clinical radioimmunotherapy settings, there have been few published pretargeting studies with 177Lu. We therefore compared the therapeutic potential of targeting either 90Y or 177Lu to human B-cell lymphoma xenografts in mice. Methods Parallel experiments evaluating the biodistribution, imaging, dosimetry, therapeutic efficacy, and toxicity were performed in female athymic nude mice bearing either Ramos (Burkitt lymphoma) or Granta (mantle cell lymphoma) xenografts, utilizing an anti-CD20 antibodystreptavidin conjugate (1F5-SA) and an 90Y- or 177Lu-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-biotin second step reagent. Results The two radionuclides displayed comparable biodistributions in tumors and normal organs; however, the absorbed radiation dose delivered to tumor was more than twice as high for 90Y (1.3 Gy/MBq) as for 177Lu (0.6 Gy/MBq). More importantly, therapy with 90Y-DOTAbiotin was dramatically more effective than with 177Lu-DOTA-biotin, with 100% of Ramos xenograft-bearing mice cured with 37 MBq 90Y, whereas 0% were cured using identical amounts of 177Lu-DOTA-biotin. Similar results were observed in mice bearing Granta xenografts, with 80% of the mice cured with 90Y-PRIT and 0% cured with 177Lu-PRIT. Toxicities were comparable with both isotopes. Conclusion 90Y was therapeutically superior to 177Lu for streptavidin-biotin PRIT approaches in

  5. Comparative efficacy of 177Lu and 90Y for anti-CD20 pretargeted radioimmunotherapy in murine lymphoma xenograft models.

    Sofia H L Frost

    Full Text Available Pretargeted radioimmunotherapy (PRIT is a multi-step method of selectively delivering high doses of radiotherapy to tumor cells while minimizing exposure to surrounding tissues. Yttrium-90 (90Y and lutetium-177 (177Lu are two of the most promising beta-particle emitting radionuclides used for radioimmunotherapy, which despite having similar chemistries differ distinctly in terms of radiophysical features. These differences may have important consequences for the absorbed dose to tumors and normal organs. Whereas 90Y has been successfully applied in a number of preclinical and clinical radioimmunotherapy settings, there have been few published pretargeting studies with 177Lu. We therefore compared the therapeutic potential of targeting either 90Y or 177Lu to human B-cell lymphoma xenografts in mice.Parallel experiments evaluating the biodistribution, imaging, dosimetry, therapeutic efficacy, and toxicity were performed in female athymic nude mice bearing either Ramos (Burkitt lymphoma or Granta (mantle cell lymphoma xenografts, utilizing an anti-CD20 antibody-streptavidin conjugate (1F5-SA and an 90Y- or 177Lu-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA-biotin second step reagent.The two radionuclides displayed comparable biodistributions in tumors and normal organs; however, the absorbed radiation dose delivered to tumor was more than twice as high for 90Y (1.3 Gy/MBq as for 177Lu (0.6 Gy/MBq. More importantly, therapy with 90Y-DOTA-biotin was dramatically more effective than with 177Lu-DOTA-biotin, with 100% of Ramos xenograft-bearing mice cured with 37 MBq 90Y, whereas 0% were cured using identical amounts of 177Lu-DOTA-biotin. Similar results were observed in mice bearing Granta xenografts, with 80% of the mice cured with 90Y-PRIT and 0% cured with 177Lu-PRIT. Toxicities were comparable with both isotopes.90Y was therapeutically superior to 177Lu for streptavidin-biotin PRIT approaches in these human lymphoma

  6. Contribution of soil-32P, fertilizer-32P and VA mycorrhizal fungi to phosphorus nutrition of corn plant

    32P labelled fertilizer and five synthetic phosphates (dicalcium phosphate, octocalcium phosphate, iron phosphate, aluminium phosphate and apatite), which were used to simulate inorganic phosphates such as Ca2-P, Ca8-P, FeP, Al-P and Ca10-P in calcareous soil, were applied to corn plants inoculating with and without vesicular-arbuscular (VA) mycorrhizal fungi in a calcareous soil. The results showed that VA mycorrhizal fungi and dicalcium phosphate, octocalcium phosphate, iron phosphate, aluminium phosphate promoted growth and increased phosphorus content of corn plant. The four synthetic phosphates except apatite had higher contributions to corn plant growth than VA mycorrhizal fungi. Contributions of fertilizer-P, soil-P and synthetic phosphates to phosphorus nutrition of corn plant were in order of synthetic phosphates (except apatite) > soil- P > fertilizer-P. Inoculating with VA mycorrhizal fungi increased the contribution of soil-P and decreased the contribution of synthetic phosphates, but did not affect the contribution of fertilizer-P

  7. Brachytherapy on restenosis. {sup 32}P radioisotope in animal model

    Bergoc, R.; Rivera, E.; Cocca, C.; Martin, G.; Cricco, G. [Buenos Aires Univ. (Argentina). School of Pharmacy and Biochemistry; Croci, M.; Guzman, L.

    2000-05-01

    Despite a notorious decline in age-adjusted death rates for cardiovascular pathologies, coronary artery disease still remains as the main cause of mortality above the age of 40 in men and 60 in women. More than 25% of death in persons over the age of 35 are due to coronary disease. In about 50% of men and 30% of women, the first manifestation of the disease is an acute myocardial infarction and 10% a sudden cardiac death. In Argentina it is estimated that in 1998 about 100.000-115.000 people suffered as first manifestation of coronary illness a myocardial acute infarct. Angioplasty has an important and well established site in the treatment of the coronary illness and restenosis represents the principal complication of this method for myocardial re-vascularization. About a 35-40% of treated arteries present restenosis within the first six month the intervention with the concomitant need of re-interventions, re-hospitalizations, by-pass surgery, work discontinuity and the high cost for the health system. A number of drugs were tested as anti-restenosis: anticoagulants, aspirin, antispasmodics and lipid-lowering agents but none was clearly efficient; also, experimental studies in which intravascular irradiation with different source types and energies, radiation doses and doses rate to prevent restenosis was utilized; however, there is no consensus in many aspects of this intravascular brachytherapy. The first step in this work was to induce the experimental model in rabbits. Afterwards, by means of the balloon methodology and stent implantation, brachytherapy experiments were carried out to evaluate the biological effect on different layers of arteries, with different Doses using a beta particle emitting radioisotope ({sup 32}P). The arteriosclerotic lesions were induced in New Zealand rabbits through the administration of a diet with high cholesterol content. Angioplastic interventions on femoral arteries were done with balloon methodology and controlled by

  8. Brachytherapy on restenosis. 32P radioisotope in animal model

    Despite a notorious decline in age-adjusted death rates for cardiovascular pathologies, coronary artery disease still remains as the main cause of mortality above the age of 40 in men and 60 in women. More than 25% of death in persons over the age of 35 are due to coronary disease. In about 50% of men and 30% of women, the first manifestation of the disease is an acute myocardial infarction and 10% a sudden cardiac death. In Argentina it is estimated that in 1998 about 100.000-115.000 people suffered as first manifestation of coronary illness a myocardial acute infarct. Angioplasty has an important and well established site in the treatment of the coronary illness and restenosis represents the principal complication of this method for myocardial re-vascularization. About a 35-40% of treated arteries present restenosis within the first six month the intervention with the concomitant need of re-interventions, re-hospitalizations, by-pass surgery, work discontinuity and the high cost for the health system. A number of drugs were tested as anti-restenosis: anticoagulants, aspirin, antispasmodics and lipid-lowering agents but none was clearly efficient; also, experimental studies in which intravascular irradiation with different source types and energies, radiation doses and doses rate to prevent restenosis was utilized; however, there is no consensus in many aspects of this intravascular brachytherapy. The first step in this work was to induce the experimental model in rabbits. Afterwards, by means of the balloon methodology and stent implantation, brachytherapy experiments were carried out to evaluate the biological effect on different layers of arteries, with different Doses using a beta particle emitting radioisotope (32P). The arteriosclerotic lesions were induced in New Zealand rabbits through the administration of a diet with high cholesterol content. Angioplastic interventions on femoral arteries were done with balloon methodology and controlled by fluoroscopy

  9. Experimental autoabsorption curve 90Sr in SrCO3. Efficiency calculation to detection of 90Sr, 90Y and 90Sr + 90Y in a beta gas proportional counter

    Strontium-90 has been determined by radiochemical separation techniques in environmental samples. These techniques, of course, cannot separate the two strontium radionuclides from each other of from stable strontium. Consequently the end product of the chemical separation contains all strontium isotopes in SrCO3. The beta particules emitted by 90Sr are absorbed by the SrCO3 precipitate. This is the main source of error in the activity measurement. It has been prepared sources of 90Sr in SrCO3 in order to determinate the counting efficiency and autoabsorption curve. Also detection efficiencies have been calibrated using known activities of 90Y and equilibrium mixture of 90Sr+90Y in the same geometry than our samples. The activity of 90Sr by ingrowth of 90Y has been calculated by our computer program. (author). 2 figs., 3 refs

  10. Feasibility of {sup 90}Y TOF PET-based dosimetry in liver metastasis therapy using SIR-Spheres

    Lhommel, Renaud; Elmbt, Larry van; Jamar, Francois; Pauwels, Stanislas; Walrand, Stephan [Universite Catholique de Louvain, Department of Nuclear Medicine, Cliniques Universitaires Saint Luc, Brussels (Belgium); Goffette, Pierre [Universite Catholique de Louvain, Department of Interventional Radiology, Cliniques Universitaires Saint Luc, Brussels (Belgium); Eynde, Marc van den [Universite Catholique de Louvain, Department of Oncology, Cliniques Universitaires Saint Luc, Brussels (Belgium)

    2010-09-15

    {sup 90}Y-labelled compounds used in targeted radiotherapy are usually imaged with SPECT by recording the bremsstrahlung X-rays of the {beta} decay. The continuous shape of the X-ray spectrum induces the presence of a significant fraction of scatter rays in the acquisition energy window, reducing the accuracy of biodistribution and of dosimetry assessments. The aim of this paper is to use instead the low branch of e{sup -} e{sup +} pair production in the {sup 90}Y decay. After administration of {sup 90}Y-labelled SIR-Spheres by catheterization of both liver lobes, the activity distribution is obtained by {sup 90}Y time-of-flight (TOF) PET imaging. The activity distribution is convolved with a dose irradiation kernel in order to derive the regional dosimetry distribution. Evaluation on an anatomical phantom showed that the method provided an accurate dosimetry assessment. Preliminary results on a patient demonstrated a high-resolution absorbed dose distribution with a clear correlation with tumour response. This supports the implementation of {sup 90}Y PET in selective internal radiation therapy of the liver. (orig.)

  11. Country report: Thailand. Development of Sr-90/ Y-90 Generator and Development of Radiopharmaceuticals Using Y-90

    The research project has been conducted at Thailand Institute of Nuclear Technology in accordance to the 1st RCM plan during the IAEA meeting in Warsaw. The objectives of the project include the following 5 specific aims: 1. Development of Sr-90/Y-90 ion-exchange chromatography generator 2. Development of Sr-90/Y-90 extraction chromatography generator 3. Development of quality control technique 4. Development of herapeutic radiopharmaceuticals Y-90 particulates/colloids 5. Development of Re-188 DMSA–bis-phosphonates Currently we have achieved specific aims 1 to 3. The specific aims 4 and 5 are during investigation. For specific aim 4, we are during the process to extract high purity 90Y from 90Sr/90Y generator that will yield the starting 90Y for the production of Y-90 particulates and colloids. For the 5th specific aim, we are on hold to receive the starting agent, bis- Phosphonates, from Dr. Blower group. Therefore, this progress report will cover our work focusing on specific aims 1 to 3

  12. Design and bioevaluation of a 32P-patch for brachytherapy of skin diseases

    The purpose of this study was to design and evaluate a 32P patch for brachytherapy of skin diseases. We employed Phosphoric-32P-acid and Chromic 32P-phosphate in combination with natural rubber or silicone to produce the patches. Stability studies in vitro to evaluate the leakage of radioactivity, autoradiographic studies to evaluate homogeneity and shielding, as well as therapeutic efficacy in an animal model of skin cancer of the selected 32P patch were performed. The 32P-silicone-patch demonstrated its safety for external application. Tumor growth was arrest and complete regressions of tumors were seen in some other cases with 40 Gy applied in a single-dose scheme. In conclusion, the 32P-silicone-patch is easy to prepare and use in the treatment of skin diseases

  13. Design and bioevaluation of a {sup 32}P-patch for brachytherapy of skin diseases

    Salgueiro, M.J. [Radioisotope Laboratory, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires (Argentina)], E-mail: jsalgueiro@ffyb.uba.ar; Duran, H. [Radiobiology Department, National Atomic Energy Commission (CNEA) Buenos Aires, CONICET and School of Science and Technology, University of San Martin, San Martin (Argentina); Palmieri, M. [Biodiversity and Experimental Biology Department, School of Exact and Natural Sciences, University of Buenos Aires, Buenos Aires (Argentina); Pirchio, R. [Dosimetry Department, National Atomic Energy Commission (CNEA) Buenos Aires (Argentina); Nicolini, J.; Ughetti, R. [Research and Development Department, Laboratorios Bacon SAIC (Argentina); Papparella, M.L. [Pathology Department, School of Dentistry, University of Buenos Aires, Buenos Aires (Argentina); Casale, G. [Research and Development Department, Laboratorios Bacon SAIC (Argentina); Zubillaga, M. [Radioisotope Laboratory, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires (Argentina)

    2008-03-15

    The purpose of this study was to design and evaluate a {sup 32}P patch for brachytherapy of skin diseases. We employed Phosphoric-{sup 32}P-acid and Chromic {sup 32}P-phosphate in combination with natural rubber or silicone to produce the patches. Stability studies in vitro to evaluate the leakage of radioactivity, autoradiographic studies to evaluate homogeneity and shielding, as well as therapeutic efficacy in an animal model of skin cancer of the selected {sup 32}P patch were performed. The {sup 32}P-silicone-patch demonstrated its safety for external application. Tumor growth was arrest and complete regressions of tumors were seen in some other cases with 40 Gy applied in a single-dose scheme. In conclusion, the {sup 32}P-silicone-patch is easy to prepare and use in the treatment of skin diseases.

  14. Comparative Efficacy of 177Lu and 90Y for Anti-CD20 Pretargeted Radioimmunotherapy in Murine Lymphoma Xenograft Models

    Frost, Sophia; Frayo, Shani; Miller, Brian W.; Orozco, Johnnie J.; Booth, Garrett C.; Hylarides, Mark; Lin, Yukang; Green, Damian J.; Gopal, Ajay K.; Pagel, John M.; Back, Tom; Fisher, Darrell R.; Press, Oliver W.

    2015-03-01

    Pretargeted radioimmunotherapy (PRIT) is a multi-step method of selectively delivering high doses of radiotherapy to tumor cells while minimizing exposure to surrounding tissues. Yttrium-90 (90Y) and lutetium-177 (177Lu) are two of the most promising beta-particle emitting radionuclides used for radioimmunotherapy, which despite having similar chemistries differ distinctly in terms of radiophysical features. These differences may have important consequences for the absorbed dose to tumors and normal organs. Whereas 90Y has been successfully applied in a number of preclinical and clinical radioimmunotherapy settings, there have been few published pretargeting studies with 177Lu. We therefore compared the therapeutic potential of targeting either 90Y or 177Lu to human B-cell lymphoma xenografts in mice.

  15. The curative effect of 90Sr-90Y sticking for treatment of 56 patients with underarm odor

    To explore the application of 90Sr-90Y sticking in the treatment of axillary osmidrosis, and to evaluate the curative effect and advantage of this method, 56 cases patients with axillary osmidrosis were treated with 90Sr -90Y sticking between May 2009 and May 2011. The clinical curative effect, prognosis and adverse reaction were evaluated. 42 patients were cured after 1 to 3 courses of treatment and the cure rate was 81.5% with an efficiency of 100%. There was no recurrence found in cured patients after a follow-up period. Compare with operation and other treatment method, the treatment of axillary osmidrosis with 90Sr-90Y is a simple method with good curative effect, less pain, no obvious scar and secondary injury. It is worth to promote in widely clinical application. (authors)

  16. Determination of phagocytosis of 32P-labeled Staphylococcus aureus by bovine polymorphonuclear leukocytes

    A procedure for the measurement of phagocytosis by bovine polymorphonuclear leukocytes (PMN) of 32P-labeled Staphylococcus aureus was modified so that a larger number of samples could be compared in a single run, and smaller volumes of sample, PMN, and 32P-labeled S aureus could be used. Results were highly reproducible, with a coefficient of variation between duplicate determinations of less than or equal to 2%. Lysostaphin was prepared from the supernatant of S staphylolyticus and was compared with a commercially available preparation. Effects of lysostaphin on PMN and influence of incubation media on release of 32P from 32P-labeled S aureus by lysostaphin were examined

  17. The 32P test and other methods in the diagnosis of intraocular tumours

    Why the 32P test was reintroduced into The Netherlands for the diagnosis of intraocular tumours and how the present study was started is explained. The physical features of 32P and the biochemical behaviour of radioactive phosphate in healthy and neoplastic tissue are described. The complications, which can be encountered after the administration of 32P, are mentioned. A review of the 32P test in ophthalmology is given, with special attention to the methods used and the development of instruments for the measurements. The way in which the 32P test was performed in this study is described. The 32P test results obtained in the patients of this study are described. A good diagnostic accuracy of the 32P test was present in the 192 lesions located in the posterior segment, with a correct result obtained in 186 patients. Only three malignant and three benign lesions showed an incorrect test result. The results obtained with scintigraphy, fluorescein angiography, perimetry, transillumination, and ultrasonography are given and compared with data in the literature. The value of fluorescein angiography, perimetry, and the 32P test for the diagnosis of various lesions, with relevance to the differential diagnosis of a choroidal tumour, is described. The 32P tests performed in 12 patients with an extraocular lesion are mentioned. (Auth.)

  18. Separation of 90Sr from Purex high level waste and development of a 90Sr-90Y generator

    90Y (T1/2=64.2 h) finds several applications in nuclear medicine. It is formed from the decay of 90Sr which has a long half-life of 28.8 years. 90Sr can be used as a long-lasting source for the production of carrier-free 90Y. 90Sr itself is abundantly available in high level waste (HLW) of PUREX origin. The present studies deal with the separation of pure 90Sr from HLW and the subsequent separation of 90Y from 90Sr. Actinides and some of the fission products like lanthanides, zirconium, molybdenum and cesium were first removed from the HLW using methods based on solvent extraction and ion-exchange studied earlier in our laboratory. The resulting waste solution was used as a feed for the present process. The separation of 90Sr from HLW was based on radiochemical method which involved a repeated scavenging with ferric hydroxide followed by strontium carbonate precipitation. The separation of 90Y from 90Sr was achieved by membrane separation technique. A compact generator is developed for this separation using a commercially available polytetrafluoroethylene (PTFE) membrane, impregnated with indigenously synthesised 2-ethylhexyl 2-ethylhexyl phosphonic acid (KSM-17). Generator system overcomes the drawbacks associated with conventional solvent extraction and ion-exchange based generators. The product is in chloride form and is suitable for complexation studies. After gaining an operating experience of ∼3 years in generating carrier-free 90Y at 2 mCi level for initial studies in radiotherapeutic applications, the process was scaled up for the production of about 12 mCi of 90Y to be used for animal studies before its application to patients. Radiochemical and chemical purity of the product was critically assayed by radiometry, ICP-AES, etc. The process is amenable for further scaling up. (author)

  19. A performance evaluation of {sup 90}Y dose-calibrator measurements in nuclear pharmacies and clinics in the United States

    Schultz, Michael K. [National Institute of Standards and Technology, Nuclear Medicine Standards Program, 100 Bureau Drive, MS 8462, Gaithersburg, MD 20899 (United States)], E-mail: michael-schultz@uiowa.edu; Cessna, Jeffrey T. [National Institute of Standards and Technology, Nuclear Medicine Standards Program, 100 Bureau Drive, MS 8462, Gaithersburg, MD 20899 (United States); Anderson, Tamara L. [College of Pharmacy, Univ. of New Mexico Health Sciences Center, New Mexico Center for Isotopes in Medicine, 2502 Marble, NE MSC09 5360, Albuquerque, NM 87131-0001 (United States); Ponto, James A. [Dept. of Radiology, Div. of Nuclear Medicine, Univ. of Iowa Hospital and Clinics, 200 Hawkins Drive, 3832 JPP, Iowa City, IA 52242 (United States); Petry, Neil [Dept. of Radiology, Dept. of Nuclear Medicine, Duke Univ. Medical Center, 133 Bell Building, Box 3304, Durham, NC 27710-3304 (United States); Kowalsky, Richard J. [Dept. of Radiology, Univ. of North Carolina, 1312 Kerr Hall, CB 7360, Chapel Hill, NC 27599 (United States); Palmer, Matthew R. [Dept. of Radiology, Div. of Nuclear Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215-5400 (United States); Beinlich, Uwe F. [QSA Global, Inc., Auriga Medical Div., 40 North Avenue, Burlington, MA 01803 (United States); Baker, William [Pharmaceutical and Diagnostic Services, 1152 West 2240 South St. E., West Valley City, UT 84119 (United States); Hinkle, George H. [Ohio State Univ. Medical Center, Room 203D, Doan Hall, 410 West 10th Avenue, Columbus, OH 43210 (United States); Hung, Joseph C. [Mayo Clinic, Div. of Nuclear Medicine, Dept. of Radiology, 200 First Street SW, Rochester, MN 55905 (United States); Quinton, Timothy [Radiopharmacy, Inc., 1409 E. Virginia St., Evansville, IN 47711 (United States); Rice, Peter A. [Massachusetts General Hospital, Div. of Nuclear Medicine, Tilton-2, 55 Fruit Street, Boston, MA 02114 (United States)] (and others)

    2008-02-15

    A blind performance test was conducted to evaluate dose-calibrator measurements at nuclear pharmacies in the United States (US). Two test-sample geometries were chosen to represent those used for measurements of {sup 90}Y-ibritumomab tiuxetan (ZEVALIN). The radioactivity concentration of test-samples was verified by the US National Institute of Standards and Technology. Forty-five results were reported by 10 participants. Eighty percent of reported values were within the US Pharmacopoeia content standard ({+-}10%) for {sup 90}Y-ZEVALIN. All results were within US Nuclear Regulatory Commission conformance limits ({+-}20%) for defining therapeutic misadministrations.

  20. Separation of 90Y from 90Sr using hollow fiber supported liquid membrane containing PC-88A as the carrier

    2-Ethylhexylphosphonic acid -2- ethyl hexylmonoester (PC-88A) has been used as the extractant for Y3+ and Eu3+ (used as a surrogate) from pH solutions where Sr2+ remained inextractable. The relative extraction efficiency of PC-88A towards Y3+ and Sr2+ was investigated from dilute HNO3 media using solvent extraction, as well as hollow fiber supported liquid membrane (HFSLM) methods. A separation method for 90Y from 90Sr + 90Y mixture was developed using HFSLM method and discussed in the present paper. (author)

  1. 90Y-DOTA-CHS Microspheres for Live Radiomicrosphere Therapy: Preliminary In Vivo Lung Radiochemical Stability Studies

    Alejandro Amor-Coarasa; Andrew Milera; Denny Carvajal; Seza Gulec; McGoron, Anthony J

    2014-01-01

    Chitosan (CHS) is used to prepare microspheres of 31 ± 8 µm size. Surface modification with p-SCN-Bn-DOTA was performed. A maximum 90Y capacity was found to be 12.1 ± 4.4 µCi/particle. The best obtained labeling yield was 87.7 ± 0.6%. More than 90% in vitro stability was found. Particle in vitro degradation half-life in PBS was found to be greater than 21 days. In vivo studies with 90Y-DOTA-CHS showed more than 95% of the injected activity (decay corrected) in the lungs 24 hours after tail ve...

  2. A performance evaluation of 90Y dose-calibrator measurements in nuclear pharmacies and clinics in the United States

    A blind performance test was conducted to evaluate dose-calibrator measurements at nuclear pharmacies in the United States (US). Two test-sample geometries were chosen to represent those used for measurements of 90Y-ibritumomab tiuxetan (ZEVALIN). The radioactivity concentration of test-samples was verified by the US National Institute of Standards and Technology. Forty-five results were reported by 10 participants. Eighty percent of reported values were within the US Pharmacopoeia content standard (±10%) for 90Y-ZEVALIN. All results were within US Nuclear Regulatory Commission conformance limits (±20%) for defining therapeutic misadministrations

  3. Radioembolisation with {sup 90}Y-microspheres: dosimetric and radiobiological investigation for multi-cycle treatment

    Cremonesi, Marta; Ferrari, Mahila; Pedroli, Guido [European Institute of Oncology, Unit of Medical Physics, Milan (Italy); Bartolomei, Mirco; Arico, Demetrio; De Cicco, Concetta [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); Orsi, Franco; Bonomo, Guido [European Institute of Oncology, Unit of Interventistic Radiology, Milan (Italy); Mallia, Andrew [Gamma Unit, Radiology Department, St. Luke' s Hospital (Malta); Paganelli, Giovanni [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy)

    2008-11-15

    Radioembolisation with {sup 90}Y-microspheres is a new locoregional treatment of hepatic lesions, usually applied as single cycle. Multi-cycle treatments might be considered as a strategy to improve the risk-benefit balance. With the aim to derive suitable information for patient tailored therapy, available patients' dosimetric data were reviewed according to the linear-quadratic model and converted into biological effective dose (BED) values. Single vs. multi-cycle approaches were compared through radiobiological perspective. Twenty patients with metastatic lesions underwent radioembolisation. The {sup 90}Y-administered activity (AA) was established in order to respect a precautionary limit dose (40 Gy) for the non-tumoral liver (NTL). BED was calculated setting {alpha}/{beta} = 2.5 Gy (NTL), 10 Gy (tumours); T{sub 1/2,eff} = T{sub 1/2,phys} = 64.2 h; T{sub 1/2,rep} = 2.5 h (NTL), 1.5 h (tumours). The BED to NTL was considered as a constraint for multi-cycle approach. The AA for two cycles and the percent variations of AA, tumour dose, BED were estimated. In one-cycle, for a prescribed BED to NTL of 64 Gy (NTL dose = 40 Gy), AA was 1.7 (0.9-3.2) GBq, tumour dose was 130 (65-235) Gy, and tumour BED was 170 (75-360) Gy. Considering two cycles, {proportional_to}15% increase was found for AA and dose to NTL, with unvaried BED for NTL. Tumour dose increase was 20 (10-35) Gy; tumour BED increase was 10 (3-11) Gy. In different protocols allowing 80 Gy to NTL, the BED sparing estimated was {proportional_to}50 Gy (two cycles) and 65 Gy (three cycles). From a radiobiological perspective, multi-cycle treatments would allow administering higher activities with increased tumour irradiation and preserved radiation effects on NTL. Trials comparing single vs. multiple cycles are suggested. (orig.)

  4. Three dosimetry models of lipoma arborescens treated by {sup 90}Y synovectomy

    O’Doherty, Jim, E-mail: jim.odoherty@kcl.ac.uk [Department of Medical Physics-Nuclear Medicine, Royal Surrey County Hospital, Guildford GU2 7XX, United Kingdom and Division of Imaging Sciences, PET Imaging Centre at St. Thomas’ Hospital, King' s College London, London SE1 7EH (United Kingdom); Clauss, Ralf [Department of Nuclear Medicine, Royal Surrey County Hospital, Guildford GU2 7XX (United Kingdom); Scuffham, James [Department of Medical Physics-Nuclear Medicine, Royal Surrey County Hospital, Guildford GU2 7XX (United Kingdom); Khan, Aman [Department of Rheumatology, Royal Surrey County Hospital, Guildford GU2 7XX (United Kingdom); Petitguillaume, Alice; Desbrée, Aurélie [Service de Dosimétrie Interne, Institut de Radioprotection et de Sûreté Nucléaire, 92260 Fontenay-aux-Roses (France)

    2014-05-15

    Purpose: Lipoma arborescens (LA) is a benign intra-articular lipomatous proliferation of the synovial membrane. This extremely rare condition has previously been treated by intra-articular{sup 90}Y radiosynoviorthesis but dosimetry literature on this form of radionuclide therapy is nonexistent. The authors detail methodology for successful treatment of LA and provide for the first time estimates of radiation dosimetry. The authors also analyze the biodistribution of the radiopharmaceutical over the course of the patient's treatment through sequential imaging. Methods: A patient with bilateral LA underwent intracavity injection of{sup 90}Y citrate colloid to the right and left knee joint spaces (181 and 198 MBq, respectively). SPECT/CT datasets were acquired over 9 days to quantify the biodistribution and kinetics of the radiopharmaceutical. Radiation dosimetry was performed using the MIRD schema (through OLINDA software), a custom voxel-based method, and a direct Monte Carlo calculation (OEDIPE). Results: Follow-up MRI showed marked reduction in LA size in both knees. Mean absorbed doses to the LA were 21.2 ± 0.8 and 42.9 ± 2.3 Gy using OLINDA, 8.1 ± 0.3 and 16.7 ± 0.5 Gy using voxel based methodology, and 8.2 ± 0.3 and 15.7 ± 0.5 Gy for OEDIPE in the right and left LA, respectively. Distribution of the radiopharmaceutical within the joint space alters over the imaging period, with less than 1% of the remaining activity having moved posteriorly in the knee cavity. No uptake was detected outside of the joint space after assessment with whole-body scintigraphy. Conclusions: An activity of approximately 185 MBq successfully relieved clinical symptoms of LA. There was good correlation between direct Monte Carlo and voxel based techniques, but OLINDA was shown to overestimate the absorbed dose to the tumor. Accurate dosimetry may help select an activity more tailored to the specific size and location of the LA.

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

    Kunikowska, Jolanta; Krolicki, Leszek [Medical University of Warsaw, Nuclear Medicine Department, Warsaw (Poland); Hubalewska-Dydejczyk, Alicja; Sowa-Staszczak, Anna [Collegium Medicum Cracow, Cracow (Poland); Mikolajczak, Renata; Pawlak, Dariusz [Institute of Atomic Energy POLATOM, Swierk-Otwock (Poland)

    2011-10-15

    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 {sup 90}Y beta emitter for larger lesions and the lower energy {sup 177}Lu for smaller lesions has been postulated in the literature.The aim of the study was to evaluate combined {sup 90}Y/{sup 177}Lu-DOTATATE therapy in comparison to {sup 90}Y-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 {sup 90}Y-DOTATATE, whereas group B (n = 25) received the 1:1 {sup 90}Y/{sup 177}Lu-DOTATATE. The administered activity was based on 3.7 GBq/m{sup 2} 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 ({sup 90}Y/{sup 177}Lu-DOTATATE) provides longer overall survival than with a single radioisotope ({sup 90}Y-DOTATATE) and the safety of both methods is comparable. (orig.)

  6. A complete dosimetric characterization of two 90Sr-90Y dermatologic applicators

    A complete dosimetric characterization of two Amershan 90Sr-90Y dermatologic applicators is described in this present work. The dosimetric parameters analyzed are: percentage depth dose curve, radial dose distribution, non-uniformity and asymmetry. Both applicators are planar-circular having 22.57 and 9.0 mm diameters. In the range where the percentage depth dose goes from 100% down to 20%, the measured percentage depth dose and that obtained by the Monte Carlo simulation have shown maximum discrepancy of 5.3% for both applicators. The radial dose distribution has been measured at several depths using a GafChromic EBT QD+ films and it was also calculated by simulation. The discrepancies found did not exceed 5.9% up to the depth of 1.8 mm, where the percentage depth dose drops to 40% of the maximum. The maximum non-uniformity and asymmetry are 1.7% and 5.3% for the first applicator and 22.7% and 25.9% for the second applicator, respectively. Both applicators meet the specification for the maximum non-uniformity established by the adopted protocol, whose limit is 30%. As for the asymmetry the limit is 20% and the second applicator exceeded it in about 5.9%.

  7. Monitoring 90Y-SIRsphere treatment response with 18FDG-PET

    A 75-year-old male presented to emergency with severe abdominal pain and vomiting which had increased over 3 months. This patient also had a history of type 2 Diabetes Mellitus, Chronic Renal Failure, Primary Heart Block and Colonic Polyps. An abdominal CT displayed a soft tissue density mass or thickening within the descending colon, causing incomplete obstruction and significant distension of the colon. He also had a positive faecal occult blood test and his Carcino-embryonic antigen blood test (CEA) was 3.9μg/L (normal 4N0Mx). He declined chemotherapy post-surgery His CEA dropped to 1.3μg/L immediately post-surgery. 3-monthly CEA measurements were made. At 12 months post-surgery, his CEA level had risen to 5.9μg/L, and an abdominal CT scan revealed 2 hypo-dense lesions in segment 4a of the liver, adjacent to the Inferior Vena Cava (IVC). These lesions measured 3.2cm (medial lesion) and 2.6cm (lateral lesion) at their maximum diameters. The patient underwent an l8FDG-PET scan on a Philips Allegro dedicated PET scanner [Philips medical Systems, Cleveland OH, USA], using a standard l8FDG dose of 5.14MBq/kg. The patient fasted for 6 hours prior to the test and withheld his oral hypoglycae-mics. Scanning commenced at 1 hour post-injection. The PET scan displayed 2 lesions within the liver, corresponding to the CT findings. The PET scan showed these lesions to be avid (SUV = 5.1 and 4.1 respectively, normal liver SUV = 1.3), with no evidence of extrahepatic disease. Due to proximity to the IVC, these lesions were deemed unresectable and unable to be treated with Radiofrequency (RF) ablation. The patient discussed treatment options with his surgeon and agreed to undergo 90Y-SIRsphere (Sirtex Medical Ltd, Sydney Australia) Selective Internal Radiation Treatment (SIRT) for his liver metastases, but again declined chemotherapy. Work-up for this treatment included hepatic angiography and embolic coiling of the hepatic artery branches to eliminate pathways for visceral

  8. Study On The Preparation Of 90Y-DTPA-Rituximab For Non-Hodgkin Lymphoma Treatment

    Yttrium is one of the most useful radionuclides for radioimmunotherapeutic applications, especially labelling with monoclonal antibodies. Rituximab was bound to the DTPA chelating agent using Hnatowich methods. Cyclic anhydride DTPA (cDTPAa, 0.1 mg/ml) was dissolved in chloroform and was degassed under a stream of nitrogen for 30 minutes. Rituximab solution in 0.05 M bicarbonate buffer was immediately added and mixed for one minute at room temperature. The antibody Rituximab at different concentration (5 mg/ml and 10 mg/ml) was coupled with the cDTPAa, at molar ratios (cDTPAa : Rituximab) of 1:1, 3:1, 5:1, 10:1 and 20:1. The conjugation of DTPA-Rituximab mixture was labelled with Y-90, then using Sephadex G25 in order to determine coupling efficiency. Coupling efficiency at a 3:1 mole ratio was 70%. After purification, the conjugation DTPA-Rituximab was labeled with Y-90 in 0.5 M acetate buffer, pH 5, at room temperature. The labeling yield was about 99%. The radiochemical purity of 90Y-DTPA-Rituximab was more than 98 % which determined by ITLC in 0.1 M acetate at pH 6 as mobile phase. The radiopharmaceuticals have been test for sterility, apyrogenicity and biodistribution. This is a potential radiopharmaceutical for clinical application in therapeutic Non Hodgkin Lymphoma treatments. (author)

  9. Anti-CD45 Radioimmunotherapy with 90Y but Not 177Lu Is Effective Treatment in a Syngeneic Murine Leukemia Model

    Orozco, Johnnie J.; Ethan R. Balkin; Gooley, Ted A.; Kenoyer, Aimee; Hamlin, Donald K.; Wilbur, D. Scott; Fisher, Darrell R.; Hylarides, Mark D.; Shadman, Mazyar; Green, Damian J.; Gopal, Ajay K.; Press, Oliver W.; Pagel, John M.

    2014-01-01

    Radioimmunotherapy (RIT) for treatment of hematologic malignancies has primarily employed monoclonal antibodies (Ab) labeled with 131I or 90Y which have limitations, and alternative radionuclides are needed to facilitate wider adoption of RIT. We therefore compared the relative therapeutic efficacy and toxicity of anti-CD45 RIT employing 90Y and 177Lu in a syngeneic, disseminated murine myeloid leukemia (B6SJLF1/J) model. Biodistribution studies showed that both 90Y- and 177Lu-anti-murine CD4...

  10. Radiophosphorus (/sup 32/P) treatment of bone marrow disorders in dogs: 11 cases (1970-1987)

    Smith, M.; Turrel, J.M.

    1989-01-01

    Between March 1970 and February 1987, radiophosphorus (/sup 32/P) was used to treat bone marrow disorders in 6 dogs; 4 had polycythemia vera and 2 had essential thrombocythemia. Activities of /sup 32/P given initially ranged from 2.4 to 3.3 mCi/m2. Four dogs responded well to /sup 32/P treatment, with gradual resolution of high RBC or platelet counts. Two of these dogs died of intercurrent disease unrelated to their bone marrow disorder, before blood counts could be stabilized. Two dogs did not respond to the initial /sup 32/P treatment nor to additional treatments with /sup 32/P, and had clinical signs and blood counts stabilized by use of phlebotomy or chemotherapeutic agents. We reviewed and analyzed 5 other cases of bone marrow disorders in dogs treated with /sup 32/P and included the findings from their records with the records of our 6 dogs in this retrospective analysis. Of the 8 dogs with polycythemia vera treated with /sup 32/P, 5 were given a single treatment that controlled clinical signs and blood counts for the remainder of the follow-up period. Of the 3 dogs treated for thrombocytosis with /sup 32/P, 2 had blood counts that responded to a single treatment.

  11. Clinical efficacy of 90Sr-90Y applicator combined with propranolol treatment on large infantile cutaneous hemangiomas

    Objective: To investigate the clinical efficacy of 90Sr-90Y applicator combined with propranolol (inderal) treatment for infants with large areas of cutaneous hemangiomas. Methods: Thirty-nine infants with large areas of cutaneous hemangiomas were randomly divided into two groups: study group (n=18) treated with 90Sr-90Y applicator in conjunction with propranolol, and control group (n =21) treated by 90Sr-90Y applicator only. The results of curative effects between the two groups were analyzed using rank sum test and χ2 test. Results: The cure rate, remission rate and effective rate for the study group were 44.4%(8/18), 55.6% (10/18) and 100.0% (18/18), respectively, and the corresponding rates for the control group were 14.3% (3/21), 52.4% (11/21) and 66.7% (14/21), respectively. The effective rate in the study group was significantly higher than that in the control group (Z=-2.861, P<0.05). The adverse reaction rates in the study and control groups were 66.7% (12/18) and 19.0% (4/21; χ2=9.084, P<0.05), respectively. Conclusion: Combined propranolol with 90Sr-90Y treatment for large infantile hemangiomas is clinically effective, but its side effects should be closely monitored. (authors)

  12. Receptor-mediated radionuclide therapy with 90Y-DOTATOC in association with amino acid infusion: a phase I study

    The aim of this study was to determine the maximum tolerated dose of 90Y-DOTATOC per cycle administered in association with amino acid solution as kidney protection in patients with somatostatin receptor-positive tumours. Forty patients in eight groups received two cycles of 90Y-DOTATOC, with activity increased by 0.37 GBq per group, starting at 2.96 and terminating at 5.55 GBq. All patients received lysine ± arginine infusion immediately before and after therapy. Forty-eight percent developed acute grade I-II gastrointestinal toxicity (nausea and vomiting) after amino acid infusion whereas no acute adverse reactions occurred after 90Y-DOTATOC injection up to 5.55 GBq/cycle. Grade III haematological toxicity occurred in three of seven (43%) patients receiving 5.18 GBq, which was defined as the maximum tolerable activity per cycle. Objective therapeutic responses occurred. Five GBq per cycle is the recommended dosage of 90Y-DOTATOC when amino acids are given to protect the kidneys. Although no patients developed acute kidney toxicity, delayed kidney toxicity remains a major concern, limiting the cumulative dose to 25 Gy. The way forward with this treatment would seem to be to identify more effective renal protective agents, in order to be able to increase the cumulative injectable activity and hence tumour dose. (orig.)

  13. (90)Y microspheres prepared by sol-gel method, promising medical material for radioembolization of liver malignancies.

    Łada, Wiesława; Iller, Edward; Wawszczak, Danuta; Konior, Marcin; Dziel, Tomasz

    2016-10-01

    A new technology for the production of radiopharmaceutical (90)Y microspheres in the form of spherical yttrium oxide grains obtained by sol-gel method has been described. The authors present and discuss the results of investigations performed in the development of new production technology of yttrium microspheres and determination of their physic-chemical properties. The final product has the structure of spherical yttrium oxide grains with a diameter 25-100μm, is stable and free from contaminants. Irradiation of 20mg samples of grains with diameter of 20-50μm in the thermal neutron flux of 1.7×10(14)cm(-2)s(-1) at the core of MARIA research nuclear reactor allowed to obtain microspheres labelled with the (90)Y isotope on the way of the nuclear reaction (89)Y(n, ɤ)(90)Y. Specific activity of irradiated microspheres has been determined by application of absolute triple to double coincidence ratio method (TDCR) and has been evaluated at 190MBq/mg Y. (90)Y microspheres prepared by the proposed technique can be regarded as a promising medical material for radioembolization of liver malignancies. PMID:27287162

  14. Feasibility of bremsstrahlung dosimetry for direct dose estimation in patients undergoing treatment with {sup 90}Y-ibritumomab tiuxetan

    Arrichiello, C.; Aloj, L.; Mormile, M.; D' Ambrosio, L.; Caraco, C.; De Martinis, F. [Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione ' ' G. Pascale' ' , Nuclear Medicine Department, Napoli (Italy); Frigeri, F.; Arcamone, M.; Pinto, A. [Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione ' ' G. Pascale' ' , Hematology-Oncology, Napoli (Italy); Stem Cells Transplantation Unit, Department of Hematology, Napoli (Italy); Lastoria, S. [Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione ' ' G. Pascale' ' , Nuclear Medicine Department, Napoli (Italy); Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione ' ' G. Pascale' ' , IRCCS, Napoli (Italy)

    2012-06-15

    Radioimmunotherapy with {sup 90}Y-ibritumomab tiuxetan has been used successfully used in the treatment of CD20-positive non-Hodgkin's lymphoma (NHL). Pretherapy imaging with {sup 111}In-ibritumomab tiuxetan has been used in provisional dosimetry studies. Posttherapy imaging of {sup 90}Y-ibritumomab tiuxetan for clinical use is appealing as it would simplify the data acquisition process and allow measurements of actual doses absorbed during treatment. The study included 29 patients with non-Hodgkin's lymphoma, of whom 16 (group I) received a pretherapy {sup 111}In-ibritumomab tiuxetan diagnostic study and {sup 90}Y-ibritumomab tiuxetan treatment 1 week later, and 13 (group II) received only {sup 90}Y-ibritumomab tiuxetan treatment. Planar imaging and blood sampling were performed in all patients. The doses absorbed by organs at risk were calculated using a whole-body average attenuation correction factor (relative dosimetry approach) and, in the case of the {sup 111}In-ibritumomab tiuxetan image sets, also using organ-specific attenuation correction factors (absolute dosimetry method). Red marrow absorbed doses were based on gamma counting of blood samples. The estimated red marrow absorbed doses from {sup 111}In and {sup 90}Y data were equivalent. In all cases, the doses absorbed by organs at risk were found to be within prescribed limits. The relative dosimetry approach applied to both the {sup 90}Y and {sup 111}In data significantly underestimated the doses relative to those obtained with the {sup 111}In absolute dosimetry method which is generally accepted as the reference method (MIRD 16). In the case of {sup 111}In, the relative dosimetry approach values were highly correlated (R {sup 2} = 0.61) with the reference method values. Relative dosimetry estimates may be adjusted multiplying by a correction factor of 2.8. The {sup 90}Y-ibritumomab tiuxetan relative dosimetry data correlated poorly with the reference method values (R {sup 2} = 0.02). Based

  15. Synthesis and evaluation of a new bifunctional NETA chelate for molecular targeted radiotherapy using90Y or177Lu

    Introduction: Therapeutic potential of β-emitting cytotoxic radionuclides 90Y and 177Lu has been demonstrated in numerous preclinical and clinical trials. A bifunctional chelate that can effectively complex with the radioisotopes is a critical component for molecular targeted radiotherapy 90Y and 177Lu. A new bifunctional chelate 5p-C-NETA with a relatively long alkyl spacer between the chelating backbone and the functional unit for conjugation to a tumor targeting moiety was synthesized. 5p-C-NETA was conjugated to a model targeting moiety, a cyclic Arg-Gly-Asp-D-Tyr-Lys (RGDyK) peptide binding integrin αvβ3 protein overexpressed on various cancers. 5p-C-NETA was conjugated to c(RGDyK) peptide and evaluated for potential use in molecular targeted radiotherapy of 90Y and 177Lu. Methods: 5p-C-NETA conjugated with c(RGDyK) was evaluated in vitro for radiolabeling, serum stability, binding affinity, and the result of the in vitro studies of 5p-C-NETA-c(RGDyK) was compared to that of 3p-C-NETA-c(RGDyK). 177Lu-5p-C-NETA-c(RGDyK) was further evaluated for in vivo biodistribution using gliobastoma bearing mice. Result: The new chelate rapidly and tightly bound to a cytotoxic radioisotope for cancer therapy, 90Y or 177Lu with excellent radiolabeling efficiency and maximum specific activity under mild condition (> 99%, RT, < 1 min). 90Y- and 177Lu-radiolabeled complexes of the new chelator remained stable in human serum without any loss of the radiolanthanide for 14 days. Introduction of the tumor targeting RGD moiety to the new chelator made little impact on complexation kinetics and stability with 90Y or 177Lu. 177Lu-radiolabeled 5p-C-NETA-c(RGDyK) conjugate was shown to target tumors in mice and produced a favorable in vivo stability profile. Conclusion: The results of in vitro and in vivo evaluation suggest that 5p-C-NETA is an effective bifunctional chelate of 90Y and 177Lu that can be applied for generation of versatile molecular targeted radiopharmaceuticals

  16. Gastric injury from 90Y to left hepatic lobe tumors adjacent to the stomach: fact or fiction?

    Radioembolization with 90Y microspheres is a locoregional radiation therapy for unresectable hepatic neoplasm. Non-target delivery of 90Y microspheres resulting in gastrointestinal (GI) symptoms is a recognized complication; there is minimal knowledge regarding the radiation effect to the gastric wall from left hepatic lobe 90Y treatments. Our aim was to study the incidence of GI complications when the target tissue (hepatic parenchyma ± tumor) is in close proximity to the gastric wall. We hypothesized that liver (tumor) to stomach proximity does not correlate with increased toxicity. Between November 2011 and September 2013, we studied all patients who underwent left lobe radioembolization with 90Y glass microspheres. With Institutional Review Board (IRB) approval, we retrospectively reviewed MRI/CT images of these patients, identifying a subset of patients with the left hepatic lobe <1 cm from the gastric wall. Patients were seen in clinic 1 month posttreatment and subsequently at 3-month intervals. Short- and long-term gastric adverse events were tabulated. Ninety-seven patients successfully underwent left hepatic lobe 90Y microsphere radioembolization in which the average distance from the liver to the stomach wall was 1.0 ± 2.8 mm. The average dose for patients who received radioembolization to the left hepatic lobe was 109 ± 57 Gy. Fifty patients had tumor within 1 cm of the gastric wall. The average dose for patients who received radioembolization to the left hepatic lobe with tumor within 1 cm of the gastric wall was 121 ± 41 Gy. There were no reportable or recordable medical events. Of the patients, 34 % reported abdominal pain that was grade 1-2; 65 % of the patients reported no abdominal pain. None of the 97 patients developed a clinically evident GI ulcer. Patients with left lobe tumors adjacent to or abutting the stomach do not exhibit acute or chronic radiation effects following radioembolization with glass microspheres. (orig.)

  17. Gastric injury from {sup 90}Y to left hepatic lobe tumors adjacent to the stomach: fact or fiction?

    Gates, Vanessa L.; Hickey, Ryan; Marshall, Karen; Williams, Melissa; Salzig, Krystina; Lewandowski, Robert J. [Robert H. Lurie Comprehensive Cancer Center, Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Chicago, IL (United States); Salem, Riad [Robert H. Lurie Comprehensive Cancer Center, Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Chicago, IL (United States); Northwestern University, Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Chicago, IL (United States)

    2015-12-15

    Radioembolization with {sup 90}Y microspheres is a locoregional radiation therapy for unresectable hepatic neoplasm. Non-target delivery of {sup 90}Y microspheres resulting in gastrointestinal (GI) symptoms is a recognized complication; there is minimal knowledge regarding the radiation effect to the gastric wall from left hepatic lobe {sup 90}Y treatments. Our aim was to study the incidence of GI complications when the target tissue (hepatic parenchyma ± tumor) is in close proximity to the gastric wall. We hypothesized that liver (tumor) to stomach proximity does not correlate with increased toxicity. Between November 2011 and September 2013, we studied all patients who underwent left lobe radioembolization with {sup 90}Y glass microspheres. With Institutional Review Board (IRB) approval, we retrospectively reviewed MRI/CT images of these patients, identifying a subset of patients with the left hepatic lobe <1 cm from the gastric wall. Patients were seen in clinic 1 month posttreatment and subsequently at 3-month intervals. Short- and long-term gastric adverse events were tabulated. Ninety-seven patients successfully underwent left hepatic lobe {sup 90}Y microsphere radioembolization in which the average distance from the liver to the stomach wall was 1.0 ± 2.8 mm. The average dose for patients who received radioembolization to the left hepatic lobe was 109 ± 57 Gy. Fifty patients had tumor within 1 cm of the gastric wall. The average dose for patients who received radioembolization to the left hepatic lobe with tumor within 1 cm of the gastric wall was 121 ± 41 Gy. There were no reportable or recordable medical events. Of the patients, 34 % reported abdominal pain that was grade 1-2; 65 % of the patients reported no abdominal pain. None of the 97 patients developed a clinically evident GI ulcer. Patients with left lobe tumors adjacent to or abutting the stomach do not exhibit acute or chronic radiation effects following radioembolization with glass

  18. A modified method for synthesis of [γ-32P] labelled adenosine triphosphate

    Production of [γ-32P]-ATP using three glycolysis enzymatic reaction i.e. glyceraldehyde 3-phosphate dehydrogenase, 3-phosphoglyceric phosphokinase and lactate dehydrogenase has been conducted. dl-glyceraldehyde 3-phosphate, Adenosine Diphosphate and H332PO4 was used as precursors for this reaction. Purification of [γ-32P]-ATP was performed by using DEAE-Sephadex column chromatography. The result suggested that this simple method could be used for producing [γ-32P]-ATP to support the provision of radiolabeled nucleotide for biotechnology research in Indonesia. (author)

  19. Study on the dynamics in absorption of 32P by hybrid wheat at elongate stage

    The dynamics of absorbing 32P of hybrid wheat at elongate stage is studied under pot culture conditions. The results show that the absorption capacity of hybrid wheat to 32P is in agreement with regression equation. The increased extent of absorption for them is greater than that for parent with time, and the reduction rate of absorption is lower than the parent significantly. Their root activity is much higher than that of the parent, too. The overall heterotic vigor of hybrid wheat on the absorption capacity to 32P is the sum of that of all organs

  20. Investigation on the chirality of electrons from /sup 90/Sr-/sup 90/Y beta-decay and their asymmetrical interactions with D- and L-alanines

    Conte, E.

    1985-12-16

    An investigation on the chirality of the electrons from /sup 90/Sr-/sup 90/Y beta decay and on their asymmetrical interactions with D- and L-alanines was carried out. By using ESR measurements, the asymmetrical yields were proved to be induced in /sup 90/Sr-/sup 90/Y-beta-irradiated alanines, with a distinguishably asymmetrical effect.

  1. Role of neutron and proton system in spin cut off parameter and entropy of {sup 89,90}Y

    Rahmatinejad, A. [Department of Physics, Faculty of Science, University of Zanjan, Zanjan (Iran, Islamic Republic of); Razavi, R., E-mail: rrazavin@ihu.ac.ir [Physics Department, Faculty of Science, Imam Hossein Comprehensive University, Tehran (Iran, Islamic Republic of); Kakavand, T. [Department of Physics, Faculty of Science, Imam Khomeini International University, Qazvin (Iran, Islamic Republic of)

    2015-09-15

    The nuclear level densities, entropies and spin cut off parameters have been determined in {sup 89,90}Y nuclei using the BCS model with inclusion of pairing interaction. The results have a good agreement with the recent experimental data on the level densities measured by the Oslo group. In addition, the entropy excess of {sup 90}Y compared to {sup 89}Y as a function of temperature has been extracted. Also, the role of neutron and proton systems in the entropy excess as well as the spin cut off excess have been investigated using the entropy excess ratio and spin cut off excess ratio introduced in our previous publication. The role of the neutron system at low temperatures, the temperatures below critical temperature, in the semi-magic nucleus {sup 89}Y is similar compared to the closed shell proton system in the tin isotopes.

  2. Preparation of 90Y-labeled different cyclic RGD peptides and evaluation in nude mice bearing human glioma xenografts

    90Y-DTPA-Bz-NH-SA-c(KRGDf) and 90Y-DTPA-Bz-NH-c(ERGDf) were prepared, and their in vitro and in vivo properties were compared. ITLC and HPLC show that the labeling yields of both compounds are more than 99% under the optimal conditions(pH=5.5, reac- ting at 80 degree C for 20 min), and they are stable in vitro. The biodistribution in nude mice bearing human glioma xenografts reveals no significant difference between these two radiolabeled com- pounds on uptake for all of tissues at the experimental time points; and pretty good tumor targeting and in vivo stability; and two radiolabeled compounds are mainly excreted through kid- neys, partly excreted through hepatobiliary system. The experimental data demonstrate that both of cyclic KRGDf and cyclic ERGDf are suitable for the further development of polymerconjugated RGD peptide drugs. (authors)

  3. Hepatectomy After Yttrium-90 (Y90) Radioembolization-Induced Liver Fibrosis.

    Maker, Ajay V; August, Carey; Maker, Vijay K; Weisenberg, Elliot

    2016-04-01

    An obese 55-year-old woman with nonalcoholic fatty liver disease presented 7 years after resection of a T3N1 ileal carcinoid tumor with an elevated chromogranin A, multifocal metastatic disease to the liver, and carcinoid syndrome. She underwent right hepatic artery yttrium-90 (Y90) radioembolization, followed a month later by selective Y90 treatment to segment IV. She then presented to our clinic 10 months later, remaining symptomatic with flushing, diarrhea, anxiety, myalgia, pain, and persistent night sweats despite Sandostatin administration. At least 11 tumors were identified in the right lobe of the liver and three in segment IV on liver-specific imaging. These lesions were stable over a year with no new lesions. At exploration, there was marked hypertrophy of the left lateral segment due to the yttrium-90 treatment of segments IV-VIII, corresponding with preoperative volumetrics predicting a functional liver remnant (FLR) of 40% after extended right hepatectomy. The right lobe and segment IV were fibrotic, hard, and visibly damaged. The gland had a thick, fibrotic capsule, and the parenchyma was dense, inflexible, and difficult to dissect, consistent with the previously reported morbidity of these operations. Extended right hepatectomy was performed. Final pathology demonstrated 15 foci of metastatic well-differentiated neuroendocrine carcinoma that were negative for necrosis, as was expected given her continued symptoms despite radioembolization. Numerous amorphous spheres, frequently in clusters, were present in segments IV-VIII in vessels and approximating tumors consistent with prior Y90 radioembolization. The patient had an uneventful post-operative recovery and remains symptom free on follow-up. Treatment options for metastatic tumors to the liver have increased in recent years and currently include radioembolization in selected patients. Surgical cytoreduction and complete metastasectomy continue to offer improvement in symptoms, quality of life, and

  4. Root activity studies of cashew plants (Anacardium Occidentale L.) using 32P radioisotope

    In this preliminary study, we are looking at levels 32P and depths of soil injections on uptake by plants using the injection techniques in root activity studies. 32P activities can be detected in the leaves and flower parts of plants two weeks after injection in the soil. Reasonable count rate can be obtained by using lower level of 32P (1.6 mCi/tree) than recommended (5 mCi/tree). 32P counts were higher in younger than older leaves. Flowers had the least count. Differences in injection depths (5 and 15 cm) could not be detected. Differences in count rate were detected due to position of leaves and flowers (upper and lower canopy) in some of the sampling intervals. (author)

  5. Uptake and distribution of 32P in the budded and self-rooted grape varieties

    In the self-rooted and budded varieties of grape (Vitis vinifera L.), the total P and 32P contents were high in 'Anabee-Shahi', but low in in 'Muscat'. The growing shoots contained more P than old stems and roots in all the varieties. In the budded plants, 'Kali Sahebi' scion budded on 'Anab-e-Shani showed the maximum 32P and total P in the shoots, but 'Muscat' scion budded on 'Anab-e-Shahi' accumulated more P in the roots and very low 32P in the growing shoots. Auto-radiographs of shoots also showed that 'Kali Sahebi' budded on 'Anab-e-Shani' rootstock accumulated more 32P in the shoots. (author)

  6. Determination of phagocytosis of /sup 32/P-labeled Staphylococcus aureus by bovine polymorphonuclear leukocytes

    Dulin, A.M.; Paape, M.J.; Weinland, B.T.

    1984-04-01

    A procedure for the measurement of phagocytosis by bovine polymorphonuclear leukocytes (PMN) of /sup 32/P-labeled Staphylococcus aureus was modified so that a larger number of samples could be compared in a single run, and smaller volumes of sample, PMN, and /sup 32/P-labeled S aureus could be used. Results were highly reproducible, with a coefficient of variation between duplicate determinations of less than or equal to 2%. Lysostaphin was prepared from the supernatant of S staphylolyticus and was compared with a commercially available preparation. Effects of lysostaphin on PMN and influence of incubation media on release of /sup 32/P from /sup 32/P-labeled S aureus by lysostaphin were examined.

  7. Optimization time synthesis of nucleotide labelled [γ-32P]-ATP

    Adenosine triphosphate-labelled with γ-32P([γ-32p]-ATP) has been widely used in the biotechnology research, usually as a tracer to study aspects of physiological and pathological processes. In order to support biotechnology research in Indonesia, a process for production of [γ-32P]-ATP with enzymatic reaction was used as precursors DL-glyceraldehydde 3-phosphate, Adenosine Diphosphate (ADP) and H332PO4, and enzyme glyceraldehid 3-phosphate dehydrogenase, 3-phosphoglyceryc phosphokinase and lactate dehydrogenase. Optimization of incubation time labeled nucleotide synthesis process is performed to find the optimum conditions, in terms of the most advantageous time in the synthesis process. With the success of the synthesis and optimization is done incubation time of synthesis labeled nucleotide, the result suggested can be used for producing [γ-32P] -ATP to support the provision of radiolabeled nucleotide for biotechnology research in Indonesia. (author)

  8. Reactor production and separation of no-carrier added 32P for medical applications

    Phosphorous-32 is an attractive and widely used therapeutic radionuclide owing to its favorable nuclear characteristics. The major application of 32P is the treatment option for a distinct subgroup of elderly patients with polycythemia vera and leukemia. The tremendous prospects associated with the use of 32P along with the challenge of providing 32P of acceptable specific activity and purity amenable for in vivo therapy, led to development of a 32P production strategy. The 32S(n,p)32P route of production provide the scope of obtaining high specific activities or no carrier added (NCA) 32P. In a typical batch of 14 nos. of neutron irradiated Al containers, each containing 18 g of sulphur, were processed. In the quest for an effective separation method to isolate micro gram of 32P formed during the neutron irradiation of sulphur, the prospect of using distillation under reduced pressure to achieve complete removal of sulfur seemed to be an effective proposition and motivated us to adopt. The experimental parameters that influence the distillation were identified and a careful control has been exercised to ensure complete removal of sulphur from 32P within reasonable time period. The 32P remained in the distillation flask was quantitatively collected by leaching with 0.05 N HCl with gentle heating at 80℃ for 3 hours. In the light of the perceived need to remove cationic impurities from the 32P leachate, it was passed through an ion-exchange chromatography column containing a cation exchange resin (Dowex 50 x 8 H+, 100-200 mesh) wherein all the cationic impurities get trapped and H332PO4 solution was collected as effluent. Recognizing the fact that H332PO4 produced is to be used for clinical applications, a thorough quality assessment was carried out. Radionuclidic purity was ascertained by a measurement of its half-life. In order to establish the absence of extraneous gamma emitting radionuclide impurities, gamma spectrum of the appropriately diluted samples of 32P

  9. Development of anthropomorphic hand phantoms for personal dosimetry in 90Y-zevalin preparation and patient delivering

    Anthropomorphic tissue-equivalent hand phantoms were achieved to measure the extremity dose involved in Zevalin 90Y-labelling and patient delivering procedure for radioimmunotherapy treatment of non-Hodgkin lymphoma. The extremity doses to hands and wrists of operators were measured by using thermoluminescent detectors mounted on the developed phantoms. Measurements of chest- and lens-equivalent doses performed on a Rando phantom are also reported. (authors)

  10. Development of anthropomorphic hand phantoms for personal dosimetry in 90Y-Zevalin preparation and patient delivering.

    Ciolini, R; d'Errico, F; Traino, A C; Paternostro, E; Laganà, A; Romei, C; Pazzagli, F; Del Gratta, A

    2014-01-01

    Anthropomorphic tissue-equivalent hand phantoms were achieved to measure the extremity dose involved in Zevalin (90)Y-labelling and patient delivering procedure for radioimmunotherapy treatment of non-Hodgkin lymphoma. The extremity doses to hands and wrists of operators were measured by using thermoluminescent detectors mounted on the developed phantoms. Measurements of chest- and lens-equivalent doses performed on a Rando phantom are also reported. PMID:23960242

  11. Production of glass microspheres comprising 90Y and 177Lu for treating of hepatic tumors with SPECT imaging capabilities

    Our objective was to determine if glass microspheres impregnated with two radionuclides,90Y as source of therapeutic beta emissions and 177Lu as source of diagnostic gamma emissions can be useful for SPECT imaging during or after application of the 90Y microspheres for treating of hepatic tumors. The glass-based microspheres labeled with 89Y and lutetium (YAS (Lu)) or 89Y and ytterbium (YAS (Yb)) were prepared by the sol-gel process where sol droplets directly were formed to gel microspheres. Results of the neutron activation indicate that such a combination of glass, microspheres allow bio-distribution studies by SPECT imaging with high resolution. - Highlights: → A radioactive microsphere composed of glass was impregnated with two radionuclide 90Y and 177Lu. 177Lu is as a dopant for diagnostic gamma emissions. → The glass-based microspheres labeled with 89Y and lutetium (YAS (Lu)) or 89Y and ytterbium (YAS (Yb)) were prepared by the sol-gel process where gel microspheres directly were formed from sol droplets. → After neutron activation, such a combination of glass, allows SPECT imaging so bio-distribution is possible with better resolution.

  12. Sodium titanium silicate as ion exchanger: synthesis, characterization and application in separation of 90Y from 90Sr

    Full text: Solid phase extraction is a well-established sample pretreatment technique in pharmaceutical and environmental, biomedical and environmental field because it demands less organic solvents and can remove interferences and preconcentrates the objective simultaneously. There are considerable interests in developing new selective sorbents for extracting and isolating components from complicated matrices, and also for the separation of short-lived radio-nuclides from radionuclide generators in an inexpensive method. Many successful studies of site-specific monoclonal antibody labeling involving 90Y have been applied in radioimmuno-therapy. A newly designed and well characterized inorganic ion exchanger, sodium titanium silicate (Na2TiSiO5, H2O) has been employed in the separation of carrier free 90Y from its parent 90Sr from an equilibrium mixture at pH 7.0. The absorbed daughter was recovered by 1.0% EDTA solution as eluting agent successfully. The decay curve of the eluate and the Feather analysis confirmed the presence of carrier free 90Y. This material is quite stable up to 600 deg C. The study of the radiation stability of the exchanger by checking the crystallinity of the material by XRD spectra showed that the exchanger is stable up to a total dose of 64 KGy

  13. Update on the rational use of (90Y-ibritumomab tiuxetan in the treatment of follicular lymphoma

    Martina Lehnert

    2009-07-01

    Full Text Available Martina Lehnert, Heinz Ludwig, Niklas Zojer 1st Department of Medicine, Center for Oncology and Hematology, Wilhelminenspital, Vienna, AustriaAbstract: The development of radiolabeled antibodies against CD20 has facilitated targeted treatment of follicular lymphoma (FL. By using 90Y-ibritumomab tiuxetan (Zevalin®, a radionuclide (yttrium-90, linked by the chelator tiuxetan to the antibody ibritumomab is brought into the vicinity of lymphoma cells. By the so-called cross-fire effect, this beta emitter has the capacity to destroy not only the lymphoma cells having bound the antibody, but also neighboring lymphoma cells. Currently this antibody is licensed in the European Union for use in relapsed or refractory FL. It is anticipated that this drug will also be approved for use as consolidation therapy after successful first-line treatment. Here we first will review the published literature supporting the use of 90Y-ibritumomab tiuxetan in the aforementioned indications and emerging data showing applicability of ibritumomab tiuxetan as sole first-line therapy for FL, as well as in the transplant setting. Possible strategies of incorporating ibritumomab tiuxetan into the treatment algorithm of FL are discussed.Keywords: follicular lymphoma, 90Y-ibritumomab tiuxetan

  14. Synthesis and biological evaluation of 90Y-labeled porphyrin-DOTA conjugate for targeted tumor therapy

    Development of tumor-avid substances has received considerable attention in current cancer diagnostic and therapeutic protocols. Among the various substances exhibiting tumor specificity, hematoporphyrin and its derivatives have been extensively investigated with the aim to identifying potential agents for targeted tumor diagnosis and therapy. Working in this direction, a water soluble unsymmetrical porphyrin, namely 5-(4-(3-amino)-n-propyloxyphenyl)-10,15,20-tris-(4 carboxymethyleneoxyphenyl)porphyrin was synthesized and subsequently coupled with a bi-functional chelating agent (BFCA), namely p-isothiocyanato-benzyl-1,4,7,10 -tetraazacyclododecane- 1,4,7,10-tetraacetic acid (p-NCS-benzyl-DOTA), for its radiolabeling with 90Y. 90Y was chosen as a therapeutic radionuclide owing to its suitable nuclear decay characteristics (Eβmax= 2.28 MeV, T1/2= 64h) and easy availability in high radionuclidic purity from a 90Sr-90Y generator. The emission of high energy β- particle makes it a suitable candidate for therapy in large-sized tumors

  15. 32P-labeled hydroxyapatite particles for use in radiation synovectomy

    Radionuclides decaying by emission of β- particles of varying energies have been proposed for treating arthritis of various joints. Hydroxyapatite (HA) (Ca10(PO4)6(OH)2) is a preferred substrate for developing radiochemical agents for management of arthritis. Reactor produced 32P was evaluated for its suitability for preparation of a potent radiolabeled agent for the treatment of arthritis based on HA particles. 32P is produced by both (n,γ) and (n,p) routes from red phosphorus and elemental sulfur respectively. The preparation of 32P labeled HA particles (particle size 2-10 μm) was carried out using 10 mg HA at pH 7-8. The maximum achievable specific activity of 222 MBq 32P/mg of P in Dhruva research reactor employing radiative neutron capture reactions on red P has limitations in its utility in HA formulation, however, using no carrier added (NCA) 32P, HA could be labeled in high radiochemical purity (>95%). The radiolabeled particulates showed excellent in vitro stability at room temperature. Intra-articular injection of 32P-HA particles in the knee joint showed complete retention of activity within the synovial cavity with no measurable activity leaching out from the joint till 14 d post injection, in case of Wistar rats bearing arthritis. (author)

  16. Radioactive 32P incorporation in liver of mice fed with Aspergillus terreus contaminated feed

    The distribution of 32P during toxicosis due to Aspergillus terreus, a common food contaminant, reported to procedure the toxin terreic acid, in addition to few others, was studied in mice. Radioactive 32P was injected intraperitoneally to the control mice and the experimental ones, which were fed with Aspergillus terreus contaminated feed, as well as the toxin terreic acid. After 24 hrs, both control and experimental animals were sacrificed. 32P incorporation in various fractions of liver were studied. 0.5 cm3 of each fractions was spread on a planchette and dried at 60 deg C. 32P activity was measured using a thin end window Geiger Mueller tube connected to Panax-type 100 C counter. No corrections were necessary for self absorption. In mice, fed with the contaminated feed, more 32P got incorporated in the nucleic acid fraction than seen in protein, barium soluble and barium insoluble fractions, whereas 32P incorporation in lipid fraction was lower. (T.G.)

  17. Internal radiotherapy using 32P colloid or microsphere for refractory solid tumors

    The aim of this work was to study the effectiveness of 32P colloids or microspheres, by arterial interventional administration or stromal injection in the treatment of refractory solid tumors. By arterial intervention, under the guidance of computerized tomography, X-ray, ultrasonogram, or under direct vision of the surgical field, 32P microspheres (259-685 MBq) or radioactive colloid (281-666 MBq) was administered to 60 cases with refractory solid tumors. Tumor inhibition rate, side effects, survival period, and so on were observed. The tumor growth was obviously inhibited after the intratumoral injection of 32P colloid. The average survival time in the 60 cases was 35 months with a high tumor inhibition rate (93.4%). Thirty-one cases were completely relieved (51.7%), and 25 cases achieved partial remission (PR, 41.7%). One case with right lobe hepatocellular carcinoma has survived 90 months. The drug was ineffective only in four cases, including one patient who died of gastrointestinal hemorrhage and three of hepatic failure. No other obvious side effects were observed. Intratumoral necrosis, intense fibrosis in the tumor mass, and an integrated capsule encompassing the tumor were revealed by histological examination. Arterial interventional administration or stromal injection with 32P microspheres or colloid revealed a very fair clinical effectiveness in the treatment of refractory solid tumors. The range of safe effective dosage for 32P glass microspheres and 32P chromic phosphate in one treatment course is 555-740 MBq and 185-370 MBq, respectively. (author)

  18. Fractionated Radioimmunotherapy With 90Y-Clivatuzumab Tetraxetan and Low-Dose Gemcitabine Is Active in Advanced Pancreatic Cancer

    Ocean, Allyson J.; Pennington, Kenneth L.; Guarino, Michael J.; Sheikh, Arif; Bekaii-Saab, Tanios; Serafini, Aldo N.; Lee, Daniel; Sung, Max W.; Gulec, Seza A.; Goldsmith, Stanley J.; Manzone, Timothy; Holt, Michael; O’Neil, Bert H.; Hall, Nathan; Montero, Alberto J.; Kauh, John; Gold, David V.; Horne, Heather; Wegener, William A.; Goldenberg, David M.

    2014-01-01

    BACKGROUND It has been demonstrated that the humanized clivatuzumab tetraxetan (hPAM4) antibody targets pancreatic ductal carcinoma selectively. After a trial of radioimmunotherapy that determined the maximum tolerated dose of single-dose yttrium-90-labeled hPAM4 (90Y-hPAM4) and produced objective responses in patients with advanced pancreatic ductal carcinoma, the authors studied fractionated radioimmunotherapy combined with low-dose gemcitabine in this disease. METHODS Thirty-eight previously untreated patients (33 patients with stage IV disease and 5 patients with stage III disease) received gemcitabine 200 mg/m2 weekly for 4 weeks with 90Y-hPAM4 given weekly in Weeks 2, 3, and 4 (cycle 1), and the same cycle was repeated in 13 patients (cycles 2–4). In the first part of the study, 19 patients received escalating weekly 90Y doses of 6.5 mCi/m2, 9.0 mCi/m2, 12.0 mCi/m2, and 15.0 mCi/m2. In the second portion, 19 additional patients received weekly doses of 9.0 mCi/m2 or 12.0 mCi/m2. RESULTS Grade 3/4 thrombocytopenia or neutropenia (according to version 3.0 of the National Cancer Institute’s Common Terminology Criteria for Adverse Events) developed in 28 of 38 patients after cycle 1 and in all retreated patients; no grade >3 nonhematologic toxicities occurred. Fractionated dosing of cycle 1 allowed almost twice the radiation dose compared with single-dose radioimmunotherapy. The maximum tolerated dose of 90Y-hPAM4 was 12.0 mCi/m2 weekly for 3 weeks for cycle 1, with ≤9.0 mCi/m2 weekly for 3 weeks for subsequent cycles, and that dose will be used in future trials. Six patients (16%) had partial responses according to computed tomography-based Response Evaluation Criteria in Solid Tumors, and 16 patients (42%) had stabilization as their best response (58% disease control). The median overall survival was 7.7 months for all 38 patients, including 11.8 months for those who received repeated cycles (46% [6 of 13 patients] ≥1 year), with improved efficacy at

  19. Electrochemical separation of 90-yttrium in the electrochemical 90Sr/90Y generator and its use for radiolabelling of DOTA-conjugated somatostatin analog [DOTA0, Tyr3] octreotate

    Petrović Đorđe Ž.; Nikolić Nadežda S.; Stanković Dragana T.; Đokić Divna Đ.

    2012-01-01

    Radiopharmaceuticals based on 90Y are widely used in the treatment of malignant deseases. In order to meet the requirements for their future application, a 90Sr/90Y generator was developed and 90Y eluted from this locally produced generator was used for the radiolabelling of the DOTA-conjugated somatostatin analog [DOTA0,Tyr3] octreotate and the preparation of [90Y-DOTA0,Tyr3] octreotate (90Y-DOTATATE) for peptide receptore radionuclide therapy. 90Sr/90Y generator was based on the elec...

  20. Investigation on the influence of metal ion impurities on the complexation behavior of generator produced {sup 90}Y with different bifunctional chelators

    Pandey, Usha; Gamre, Naresh; Chakravarty, Rubel; Pillai, Maroor Raghavan Ambikalmajan; Dash, Ashutosh [Bhabha Atomic Research Centre, Trombay, Mumbai (India). Radiopharmaceuticals Div.

    2014-07-01

    While the {sup 90}Sr/{sup 90}Y generator is the exclusive source of obtaining 'no carrier added' {sup 90}Y for targeted therapy, the presence of trace metals in the radiolabeling solutions poses a serious challenge owing to their ability to diminish the {sup 90}Y complexation yields with bifunctional chelators (BFCs). p-SCN-Bn-PCTA is a novel ligand having faster complexation kinetics with a number of radiometals. In this work, a systematic investigation was performed to evaluate the chelating ability of p-SCN-Bn-PCTA for {sup 90}Y and the influence of trace metal ions on it's complexation with {sup 90}Y in comparison to p-SCN-Bn-DTPA and p-SCN-Bn-DOTA using {sup 90}YCl{sub 3} obtained from an electrochemical generator. Results from our study indicate that while p-SCN-Bn-PCTA gave very good radiolabeling yields with {sup 90}Y when the reaction was carried out by heating for few minutes, it was most sensitive to the presence of trace metals, especially Fe(III). An independent and useful observation is that p-SCN-Bn-PCTA could be considered as the ligand of choice for assessing the chemical purity of generator derived {sup 90}Y.

  1. Bioaccumulation factor for 32P measured in bluegill, Lepomis macrochirus, and catfish, Ictalurus punctatus

    The ratio of the bioaccumulation factors for 32P and phosphorus was determined for edible tissue in two species of freshwater fish by measuring the specific activity (32P activity per milligram phosphorus) in muscle relative to feed. The 32P tracer was added to the feed at a uniform level throughout the study. Feeding was at two levels: ad libitum and at a lower but constant intake per body weight. In the main experiment, bluegill were maintained in a large flow-through tank and sacrificed at approximately weekly intervals for 51 d of 32P accumulation and 28 d of depuration to compare the specific activity with values predicted with a calculational model. In experiments performed in smaller aquaria, the specific activity in bluegill and catfish muscle was compared at two feeding levels and two temperatures. In addition, unfed fish were exposed to 32P in water at a known specific activity to determine the extent of phosphorus uptake directly from water. The pattern of specific activity increase and decrease in fish muscle during the accumulation/depuration experiment was consistent with a one-compartment model, so that specific activity ratios at steady state could be predicted from measurements during relatively brief exposures. On this basis, the ratio of the bioaccumulation factors of 32P and phosphorus in fish feeding ad libitum was 0.081 for bluegill and 0.17 for catfish. Hence, at a mean phosphorus bioaccumulation factor of 70,000, the factors for 32P are 6000 and 12,000, respectively. The ratios were less at lower phosphorus intakes associated with lower feeding rates; moreover, the lesser value for bluegill occurred at a much lower phosphorus intake than by catfish

  2. Lethal Effect on Bacterium of Decay of Incorporated Radioactive Atoms (3H, 14C, 32P)

    The biological effect of decay of 3H, 14C and 32P incorporated into a bacterium depends on the nature of the organic molecule labelled, on the position of the isotope within it and on the isotope itself. In sum, results obtained to date show that: The decay of 3H atoms incorporated into certain macromolecules of a bacterium causes sterilization through ionization by the ß- particle emitted; transmutation is of negligible importance. This self-irradiation is comparable in effect with X-rays and is affected in a similar manner by the same factors: temperature, presence of a radioprotector, radiosensitivity of the strain. Decay of 14C or 32P atoms incorporated into bacterial DNA is lethal because of the transmutation effect; ionizations produced by emitted ß- particles may be disregarded. Survival curves for 32P transmutations depend on the experimental conditions. Some of the results obtained with 32P are similar to those obtained with X-rays, e.g. effects of temperature, radical capture and oxygen, while others are similar to those of u.v. light, e.g., effect of growth conditions. Comparative tests made with 32P indicate that the recoil energy of transmutation is not the phenomenon responsible for the lethal effect observed. Comparison of the results obtained after X-irradiation or decay of 3H or 32P incorporated into the DNA of bacteria of the same strain of E. coli shows that the efficiency of a 32P transmutation is about four times greater than that of an ionization produced at random within the same DNA. (author)

  3. Fractionation of phosphorus added as a vegetal residue (32 P) and a fertilizer (32 P) between soil, plant and microbial biomass

    Sugar cane straw and/or P-fertilizer phosphorus-32 labelled were added to a Red Yellow podzolic soil from Goiana-PE. The treated samples were used in a pot experiment, growing sorghum plants for 4 and 6 weeks, and in an incubation experiment with incubation periods of 1, 2, 3, 4 and 6 weeks without plants in order to follow the dynamics of the P added. After each harvest and incubation period the soil were analysed for 31 P and 32 P in the microbial biomass and in sequential extracts with resin (Pi), 0.5 M Na H Co3 (Pi, Po) and 0.1 N NaOH (Pi, Po). The 31 P and 32 P contents of the sorghum in the pot experiment were also determined. (author)

  4. Anti-CD45 radioimmunotherapy with 90Y but not 177Lu is effective treatment in a syngeneic murine leukemia model.

    Johnnie J Orozco

    Full Text Available Radioimmunotherapy (RIT for treatment of hematologic malignancies has primarily employed monoclonal antibodies (Ab labeled with 131I or 90Y which have limitations, and alternative radionuclides are needed to facilitate wider adoption of RIT. We therefore compared the relative therapeutic efficacy and toxicity of anti-CD45 RIT employing 90Y and 177Lu in a syngeneic, disseminated murine myeloid leukemia (B6SJLF1/J model. Biodistribution studies showed that both 90Y- and 177Lu-anti-murine CD45 Ab conjugates (DOTA-30F11 targeted hematologic tissues, as at 24 hours 48.8 ± 21.2 and 156 ± 14.6% injected dose per gram of tissue (% ID/g of 90Y-DOTA-30F11 and 54.2 ± 9.5 and 199 ± 11.7% ID/g of 177Lu-DOTA-30F11 accumulated in bone marrow (BM and spleen, respectively. However, 90Y-DOTA-30F11 RIT demonstrated a dose-dependent survival benefit: 60% of mice treated with 300 µCi 90Y-DOTA-30F11 lived over 180 days after therapy, and mice treated with 100 µCi 90Y-DOTA-30F11 had a median survival 66 days. 90Y-anti-CD45 RIT was associated with transient, mild myelotoxicity without hepatic or renal toxicity. Conversely, 177Lu- anti-CD45 RIT yielded no long-term survivors. Thus, 90Y was more effective than 177Lu for anti-CD45 RIT of AML in this murine leukemia model.

  5. New modalities (setting, fractionation) of radioimmunotherapy by 90Y-ibritumomab tiuxetan (90Y zevalin) in first line treatment of follicular type non Hodgkin malignant lymphomas: efficiency, toxicity and personalized dosimetry approach

    Rationale: radioimmunotherapy (R.I.T.) with 90Y-ibritumomab tiuxetan ([90Y] Zevalin ) is a new treatment option for patients with relapsed/refractory non Hodgkin follicular lymphoma (F.L.). Efficacy increases when Zevalin is used earlier in the disease course. Currently, Zevalin dosage is based on weight and not dosimetry. This most likely results in a wide range of absorbed dose to critical organs and tumor, which in turn translates in unpredictable efficacy and toxicity. Optimizing R.I.T. with [90Y] Zevalin will require its use as part of first-line therapy and implementation of patient-specific dosimetry methods in clinical trials. Objectives and methods: we have consecutively studied 2 new modalities of using Zevalin in first line therapy of F.L.. First, we conducted an international, randomized, phase 3 trial to evaluate the efficacy and safety of consolidation with Zevalin(15 MBq/Kg) in patients with advanced-stage F.L. achieving at least a partial response after induction immuno chemotherapy. A second approach consisted of evaluating a fractionated schedule with 2 doses of Zevalin (11.1 MBq/kg each), 9 to 13 weeks apart, as front line therapy in F.L. patients with high tumor burden. As part of this second approach, we designed a refined imaging-based (planar and 3-dimensional) dosimetry protocol to improve prediction of dose efficacy and toxicity after each dose of zevalin. Data acquisition was performed in 3 centers (Lille, Nantes and Manchester) while data treatment and specific dose calculations for major organ, tumor masses and bone marrow were centralized. Conclusion: Consolidation of first remission with 90Y-ibritumomab tiuxetan in advanced-stage follicular lymphoma is highly effective with no unexpected toxicities, prolonging P.F.S. by 2 years and resulting in high P.R.-to-C.R. conversion rates regardless of type of first-line induction treatment. Preliminary data show the feasibility of front line fractionated R.I.T. with Zevalin in patient with high

  6. The early history of (32) P as a radioactive tracer in biochemical research: A personal memoir.

    Gest, Howard

    2005-05-01

    The concept of using radioactive isotopes as "tracers" of chemical conversions was conceived and developed by inorganic chemist Georg de Hevesy (Nobel Laureate in Chemistry 1943). In 1935, he began to apply the technique to various biological processes using (32) P, and his experiments revealed the dynamic character of physiology and metabolism. Following de Hevesy's lead, Samuel Ruben (University of California, Berkeley) exploited (32) P in 1937-38 for investigation of phospholipid metabolism. Between 1937 and 1940, Ruben and colleague Martin Kamen spearheaded tracer studies in various biological systems using (32) P, short-lived (11) C, and other radioactive isotopes. During this period, Kamen was responsible for cyclotron-produced radioactive tracers and was able to sustain de Hevesy's research by supplying him with (32) P. In 1940, Ruben and Kamen discovered long-lived (14) C, which later proved to be a very powerful tool for analysis of complex biochemical processes, such as the path of carbon in photosynthesis. Between 1946 and 1950, (32) P was used in studies of bacteriophage replication and photosynthetic metabolism. This memoir surveys the history of these early investigations. PMID:21638569

  7. Preparation and evaluation of various 32P sources for intravascular brachytherapy

    A relatively high per cent of restenoses, being a long-term complication of percutaneous transluminal coronary angioplasty (PTCA), can be significantly reduced by short-range ionizing radiation applied locally, immediately after PTCA. In search for dosimetrically favourable and easy to handle radiation sources for this purpose, we tried a pure β- emitter 32P (t1/2=14.3 days). Ways of preparation of 32 P sources were the following: (1) Neutron activation of 31P layers implanted into metallic surfaces by ionic methods; (2) Conversion coating of metallic surfaces in aqueous solutions containing 32PO43- ions; (3) Direct application of Na2H32 PO4 solutions in the angioplasty balloon. It was shown that: (1) 32 P sources obtained by 31 P ion implantation followed by neutron activation can be useful, but only if activation of the support material by thermal neutrons is negligible; (2) Phosphate layers on stainless steel surface exhibit rather poor adhesion. Similar layers on titanium require further studies; (3) Liquid 32 P sources ensure very good radial dose distribution but only utmost care in filling the balloon can give a reliable activity-dose dependence. Dosimetry of liquid sources, performed in a PMMA phantom by thermoluminescence method showed that 32 P sources of radioactive concentration of 200 MBq/cm3 can deposit therapeutic dose during about 12 min of exposition. TL detectors manufactured for this purpose in our laboratory show very good spatial resolution and can be recommended for similar studies. (author)

  8. Changes of decay rates of radioactive 111In and 32P induced by mechanic motion

    2007-01-01

    The changes of decay rates of radionuclide 111In(electron capture) and 32P(β decay) induced by exter-nal mechanic motion are studied. The results indicate that,in the external circular rotation in clockwise and anticlockwise centrifuge on Northern Hemisphere(radius 8 cm,2000 r/min) ,the half life of 111In compared with the referred(2.83 d) is decreased at 2.83% and increased at 1.77%,respectively;the half life of 32P compared with the referred(14.29 d) is decreased at 3.78% and increased at 1.75%,respec-tively. When the clockwise and anticlockwise rotations increase to 4000 r/min,the half life of 111In is decreased at 11.31% and increased at 6.36%,respectively;the half life of 32P is decreased at 10.08% and increased at 4.34%,respectively. When the circular rotation is removed,the decay rates of 111In and 32P return back to the referred,respectively. It is found that the external circular rotations in clockwise and anticlockwise centrifuge selectively increased and decreased the decay rates of 111In and 32P,respec-tively,and the effects are strongly dependent on the strength of circular rotation. It is suggested that these effects may be caused by the chiral interaction.

  9. Insulin and thyroxine effect on 32P incorporation in the phospholipids of chicken intestinal mucosa

    Trials were conducted with 56-day-old broiler chickens. The effect was followed up of insulin and alloxan as well as of L-thyroxine and 6-methylthiouracil on 32P incorporation in phospholipids of the duodenal mucosa. A segment of the duodenum was isolated and Na2H32PO4 was introduced therein. The lipids were extracted from duodenal mucosa and the individual phospholipids were separated by means of thin layer chromatography on sillica gel-G. Radioactivity was determined of individual phospholipid fractions. Blood glucose level was studied in insulin and alloxan-treated chickens. The inference was drawn that insulin significantly enhances 32P incorporation in the phospholipids in broiler chicken duodenal mucosa. The drop in blood glucose in insulin-treated chickens is inversely proportional to 32 P inclusion in individual phospholipids of duodenal mucosa. L-thyroxine exerts positive effect in chickens concerning 32P incorporation in lecithin and lysolecithin, this effect being negative with respect to sphingomyelin, cephalin and cardiolipin. Thyroid gland inhibition by 6-methylthiouracil induces negligible decline in 32P inclusion. (author)

  10. Design and construction of a prototype for the obtention of {sup 32}P; Diseno y construccion de un prototipo para la obtencion de {sup 32}P

    Duarte A, C

    2003-07-01

    The {sup 32} P are a pure emitting radioisotope of maximum energy of 1.71 MeV with half life of 14.28 days that he has applications in the industry, in agriculture, in medicine, in biology and in ecology (6,11,12,13,17,21,22,23,24,25,26,27,28,29,30,31,32 33).The {sup 32} P can be used in the industry like radiotracer in the investigation of some operations and processes and as element of measurement of some industrial meters. In agriculture is used as radiotracer (29) in the investigation of diverse biological processes that have to do with the production of diverse nutritious products. In medicine has uses but very therapeutic mainly in the treatment of some become cancerous (28, 31, 25, 27) in the diagnosis of blood disorders (24) and like part of materials of production of aortic prosthesis (6). The {sup 32} P are also used in the molecular investigation in biology and in genetics (33), and in studies of ecosystems (32) and of DNA (22). One can obtain the {sup 32} P by means of diverse nuclear reactions depending on the material used as matter it prevails, since it doesn't exist in the nature. But anyone in the ways of obtaining it it should imply a process of radiochemical separation that involves so many steps like they are required, depending on the material used as matter prevails, of the purity with which he wants himself to obtain and of the resources that it has available. The objective of this work was design, to build and to prove a prototype to obtain the {sup 32} P to leave of the irradiation of S {alpha} with fast neutrons at experimental level, which implies also to design a process that contemplates diverse stages and procedures for each one of them. The process was outlined in five stages: matter purification prevails, preparation of irradiation capsules, irradiation of irradiation capsules, transport and opening capsules of irradiation and radiochemical separation. In the last stage it was where uses the prototype of radiochemical separation

  11. Optimising conditions for radiolabelling of DOTA-peptides with 90Y, 111In and 177Lu at high specific activities

    DOTA-conjugated peptides, such as [DOTA0,Tyr3]octreotide (DOTATOC) and [DOTA0,Tyr3]octreotate (DOTA-tate), can be labelled with radionuclides such as 90Y, 111In and 177Lu. These radiolabelled somatostatin analogues are used for peptide receptor radionuclide therapy (PRRT). Radioligands for PRRT require high specific activities. However, although these radionuclides are produced without addition of carrier, contaminants are introduced during production and as decay products. In this study, parameters influencing the kinetics of labelling of DOTA-peptides were investigated and conditions were optimised to obtain the highest achievable specific activity. The effects of contaminants were systematically investigated, concentration dependently, in a test model mimicking conditions for labelling with minimal molar excess of DOTA-peptides over radionuclide. Kinetics of labelling of DOTA-peptides were optimal at pH 4-4.5; pH 90Y and 177Lu was completed after 20 min at 80 C, while labelling with 111In was completed after 30 min at 100 C. The effects of contaminants were systematically categorised, e.g. Cd2+ is the target and decay product of 111In, and it was found to be a strong competitor with 111In for incorporation in DOTA. In contrast, Zr4+ and Hf4+, decay products of 90Y and 177Lu, respectively, did not interfere with the incorporation of these radionuclides. The following conclusions are drawn: (a) DOTA-peptides can be radiolabelled at high specific activity; (b) reaction kinetics differ for each radionuclide; and (c) reactions can be hampered by contaminants, such as target material and decay products. (orig.)

  12. Evaluation of 2 amino acid protocols for kidney protection in patients treated with 90Y-DOTATOC for neuroendocrine tumors

    Full text of publication follows. Background: peptide receptor radionuclide therapy (PRRT) is an established treatment for progressive neuroendocrine tumours (NET). Nephrotoxicity is the limiting factor using 90Y-DOTATOC. Although administration of amino acids lowers the radioactive dose to the kidneys, delayed renal damage is a concern following therapy. Studies have indicated that prolonging the infusion of amino acids offers improved kidney protection. The intermittent infusion of amino acids up two days after PRRT has also been shown to further reduce renal uptake of radioactivity in pilot studies. Aim: We evaluated whether differences could be detected in GFR in patients treated with two different protocols for kidney protection using commercially available (Vamin-18) amino acid mixture (AAM); a standard protocol with 2 litres of AAM infused over 4 hours or a 24-hour infusion protocol with 3 litres of AAM. Material and method: GFR in 18 patients treated with infusion of 2 litres AAM of 4 hours was compared with GFR in 13 patients treated with 3 litres of AAM over 24 hours at 3 months, 6 months and 12 months after therapy with 90Y DOTATOC. The majority of patients received the standard treatment of 3.7 GBq/m2 90Y DOTATOC every 8-10 weeks. The glomerular filtration rate (GFR) was estimated using the 51Cr-EDTA plasma clearance by a single sample technique according to Groth and Aasted. Results: pre-existing risk factors associated with kidney failure were seen in 84 % of the patients. Other identified risk factors associated with kidney failure were former treatment with 90Y-DOTATOC and/or chemotherapy, hypertension and diabetes. In the whole group of patients a significant fall in renal function was seen up to twelve months after PRRT. The median loss of kidney function was 30 ml/min/1.73m2 (27 %) 12 months after treatment compared to pre-therapeutic values. Although no significant statistical difference was found comparing the two amino acid protocols, the use

  13. Clinical and laboratory toxicity after intra-arterial radioembolization with (90y-microspheres for unresectable liver metastases.

    Maarten L J Smits

    Full Text Available OBJECTIVE: To investigate clinical and laboratory toxicity in patients with unresectable liver metastases, treated with yttrium-90 radioembolization ((90Y-RE. METHODS: Patients with liver metastases treated with (90Y-RE, between February 1(st 2009 and March 31(st 2012, were included in this study. Clinical toxicity assessment was based on the reporting in patient's charts. Laboratory investigations at baseline and during a four-month follow-up were used to assess laboratory toxicity according to the Common Terminology Criteria for Adverse Events version 4.02. The occurrence of grade 3-4 laboratory toxicity was stratified according to treatment strategy (whole liver treatment in one session versus sequential sessions. Response assessment was performed at the level of target lesions, whole liver and overall response in accordance with RECIST 1.1 at 3- and 6 months post-treatment. Median time to progression (TTP and overall survival were calculated by Kaplan-Meier analysis. RESULTS: A total of 59 patients, with liver metastases from colorectal cancer (n = 30, neuroendocrine tumors (NET (n = 6 and other primary tumors (n = 23 were included. Clinical toxicity after (90Y-RE treatment was confined to grade 1-2 events, predominantly post-embolization symptoms. No grade 3-4 clinical toxicity was observed, whereas laboratory toxicity grade 3-4 was observed in 38% of patients. Whole liver treatment in one session was not associated with increased laboratory toxicity. Three-months disease control rates for target lesions, whole liver and overall response were 35%, 21% and 19% respectively. Median TTP was 6.2 months for target lesions, 3.3 months for the whole liver and 3.0 months for overall response. Median overall survival was 8.9 months. CONCLUSION: The risk of severe complications or grade 3-4 clinical toxicity in patients with liver metastases of various primary tumors undergoing (90Y-RE is low. In contrast, laboratory toxicity grade 3

  14. Behavior of 32P, 35S, 36Cl and 42K in magnesium oxide

    A separation method of 32P from 35S using magnesium oxide as adsorbent of radiophosphorus is described. The behaviour of 32P and 35S, both carrier-free, on magnesium oxide, individually, in dependence of the amount of the adsorbent, of mixing time, of the pH of the loading solution and of potassium chloride concentration, is studied. The separation of the mentioned radioisotopes, using a misture of them, is also analysed. In order to apply this method to the routine production of carrier-free 35S by potassium chloride irradiation, the adsorption behaviour of the chloride and potassium on magnesium oxide using radioactive tracers of these elements, is studied. The separation of 35S from 32P is analyzed by the maximum range of β- particles in aluminum. The absorption curves are presented and compared. (Author)

  15. Thermoluminescent dosimetry of beta radiations of {sup 90} Sr/ {sup 90} Y using amorphous ZrO{sub 2}; Dosimetria termoluminiscente de radiaciones beta de {sup 90} Sr/ {sup 90} Y usando ZrO{sub 2} amorfo

    Rivera M, T. [CICATA-Legaria, IPN, Legaria Num. 694, 11500 Mexico D.F. (Mexico); Olvera T, L.; Azorin N, J.; Barrera R, M.; Soto E, A.M. [UAM-I, 09340 Mexico D.F. (Mexico)

    2005-07-01

    In this work the results of studying the thermoluminescent properties (Tl) of the zirconium oxide in its amorphous state (ZrO{sub 2}-a) before beta radiations of {sup 90} Sr/ {sup 90} Y are presented. The amorphous powders of the zirconium oxide were synthesized by means of the sol-gel technique. The sol-gel process using alkoxides like precursors, is an efficient method to prepare a matrix of zirconium oxide by hydrolysis - condensation of the precursor to form chains of Zr-H{sub 3} and Zr-O{sub 2}. One of the advantages of this technique is the obtention of gels at low temperatures with very high purity and homogeneity. The powders were characterized by means of thermal analysis and by X-ray diffraction. The powders of ZrO{sub 2}-a, previously irradiated with beta particles of {sup 90} Sr/{sup 90} Y, presented a thermoluminescent curve with two peaks at 150 and 257 C. The dissipation of the information of the one ZrO{sub 2}-a was of 40% the first 2 hours remaining constant the information for the following 30 days. The reproducibility of the information was of {+-} 2.5% in standard deviation. The studied characteristics allow to propose to the amorphous zirconium oxide as thermoluminescent dosemeter for the detection of beta radiation. (Author)

  16. Methodology development for dosimetry of {sup 90}Sr + {sup 90}Y beta therapy applicators;Desenvolvimento de uma metodologia para dosimetria de aplicadores de betaterapia de {sup 90}Sr + {sup 90}Y

    Coelho, T.S.; Yoriyaz, H. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Fernandes, M.A.R. [Universidade Estadual Paulista (UNESP), Botucatu, SP (Brazil). Fac. de Medicina. Servico de Radioterapia

    2009-07-01

    The {sup 9}0Sr+{sup 9}0Y applicators, used in beta therapy for prevention of keloids and pterigio, are imported and its dosimetric features are only illustrated by the manufacturers. The exhaustive routine of the medical physicists in the clinic do not make possible the accomplishment of procedures for the confirmation of these parameters. This work presents a methodology development for dosimetry in two {sup 9}0Sr+{sup 9}0Y beta therapy applicators of the Amersham brand. The Monte Carlo code MCNP 4 C was used for the simulation of the percentage depth dose curves. The experimental measurements of the radiation attenuation had been done with a mini-extrapolation chamber. The results of the experimental measures had been compared with the simulated values. Both percentage deep dose curves, the theoretical and the experimental ones, had presented similar behavior, which may validate the use of the MCNP 4 C for these simulations, strengthening the usage of this method at procedures of dosimetry of these beta radiation sources. (author)

  17. Thermoluminescent dosimetry of beta radiations of {sup 90} Sr/ {sup 90} Y using ZrO{sub 2}: Eu; Dosimetria termoluminiscente de radiaciones beta de {sup 90} Sr/ {sup 90} Y usando ZrO{sub 2}: Eu

    Olvera T, L.; Azorin N, J.; Barrera S, M.; Soto E, A.M. [UAM-I, 09340 Mexico D.F. (Mexico); Rivera M, T. [CICATA-IPN, Legaria 694, 11500 Mexico D.F. (Mexico)

    2005-07-01

    In this work the results of studying the thermoluminescent properties (TL) of the doped zirconium oxide with europium (ZrO{sub 2}: Eu{sup 3+}) before beta radiations of {sup 90}Sr/ {sup 90}Y are presented. The powders of ZrO{sub 2}: Eu{sup 3+} were obtained by means of the sol-gel technique and they were characterized by means of thermal analysis and by X-ray diffraction. The powders of ZrO{sub 2}: Eu{sup 3+}, previously irradiated with beta particles of {sup 90}Sr/ {sup 90}Y, presented a thermoluminescent curve with two peaks at 204 and 292 C respectively. The TL response of the ZrO{sub 2}: Eu{sup 3+} as function of the absorbed dose was lineal from 2 Gy up to 90 Gy. The fading of the information of the ZrO{sub 2}: Eu{sup 3+} was of 10% the first 2 hours remaining almost constant the information by the following 30 days. The ZrO{sub 2} doped with the (Eu{sup 3+}) ion it was found more sensitive to the beta radiation that the one of zirconium oxide without doping (ZrO{sub 2}) obtained by the same method. Those studied characteristics allow to propose to the doped zirconium oxide with europium like thermoluminescent dosemeter for the detection of the beta radiation. (Author)

  18. Development of a dosimetric system for {sup 90}Sr + {sup 90}Y betatherapy applicators; Desenvolvimento de um sistema de dosimetria para aplicadores de betaterapia de {sup 90}Sr + {sup 90}Y

    Coelho, Talita Salles

    2010-07-01

    The {sup 90}Sr+{sup 90}Y applicators, used in betatherapy for prevention of keloids and pterigium, are imported and many times their dosimetric features are shown only in an illustrated form by the manufacturers. The exhaustive routine of the medical physicists in the clinic do not make possible the accomplishment of procedures for the confirmation of these parameters. This work presents the development of a methodology for the dosimetry of {sup 90}Sr+{sup 90}Y betatherapy applicators. The Monte Carlo code MCNP5 was used for the simulation of the percentage depth dose curves and dose distribution profiles produced by these applicators. The experimental measurements of the radial and axial radiation attenuation, have been done with a mini-extrapolation chamber, thermoluminescent dosimeters and radiographic films. The experimental results have been compared with the simulated values. Both percentage depth dose curves and the radial dose profiles, the theoretical and the experimental ones, have presented good agreement, which may validate the use of the MCNP5 for these simulations, confirming the viability of the usage of this method in procedures of beta emitter sources dosimetry. (author)

  19. Development of A 32P-Postlabeling Technic for Detection of the Initiation of Cancer

    It is well know that the interaction between exogenous and also endogenous subs-trances with macromolecular biology (Protein or DNA) in human with in sublethal or lethal level can lead to the initiation of cancer (Auerbach, 1946, Phillips, 1981). In the assessment of carcinogen exposure (exo genus or endo genus), bio markers are chosen based on a knowledge of the internal interactions of carcinogen molecules/metabolites with cellular macromolecules such as DNA, i.e. formation DNA adduct. The 32P-postlabeling assay is most sensitive, fast and applicability methods to structurally diverse classes of chemical. It has been developed to detect DNA adduct (Randerath at. All, 1993, Reddy, 1986). The 32P-Postlabeling technic has emerged as the method of choice for qualitative detection and quantitation of carcinogen-DNA adducts in human. The result of detection of the Adduct will lead the understand of the mechanism reaction of the substance in human organ. The assay of the 32P-Postlabeling involves a stepwise sequence of biochemical reaction entailing: Isolation DNA and following with cleavage by enzymatic hydrolyzed of intact DNA (Nucleotide) with phosphate in 3 position. Attachment of a 32P- label to the 5-hydroxyl end of DNA (Nucleotide) creating a 3,5-biphosphate; following by separation and detection of adducts by high-regulation TLC and autoradiography respectively and quantitation of adducts by measurement of radioactivity. The 32P-Postlabeling was used to detection of DNA adduct of Polycyclic aromatic and alpha, beta unsaturated carbonyl compound such crotonaldehyde, which is in this paper to discussed. We have investigated and developed the 32P-Postlabeling for detection of modified DNA of crotonaldehyde in vitro and in vivo as markers for initiation of cancer. From the result of study were found the adduct the adduct in several organs of F-344 rast after gavage and persisted to a certain extent (Eder dan Budiawan, 1997)

  20. The use of 32P and 15N to estimate fertilizer efficiency in oil palm

    Improving efficiency of use of fertilizers has attracted a great deal of interest on oil-palm estates because of increasing input costs. It is assumed that higher efficiency of use of fertilizers for estate crops, including oil palm, would result in significant savings and less environmental pollution. One way to enhance efficiency of use of fertilizers by oil palm is to apply them where the most active roots are located. Previous work has indicated the possibility of determining the most active roots of tea and chinchona by using 32P. In this experiment, 32P was again used, to determine the locations of the most active roots of oil palm trees

  1. Formation of 32P-labelled Polyphosphates in Reactor-irradiated Solutions of Orthophosphate

    Fenger, Jørgen Folkvard; Pagsberg, Palle Bjørn

    1973-01-01

    Aqueous solutions of potassium orthophosphate were reactor irradiated and analysed by electrophoresis. The resulting distributions of 32P-activity in phosphorus oxyanions resemble the ones obtained with reactor-irradiated solid phosphates. Even in dilute solutions, polymers are formed; their total...... yield increases with the concentration of the irradiated solution and varies in a complicated way with the pH. These observations and some experiments with addition of radical scavengers indicate that oxidation of the 32P-recoils by OH-radicals is an important step in the polymerization. It is suggested...

  2. Somatostatin-based radiotherapy with [90Y-DOTA]-TOC in neuroendocrine tumors: long-term outcome of a phase I dose escalation study

    Marincek Nicolas; Jörg Ann-Catherine; Brunner Philippe; Schindler Christian; Koller Michael T; Rochlitz Christoph; Müller-Brand Jan; Maecke Helmut R; Briel Matthias; Walter Martin A

    2013-01-01

    Abstract Background We describe the long-term outcome after clinical introduction and dose escalation of somatostatin receptor targeted therapy with [90Y-DOTA]-TOC in patients with metastasized neuroendocrine tumors. Methods In a clinical phase I dose escalation study we treated patients with increasing [90Y-DOTA]-TOC activities. Multivariable Cox regression and competing risk regression were used to compare efficacy and toxicities of the different dosage protocols. Results Overall, 359 patie...

  3. Somatostatin-based radiotherapy with [90Y-DOTA]-TOC in neuroendocrine tumors: long-term outcome of a phase I dose escalation study

    Marincek, Nicolas; Jörg, Ann-Catherine; Brunner, Philippe; Schindler, Christian; Koller, Michael T.; Rochlitz, Christoph; Müller-Brand, Jan; Maecke, Helmut R.; Briel, Matthias; Walter, Martin Alexander

    2013-01-01

    BACKGROUND We describe the long-term outcome after clinical introduction and dose escalation of somatostatin receptor targeted therapy with [90Y-DOTA]-TOC in patients with metastasized neuroendocrine tumors. METHODS In a clinical phase I dose escalation study we treated patients with increasing [90Y-DOTA]-TOC activities. Multivariable Cox regression and competing risk regression were used to compare efficacy and toxicities of the different dosage protocols. RESULTS Overall...

  4. Organ doses from hepatic radioembolization with 90Y, 153Sm, 166Ho and 177Lu: A Monte Carlo simulation study using Geant4

    Hashikin, N. A. A.; Yeong, C. H.; Guatelli, S.; Abdullah, B. J. J.; Ng, K. H.; Malaroda, A.; Rosenfeld, A. B.; Perkins, A. C.

    2016-03-01

    90Y-radioembolization is a palliative treatment for liver cancer. 90Y decays via beta emission, making imaging difficult due to absence of gamma radiation. Since post-procedure imaging is crucial, several theranostic radionuclides have been explored as alternatives. However, exposures to gamma radiation throughout the treatment caused concern for the organs near the liver. Geant4 Monte Carlo simulation using MIRD Pamphlet 5 reference phantom was carried out. A spherical tumour with 4.3cm radius was modelled within the liver. 1.82GBq of 90Y sources were isotropically distributed within the tumour, with no extrahepatic shunting. The simulation was repeated with 153Sm, 166Ho and 177Lu. The estimated tumour doses for all radionuclides were 262.9Gy. Tumour dose equivalent to 1.82GBq 90Y can be achieved with 8.32, 5.83, and 4.44GBq for 153Sm, 166Ho and 177Lu, respectively. Normal liver doses by the other radionuclides were lower than 90Y, hence beneficial for normal tissue sparing. The organ doses from 153Sm and 177Lu were relatively higher due to higher gamma energy, but were still well below 1Gy. 166Ho, 177Lu and 153Sm offer useful gamma emission for post-procedure imaging. They show potential as 90Y substitutes, delivering comparable tumour doses, lower normal liver doses and other organs doses far below the tolerance limit.

  5. Attenuation of bremsstrahlung from 90Sr-90Y, 147Pm and 204Tl in thick target compounds

    Manjunatha, H. C.

    2014-11-01

    The external bremsstrahlung (EB) produced by beta particles such as from 90Sr-90Y, 147Pm and 204Tl in PbCl2, PbF2, Pb(NO3)2 and CdO were measured using NaI(Tl) crystal. The beta stopper technique is employed to measure the integral intensities above 100 keV energy in different absorber thicknesses. Attenuation of the external bremsstrahlung, excited by 90Sr-90Y, 147Pm and 204Tl beta-emitters in the same compounds has also been studied. The measured attenuation parameter is not constant with absorber thickness and it increases with increasing Zmod of the absorber. Whereas, the mass attenuation coefficient of gamma rays of equivalent energy is independent of the absorber thickness. This confirms that the attenuation of EB in an absorber does not conform to a single exponential law, unlike the absorption of monoenergetic gamma rays. Rather it may be a combination of a large number of exponential terms.

  6. Treatment Parameters and Outcome in 680 Treatments of Internal Radiation With Resin 90Y-Microspheres for Unresectable Hepatic Tumors

    Purpose: Radioembolization (RE) using 90Y-microspheres is an effective and safe treatment for patients with unresectable liver malignancies. Radiation-induced liver disease (RILD) is rare after RE; however, greater understanding of radiation-related factors leading to serious liver toxicity is needed. Methods and Materials: Retrospective review of radiation parameters was performed. All data pertaining to demographics, tumor, radiation, and outcomes were analyzed for significance and dependencies to develop a predictive model for RILD. Toxicity was scored using the National Cancer Institute Common Toxicity Criteria Adverse Events Version 3.0 scale. Results: A total of 515 patients (287 men; 228 women) from 14 US and 2 EU centers underwent 680 separate RE treatments with resin 90Y-microspheres in 2003-2006. Multifactorial analyses identified factors related to toxicity, including activity (GBq) Selective Internal Radiation Therapy delivered (p < 0.0001), prescribed (GBq) activity (p < 0.0001), percentage of empiric activity (GBq) delivered (p < 0.0001), number of prior liver treatments (p < 0.0008), and medical center (p < 0.0001). The RILD was diagnosed in 28 of 680 treatments (4%), with 21 of 28 cases (75%) from one center, which used the empiric method. Conclusions: There was an association between the empiric method, percentage of calculated activity delivered to the patient, and the most severe toxicity, RILD. A predictive model for RILD is not yet possible given the large variance in these data.

  7. A new approach for dose calculation in targeted radionuclide therapy (TRT) based on collapsed cone superposition: validation with 90Y

    To speed-up the absorbed dose (AD) computation while accounting for tissue heterogeneities, a Collapsed Cone (CC) superposition algorithm was developed and validated for 90Y. The superposition was implemented with an Energy Deposition Kernel scaled with the radiological distance, along with CC acceleration. The validation relative to Monte Carlo simulations was performed on 6 phantoms involving soft tissue, lung and bone, a radioembolisation treatment and a simulated bone metastasis treatment. As a figure of merit, the relative AD difference (ΔAD) in low gradient regions (LGR), distance to agreement (DTA) in high gradient regions and the γ(1%,1 mm) criterion were used for the phantoms. Mean organ doses and γ(3%,3 mm) were used for the patient data. For the semi-infinite sources, ΔAD in LGR was below 1%. DTA was below 0.6 mm. All profiles verified the γ(1%,1 mm) criterion. For both clinical cases, mean doses differed by less than 1% for the considered organs and all profiles verified the γ(3%,3 mm). The calculation time was below 4 min on a single processor for CC superposition and 40 h on a 40 nodes cluster for MCNP (108 histories). Our results show that the CC superposition is a very promising alternative to MC for 90Y dosimetry, while significantly reducing computation time. (paper)

  8. The exploration of nursing care for patients with benign prostatic hyperplasia treated using 90Sr-90Y

    An exploration of nursing care for patients with benign prostatic hyperplasia (BPH) treated using 90Sr-90Y through the rectum was carried out . The treatment result and nursing experience in 90 cases were reported in this paper. Before the therapy nurses explained the method and principle of this treatment to the patients for the sake of increasing their confidence and to help them complete the treatment course successfully. During the radiotherapy, nurses practiced strictly radiation protection principles and operating instructions. They assisted the patients to have a healthy life style and good diet . The result of treatment indicated that the total effectiveness rate was 96.7%. The symptoms of lower urinary obstruction were improved evidently and the life quality of the patients elevated. Observation of clinical system confirmed that 90Sr-90Y may be a new treatment method of BPH with benefits of safe irradiation dos, easy operation, non-traumatization, painlessness, and remarkable curative effects. However, it should be stressed that nursing care plays a pivotal role in the treatment result. (authors)

  9. A new approach for dose calculation in targeted radionuclide therapy (TRT) based on collapsed cone superposition: validation with 90Y

    Sanchez-Garcia, Manuel; Gardin, Isabelle; Lebtahi, Rachida; Dieudonné, Arnaud

    2014-09-01

    To speed-up the absorbed dose (AD) computation while accounting for tissue heterogeneities, a Collapsed Cone (CC) superposition algorithm was developed and validated for 90Y. The superposition was implemented with an Energy Deposition Kernel scaled with the radiological distance, along with CC acceleration. The validation relative to Monte Carlo simulations was performed on 6 phantoms involving soft tissue, lung and bone, a radioembolisation treatment and a simulated bone metastasis treatment. As a figure of merit, the relative AD difference (ΔAD) in low gradient regions (LGR), distance to agreement (DTA) in high gradient regions and the γ(1%,1 mm) criterion were used for the phantoms. Mean organ doses and γ(3%,3 mm) were used for the patient data. For the semi-infinite sources, ΔAD in LGR was below 1%. DTA was below 0.6 mm. All profiles verified the γ(1%,1 mm) criterion. For both clinical cases, mean doses differed by less than 1% for the considered organs and all profiles verified the γ(3%,3 mm). The calculation time was below 4 min on a single processor for CC superposition and 40 h on a 40 nodes cluster for MCNP (108 histories). Our results show that the CC superposition is a very promising alternative to MC for 90Y dosimetry, while significantly reducing computation time.

  10. Radioembolisation with {sup 90}Y-labelled resin microspheres in the treatment of liver metastasis from breast cancer

    Cianni, R.; Pelle, G.; Notarianni, E.; Saltarelli, A.; Rabuffi, P. [Santa Maria Goretti Hospital, Department of Diagnostic and Interventional Radiology, Latina (Italy); Bagni, O.; Filippi, L. [Santa Maria Goretti Hospital, Department of Nuclear Medicine, Latina (Italy); Cortesi, E. [University of Rome ' ' Sapienza' ' , Department of Oncology, Rome (Italy)

    2013-01-15

    Metastatic breast cancer is a heterogeneous disease, commonly affecting the liver. We report our experience with {sup 90}Y radioembolisation (RE) and its effects on the survival of patients with treatment-refractory breast cancer liver metastases. A total of 77 female patients affected by breast cancer were accepted into our department for RE. Inclusion criteria were inoperable and chemotherapy-refractory hepatic metastases, acceptable performance status, sufficient residual liver, no significant hepato-pulmonary shunts. Patients were divided in two groups: group 1 (29 patients) included those with Eastern Cooperative Oncology Group (ECOG) score 0, liver involvement (0-25 %) and no extrahepatic disease (EHD); group 2 (23 patient) included patients with ECOG score 1-2, liver involvement (26-50 %) and evidence of EHD. A total of 25 patients were considered ineligible. The median age of the remaining 52 patients was 57.5 years. The median overall survival was 11.5 months and better in those whose performance status and liver function were preserved (14.3 versus 8.2 months). According to Response Evaluation Criteria in Solid Tumor (RECIST), partial response (PR) was achieved in 29 patients (56 %), stable disease (SD) was achieved in a further 18 patients (35 %) and 5 patients showed progressive disease (PD) (10 %). {sup 90}Y RE is effective in the treatment of liver metastases from breast cancer. We demonstrated a relevant survival and encouragingly high response rate in patients with treatment-refractory disease. (orig.)

  11. Attenuation of bremsstrahlung from 90Sr–90Y, 147Pm and 204Tl in thick target compounds

    The external bremsstrahlung (EB) produced by beta particles such as from 90Sr–90Y, 147Pm and 204Tl in PbCl2, PbF2, Pb(NO3)2 and CdO were measured using NaI(Tl) crystal. The beta stopper technique is employed to measure the integral intensities above 100 keV energy in different absorber thicknesses. Attenuation of the external bremsstrahlung, excited by 90Sr–90Y, 147Pm and 204Tl beta-emitters in the same compounds has also been studied. The measured attenuation parameter is not constant with absorber thickness and it increases with increasing Zmod of the absorber. Whereas, the mass attenuation coefficient of gamma rays of equivalent energy is independent of the absorber thickness. This confirms that the attenuation of EB in an absorber does not conform to a single exponential law, unlike the absorption of monoenergetic gamma rays. Rather it may be a combination of a large number of exponential terms

  12. Direct measurement of intratumor dose-rate distributions in experimental xenografts treated with 90Y-labeled radioimmunotherapy

    Purpose: To measure, quantify, and evaluate the planar dose-rate distribution for human tumor xenografts implanted into mice that are treated with 90Y-labeled monoclonal antibodies or bispecific antibodies and 90Y-labeled haptens. Methods and Materials: Twenty-five LS174T human colon carcinoma tumors grown subcutaneously in nude mice were treated with 90Y by either directly labeled ZCE025 or bispecific ECA001-DBX antibody systems. A simple, quick technique using GAFTM radiochromic medium determined the dose-rate distribution in a plane passing through the tumor center. The dose-rate distribution is generated from exposure to activity situated in one-half of the tumor (0.045 to 0.83 g). Results: Planar dose-rate distributions were obtained from the tumor xenografts. Planar dose-rate histograms were computed along with the coefficients of variance and skewness of the distributions. The observed dose-rate distributions were quantitatively compared to those calculated for a uniformly distributed activity in a half-ellipsoid of the same volume and approximate shape as the tumor half. The observed dose-rate distributions were usually broader with a more positive coefficient of skewness than the dose-rate distributions calculated from the uniformly active half-ellipsoids. For 90Y, tumor shape plays an important role in determining the minimum tumor dose. For these tumors, the tumor minimum dose-rate is always observed along the edge, usually where the edge curvature is most convex. Larger tumors tended to have broader dose-rate distributions and more positive coefficients of skewness. Exceptions to this trend were associated with dose-rate maxima displaced from the central regions due to activity heterogeneity or tumor size greatly exceeding the range of emission. Calculations for dose rate from the conventional Medical Internal Radiation Dose (MIRD) formulation exceeded the average and minimum dose rate derived from radiochromic media. The coefficient of skewness became

  13. Liver internal selective radiation therapy with 90Y microspheres: comparison between different pre-treatment activity calculation methods

    Full text of publication follows. Aim: our purpose was to compare different Methods of calculating 90Y microspheres activity for liver treatment by Internal Selective Radiation Therapy (SIRT). Such comparison is not yet available and is needed in clinics to optimize patient specific dosimetry. We also investigated lungs breakthrough (LB) calculation and its impact on the maximum injectable activity. Materials and Methods: 31 consecutive evaluations based on 99mTc macro-aggregates (MAA), followed by 25 treatments with 90Y microspheres SIR-spheresR (SIRTEX) were performed. Tumor and healthy liver volumes were determined by the interventional radiologist on anatomical images acquired with a standard contrast enhanced CT (ceCT) protocol. To determine the Tumor to Normal liver uptake ratio (T/N), regions of interest (ROIs) were drawn on 99mTc MAA SPECT/CT images acquired with a hybrid gamma camera Infinia-Hawkeye (GE). The ROIs were drawn by both a nuclear physicist and a physician via a triple fusion between SPECT/CT data, ceCT and either PET or MRI. For each treatment, four different Methods of calculating 90Y activity were applied retrospectively: 3 based on Body Surface Area (BSA-1, BSA-2 and BSA Kennedy) and one based on MIRD formalism (Partition Model). Relationships between calculated activities, LB, T/N ratio and tumor involvement were investigated. In the same way, lobar and total liver treatments were analysed separately. Results: when attenuation correction was not considered, overestimation of LB was on average 65%, but in any case the estimated lungs' doses were below 30 Gy. Moreover, LB was not significantly related to the T/N ratio, neither to tumor involvement nor Radiochemical Purity. Differences in calculated 90Y activities were extremely large, being greater for lobar treatments (from -85% to 417%) than whole liver treatments (from -49% to 58%). Besides, 2 values of T/N ratio were identified as thresholds: one for BSA-based Methods (average dose

  14. Chromium(III) phosphate labelled with 32P for use in metabolic radiotherapy

    It was obtained for the first time a suspension of chromium Phosphate (III) labelled with 32P, with predominant size of particles among 5-10 μm, potentially useful in the treatment of solid tumors and Radiosynoctomy. A dispersion was obtained with prevalence of sizes of the colloidal order with 80% above 0,2 μm, potentially useful for Radiosynovectomy

  15. /sup 32/P and acute leukemia: development of leukemia in a patient with hemoglobin Yakima

    Bagby, G.C. Jr.; Richert-Boe, K.; Koler, R.D.

    1978-08-01

    In 1954 a then 31-yr-old male was found to have erythrocytosis. Over the ensuing decade he received 72 mCi /sup 32/P. In 1964 his daughters were found to have erythrocytosis. Further investigation led to the discovery of hemoglobin Yakima, a variant with high oxygen affinity. He received no further therapy and was well until 1975, when he developed the preleukemic syndrome. Within 12 mo he developed acute nonlymphocytic leukemia accompanied by fetal erythropoiesis. Because the initial discovery of this type of hemoglobinopathy came 27 yr after the introduction of /sup 32/P for use in the treatment of polycythemia vera, and because there are now known to be more than 39 different high-oxygen-affinity hemoglobins, we anticipate that more patients such as ours have been exposed to /sup 32/P. The exposed population should be closely followed, since this will likely permit assessment of the risk of /sup 32/P-induced leukemia in a nonneoplastic condition.

  16. Photoaffinity labelling of tobacco subcellular fractions with [32P]-azido-UDP-glucose

    Subcellular fractions from tobacco (N. rustica) leaves were photolabelled with the UDPG analog, [32P]-N3 UDPG. Two stromal polypeptides (Mr = 42 and 21 kD) were the major photolabelled chloroplast polypeptides. UDPG protected the 42 but not the 21 kD polypeptide against photoincorporation of [32P]-N3 UDPG. In a cytosol-enriched fraction, the major photolabelling polypeptides had Mr of 92, 50, 42, 30 and 17 kD. Photolabelling of the 42, 30, and 17 kD polypeptides was unaffected by UDPG, but UDPG blocked incorporation into the 92 and 50 kD polypeptides. In addition to photolabelled polypeptides, a polypeptide identified as phosphoglucomutase (PGM) was labelled in both the chloroplast and cytosol fraction. 32P-labelling of PGM was independent of UV irradiation, occurring via phosphoryl transfer from contaminating [32P]G-I-P. The plastid and cytosolic PGM isozymes had Mr of 69 and 62.8 kD, respectively, and both were labelled in a leaf extract

  17. Formation of 32P-labelled Polyphosphates in Reactor-irradiated Solutions of Orthophosphate

    Fenger, Jørgen Folkvard; Pagsberg, Palle Bjørn

    1973-01-01

    Aqueous solutions of potassium orthophosphate were reactor irradiated and analysed by electrophoresis. The resulting distributions of 32P-activity in phosphorus oxyanions resemble the ones obtained with reactor-irradiated solid phosphates. Even in dilute solutions, polymers are formed; their total...

  18. Rose Atoll Site 32P 8/2/2004 10-11M

    US Fish and Wildlife Service, Department of the Interior — Onemetersquare 1 meter x 1 meter benthic substrate at Rose Atoll, site 32P 14 32.361S, 168 09.430W, between 10 and 11 meters along a permanent transect.

  19. High-performance liquid chromatography for analysis of 32P-Postlabeled DNA adducts

    Zeisig, Magnus

    1996-01-01

    High-Performance Liquid Chromatography for Analysis of 32P-Postlabeled DNA Adducts Magnus Zeisig Center for Nutrition and Toxicology, Department of Bioscience at Novum, Karolinska Institutet, Novum, S-141 57 Huddinge, SwedenThe formation of DNA adducts, i.e. the covalent binding of chemicals and chemical groups to DNA,isbelieved to be an important step in chemical carciwg...

  20. Uptake of 3HHO and 32P by roots of wheat and rape

    Direct measurements were made of 3HHO and 32P taken up from labelled soil by roots of wheat (Triticum aestivum L.) and rape (Brassica campestris L.). Single roots were encased in labelled soil for 3 days, and the amount of 3HHO and 32P retained in the shoots was determined. Plants were grown to five stages of maturity in growth boxes under controlled conditions. Roots were labelled at up to four depths (to 90 cm) depending on the rooting depth at each stage of maturity. Uptake of 3HHP per unit length of root increased as the plant age increased, while uptake of 32P decreased to below detection levels by 45 days after germination. Larger amounts of both nutrients were translocated to and retained in the shoots from surface roots than from roots located deeper in the soil although the soil was uniform in temperature, bulk density, and composition through the growth boxes. Wheat roots were more efficient than rape roots in absorbing 3HHO; however, rape roots took up larger amounts of 32P per unit length of root. Neither native nor added P located more than 30 cm deep is of much importance to these annual crops, since uptake is minimal and the main demand for this nutrient occurs at early growth stages when the root system is restricted to the surface layers

  1. Labeling of specific proteins in rat ovarian plasma membranes with [γ-32P]GTP

    The authors report evidence that [γ-32P]GTP preferentially labels two proteins in rat ovary and parotid membranes that differ structurally from the proteins that are substrates for ADP-ribosylation by cholera toxin and which are thought to be involved in the regulation of adenylate cyclase by GTP. (Auth.)

  2. Rose Atoll Site 32P 2/22/2012 36-37M

    US Fish and Wildlife Service, Department of the Interior — Onemetersquare 1 meter x 1 meter benthic substrate at Rose Atoll, site 32P 14 32.361S, 168 09.430W, between 36 and 37 meters along a permanent transect.

  3. Infection of neuroblastoma cells with Semliki Forest virus. Incorporation of 35S or 32P

    Phosphate-free medium is used for the incorporation of 32P and methionine-free medium for 35S-methionine labelling. After virus replication, the culture shows a clear CPE all of the cells appearing round and dead. Materials used are presented and experimental procedure is described

  4. Rose Atoll Site 32P 2/22/2012 45-46M

    US Fish and Wildlife Service, Department of the Interior — Onemetersquare 1 meter x 1 meter benthic substrate at Rose Atoll, site 32P 14 32.361S, 168 09.430W, between 45 and 46 meters along a permanent transect.

  5. Effects of 32 P incorporated in plasmid DNA: strand breaks and mutagenesis

    In order to study the 32 P decay effects in DNA, bacterial plasmid were labeled with different activities of the radioisotope in vivo: 1,2 and 6 x 105 Bk/ml of bacterial culture, leading to 1,2 and 6 x 103 Bk/μg of nucleic acid or in vitro: 0.7, 1.5 and 3.5 x 103 Bk/μg of nucleic acid, stored at -20 deg C and its electroforetic profiles, transformation capacity of wild type and DNA repair. E. coli mutants cells and mutagenesis, were followed during three months. The results achieved in this work suggest that: the decay of the incorporated 32 P in vivo is able to change the pBR322 electroforetic profile, we detected a decrease on the form III (super coiled) and increase on the form II (circular), indicating single strands breaks; the decay incorporated 32 in vitro does not modify the electrophoretic profile of pBR322, suggesting that in some way the effects of the radioactive decay of incorporated 32 P is dependent of the DNA topology, the damages induced by 32 P decay increase mutation frequency in pAC189 plasmids. MRF is increased by a factor of three after 6 t1/2 of storage, indicating direct or indirect action through mismatch DNA repair pathway. (author)

  6. Rose Atoll Site 32P 2/22/2012 38-39M

    US Fish and Wildlife Service, Department of the Interior — Onemetersquare 1 meter x 1 meter benthic substrate at Rose Atoll, site 32P 14 32.361S, 168 09.430W, between 38 and 39 meters along a permanent transect.

  7. SPECT/CT images in the calculation of absorbed dose ration between radio-synovectomy procedures with 153Sm-HA and 90Y-HA

    Full text of publication follows. Heterogeneity in the intra-articular distribution of hydroxyapatite (HA) labeled with 90Y or 153Sm at radio-synovectomy (RSV) procedures can be detected by using the fusion between transmission (SPECT) and emission (CT) tomographic images. To avoid this heterogeneity, commonly it is preferred to use 90Y over 153Sm assuming that the larger penetration range of the emitted beta particles will make the absorbed dose distribution more uniform. In this study, we evaluated the validity of this assumption by determining the affected area of RSV procedures in human joints treated with 90Y-HA and 153Sm-HA. Using SPECT/CT images of 3 patients treated with 90Y-HA (185 MBq) or 153Sm-HA (740 MBq), a voxel-by-voxel (voxel size=9.06 mm3) analysis was performed to build 3D distribution of 90Y and 153Sm activity. With the 3D image of the activity correlated to the mass of each voxel, provided by CT images via Housfield scale, the absorbed dose was calculated using the generic equation of absorbed dose rate and the average range of beta particles emitted from 90Y and 153Sm. We have chosen the generic dose equation rather than the MIRD model of voxel dosimetry or the Dose-Point Kernel method because the later models do not allow for a voxel mass dependent dose calculation. In addition, there is little information on 153Sm data and voxel sizes in these models. Considering the average energy and the therapeutic range of emitted beta particles we concluded that the dose in each voxel is not affected by the activity of neighboring voxels. Difference in the RSV procedures using 90Y-HA and 153Sm-HA should be just the dose difference per activity injected. Collisional Stopping Power shows us that the relative dose between these two compounds is 4.12:1. With these results we conclude that beta particles emitted from 90Y and 153Sm do not have range enough to reach cold spots found in heterogeneous distributions of radionuclide at RSV. Hence the spatial dose

  8. Development of Technology for the Preparation of 90Sr/90Y Generators at the Radiopharmacy Directory of IPEN/CNEN-SP

    90Y (T/2 = 2,67 d; Eβmax = 2,28 MeV) is a radionuclide with efficacy established for various cancer therapies, labeling biomolecules and treating of radiosinovectomy. Due to its nuclear properties, is obtained through the decay of 90Sr T/2 = 28 y in the form of a generator. Several types of 90Sr/90Y generators were developed, and the most employed are the cation exchange resins, where Sr and Y are adsorbed and 90Y is selectively eluted with acetate or EDTA. The disadvantage of this type of generator is the radiolysis, which degrades its use. The electrochemical generator is a proposed solution because there is no significant effect of radiation. In this concept, the difference between the electrochemical potentials of the elements Sr and Y is used to obtain a rapid separation of 90Y from 90Sr. The production of 90Y via colloid formation is the simplest method for the separation, based on the colloid formation of Y in high alkaline pH, which can be filtered and separated from Sr, and subsequently dissolved in HCl. The objective of this work was the development of technologies for the preparation of 90Sr/90Y generators, and three technologies were developed: generators using cation resins columns, generators through colloid formation and electrochemical generators. Radionuclidic quality control of 90Y was also evaluated by liquid scintillation, radionuclide identity, extraction paper chromatography (EPC) using complexing agents for 90Y and by Optical Emission Spectrometry with Inductively Coupled Plasma (ICP-OES). The results showed that generators using cation resins have the best results related to the elution efficiency (∼83%), the reproducibility and radionuclidic purity. The electrochemical generator showed a potential for development, having the advantage of not suffering the effects of radiolysis of the pair 90Sr/90Y as the resin. A comparison and evaluation of the methods of the radionuclidic quality control showed that the EPC is very sensitive and allows

  9. Experimental study of 32P-CP-PLLA microparticle on human pancreatic carcinoma in nude mice

    Objective: To study the therapeutic and toxic effects of 32P-chromic phosphate-poly (L-lactic) acid (32P-CP-PLLA) microparticle intratumoral administration into BALB/c nude mice bearing BxPc-3 human pancreatic carcinoma. Methods: Twenty four nude mice bearing tumors were injected with 0, 9.3, 18.5 and 37.0 M Bq 32P-CP-PLLA microparticle, respectively. The relative tumor growth rates were observed every day, and white blood cells, platelets and body weight were measured. At 14 d after administration, the tumors were removed, histological examination and immunohistochemical analysis were performed. Results: The relative tumor growth rates of each treatment group was lower than 40%. Histological examination showed the degenerative necrosis at the site nearby the microparticle. Immunohistochemical analysis showed that the Microvessel density (MVD) and the expression of Bcl-2 in treated group were lower than those in control group.In contrast, the expression of bax in treated group were higher than those in control group. The ratio of Bcl-2/Bax protein significantly decreased in the treatment group,which were 3.83 ± 0.43, 0.47 ± 0.13, 1.10 ± 0.32, 2.19 ± 0.57 for 0, 9.3, 18.5 and 37.0 MBq 32P-CP-PLLA microparticle, respectively (t=2.36-2.77, P<0.05). MVD were 31.2 ± 2.3, 23.8 ± 1.5, 14.8 ±0.8, 11.0 ± 1.2, respectively. Dose dependence was observed in both HE and IHC staining after 14 d treatment (t=2.30-2.57, P<0.05). Conclusions: Intratumoral injection of 32P-CP-PLLA microparticle might be a safe, easy and effective radionuclide interventional therapy for pancreatic carcinoma. (authors)

  10. Treatment of verruca of hands and feet with 32P application therapy and laser

    To study and compare the clinical curative effect of extremity verruca with 32P and laser as well as their application values, 229 patients with extremity verruca were chosen by random from outpatient. Out of them, 83 patients were male and 146 were female, with the average age of 34.6 ± 19.5 (x-bar ± s) years. They were randomly divided into two groups: for the laser treatment group consisting of 127 individuals, the wart bodies were eliminated by CO2 laser under local anaesthetization, if there were a lot of locus, the wart bodies were treated in turn. 102 individuals were treated with 32P application therapy. The liquid containing radionuclide 32P was dropped on filter papers, dried and then fixed on the corresponding focus surface for application therapy, applying 4-8 hours continuously (the absorbed dose at the lesion surface reaching 984-1968 cGy) each time and once a week until the lesion recovered. The clinical reaction and curative effect were observed. The clinical effective rate, cure rate, recurrence rate, side effective rate occurrence rate and complication occurrence rate for the laser treatment group are 100%, 55.9%, 44.1%, 17.3% and 25.2%, respectively while they are 100%, 91.2%, 5.9%, 19.6% and 7.8% respectively for the group of 32P application therapy. It is concluded that the treatment of extremity verruca with 32P application therapy is a simple and effective method with features such as safety, little pain, notable curative effect, lower recurrence rate, less side effect and complication. (authors)

  11. Somatostatin-based radiopeptide therapy with [{sup 177}Lu-DOTA]-TOC versus [{sup 90}Y-DOTA]-TOC in neuroendocrine tumours

    Romer, A.; Seiler, D.; Brunner, P.; Ng, Q.K.T.; Mueller-Brand, J. [University Hospital Basel, Institute of Nuclear Medicine, Basel (Switzerland); Marincek, N.; Walter, M.A. [University Hospital Basel, Institute of Nuclear Medicine, Basel (Switzerland); University Hospital Bern, Institute of Nuclear Medicine, Bern (Switzerland); Koller, M.T. [University Hospital Basel, Basel Institute for Clinical Epidemiology and Biostatistics, Basel (Switzerland); Maecke, H.R. [University Hospital Basel, Division of Radiochemistry, Basel (Switzerland); Rochlitz, C. [University Hospital Basel, Department of Oncology, Basel (Switzerland); Briel, M. [University Hospital Bern, Institute of Nuclear Medicine, Bern (Switzerland); University Hospital Basel, Basel Institute for Clinical Epidemiology and Biostatistics, Basel (Switzerland); McMaster University, Department of Clinical Epidemiology and Biostatistics, Hamilton (Canada); Schindler, C. [University of Basel, Swiss Tropical and Public Health Institute, Basel (Switzerland)

    2014-02-15

    Somatostatin-based radiopeptide treatment is generally performed using the β-emitting radionuclides {sup 90}Y or {sup 177}Lu. The present study aimed at comparing benefits and harms of both therapeutic approaches. In a comparative cohort study, patients with advanced neuroendocrine tumours underwent repeated cycles of [{sup 90}Y-DOTA]-TOC or [{sup 177}Lu-DOTA]-TOC until progression of disease or permanent adverse events. Multivariable Cox regression and competing risks regression were employed to examine predictors of survival and adverse events for both treatment groups. Overall, 910 patients underwent 1,804 cycles of [{sup 90}Y-DOTA]-TOC and 141 patients underwent 259 cycles of [{sup 177}Lu-DOTA]-TOC. The median survival after [{sup 177}Lu-DOTA]-TOC and after [{sup 90}Y-DOTA]-TOC was comparable (45.5 months versus 35.9 months, hazard ratio 0.91, 95 % confidence interval 0.63-1.30, p = 0.49). Subgroup analyses revealed a significantly longer survival for [{sup 177}Lu-DOTA]-TOC over [{sup 90}Y-DOTA]-TOC in patients with low tumour uptake, solitary lesions and extra-hepatic lesions. The rate of severe transient haematotoxicities was lower after [{sup 177}Lu-DOTA]-TOC treatment (1.4 vs 10.1 %, p = 0.001), while the rate of severe permanent renal toxicities was similar in both treatment groups (9.2 vs 7.8 %, p = 0.32). The present results revealed no difference in median overall survival after [{sup 177}Lu-DOTA]-TOC and [{sup 90}Y-DOTA]-TOC. Furthermore, [{sup 177}Lu-DOTA]-TOC was less haematotoxic than [{sup 90}Y-DOTA]-TOC. (orig.)

  12. Synthesis and characterisation of [90Y]-Bz-DTPA-oct: a yttrium-90-labelled octreotide analogue for radiotherapy of somatostatin receptor-positive tumours

    An investigation into the in vitro behaviour of two yttrium-90-labelled somatostatin analogues was performed. Further in vivo characterisation was performed with the most promising agent. A new DTPA-octreotide analogue (Bz-DTPA-oct) was synthesised by coupling a bifunctional DTPA chelator to the N-terminal amine of the D-Phe1 of Tyr3-octreotide. This new SRIF analogue and DTPA-octreotide (OctreoScan) were radiolabelled with 90Y prior to serum stability being evaluated. Receptor binding assays were also performed on the two radioligands using rat cortex membranes. The [90Y]-Bz-DTPA-oct was further evaluated in vivo using tumour-bearing rats. The first conjugate (DTPA-octreotide) bound with a high affinity to SRIF receptors and the 90Y complex was relatively stable in human serum (t 1/2 3.8 d for 90Y lost to serum proteins). The second conjugate (Bz-DTPA-oct) also exhibited a high binding affinity to SRIF receptors, but it demonstrated an even slower loss of 90Y to serum proteins (t1/2 12.1 d). The in vivo evaluation of the more stable [90Y]-Bz-DTPA-oct showed a very rapid and high accumulation in somatostatin receptor-positive tumours, which after 1 h resulted in tumour/nontumour ratios of 3.8, 21, and 4.9 (for blood, muscle, and liver, respectively). These tumour/nontumour ratios increased, and were by 24 h postinjection 138, 285, and 6.1 (for blood, muscle, and liver). Yttrium-90-labelled Bz-DTPa-oct is rapidly and selectively accumulated in somatostatin receptor-positive tissue. Octadentate Bz-DTPA-oct could be ligand for 90Y radiotherapy of somatostatin receptor-positive tumours and their metastases

  13. Lower biological efficacy of 90Y-loaded glass microspheres results from microspheres transport in the arterial hepatic tree

    Full text of publication follows. Aim: 90Y resin and glass microspheres liver radio-embolization delivering liver dose of 40 and of 120 Gy, respectively, display similar hepatic toxicity risk than 40 Gy fractionated EBRT. We investigated why. Materials and methods: the microscopic dose distribution was assessed in the realistic liver model developed by Gulec et al., but using the Russels dose deposition kernel: D(r) = 0.989*A*(1-r/8)*r2 (1) where r: radial distance in mm, D: dose in Gy and A: microsphere activity in kBq. A lattice of hexagonal prisms represented the hepatic lobules. The central vein and the six portal tracts were located in the hexagon centre and corners, respectively. Each branch segment of the arterial tree was assumed to split in two smaller branch daughters owing different curvatures which results in a 40-60% microspheres distribution as derived by Kennedy et al. from computer modelling. We performed four 120 Gy to liver simulations. Two uniform: 1 and 6 glass microspheres trapped in all and in only 1 portal tract per lobule, respectively. Two random: glass microspheres trapping assuming an equal probability for all the portal tracts or a variable probability depending on the successions of artery connections leading to the portal tract. Results: Eq. 1 fitted well the 90Y dose kernel obtained from Monte Carlo simulation by Gulec et al. For the two uniform simulations all hepatic structures received at least 110 Gy. The fast decrease of the 90Y kernel (eq. 1) as the inverse of the square distance r is counter-balanced by the number of contributing microspheres that increases as the square of this distance r. The major part of a dose everywhere in a lobule does not arise from the microsphere tapped in the portal tracts of this lobule, but arises from the farther lobules (75%) as already pointed out by Gulec et al. The Russels law clearly explains this observation. The first random simulation gave for the less irradiated tissue a dose distribution

  14. Limoges' Hospital experience of 90Y-Zevalin in non-Hodgkin's lymphoma treatment

    Full text of publication follows. Background: Non-Hodgkin Lymphomas (NHL) B CD20+ are the most common hematological malignancies in France. Many immuno-chemotherapy protocols are available. However, complete and sustained remission in patients with NHL remains a real issue. Radioimmunotherapy (RIT) with 90Y-Zevalin could be a rational approach, which involves administration of monoclonal anti-CD20 antibody labeled with radionuclide, leading to lymphoma cells significant radiation exposure. Materials and methods: data from 62 patients having received 90Y-Zevalin standard-dose (14.8 MBq/kg for patients with platelet counts ≥ 150,000 cells/μl and 11 MBq/kg for patients with platelet counts between 100,000 and 150,000 cells/μl), between 2005 and 2012, both in monotherapy (n=16) or in addition to autologous stem cell transplant (ASCT) with BEAM conditioning regimen (n=46), have been analyzed in order to evaluate treatment usefulness and to compare results with literature. Disease tissues were diffuse large B-cell (n = 12), follicular (n = 30) and transformed lymphomas (n = 20). Endpoints included overall survival rate (OS), progression-free survival rate (PFS), and safety. Results: for patients treated in monotherapy for relapsed NHL B CD20+, our results are lower than those obtained in the literature: after a median follow-up of 47 months, 2-year PFS and OS were 25% and 58% respectively. Hematologic toxicities are frequently observed (70% grade 3-4 cytopenias). These results, both in terms of efficiency and tolerance, could be explained by a delayed RIT in disease progression. For patients treated in addition to ASCT conditioning, with a median follow-up of 6 months (range, 0,5 to 44,6 months) the estimated 2-year PFS and OS were 100% and 73% for patients treated for a relapsed follicular NHL (n=21). These results are very closed to GELA study (Decaudin et al., 2011) without hematologic toxicity increasing versus BEAM alone. For patients treated as first line

  15. Comparison of 90Y/177Lu labeled DOTA-Bz-RGD tetramer and DOTA-RGD tetramer

    90Y/177Lu labeled DOTA-Bz-RGD tetramer and DOTA-RGD tetramer were prepared, and the effect of Bz-DOTA and DOTA on labeling conditions and in vitro stability of radiolabeled compounds was compared. The labeling conditions, including reaction pH, reaction temperature and reaction time, were investigated. ITLC and HPLC show that the labeling yields of four radiolabeled compounds are more than 95% under optimal conditions (pH=6.0, reacting at 100 degree C for 15-20 min); the four radiolabeled compounds show pretty good stability in saline and fetal bovine serum. Although introducing of Bz has no effect on labeling conditions and in vitro stability of radiolabeled compounds, it brings a little change on molecule polarity. HPLC analysis and lg P values reveal that introducing of Bz increases the lipophilicity of radiolabeled compounds. (authors)

  16. A multicentre comparison of quantitative (90)Y PET/CT for dosimetric purposes after radioembolization with resin microspheres

    Willowson, Kathy P; Tapner, Michael; Bailey, Dale L

    2015-01-01

    the NEMA 2007/IEC 2008 PET body phantom with an 8-to-1 sphere-to-background ratio of (90)Y solution. The phantom was imaged over a 7-day period (activity ranging from 0.5 to 3.0 GBq) and all reconstructed data were analysed at a core laboratory for consistent processing. Quantitative accuracy was...... assessed through measures of total phantom activity, activity concentration in background and hot spheres, misplaced counts in a nonradioactive insert, and background variability. RESULTS: Of the 69 scanners assessed, 37 had both time-of-flight (ToF) and resolution recovery (RR) capability. These current...... investigated, comparable performance between GE Healthcare and Siemens ToF systems suggests suitability for quantitative analysis in a scenario analogous to that of postradioembolization imaging for treatment of liver cancer....

  17. 32P measurement and dose conversion factor evaluation of activated human hair by criticality accident

    In order to conduct dose assessment of victims in criticality accidents, a method of fast neutron capture-activated 32P measurement of hair in which samples are treated by a chemical and analytical procedure that takes 9 h and measurement is conducted by liquid scintillation counting is presented. To validate this measurement method, hair samples spiked with a 32P reference source were measured and the results analysed and the optimal sample mass and detection efficiency were determined. To verify the correlation between 32P-specific activity and absorbed dose for spectra with two neutron mean energies, samples collected from three normal individuals were irradiated at various neutron energies and irradiation times using the MC50 Cyclotron of the Korea Institute of Radiological and Medical Sciences. The 32P-specific activity trend of the irradiated hair agreed well with the absorbed doses. Based on the results, dose conversion factors, which were 0.67±0.15 and 0.59±0.06 Gy (Bq g-1)-1 at neutron mean energies of 2.33 and 5.36 MeV, respectively, were calculated as a guide for medical treatment of criticality accident victims. In this study, a method for measuring 32P changes activated by the neutron irradiation of hair samples of criticality accident victims was developed and tested. In addition, a dose conversion factor for two neutron mean energy spectra based on these measurement results was developed. These results agree well with measured absorbed doses from exposure to fast neutron fields. The advantage of the proposed activated hair analysis method based on liquid scintillation counting is that it enables the acquisition of dose information from victims in a short time and with relatively high detection efficiency. In addition, sampling of hair is simpler than it is for other biological samples, and, finally, the conversion factor the authors developed using hair analysis data will be useful for dose assessment in real cases. However, the relation between

  18. Comparison of 131I- and 90Y-labeled monoclonal antibody 17-1A for treatment of human colon cancer xenografts

    The choice of radionuclide remains an important question in clinical radioimmunotherapy. Therefore, a study was initiated, using an in vivo model system, to assess the relative merits of 131I- and 90Y-labeled 17-1A monoclonal antibody as therapeutic agents in the treatment of colon cancer. 131I- and 90Y-labeled 17-1A were assessed in animal therapy trials using athymic nude mice bearing LS174T human colon cancer xenografts. 131I-labeled 17-1A decreased tumor growth in a dose-dependent fashion without lethality. In contrast, the doses of 90Y-labeled 17-1A which were required to produce a significant increase in tumor doubling time also caused marked toxicity. Although similar tumor growth inhibition was produced by 250 μCi 90Y- and 150 μCi 131I-labeled 17-1A, Medical Internal Radiation Dose calculations based on biodistribution data estimated that the dose delivered by 90Y was greater than that delivered by 131I. To investigate this discrepancy, 3-dimensional dose distributions within LS174T tumors were assessed using autoradiography and 3-dimensional calculational techniques. It was found that a greater fraction of the dose was deposited in the tumor after treatment with 131I- compared to 90Y-labeled 17-1A. When the Medical Internal Radiation Dose calculations were adjusted using the 3-dimensional dose distributions, 250 μCi of 90Y- and 150 μCi of 131I-labeled 17-1A were found to deliver similar tumor doses. These studies suggest that 131I-labeled 17-1A is superior to 90Y-labeled 17-1A, since 131I-labeled antibody produced less hematological and animal toxicity and was more effective at inhibiting LS174T tumor growth than 90Y-labeled antibody across the range of radionuclide doses tested. Furthermore, they suggest that it will be necessary to perform 3-dimensional dose calculations. 33 refs., 7 figs., 4 tabs

  19. Review of 90Y-ibritumomab tiuxetan as first-line consolidation radio-immunotherapy for B-cell follicular non-Hodgkin’s lymphoma

    Several studies have indicated that radioimmunotherapy is an effective and clinically relevant complementary therapeutic approach for patients with B-cell non-Hodgkin’s lymphoma (NHL) and may convert partial to complete response when given as consolidation after induction chemotherapy. Yttrium-90(90Y)-ibritumomab tiuxetan (90Y-IT, Zevalin®, Y2B8) has documented efficacy for both indolent and aggressive NHL. Patients considered eligible for 90Y-IT treatment should satisfy several screening criteria. A recently completed randomized study for patients with follicular lymphoma has demonstrated that 90Y-ibritumomab consolidation also produced a marked prolongation of the median time to progression from 13.5 to 37 months, while partial responders seem to derive relatively more benefit. Other published and ongoing studies explore a similar use for patients with aggressive lymphoma. Studies are comparing the use of 90Y-IT consolidation with the anti-CD20 antibody rituximab maintenance, which is also gaining acceptance. In conclusion, the documented benefit of radioimmunotherapy should be viewed in the context of the goals of treatment and the changing standards of care for lymphoma

  20. Review of (90Y-ibritumomab tiuxetan as first-line consolidation radio-immunotherapy for B-cell follicular non-Hodgkin’s lymphoma

    Christos Emmanouilides

    2009-10-01

    Full Text Available Christos EmmanouilidesDepartment of Medical Oncology, Interbalkan Hospital, Thessaloniki, GreeceAbstract: Several studies have indicated that radioimmunotherapy is an effective and clinically relevant complementary therapeutic approach for patients with B-cell non-Hodgkin’s lymphoma (NHL and may convert partial to complete response when given as consolidation after induction chemotherapy. Yttrium-90(90Y-ibritumomab tiuxetan (90Υ-ΙΤ, Zevalin®, Y2B8 has documented efficacy for both indolent and aggressive NHL. Patients considered eligible for 90Y-IT treatment should satisfy several screening criteria. A recently completed randomized study for patients with follicular lymphoma has demonstrated that 90Y-ibritumomab consolidation also produced a marked prolongation of the median time to progression from 13.5 to 37 months, while partial responders seem to derive relatively more benefit. Other published and ongoing studies explore a similar use for patients with aggressive lymphoma. Studies are comparing the use of 90Y-IT consolidation with the anti-CD20 antibody rituximab maintenance, which is also gaining acceptance. In conclusion, the documented benefit of radioimmunotherapy should be viewed in the context of the goals of treatment and the changing standards of care for lymphoma. Keywords: radioimmunotherapy, 90Y-ibritumomab tiuxetan, follicular lymphoma, consolidation

  1. Radiation dosimetry of 90Y-labeled monoclonal antibody CO17-1A prepared by the site-specific NH2-Bz-DOTA-3A technique

    90Y-Labeled monoclonal antibody CO17-1A, with specificity for colorectal and pancreatic carcinomas, has shown excellent potential for radioimmunotherapy. A new bifunctional chelate technique, involving site-specific conjugation of 2-p-aminobenzyl-1,4,7,10-tetraazacyclododecanetriacetic acid (NH2-Bz-DOTA-3A) to the oligosaccharide portion of C017-1A, was recently shown to yield 90Y-CO17-1A with greater in vivo stability and tumor specificity than that produced using DTPA- based bifunctional chelate techniques. Radiation absorbed dose estimates for normal structures of reference man and for mouse tumors of various sizes were calculated for 90Y-CO17-1A prepared by the site-specific NH2-Bz-DOTA-3A technique, based on timed tissue distribution studies (6, 24, 48, 72, 120, or 168 hr) in female nude mice bearing SW 948 human colorectal carcinoma xenografts. Radiation absorbed dose estimates for tumor were 50% higher than those obtained in previously reported studies with 90Y-CO-17-1A produced by site-specific conjugation of any acyclic DTPA ligand, whereas radiation doses for normal tissues were similar for the two methods. The absorbed dose to the bone marrow, 2.7 mSv/MBq, will limit the dosage in MBq or mCi of 90Y-CO17-1A that can safely be administered

  2. Design and construction of a prototype for the obtention of {sup 32} P; Diseno y construccion de un prototipo para la obtencion de {sup 32} P

    Alanis M, J. [ININ, Departamento de Materiales Radiactivos, 52045 Ocoyoacac, Estado de Mexico (Mexico)

    2003-12-15

    In the National Institute of Nuclear Research (ININ) it was designed, built and proved a prototype to obtain {sup 32}P in form of H{sub 3} {sup 32}PO{sub 4}, starting from irradiated S{alpha}. The beginning of the prototype it is based on a distillation system in dry of the S{alpha} in nitrogen atmosphere, and in the formation of the ion {sup 32}PO{sub 4}{sup 3-} in acid solution. Due to the handling of radioactive material during the process, the prototype is inside a hot cell and it has a cylindrical oven that opens up lengthwise to the half, with controller of temperature and with a system of empty air for to transport reagents and products. The air-vacuum system is provided of filters and traps. The tests showed a recovery from 14 to 15% of the activity obtained during the irradiation. (Author)

  3. Single-Well Technique using 32P for Determining Direction and Velocity of Groundwater Flow

    A radiographic method for determining the direction, ∅, and the velocity, v, of groundwater flow has been developed. The radioisotope 32P is injected, as a point or a thin-column source, at the centre of the well by means of a simple device. The injection is performed at the desired depth without disturbing the water. The radioisotope is left to follow the horizontal flow of water. Some of the 32P is adsorbed onto the walls of two parallel detecting screens which are separated by a few centimetres and fitted inside the well. Both the inner and outer screens are radiographed; the darkest parts of the emulsions and the north direction marked on another film give the value of ∅. The blackening of each film in the screens is measured. Velocities are determined either by the displacement method or from the calibration curve of the velocity versus relative blackening. (author)

  4. Quantitative and kinetic examination of 32P-postlabeling of etheno-substituted nucleotides.

    Szyfter, K; Hemminki, K; Crane, A E; Watson, W P

    1991-01-01

    1,N6-ethenodeoxyadenosine-, 1,N2-ethenodeoxyguanosine- and 3,N4-ethenodeoxycytidine-3'-monophosphates were labeled by [gamma-32P] ATP using T4 polynucleotide kinase in conditions commonly used for the 32P-postlabeling assay. Kinetic studies showed that the reaction is fast reaching a plateau after 15-30 min. The efficiency of phosphorylation, as studied by substrate-product concentration dependency, was between 50-100% at the lower substrate concentrations. The adducts are labeled efficiently at sub-femtomole levels. All the adducts were sensitive to the 3'-dephosphorylation by P1 nuclease although the guanine derivative appeared to be more resistant than the two other adducts. PMID:1913981

  5. Effect of radioactive isotope 32P upon alpha amylase activity and glucose concentration in chickens

    An attempt has been made to investigate whether alpha amylase activity and glucose concentration in blood plasma can serve as the help in establishing on early diagnosis of organic or functional damage caused by ionizing radiation in chickens. Fifty day old hybrid chickens of heavy 'Jata' breeds of both sexes, were treated by 32P administered intramusculary as sodium orthophosphate in a single dose of 333 MBq per kilogram of body weight. Blood samples was taken from the wing vein on day 1, 3, 5, 7 and 10 after administration of 32P. Alpha amylase activity and glucose concentration were determined spectrophotometrically using kits produced by 'Radonja', Sisak. Alpha amylase activity was decreased and glucose concentration was increased during investigated period. Yet, the further investigations are needed to find out whether these two parameters can be used for early diagnosis of injury in chicken organism by ionizing radiation. (author)

  6. Uptake of 32P labelled superphosphate by endomycorrhizal papaya (Carica papaya cv. Coorg honey dew)

    In papaya (Carica papaya cv. Coorg honey dew), there was an increase in 32P uptake and total phosphorus in plants inoculated with mycorrhizal fungi Glomus mossae and G. fasciculatum. Phosphorus derived from fertilizer (Pdff) was lower in mycorrhizal plants while soil derived P, utilisation of P and A values were higher showing thereby that mycorrhizal plants had utilised forms of phosphorus not available to non-mycorrhizal plants. (author). 13 refs., 1 tab

  7. Colloidal chromic phosphate 32P synovectomy in antigen-induced arthritis in the rabbit

    Radioisotopes have been employed in the therapy of chronic arthritis, in particular, rheumatoid arthritis for many years. A variety of isotopes have been popularized, and in the last ten years a colloidal solution of radioactive chromic phosphate 32P has been in use apparently with equivalent efficacy to others such as 169erbium, 90yttrium, and 165dysprosium. No controlled studies on this modality have been reported and few animal studies were found. The efficacy of therapeutic doses of 32P as a medical synovectomy and its effect on rabbit joints with antigen-induced arthritis were observed in 62 arthritic knee joints in 31 adult rabbits treated on one side with 0.1 microCi of 32P, the opposite serving as control. The animals were observed over a period of 11 months and examined by histologic and biochemical means. The synovium showed no evidence of radiation necrosis in treated joints. Cartilage of treated and control joints showed similar changes consistent with chronic arthritis, persistent synovitis, progressive chondrocyte degeneration, and decreased matrix metachromasia. The radiosynovectomy had neither removed synovium nor protected the cartilage. Its efficacy in humans is therefore questionable

  8. Use of radioactive 32P technique to study phosphate rock dissolution in acid soils

    A laboratory experiment was conducted to evaluate the dissolution of six sources of phosphate rock in two acid soils (Ultisols): a sandy soil and a red clay soil. Labile P was determined using the radioactive 32P technique for Pi extractable P and resin extractable P. Incubations were conducted for 0, 1, 2, 3, 4 and 5 weeks for 32P exchangeable technique, 0 and 5 weeks for Pi technique and 5 weeks for resin technique. Rates of PR were 0 and 400 mgP/ha. The results showed that labile P in the sandy soil decreased from 0-1 weeks for all the PRs except Hahotoe PR and Hazara PR's. Between 1 and 5 weeks labile P remained relatively constant. The ranking of labile P from PRs was: North Carolina = Kouribga > Matam > Hahotoe = Hazara> Patos de Minas. In the red soil, labile P from all PRs appeared to be relatively unchanged during the 0-5 week incubation. Pi extractable P in sandy soil showed no significant differences due to incubation time. In the red clay soil, there was a significant decrease in Pi-P extracted from soil mixtures with PRs after 5 weeks as compared to 0 weeks. Results of the Resin-extractable P in both sandy and red soils were in agreement with labile P as measured by 32P exchange technique. (author)

  9. Effect of /sup 32/P treatment for polycythaemia vera on blood lymphocyte subpopulations and their functions

    Petrini, B.; Wasserman, J.; Stedingk, L.V.; Blomgren, H.; Svedmyr, E.; Schnell, P.O.

    1987-01-01

    The influence of /sup 32/P treatment on the blood lymphocyte population was examined in 16 patiens with polycythaemia vera who had not previously been treated with cytotoxic drugs or irradiation. Before treatment the lymphocyte counts were within the normal range but the expression of certain membrane structures, as detected by monoclonal antibodies directed against total T cells (CD 3 and 5), helper/inducer (CD 4) and suppressor/cytotoxic T cells (CD 8), were slightly reduced. In addition, mitogenic responses of the lymphocytes to PHA and PWM-induced Ig secretion were severely impaired. Following a single oral dose of /sup 32/P (150-305 MBq), which was shown to normalize the production of erythrocytes and/or platelets, the blood lymphocyte counts were reduced by approximately 40% 12 wk after treatment. Subset analysis showed that the proportion of B cells, as identified by monoclonal antibodies (CD 20), was reduced to the highest relative extent. On the other hand, lymphocytes expressing the above T cell markers were somewhat increased. /sup 32/P treatment sharply increased PHA reactivity but it further reduced PWM-induced Ig secretion. The latter observation was in line with the finding that serum concentrations of Ig were reduced following treatment.

  10. Changes of the blood lymphocyte population following sup 32 P treatment for polycythemia vera

    Blomgren, H.; Svedmyr, E. (Radiumhemmet Karolinska Hospital, Stockholm (Sweden)); Petrini, B.; Wasserman, J.; Stedingk, L.-V. von (The Stockholm County Council, Central Microbiological Laboratory, Stockholm (Sweden))

    1990-01-01

    Orally administrated NA{sub 2} {sup 32}PO{sub 4} mainly accumulates in bone marrow where it emits {beta}-particles which may damage cells. Previously, we showed that {sup 32}P treatment for polycythemia vera (PVC) increased the phytohemagglutinin reactivity and proportions of T cells in the blood. Now we have examined the effects of {sup 32}P treatment for PCV on natural killer (NK) and B-lymphocyte subsets which are considered to undergo their maturation in bone marrow. A mean isotope dose of 240 MBq given to 14 patients reduced the peripheral lymphocyte counts to 60% at 6 weeks. B cells and NK cells were reduced to the highest relative extent followed by HNK-1 cells and T cells. Although the proportion of NK cells was reduced to 50% there was no concomitant reduction of NK activity against K562 cells. Pokeweed mitogen-triggered secretion of IgM was significantly reduced, but not that of IgG or IgA. It is suggested that lymphocytes which mature in bone marrow may be affected to the highest extent by {sup 32}P treatment in PCV. (author).

  11. Chemical digestion and radionuclidic assay of TiNi-encapsulated 32P intravascular brachytherapy sources

    A very quantitative, destructive assay procedure was devised for accurately measuring the 32P activity content of TiNi-encapsulated intravascular brachytherapy sources and was applied to four different sources (termed 'seeds') which were developed and provided by Guidant Intravascular Intervention (formerly NeoCardia). These seeds are intended for use in the prophylactic treatment of restenosis following balloon angioplasty in heart-disease patients. The assays involved the dissolution of the TiNi jacket, extraction of the activity from the internal 32P-containing source material, quantitative solution transfers, and a gravimetrically-based dilution; followed by liquid scintillation (LS) spectrometry of the resulting master solution with 3H-standard efficiency tracing using composition-matched LS cocktails. The LS spectrometry utilized a previously-developed method for resolving the always-present 33P impurity. The protocol included provisions for accounting for all possible losses of 32P in the digestion procedure (based on radiochemical tracing experiments), for any unrecovered activity in the remaining source material, and for any residual activity in the solution-transfer and containing vessels. Sections of the TiNi jackets adjacent to the cut-off active seed portions were also assayed for any contained activity. Such destructive assays were required for relating measurements of the absorbed dose spatial distribution for the seeds to theoretic dose modelling and for establishing calibration factors for subsequent non-destructive radionuclidic measurements on the seeds

  12. Radioisotope labelling of several major insect pest. Dipping the pupae in /sup 32/P solution

    Sutrisno, S. (National Atomic Energy Agency, Jakarta (Indonesia). Pasar Djumat Research Centre)

    1981-12-01

    Radioisotope uptake by insects could take place through various parts i.e. mouth, cuticula, intersegmental, secretion and excretion organs. Usually insects are labelled internally by feeding them on an artificial diet containing radioisotope solution. Labelling of several insect pests of cabbage (Crocidolomia binotalis) Zell and Plutella maculipennis Curt and rice (Chilo suppressalis Walker) by dipping of the pupae in /sup 32/P solution showed a promising result. Pupae of Crocidolomia binotalis Zell dipped in 3 ml solution of /sup 32/P with specific activities of 1, 3, 5 and 7 ..mu..Ci/ml had developed labelled adults of sufficiently high radioactivity levels for ecological studies. Similar results were also obtained with Plutella maculipennis Curt and Chilo suppressalis Walker with doses of 1, 3, 5, 7 and 9 ..mu..Ci/ml /sup 32/P solution. The best doses for radioisotope labelling by dipping of the insects Crocidolomia binotalis Zell, Plutella maculipennis Curt, and Chilo suppressalis Walker were 1, 9, and 7 ..mu..Ci/ml respectivelly.

  13. DNA Labeled with 32P for Detection of the Resistance of Mycobacterium Tuberculosis to Isoniazid

    DNA labeled by 32P for detection of the resistance of M.tuberculosis to isoniazid has been carried out with molecular biology technique based on nuclear science. Tuberculosis (TB) is the first rank of death caused infectious diseases in Indonesia. One case of difficulties in controlling TB is the spreading of M.tuberculosis which resistant to the drug such as isoniazid. In this research, resistance to isoniazid can be detected by analyzing inh A gene, which is encoding isoniazid resistance. Analysis was done with polymerase chain reaction (PCR) technique to amplify deoxyribonucleic acid (DNA) from inhA gene and was labeled with alpha 32P deoxy cytosine triphosphate ([α- 32P]dCTP). Amplified product of DNA was analyzed with single strand conformation polymerism (SSCP) technique based on the alteration of DNA band mobility in acrylamide gel after visualization with autoradiography. Analyses that have been done on 100 samples, it was found that 13.0% of them were suspected resistant to isoniazid. Molecular biology technique could be used to detect resistance in a short time and specific, and could be used as supporting data in TB patient treatment. The alteration of mobility of DNA band inhA gene could be used for analyzing the resistance M.tuberculosis to isoniazid. (author)

  14. The experimental study of 32P-colloid perfusion therapy in the animal-models of chronic maxillary sinusitis

    Objective: To search for the mechanism of 32P-colloid perfusion therapy in the animal models of chronic maxillary sinusitis. Methods: 32P-colloid were injected into the male sheep maxillary sinuses of the animal-models of chronic maxillary sinusitis in different dosage group. The changes of bacteria and mucosael pathomorphology were observed by periodic germiculture and pathology in 1,3,6 months after injection. Results: After 32P-colloid perfusion therapy, the amounts of bacterial species and chronic phlogistic cells were remarkable reduced, and the structure of cilia cells did not change. The curable rate was 83.3% in 6 months. There were remarkable difference in groups. Conclusions: 32P-colloid was provided with antibiosis and reducing chronic phlogistic responses. The authors had found the optimal dose of 32P-colloid perfusion in the maxillary sinuses through the study. The curable rate of single dose of 32P-colloid perfusion in the maxillary sinuses was higher than other therapy, 32P-colloid perfusion was simple and convenient. There was high selectivity of 32P in the target organ, when there was no effect on other important organs through radiobiological measurement. (authors)

  15. Molecular response assessed by {sup 68}Ga-DOTANOC and survival after {sup 90}Y microsphere therapy in patients with liver metastases from neuroendocrine tumours

    Filippi, Luca; Salvatori, Rita; Bagni, Oreste [Santa Maria Goretti Hospital, Department of Nuclear Medicine, Latina (Italy); Scopinaro, Francesco [Sant' Andrea Hospital, Department of Nuclear Medicine, Rome (Italy); Pelle, Giuseppe; Cianni, Roberto [Santa Maria Goretti Hospital, Department of Interventional Radiology, Latina (Italy); Schillaci, Orazio [University Tor Vergata, Department of Biomedicine and Prevention, Rome (Italy)

    2016-03-15

    We investigated the prognostic role of {sup 68}Ga-DOTANOC in patients affected by hepatic metastases from neuroendocrine tumours (NET) undergoing {sup 90}Y radioembolization ({sup 90}Y-RE). A group of 15 consecutive patients with unresectable NET liver metastases underwent {sup 68}Ga-DOTANOC PET at baseline and 6 weeks after {sup 90}Y-RE. Molecular response was defined as a reduction of >50 % in the tumour-to-spleen ratio (ΔT/S). The patients were divided into two groups (responders with ΔT/S >50 % and nonresponders with ΔT/S <50 %) Patients were followed up by imaging and laboratory tests every 3 months until death or for at least 36 months following {sup 90}Y-RE. Statistical analysis was performed to identify factors predicting overall survival (OS) and progression-free survival (PFS). A decrease in T/S ratio was seen in all patients on {sup 68}Ga-DOTANOC PET scans performed after {sup 90}Y-RE. Nine patients were classified as responders and six as nonresponders. The mean OS in all patients was 31.0 months. Responders had a significantly (p < 0.001) longer OS (mean 36.0 ± 2.5 months) and PFS (mean 29.7 ± 3.4 months) than nonresponders. In a multivariate analysis, none of the other examined variables including age, unilobar vs. bilobar locations, bilirubin levels, radiological response or the presence of extrahepatic disease significantly predicted patient outcome. Molecular response assessed with {sup 68}Ga-DOTANOC PET might be a useful predictor of survival in patients affected by NET liver metastases treated with {sup 90}Y-RE. (orig.)

  16. Molecular response assessed by 68Ga-DOTANOC and survival after 90Y microsphere therapy in patients with liver metastases from neuroendocrine tumours

    We investigated the prognostic role of 68Ga-DOTANOC in patients affected by hepatic metastases from neuroendocrine tumours (NET) undergoing 90Y radioembolization (90Y-RE). A group of 15 consecutive patients with unresectable NET liver metastases underwent 68Ga-DOTANOC PET at baseline and 6 weeks after 90Y-RE. Molecular response was defined as a reduction of >50 % in the tumour-to-spleen ratio (ΔT/S). The patients were divided into two groups (responders with ΔT/S >50 % and nonresponders with ΔT/S <50 %) Patients were followed up by imaging and laboratory tests every 3 months until death or for at least 36 months following 90Y-RE. Statistical analysis was performed to identify factors predicting overall survival (OS) and progression-free survival (PFS). A decrease in T/S ratio was seen in all patients on 68Ga-DOTANOC PET scans performed after 90Y-RE. Nine patients were classified as responders and six as nonresponders. The mean OS in all patients was 31.0 months. Responders had a significantly (p < 0.001) longer OS (mean 36.0 ± 2.5 months) and PFS (mean 29.7 ± 3.4 months) than nonresponders. In a multivariate analysis, none of the other examined variables including age, unilobar vs. bilobar locations, bilirubin levels, radiological response or the presence of extrahepatic disease significantly predicted patient outcome. Molecular response assessed with 68Ga-DOTANOC PET might be a useful predictor of survival in patients affected by NET liver metastases treated with 90Y-RE. (orig.)

  17. Electrochemical separation of 90-yttrium in the electrochemical 90Sr/90Y generator and its use for radiolabelling of DOTA-conjugated somatostatin analog [DOTA0, Tyr3] octreotate

    Petrović Đorđe Ž.

    2012-01-01

    Full Text Available Radiopharmaceuticals based on 90Y are widely used in the treatment of malignant deseases. In order to meet the requirements for their future application, a 90Sr/90Y generator was developed and 90Y eluted from this locally produced generator was used for the radiolabelling of the DOTA-conjugated somatostatin analog [DOTA0,Tyr3] octreotate and the preparation of [90Y-DOTA0,Tyr3] octreotate (90Y-DOTATATE for peptide receptore radionuclide therapy. 90Sr/90Y generator was based on the electrochemical separation of 90Y from 90Sr in a two-cycle electrolysis procedure. Three electrode cells were used to perform both electrolyses. In both cycles, working electrodes were kept on constant potential. The pH of the solution was adjusted to 2.7 of the value before the electrolyses. The radionuclidic purity of the 90Y solution was analysed by ITLC and extraction paper chromatography. The labelling of peptide (100 mg DOTATATE with 90YCl3 was performed at 95°C for 30 minutes. Radiochemical purity was determined by HPLC and chromatographic separation, using a solid SepPak C-18 column. Results obtained confirmed the efficiency of our electrochemical separation technique and quality control methods for 90Y. The achieved efficiency of the 90Sr/90Y generator above 96% of the theoretical value represents a good basis for the further development of this generator. The labelling of the DOTATATE with 90Y exhibited a high efficiency, too: there was less than 1% of 90Y3+in the 90Y-DOTATATE.

  18. Preparation of highly concentrated super-hot (γ-32P)ATP using small-scale ion-exchange chromatography

    In order to obtain a highly concentrated, pure and super-hot [γ-32P]ATP, we improved the purification method of super-hot [γ-32P]ATP which was synthesized by the method of Johnson and Walseth (1979). The super-hot [γ-32P]ATP was synthesized in a relatively large volume (2 ml) of reaction mixture and purified using semi-micro scale anion exchange chromatography (Dowex 1 x 2, 60 - 70 μl column volume). In combination with washing the reaction product with certain organic solvents, this chromatography technique makes it possible to obtain a highly concentrated and pure super-hot [γ-32P]ATP (approx. 7000 Ci/mmol; 20 - 30 mCi/ml) from [32P]Pi of any commercial source in a good yield. (author)

  19. Design and construction of a prototype for the obtention of 32P

    The 32 P are a pure emitting radioisotope of maximum energy of 1.71 MeV with half life of 14.28 days that he has applications in the industry, in agriculture, in medicine, in biology and in ecology (6,11,12,13,17,21,22,23,24,25,26,27,28,29,30,31,32 33).The 32 P can be used in the industry like radiotracer in the investigation of some operations and processes and as element of measurement of some industrial meters. In agriculture is used as radiotracer (29) in the investigation of diverse biological processes that have to do with the production of diverse nutritious products. In medicine has uses but very therapeutic mainly in the treatment of some become cancerous (28, 31, 25, 27) in the diagnosis of blood disorders (24) and like part of materials of production of aortic prosthesis (6). The 32 P are also used in the molecular investigation in biology and in genetics (33), and in studies of ecosystems (32) and of DNA (22). One can obtain the 32 P by means of diverse nuclear reactions depending on the material used as matter it prevails, since it doesn't exist in the nature. But anyone in the ways of obtaining it it should imply a process of radiochemical separation that involves so many steps like they are required, depending on the material used as matter prevails, of the purity with which he wants himself to obtain and of the resources that it has available. The objective of this work was design, to build and to prove a prototype to obtain the 32 P to leave of the irradiation of S α with fast neutrons at experimental level, which implies also to design a process that contemplates diverse stages and procedures for each one of them. The process was outlined in five stages: matter purification prevails, preparation of irradiation capsules, irradiation of irradiation capsules, transport and opening capsules of irradiation and radiochemical separation. In the last stage it was where uses the prototype of radiochemical separation in basis to the outlined process and

  20. Radioembolization of hepatocarcinoma with 90Y glass microspheres: development of an individualized treatment planning strategy based on dosimetry and radiobiology

    The aim of this study was to optimize the dosimetric approach and to review the absorbed doses delivered, taking into account radiobiology, in order to identify the optimal methodology for an individualized treatment planning strategy based on 99mTc-macroaggregated albumin (MAA) single photon emission computed tomography (SPECT) images. We performed retrospective dosimetry of the standard TheraSphere registered treatment on 52 intermediate (n = 17) and advanced (i.e. portal vein thrombosis, n = 35) hepatocarcinoma patients with tumour burden < 50 % and without obstruction of the main portal vein trunk. Response was monitored with the densitometric radiological criterion (European Association for the Study of the Liver) and treatment-related liver decompensation was defined ad hoc with a time cut-off of 6 months. Adverse events clearly attributable to disease progression or other causes were not attributed to treatment. Voxel dosimetry was performed with the local deposition method on 99mTc-MAA SPECT images. The reconstruction protocol was optimized. Concordance of 99mTc-MAA and 90Y bremsstrahlung microsphere biodistributions was studied in 35 sequential patients. Two segmentation methods were used, based on SPECT alone (home-made code) or on coregistered SPECT/CT images (IMALYTICS trademark by Philips). STRATOS trademark absorbed dose calculation was validated for 90Y with a single time point. Radiobiology was used introducing other dosimetric variables besides the mean absorbed dose D: equivalent uniform dose (EUD), biologically effective dose averaged over voxel values (BEDave) and equivalent uniform biologically effective dose (EUBED). Two sets of radiobiological parameters, the first derived from microsphere irradiation and the second from external beam radiotherapy (EBRT), were used. A total of 16 possible methodologies were compared. Tumour control probability (TCP) and normal tissue complication probability (NTCP) were derived. The area under the curve (AUC

  1. Pulmonary tissue and surfactant changes in Syrian hamsters after inhalation of 90Y in fused clay particles

    Syrian hamsters received an average of 6900 rads to lung following inhalation of an aerosol of 90Y in fused clay. Animals were sacrificed in groups of four from 2 to 33 weeks post-inhalation. Controls were exposed to stable Zr in fused clay. By 8 weeks post-inhalation, total lung lipids were significantly increased (28 mg/100 g Body Weight) above the mean of the control group (21 mg/100 g B.W.) but decreased toward control levels for the remainder of the experiment. Lipid content of lung surfactant obtained by pulmonary lavage decreased from 0.93 mg/100 g B.W. to an average of 0.63 mg/100 g B.W. but more importantly, the highly surface active acetone precipitable phospholipids decreased from 0.57 +- 0.12 mg/100 g B.W. to 0.33 +- 0.09 mg/100 g B.W. during the experimental period. This change in surfactant lipid content was reflected in alterations in the surface tension properties of the pulmonary surfactant system which is intimately involved in pulmonary dynamics and alveolar stability. (U.S.)

  2. Internal radiotherapy. 2. Treatment of non-hodgkin's lymphoma with 90Y-labeled anti-CD20 monoclonal antibody

    This paper describes recent trends of radioimmunotherapy using specific monoclonal antibodies against tumors, its principle and outcomes, with major emphasis on the title. When the antibodies like rituximab (rit), anti-CD20 antibody against B-cell malignant lymphoma, are labeled by a certain radioisotope, they become more active in specifically killing malignant cells by their immune cytotoxicity following binding plus lethal effect of radiation (beta ray). In Western areas, 90Y-labeled (ibritumomab, ibrit) or 131I-labeled rit is now available for the purpose. The efficacy of the former ibrit in the phase III trial has been reported to be 83%, in contrast to that of rit alone, 56%, with the similar safety to rit, in out-patients with the tumor. The protocol for the therapy is consisted from the first therapy with intravenous rit and imaging by 111In-labeled rit on day 1 and the second with the rit and ibrit (0.4 mCi/kg) on day 8. Patients are excluded from the latter therapy when the image by 111In shows the abnormal distribution in the liver and bone marrow. In Japan, phase I/II clinical trials of ibrit have been conducted to confirm its efficacy and safety and the agent is to be approved within this year. The radioimmunotherapy is thought to become more popular. (T.I.)

  3. Absorbed dose distribution patterns in the beagle thorax after inhalation of 90Sr--90Y fused clay particles. II

    This experiment was designed to examine absorbed dose patterns in the Beagle dog thorax after inhalation of polydisperse fused montmorillonite clay particles labeled with 90Sr-90Y. Sixteen dogs were exposed nose-only to achieve initial lung burdens of 91 to 200 μCi. Dogs are being serially sacrificed and photographic data and autoradiographic data produced for a series of parallel planes approximately 1 cm apart through the thorax. Data analysis will include definition of absorbed dose patterns in the Beagle thorax at 8 days, 64 days, 1 year, 2 years, and 3 years post-exposure. To date, 8-day, 64-day, and 1-year animals have been sacrificed and partially analyzed. The result of this experiment will be a better understanding of deposition and absorbed dose patterns and allow a better correlation between absorbed dose and biological response for Beagle dogs exposed to relatively insoluble aerosols contaminated by energetic beta-emitting radionuclides. In addition, results will allow quantitating anomalies in deposition patterns, such as the striated pattern near ribs previously observed in this laboratory. (U.S.)

  4. Radioactive sputter cathodes for {sup 32}P plasma-based ion implantation

    Fortin, M.A. [INRS-EMT (Universite du Quebec), 1650 boul. Lionel Boulet, Varennes, Quebec, J3X 1S2 (Canada)]. E-mail: fortin@bms.uu.se; Paynter, R.W. [INRS-EMT (Universite du Quebec), 1650 boul. Lionel Boulet, Varennes, Quebec, J3X 1S2 (Canada); Sarkissian, A. [Plasmionique Inc., 1650 boul. Lionel Boulet, Varennes, Quebec, J3X 1S2 (Canada); Stansfield, B.L. [INRS-EMT (Universite du Quebec), 1650 boul. Lionel Boulet, Varennes, Quebec, J3X 1S2 (Canada)

    2006-05-15

    The development of clinical treatments involving the use of beta-emitting millimetric and sub-millimetric devices has been a continuing trend in nuclear medicine. Implanted a few nanometers below the surface of endovascular implants, seeds or beads, beta-emitting radioisotopes can be used in a variety of biomedical applications. Recently, new technologies have emerged to enable the rapid and efficient activation of such devices. A pulsed, coaxial electron cyclotron resonance plasma reactor was designed and tested to demonstrate the feasibility of plasma-based radioactive ion implantation (PBRII). It has been shown that such plasma reactors allow for the implantation of radioisotopes ({sup 32}P) into biomedical devices with higher efficiencies than those obtained with conventional ion beams. Fragments containing radioactive atoms are produced in the implanter by means of a negatively biased solid sputter cathode that is inserted into an argon plasma. Dilute orthophosphoric acid solutions (H{sub 3} {sup 32}PO{sub 4}) are used for the fabrication of flat sputter targets, since they offer a high radioisotope content. However, the aggregation of the radioactive solute into highly hygroscopic ring-like deposits rather than flat, thin radioactive films is observed on certain substrates. This article describes the effect of this nonuniform distribution of the radioisotopes on the efficiency of PBRII, and presents a technique which enables a better distribution of {sup 32}P by coating the substrates with iron. The iron coating is shown to enable optimal radioisotope sputtering rates, which are essential in {sup 32}P-PBRII for the efficient activation of millimetric biomedical devices such as stents or coils.

  5. Studies on the preparation and evaluation of colloidal chromic phosphate - 32P for possible therapeutic use

    Radionuclide therapy has become the focus of recent attention in nuclear medicine, thanks to the emergence of new therapeutic radionuclides as well as the known prospects of local instillation approach and the exciting promise of targeted therapy concept. This has naturally led to a revived interest in the use of established products of earlier generation also, for example 32P compounds. In response to such a demand of nuclear medicine physicians in India, 32P labelled colloidal chromic phosphate suspension (CCPS) was prepared by suitable modifications to a reported procedure. 51Cr was used as tracer for initial studies of standardisation, in order to avail the benefits of relatively greater ease and higher efficiency of assay of gamma activity at low levels. Recovery of the colloid and purification were accomplished by dialysis leading to about 60% radiochemical (RC) yield. The RC purity of the CCPS formulated in 30% dextrose solution was over 98% as assessed by paper chromatography. The particle size was below 5μM, with nearly 99% of the particles present in the size range of 0.6-2.5 μM. The stability of the colloid was found to be not less than 7 days, in terms of soluble phosphate content of the CCPS. The consistency of biological behaviour of CCPS was attempted to be studied by i.v. administration in test animals, although the envisaged end use is only by local instillation. The animal studies revealed prominent lung uptake ( 70%) indicating the presence of >10μM particles formed in vivo, most probably due to agglomeration in serum. The easy reliable preparation of CCPS in acceptable yield, purity and particle size distribution demonstrated in the present study, considered along with the added advantages of abundant, economic availability and convenient production logistics of no-carrier-added 32P, would merit further investigations on CCPS and similar *M(III)-phosphate colloids for possible therapeutic applications. (author)

  6. A rehabilitated greenhouse for 32P radioisotope studies and training in Seibersdorf

    Full text: Two major activities of the Soil Science Unit in Seibersdorf are to develop and test isotope methodologies and guidelines to support CRPs and TCPs, and to conduct training to strengthen the analytical and professional capabilities of Member States. This is achieved through regional, interregional and laboratory training. Whereas development of methodologies and guidelines for stable isotopes such as (13C, 15N, 18O) in the Unit has advanced in the area of soil-water-nutrient plant continuum, the use of isotopes of phosphorus (32P, 33P) has received little attention in the Unit during the last ten years. The main reason for this has been the lack of a greenhouse and laboratories, that conform to the required safety standards for conducting experiments because of the radioactive nature of the phosphorus isotopes. In most of the developing countries where P bio-availability in the soil is low, the use of 32P and 33P is crucial to understanding P dynamics in soil, and to quantify P pools that can be mobilized by crop genotypes with superior nutrient resource recovery. In response to a demand from Member States to train fellows in the use of P isotopes, and the need to conduct research to support the on-going CRP on Selection and Evaluation of Food (Cereal and Legume) Crop Genotypes Tolerant to Low Nitrogen and Phosphorus Soils through the Use of Isotopic and Nuclear-related Techniques (D1.50.10), the Soil Science Unit has refurbished an old glasshouse (new ventilation and cooling systems, floor renovation etc) and a laboratory to a Type B radiation standard. Fellowship training in the use of 32P and 33P radio-isotopes for soil P dynamics and P nutrition experiments, safety precautions, sample preparation, measurements using a liquid scintillation counter and calculations, will now be conducted at the Soil Science Unit in Seibersdorf. (author)

  7. Radioactive sputter cathodes for 32P plasma-based ion implantation

    The development of clinical treatments involving the use of beta-emitting millimetric and sub-millimetric devices has been a continuing trend in nuclear medicine. Implanted a few nanometers below the surface of endovascular implants, seeds or beads, beta-emitting radioisotopes can be used in a variety of biomedical applications. Recently, new technologies have emerged to enable the rapid and efficient activation of such devices. A pulsed, coaxial electron cyclotron resonance plasma reactor was designed and tested to demonstrate the feasibility of plasma-based radioactive ion implantation (PBRII). It has been shown that such plasma reactors allow for the implantation of radioisotopes (32P) into biomedical devices with higher efficiencies than those obtained with conventional ion beams. Fragments containing radioactive atoms are produced in the implanter by means of a negatively biased solid sputter cathode that is inserted into an argon plasma. Dilute orthophosphoric acid solutions (H332PO4) are used for the fabrication of flat sputter targets, since they offer a high radioisotope content. However, the aggregation of the radioactive solute into highly hygroscopic ring-like deposits rather than flat, thin radioactive films is observed on certain substrates. This article describes the effect of this nonuniform distribution of the radioisotopes on the efficiency of PBRII, and presents a technique which enables a better distribution of 32P by coating the substrates with iron. The iron coating is shown to enable optimal radioisotope sputtering rates, which are essential in 32P-PBRII for the efficient activation of millimetric biomedical devices such as stents or coils

  8. Detection of irradiation induced modifications in foodstuff DNA using 32p post-labelling

    DNA post-labelling has been used successfully to detect damage to DNA caused by a range of damaging agents. The assay results in a fingerprint of changes induced in DNA which might, in principle, be useful as a test for the detection of the irradiation of foods. The authors present their DNA extraction and 32p post-labelling methods from chicken or cooked prawn samples and their analysis method (High Performance liquid chromatography). It's hoped that these results could form the basis of a test to detect if foods have been irradiated

  9. Studies on absorption and translocation of phosphorus using radioactive superphosphate (32P) in coffee plants

    Absorption and translocation (downward as well as lateral) of phosphate ions from foliar applied superphosphate solution (pH 6.5, labelled with 32P) were considerably higher in Coffea arabica L. cv.S. 795 than in Coffea canephera Pierre cv.S. 274 plants. The differential absorption and translocation of phosphate to various plant parts and its accumulation in enlarged flowers buds suggest the possibility that the requirement of phosphorus for flower bud enlargement and blossom (anthesis) is higher in arabica than in robusta. (auth.)

  10. Targeted radionuclide therapy with RAFT-RGD radiolabelled with {sup 90}Y or {sup 177}Lu in a mouse model of αvβ3-expressing tumours

    Bozon-Petitprin, A.; Bacot, S.; Ahmadi, M.; Marti-Batlle, D.; Perret, P.; Broisat, A.; Riou, L.M. [INSERM, U1039, Grenoble (France); Universite de Grenoble, UMR-S1039, Grenoble (France); Gauchez, A.S.; Bourre, J.C.; Fagret, D.; Vuillez, J.P. [INSERM, U1039, Grenoble (France); Universite de Grenoble, UMR-S1039, Grenoble (France); CHRU Grenoble, Hopital Michallon, Service de Medecine Nucleaire, Grenoble (France); Claron, M.; Boturyn, D. [CNRS, UMR 5250, Departement de Chimie Moleculaire, Grenoble (France); Ghezzi, Catherine [INSERM, U1039, Grenoble (France); Universite de Grenoble, UMR-S1039, Grenoble (France); INSERM U1039, Radiopharmaceutiques biocliniques, Batiment Jean Roget, Domaine de la Merci, Faculte de Medecine, La Tronche (France)

    2014-08-28

    The αvβ3 integrin plays an important role in tumour-induced angiogenesis, tumour proliferation, survival and metastasis. The tetrameric RGD-based peptide, regioselectively addressable functionalized template-(cyclo-[RGDfK]){sub 4} (RAFT-RGD), specifically targets the αvβ3 integrin in vitro and in vivo. The aim of this study was to evaluate the therapeutic potential of RAFT-RGD radiolabelled with β{sup -} emitters in a nude mouse model of αvβ3 integrin-expressing tumours. Biodistribution and SPECT/CT imaging studies were performed after injection of {sup 90}Y-RAFT-RGD or {sup 177}Lu-RAFT-RGD in nude mice subcutaneously xenografted with αvβ3 integrin-expressing U-87 MG cells. Experimental targeted radionuclide therapy with {sup 90}Y-RAFT-RGD or {sup 177}Lu-RAFT-RGD and {sup 90}Y-RAFT-RAD or {sup 177}Lu-RAFT-RAD (nonspecific controls) was evaluated by intravenous injection of the radionuclides into mice bearing αvβ3 integrin-expressing U-87 MG tumours of different sizes (small or large) or bearing TS/A-pc tumours that do not express αvβ3. Tumour volume doubling time was used to evaluate the efficacy of each treatment. Injection of 37 MBq of {sup 90}Y-RAFT-RGD into mice with large αvβ3-positive tumours or 37 MBq of {sup 177}Lu-RAFT-RGD into mice with small αvβ3-positive tumours caused significant growth delays compared to mice treated with 37 MBq of {sup 90}Y-RAFT-RAD or 37 MBq of {sup 177}Lu-RAFT-RAD or untreated mice. In contrast, injection of 30 MBq of {sup 90}Y-RAFT-RGD had no effect on the growth of αvβ3-negative tumours. {sup 90}Y-RAFT-RGD and {sup 177}Lu-RAFT-RGD are potent agents targeting αvβ3-expressing tumours for internal targeted radiotherapy. (orig.)

  11. Somatostatin-based radiotherapy with [90Y-DOTA]-TOC in neuroendocrine tumors: long-term outcome of a phase I dose escalation study

    Marincek Nicolas

    2013-01-01

    Full Text Available Abstract Background We describe the long-term outcome after clinical introduction and dose escalation of somatostatin receptor targeted therapy with [90Y-DOTA]-TOC in patients with metastasized neuroendocrine tumors. Methods In a clinical phase I dose escalation study we treated patients with increasing [90Y-DOTA]-TOC activities. Multivariable Cox regression and competing risk regression were used to compare efficacy and toxicities of the different dosage protocols. Results Overall, 359 patients were recruited; 60 patients were enrolled for low dose (median: 2.4 GBq/cycle, range 0.9-7.8 GBq/cycle, 77 patients were enrolled for intermediate dose (median: 3.3 GBq/cycle, range: 2.0-7.4 GBq/cycle and 222 patients were enrolled for high dose (median: 6.7 GBq/cycle, range: 3.7-8.1 GBq/cycle [90Y-DOTA]-TOC treatment. The incidences of hematotoxicities grade 1–4 were 65.0%, 64.9% and 74.8%; the incidences of grade 4/5 kidney toxicities were 8.4%, 6.5% and 14.0%, and the median survival was 39 (range: 1–158 months, 34 (range: 1–118 months and 29 (range: 1–113 months. The high dose protocol was associated with an increased risk of kidney toxicity (Hazard Ratio: 3.12 (1.13-8.59 vs. intermediate dose, p = 0.03 and a shorter overall survival (Hazard Ratio: 2.50 (1.08-5.79 vs. low dose, p = 0.03. Conclusions Increasing [90Y-DOTA]-TOC activities may be associated with increasing hematological toxicities. The dose related hematotoxicity profile of [90Y-DOTA]-TOC could facilitate tailoring [90Y-DOTA]-TOC in patients with preexisting hematotoxicities. The results of the long-term outcome suggest that fractionated [90Y-DOTA]-TOC treatment might allow to reduce renal toxicity and to improve overall survival. (ClinicalTrials.gov number NCT00978211.

  12. Treatment with tandem [{sup 90}Y]DOTA-TATE and [{sup 177}Lu]DOTA-TATE of neuroendocrine tumours refractory to conventional therapy

    Seregni, E.; Maccauro, M.; Chiesa, C.; Pascali, C.; Lorenzoni, A.; Bogni, A.; Coliva, A.; Bombardieri, E. [Fondazione IRCCS Istituto Nazionale Tumori, Nuclear Medicine, Milan (Italy); Mariani, L.; Vullo, S.Lo [Fondazione IRCCS Istituto Nazionale Tumori, Statistics and Biometry Unit, Milan (Italy); Mazzaferro, V. [Fondazione IRCCS Istituto Nazionale Tumori, Surgery and Liver Transplantation, Milan (Italy); De Braud, F.; Buzzoni, R. [Fondazione IRCCS Istituto Nazionale Tumori, Medical Oncology, Milan (Italy); Milione, M. [Fondazione IRCCS Istituto Nazionale Tumori, Pathology Department, Milan (Italy)

    2014-02-15

    Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues has been demonstrated to be an effective therapeutic option in patients with disseminated neuroendocrine tumours (NET). Treatment with tandem [{sup 90}Y]DOTA-TATE and [{sup 177}Lu]DOTA-TATE may improve the efficacy of PRRT without increasing the toxicity. In a phase II study we evaluated the feasibility of combined PPRT with a high-energy beta emitter ({sup 90}Y) and a medium-energy beta/gamma emitter ({sup 177}Lu) in patients with metastatic NET refractory to conventional therapy. A group of 26 patients with metastatic NET were treated with four therapeutic cycles of alternating [{sup 177}Lu]DOTA-TATE (5.55 GBq) and [{sup 90}Y]DOTA-TATE (2.6 GBq). A dosimetric evaluation was carried out after administration of [{sup 177}Lu]DOTA-TATE to calculate the absorbed doses in healthy organs. The acute and long-term toxicities of repeated treatment were analysed. PRRT efficacy was evaluated according to RECIST. Administration of tandem [{sup 90}Y]DOTA-TATE and [{sup 177}Lu]DOTA-TATE induced objective responses in 42.3 % of patients with metastatic NET with a median progression-free survival longer than 24 months. Of patients with pretreatment carcinoid syndrome, 90 % showed a symptomatic response or a reduction in tumour-associated pain. The cumulative biologically effective doses (BED) were below the toxicity limit in the majority of patients, in the absence of renal function impairment The results of our study indicates that combined [{sup 90}Y]DOTA-TATE and [{sup 177}Lu]DOTA-TATE therapy is a feasible and effective therapeutic option in NET refractory to conventional therapy. Furthermore, the absence of kidney damage and the evaluated cumulative BEDs suggest that increasing the number of tandem administrations is an interesting approach. (orig.)

  13. Treatment with tandem [90Y]DOTA-TATE and [177Lu]DOTA-TATE of neuroendocrine tumours refractory to conventional therapy

    Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues has been demonstrated to be an effective therapeutic option in patients with disseminated neuroendocrine tumours (NET). Treatment with tandem [90Y]DOTA-TATE and [177Lu]DOTA-TATE may improve the efficacy of PRRT without increasing the toxicity. In a phase II study we evaluated the feasibility of combined PPRT with a high-energy beta emitter (90Y) and a medium-energy beta/gamma emitter (177Lu) in patients with metastatic NET refractory to conventional therapy. A group of 26 patients with metastatic NET were treated with four therapeutic cycles of alternating [177Lu]DOTA-TATE (5.55 GBq) and [90Y]DOTA-TATE (2.6 GBq). A dosimetric evaluation was carried out after administration of [177Lu]DOTA-TATE to calculate the absorbed doses in healthy organs. The acute and long-term toxicities of repeated treatment were analysed. PRRT efficacy was evaluated according to RECIST. Administration of tandem [90Y]DOTA-TATE and [177Lu]DOTA-TATE induced objective responses in 42.3 % of patients with metastatic NET with a median progression-free survival longer than 24 months. Of patients with pretreatment carcinoid syndrome, 90 % showed a symptomatic response or a reduction in tumour-associated pain. The cumulative biologically effective doses (BED) were below the toxicity limit in the majority of patients, in the absence of renal function impairment The results of our study indicates that combined [90Y]DOTA-TATE and [177Lu]DOTA-TATE therapy is a feasible and effective therapeutic option in NET refractory to conventional therapy. Furthermore, the absence of kidney damage and the evaluated cumulative BEDs suggest that increasing the number of tandem administrations is an interesting approach. (orig.)

  14. Sampling system for pulsed signals. Study of the radioactive lifetimes of excited 32P1/2 and 32P3/2 states of Na, excited by a tunable dye laser

    A system for sampling and averaging repetitive signals in the order of nanoseconds is discussed. The system uses as storage memory a multichannel analyzer operating in multi scaling mode. This instrument is employed for the measurement of atomic level lifetimes using a dye laser to excite the atoms and is applied to the study of lifetimes of the 32P1/2 and 32P3/2 states of sodium. (Author) 32 refs

  15. Intraperitoneal distribution of 32P-chromic phosphate suspension in the dog

    Intraperitoneal administration of radioactive chromic phosphate suspension is receiving renewed attention as a therapeutic treatment to limit metastatic dissemination of ovarian carcinoma. Our study utilized mongrel dogs to approximate the uptake and distribution of 3.0 millicuries 32P-chromic phosphate suspension administered intraperitoneally (IP). Lymph nodes, omentum, retroperitoneum, peritoneum, diaphragm, abdominal wall muscle, pleura, spleen, liver, kidneys, lung, small intestine, and blood were sampled for liquid scintillation counting and autoradiography. Whole blood showed the least activity (1800 cpm/100 lambda at day one, declining to 2800 cpm/100 lambda by day 16). Omentum and diaphragm maintained the greatest concentrations (183 x 106 dpm/g and 4 x 106 dpm/g respectively). These initial high values were 100 times greater than the highest values found for the small intestine, abdominal wall muscle, mediastinal and retroperitoneal lymph nodes and pleura. The peritoneum increased in specific activity until day three (5.9 x 106 dpm/g) and then rapidly declined. Our results show that following IP administration to the dog, 32P suspension is associated with the serous membranes of the peritoneal cavity (most notably omentum, diaphragm, peritoneum, and retroperitoneum). This distribution could be valuable in adjuvant tumor therapy since serosal surfaces of the peritoneum (both visceral and parietal) and the omentum are the most common sites of tumor metastases associated with ovarian carcinoma

  16. Detection of oxidative damage by 32P-postlabelling: 8-hydroxydeoxyguanosine as a marker of exposure.

    Povey, A C; Wilson, V L; Weston, A; Doan, V T; Wood, M L; Essigmann, J M; Shields, P G

    1993-01-01

    Human exposure to reactive oxygen species is unavoidable and has been implicated in the etiology of a number of human diseases. This exposure results in the formation of various modified DNA bases: the promutagenic lesion 8-hydroxydeoxyguanosine (8OHdG), in particular, is a major product. We have developed an assay using ion-pair HPLC and 32P-postlabelling to quantify 8OHdG in human DNA with high specificity and sensitivity. An internal standard is used to account for variations in labelling efficiency. Chemically synthesized 8OHdG 3'-monophosphate and 5'-monophosphate standards were used to optimize the HPLC-32P-postlabelling and TLC separative steps, respectively. The assay was validated using known ratios of 8OHdG to normal nucleotides. The limit of detection is in the range of one 8OHdG residue per 10(6)-10(7) dG residues. Using this procedure, 8OHdG levels of 16-35 8OHdG adducts per 10(5) dG residues have been found in leukocytes isolated from patients who received 180-200 cGy of ionizing radiation. These levels were 2-4-fold greater than those found in an unexposed individual. Since 8OHdG may be formed during DNA extraction and digestion, current procedures for measuring background levels are discussed. PMID:8225472

  17. Multiple DNA adducts in lymphocytes of smokers and nonsmokers determined by 32P-postlabeling analysis

    Identification of DNA adducts in peripheral lymphocytes could serve as a means of monitoring human exposure to potential genotoxic agents. In the study, DNA from peripheral lymphocytes of smokers and nonsmokers was examined for adducts by the P1 nuclease 32P-post-labeling technique. Thin layer chromatography (TLC) maps from both groups revealed multiple DNA adducts which ranged from no adducts for one individual to six adducts for a different individual. The total DNA adduct concentrations were approximately one adduct in 10 to the seventh-10 to the eighth power normal nucleotides. Comparison of the adduct TLC profiles revealed individual variation in both pattern and level of DNA adducts. The type and amount of adduct was not influenced by smoking history and remained unchanged in four out of six subjects who were resampled after a one month interval. One adduct detected in lymphocyte DNA co-migrated on TLC with an adduct derived by in vitro incubation of lymphocytes with benzo(a)pyrene (B(a)P). The 3H-nucloside values were consistent with values obtained by 32P-postlabeling of the same sample (correlation coefficient of 0.88). No relationship was apparent between the capacity of lymphocytes to form a (3H)-B(a)P-derived adduct in vitro and the concentration of the adduct, or total adducts present in untreated lymphocytes

  18. Histological study of the early stage of 32P-induced experimental osteosarcoma

    32P radioisotope as an orthophosphate solution was injected intraperitoneally into C.F. Wistar strain albino rats to induce primary osteosarcoma. To capture the early stage of tumor formation, bone scintigraphy employing technetium-99m ethane-1-hydroxy-1,1-diphosphonate and soft radiography were conducted from week 16 after the beginning of 32P administration. The histological findings were compared at the stages when both the soft radiogram and bone scintigram showed no abnormalities (Group A), the soft radiogram showed no abnormality but the bone scintigram revealed abnormal deposition (Group B), similar findings to those in Group B were obtained but 2 weeks later (Group C), and both the soft radiogram and bone scintigram were positive (Group D). The histological picture before osteosarcoma formation demonstrated a marked reduction of bone marrow tissue, many irregular bone trabeculae in the metaphysis due to abnormal endochondral ossification, and zonal obliteration of the medullary cavity in the diaphysis. The histological findings at the ultra-early stage of osteosarcoma formation included irregularity in the growing cartilage zone and highly atypical osteoblast-like cells among the irregular trabeculae. Osteoid formation occurred 2 weeks later. In conclusion, we were able to observe the morphological changes of the osteosarcoma tissue at a very early stage of tumor formation. (author)

  19. 32P-adduct assay: Comparative recoveries of structurally diverse DNA adducts in the various enhancement procedures

    A (32)P-adduct assay for the measurement of low levels (1 adduct per 10(sup 7) nucleotides) of binding of carcinogens to DNA has been reported previously. In this procedure, DNA is enzymatically hydrolyzed to 3'-monophosphates of normal nucleosides and adducts, which are 5'-(32)P-labeled by T4 polynucleotide kinase and (lambda(32)P)ATP. Labeled adducts are resolved by TLC. Enrichment of adducts by extraction in 1-butanol or digestion with nuclease P1 prior to (32)P-labeling, however, increased the sensitivity of detection for many adducts to a level of 1 per 10(sup 9-10) nucleotides, although adduct recovery particularly in the latter assay depended on the chemical nature of adducts. The observation that chemical structure of an adduct may be detrimental in its recovery in the enzyme- and extraction-mediated enrichment procedures may serve as a probe in the structural characterization of adducts of unknown carcinogens

  20. Co-isolation of in vivo 32P-labeled specific transcripts and DNA without phenol extraction of nuclease digestion

    A method is described for isolation and quantitation of specific intact transcripts, for which a hybridization probe is available, from 32P-labeled bacterial cells. The RNA is extracted in the absence of R Nase activity by incorporating an inert, physically removable R Nase inhibitor throughout the spheroplasting, cell lysis, and pronase digestion steps. [/sup 32/P]RNA is separated from [32P]DNA, without recourse to phenol extraction of DNase treatment, on a Cs2SO/sub 4-/HCONH2 step gradient in which the precipitated RNA forms a sharp band. Specific transcripts are purified from [32P]RNA by physical separation of the transcript and hybridization probe using gel-exclusion chromatography. The gentleness of this technique enables the co-isolation of DNA and can facilitate the analysis of covalently joined RNA-DNA replication intermediates

  1. Effect of varying carbohydrate levels on the uptake and translocation of 32P in Eragrostis curvula (Schrad.) Nees

    The uptake and subsequent translocation of 32P among root, crown and leaf tissues of Eragrostis curvula were investigated in plants with varying carbohydrate levels. Plants were depleted of carbohydrates by being subjected to 3 days of continuous darkness and by defoliation. Plant roots were introduced to nutrient solutions containing 32P, at 0, 3, 6, 9, 12, 15 and 21 days after the depletion treatments. Initially, plants depleted of carbohydrates absorbed and translocated less 32P than the controls. Subsequently, uptake and translocation increased probably to restore the pools of phosphate to levels prior to the depletion treatments. Increased 32P uptake and translocation were related to an adequate supply of reserve carbohydrates

  2. Determination of phosphorous in cannabis by neutron activation analysis - measurement of 32P Cerenkov radiation by liquid scintillaton spectrometer

    Thermal neutron activaton analysis with measurement of 32P Cerenkov radiation by liquid scintillation spectrometer was used to determine phosphorus in cannabis. After irradiation of the sample, wet ashing was carried out with conc. nitric acid and 70% perchloric acid. The solution in l M perchloric acid transferred to an inorganic ion-exchange column containing acid aluminium oxide and phosphorus was quantitatively eluted with 1M hydrofluoric acid. The 32P radioactivity of each fraction of the eluate was counted with Cerenkov radiation by a liquid scintillation spectrometer from 2 to 7 weeks after the irradiation. The activity curve decayed with 32P half-life. The isotope channel ratio technique was applied for the quench correction. The optimal experimental conditions for chemical separation of phosphorus and for measuring the 32P Cerenkov radiation were also examined. (Author)

  3. Evaluation of EGS4/PRESTA multiple-scattering algorithms for 90Sr/90Y intravascular brachytherapy dosimetry

    The purpose of this work is to evaluate the EGS4/PRESTA electron multiple-scattering (MS) algorithms for dose calculation in intravascular brachytherapy (IVBT) using a 90Sr/90Y source. The small source size and the small volume of interest in IVBT require very fine spatial resolution, which may break down the constraints of Moliere's MS theory as implemented in EGS4. The theory is accurate only when the electron step sizes are large enough to allow the number of collisions Ω0 to be much greater than e = 2.7183. When step sizes are too small to allow at least 2.7183 collisions, as may be necessitated by the fine geometry, the algorithm may switch off MS, producing dosimetric artefacts. This study showed that switching off MS could produce a dose deviation of up to 6% when the half-thickness (d/2) of the dose scoring region is comparable with the Moliere minimum step size (tmin = 2.7183). The effect of switching off MS is negligible if d/2>>tmin. For the case of Ω0>e, if the electron step sizes are chosen to allow five to 40 collisions, with increasing step size, the doses surrounding the source increase and the error decreases. On the other hand, when larger step sizes are chosen, the dose calculation voxel size must also be increased in order for the calculations to converge. A good compromise between accuracy and applicability for IVBT simulation can be made, if the thickness of the scoring region is 0.1 mm and the electron step sizes are in the range allowing 10 to 30 collisions. (author)

  4. Early post-treatment FDG PET predicts survival after 90Y microsphere radioembolization in liver-dominant metastatic colorectal cancer

    The aim of this study was to evaluate the predictive value of early metabolic response 4 weeks post-treatment using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in patients with unresectable hepatic metastases of colorectal cancer (CRC) undergoing radioembolization (RE) with 90Y-labelled microspheres. A total of 51 consecutive patients with liver-dominant metastases of CRC were treated with RE and underwent 18F-FDG PET/CT at baseline and 4 weeks after RE. In each patient, three hepatic metastases with the highest maximum standardized uptake value (SUVmax) were selected as target lesions. Metabolic response was defined as >50 % reduction of tumour to liver ratios. Survival analyses using Kaplan-Meier and multivariate analyses were performed to identify prognostic factors for overall survival (OS). Investigated baseline characteristics included age (>60 years), performance status (Eastern Cooperative Oncology Group >1), bilirubin (>1.0 mg/dl), hepatic tumour burden (>25 %) and presence of extrahepatic disease. The median OS after RE was 7 months [95 % confidence interval (CI) 5-8]; early metabolic responders (n = 33) survived longer than non-responders (p 25 % metastatic liver replacement vs 14 months (95 % CI 6-22) for the less advanced patients. Both factors (early metabolic response and low hepatic tumour burden) remained as independent predictors of improved survival on multivariate analysis. These are the first findings to show that molecular response assessment in CRC using 18F-FDG PET/CT appears feasible as early as 4 weeks post-RE, allowing risk stratification and potentially facilitating early response-adapted treatment strategies. (orig.)

  5. Comparative study on DOTA-derivatized bombesin analog labeled with 90Y and 177Lu: in vitro and in vivo evaluation

    Introduction: The aim of the study was to compare in vitro and in vivo a novel DOTA-chelated bombesin (BN) analog of the amino acid sequence, QRLGNQWAVGHLM-CONH2 (BN[2-14]NH2), labeled with 90Y and 177Lu, for its potential use in targeted radiotherapy of tumors expressing gastrin releasing peptide (GRP) receptors. The same amino acid sequence, but with different chelator, referred as BN1.1 (Gly-Gly-Cys-Aca-QRLGNQWAVGHLM-CONH2), has already been studied and reported; however, the DOTA-chelated one, suitable for labeling with M+3 type radiometals, was not yet described. Methods: The conditions for labeling of DOTA-BN[2-14]NH2 with noncarrier added 90Y and with 177Lu [specific activity (SA), 15 Ci/mg Lu] were investigated and optimized to provide 90Y-DOTA-BN[2-14]NH2 and 177Lu-DOTA-BN[2-14]NH2 of high SA. The stability of the radiolabeled compounds in human serum was evaluated over a period of 24 h. The human prostate cancer cell line PC-3, known to express GRP receptors, was used for in vitro evaluation of radiolabeled peptide affinity to GRP receptors and for assessment of cytotoxicity of both nonlabeled and radiolabeled peptide. Biodistribution accompanied by receptor blocking was studied in normal Swiss mice. Results: 90Y-DOTA-BN[2-14]NH2 and 177Lu-DOTA-BN[2-14]NH2 were obtained with radiochemical yield >98% and high SA (67.3 GBq 90Y/μmol and 33.6 GBq 177Lu/μmol, respectively). They were stable when incubated in human serum for up to 24 h. The binding affinities of DOTA-BN[2-14]NH2 and both natY- and natLu-labeled analogs to GRP receptors were high (IC50=1.78, 1.99, and 1.34 nM, respectively), especially for the natLu-DOTA-BN[2-14]NH2 complex. The cytotoxicity study of DOTA-BN[2-14]NH2 to PC-3 cells revealed an IC50=6300 nM after 72 h of exposition, while the labeled derivatives showed no significant cytotoxic effect. The internalization rate to PC-3 cells was more rapid for 177Lu-labeled peptide (84.87%) than for the 90Y-labeled one (80.79%), while the efflux

  6. Uptake of 32P and 86Rb as influenced by temperature, transpiration suppress and shading treatment in rice plants

    This study was carried out to know the uptake pattern of phosphorous and potassium in rice plants using by two radioisotopes, 32P and 86Rb as tracers for two years, 1987 and 1988. Rice plants were grown in the hydroponic culture with Yoshida's solution, and treated with different temperatures, transpiration suppress, shading, and phosphorous and potassium deletions. The uptake amount of 32P and 86Rb were increased with the increasing temperature in root sphere of rice plant, particularly remarkable increase of 86Rb uptake at 35deg C. The uptake of 32P tended to be promoted at the treatment of low air-high water temperature (17-30deg C), while that of 86Rb was not significantly differenced from different temperature treatments. The effect of transpiration on the uptake of 32P and 86Rb was extremely low. This phenomenon may suggest that the absorption be depending on active uptake rather than passive one by transpiration stream. The total carbohydrate contents of rice root were decreased by shading treatment, resulting significant reduction in the uptake of 32P and 86Rb. The uptake of 86Rb was remarkably increased in the treatment of potassium deletion, but that of 32P was not significantly increased in the delection of phosphorous

  7. Comparison of /sup 32/P therapy and sequential hemibody irradiation (HBI) for bony metastases as methods of whole body irradiation

    Aziz, H.; Choi, K.; Sohn, C.; Yaes, R.; Rotman, M.

    1986-06-01

    We report a retrospective study of 15 patients with prostate carcinoma and diffuse bone metastases treated with sodium /sup 32/P for palliation of pain at Downstate Medical Center and Kings County Hospital from 1973 to 1978. The response rates, duration of response, and toxicities are compared with those of other series of patients treated with /sup 32/P and with sequential hemibody irradiation. The response rates and duration of response are similar with both modalities ranging from 58 to 95% with a duration of 3.3 to 6 months with /sup 32/P and from 75 to 86% with a median duration of 5.5 months with hemibody irradiation. There are significant differences in the patterns of response and in the toxicities of the two treatment methods. Both methods cause significant bone marrow depression. Acute radiation syndrome, radiation pneumonitis, and alopecia are seen with sequential hemibody irradiation and not with /sup 32/P, but their incidence can be reduced by careful treatment planning. Hemibody irradiation can provide pain relief within 24 to 48 h, while /sup 32/P may produce an initial exacerbation of pain. Lower hemibody irradiation alone is less toxic than either upper hemibody irradiation or /sup 32/P treatment.

  8. Comparison of 32P therapy and sequential hemibody irradiation (HBI) for bony metastases as methods of whole body irradiation

    We report a retrospective study of 15 patients with prostate carcinoma and diffuse bone metastases treated with sodium 32P for palliation of pain at Downstate Medical Center and Kings County Hospital from 1973 to 1978. The response rates, duration of response, and toxicities are compared with those of other series of patients treated with 32P and with sequential hemibody irradiation. The response rates and duration of response are similar with both modalities ranging from 58 to 95% with a duration of 3.3 to 6 months with 32P and from 75 to 86% with a median duration of 5.5 months with hemibody irradiation. There are significant differences in the patterns of response and in the toxicities of the two treatment methods. Both methods cause significant bone marrow depression. Acute radiation syndrome, radiation pneumonitis, and alopecia are seen with sequential hemibody irradiation and not with 32P, but their incidence can be reduced by careful treatment planning. Hemibody irradiation can provide pain relief within 24 to 48 h, while 32P may produce an initial exacerbation of pain. Lower hemibody irradiation alone is less toxic than either upper hemibody irradiation or 32P treatment

  9. Studies on the effects of acetylcholine and antiepileptic drugs on 32P incorporation into phospholipids of rat brain synaptosomes

    Studies were conducted on the effects of antiepileptic drugs on the acetylcholine-stimulated 32P labeling of phospholipids in rat brain synaptosomes. Of the four antiepileptic drugs investigated in the present study, namely phenytoin, carbamazepine, phenobarbital, and valproate, only phenytoin blocked the acetylcholine-stimulated 32P labeling of phosphatidylinositol and phosphatidic acid, and the acetylcholine-stimulated breakdown of polyphosphoinositides. Phenytoin alone, like atropine alone, had no effect on the 32P labeling of phospholipids nor on the specific radioactivity of [32P]ATP. Omission of Na+ drastically reduced both the 32P labeling of synaptosomal phospholipids and the specific radioactivity of [32P]ATP and furthermore it significantly decreased the phosphoinositide effect. It was concluded that certain antiepileptic drugs, such as phenytoin, could exert their pharmacological actions through their antimuscarinic effects. In addition the finding that phenytoin, which acts to regulate NA+ and Ca2+ permeability of neuronal membranes, also inhibited the phosphoinositide effects in synaptosomes, support the conclusions that Ca2+ and Na+ are probably involved in the molecular mechanism underlying this phenomenon in excitable tissues

  10. Chromosome Studies in Patients with Polycythaemia Vera after Treatment with 32P

    The chromosomes of bone-marrow cells and blood lymphocytes of forty-six patients with polycythaemia vera were analysed to trace the sequence of events leading to the development of bone-marrow failure or 'leukaemia'. All except one of the patients had received radiophosphorus (32P). It might be expected that the yield of chromosomal aberrations of the two-break type (translocations etc.) from the low dose-rate beta radiation of 32P would be small. However, 'unstable' types of abnormality (dicentrics, fragments) and stable types (translocations, inversions, deletions) were observed in 6-25% of the blood lymphocytes; there was no evidence of clones of abnormal cells. In the majority of patients the bone marrow was predominantly normal diploid; occasional sporadic cells with 'stable' chromosomal abnormalities were seen in two-thirds of the cases, but 'unstable' aberrations were rare. In seven cases there were clones of cells characterised by deletions or translocations. All these chromosomal changes are probably radiation-induced. Clones of cells with a similar abnormality, an apparent deletion of one of the F-group chromosomes, were observed in the bone marrow in ten patients. Eight of these had received 32P and two busulphan. In two cases the clone appeared to develop after treatment. A similar anomaly has been reported in several cases of idiopathic sideroblastic anaemia who had not been irradiated. Progression into the leukaemic phase of the disease is associated in some cases with gross chromosomal abnormalities, such as shift of the stem line chromosome number and bizarre chromosome 'markers'. In other cases, some of whom have not been irradiated for several years, the chromosomal changes are less pronounced and may result from non-disjunctional gain of one or more chromosomes or chromosome loss. One case showed a step-by-step clonal evolution over a two-year period. None of the chromosomal abnormalities in the 'leukaemic' phase appear to be a direct result of

  11. Cellular and molecular properties of {sup 90}Y-labeled cetuximab in combination with radiotherapy on human tumor cells in vitro

    Saki, M.; Toulany, M.; Rodemann, H.P. [Tuebingen Univ. (Germany). Div. of Radiobiology and Molecular Environmental Research; Sihver, W.; Zenker, M.; Heldt, J.M.; Mosch, B.; Pietzsch, H.J.; Steinbach, J. [Helmholtz-Zentrum Dresden-Rossendorf (HZDR) e.V., Dresden (Germany). Inst. of Radiopharmacy; Baumann, M. [Technische Univ. Dresden (Germany). Dept. of Radiation Oncology

    2012-09-15

    Purpose: Anti-EGFR antibody cetuximab (C225) is used in combination with radiotherapy of head and neck squamous cell carcinoma (HNSCC) patients. We investigated whether conjugation of cetuximab with trans-cyclohexyl-diethylene-triamine-pentaacetic acid (CHX-A''-DTPA) and radiolabeling with {sup 90}Yttrium affect the molecular and cellular function of cetuximab and improve its combined effect with external-beam irradiation (EBI). Methods: The following cell lines were used: HNSCC UT5, SAS, FaDu, as well as A43, Chinese hamster ovary cells (CHO), and human skin fibroblast HSF7. Binding affinity and kinetics, specificity, retention, and the combination of {sup 90}Y-cetuximab with EBI were evaluated. Results: Control cetuximab and CHX-A''-DTPA-cetuximab blocked the proliferation activity of UT5 cells. In combination with EBI, CHX-A''-DTPA-cetuximab increased the radiosensitivity of UT5 to a similar degree as control cetuximab did. In contrast, in SAS and HSF7 cells neither proliferation nor radiosensitivity was affected by either of the antibodies. Binding [{sup 90}Y]Y-CHX-A''-DTPA-cetuximab ({sup 90}Y-cetuximab) to EGFR in HNSCC cells occurred time dependently with a maximum binding at 24 h. Retention of {sup 90}Y-cetuximab was similar in both HNSCC cell lines; 24 h after treatment, approximately 90% of bound activity remained in the cell layer. Competition assays, using cell membranes in the absence of an internalized fraction of cetuximab, showed that the cetuximab affinity is not lost as a result of conjugation with CHX-A''-DTPA. Cetuximab and CHX-A''-DTPA-cetuximab blocked EGF-induced Y1068 phosphorylation of EGFR. The lack of an effect of cetuximab on EGF-induced Akt and ERK1/2 phosphorylation and the inhibition of irradiation (IR)-induced Akt and ERK1/2 phosphorylation by cetuximab were not affected by DTPA conjugation. {sup 90}Y-cetuximab in combination with EBI resulted in a pronounced inhibition of

  12. Kinetic studies on NH4+-N-induced uptake of 32P by maize

    Uptake studies on intact plants and excised roots of maize showed that there was inducement in the uptake and transport of 32P due to direct supply of NH4+-N. The inducement was about 20-30% more than that obtained due to direct NO3--N supply. Kinetic analysis of these processes revealed that values of Vsub(max) and Ksub(M) increased due to increasing levels of N supply. Thus the inducement was interpreted to occur through an acceleration of the step mediating the decomposition of carrier - P complex to release more P inside the cell. The mechanism of inducement in uptake and transport of P due to NH4-N was, therefore, similar to that due to NO3-N reported earlier. (author)

  13. Separation of phosphorous by liquid-liquid extraction for the measurement of 32P

    Phosphorous containing radioisotope waste was separated and determined by liquid-liquid extraction method through liquid scintillation counter (LSC). In this process, ammonium phosphate was converted to phosphomolybdate (PMo) by the reaction of ammonium molybdate (Mo) in HCl solution (0.02 M) and maximum UV/VIS absorbance (λmax) 218 nm was observed. The PMo solution was extracted with TOA (Tri-n-Octylamine)/xylene mixture and λmax 290 nm was found for this organic layer. Absorbance of aqueous and organic layer was linear through concentration. The impurities such as Co, Cr, Gd, etc. remain in aqueous layer by treating with Mo which was determined by ICP-AES and AAS. The quenching correction curve for 32P was calculated using LSC results. No counting change was observed as the volume of quenchers increased. The recovery was 98% and 81% for the extraction and separation process from the test using H332PO4 as standard tracer. (author)

  14. Design and construction of a prototype for the obtention of 32 P

    In the National Institute of Nuclear Research (ININ) it was designed, built and proved a prototype to obtain 32P in form of H332PO4, starting from irradiated Sα. The beginning of the prototype it is based on a distillation system in dry of the Sα in nitrogen atmosphere, and in the formation of the ion 32PO43- in acid solution. Due to the handling of radioactive material during the process, the prototype is inside a hot cell and it has a cylindrical oven that opens up lengthwise to the half, with controller of temperature and with a system of empty air for to transport reagents and products. The air-vacuum system is provided of filters and traps. The tests showed a recovery from 14 to 15% of the activity obtained during the irradiation. (Author)

  15. Detection of methylation damage in DNA of gastric cancer tissues using 32P-postlabelling assay

    Gastric cancer is the most common cancer in Korea. The causes are still unknown but it has been speculated that gastric cancer is associated with consumption of foods rich in nitrates/nitrites or a high dietary intake of salt or pickled food. In the present study, we studied the level of alkylated DNA adducts formed in gastric cancer tissues in comparison with that in normal gastric mucosa. DNA was extracted from surgically removed gastric cancer tissues and patient-matched normal gastric mucosa. The level of N7-methyldeoxyguanosine was measured by 32P-postlabelling assay after high performance liquid chromatography (HPLC) enrichment. We found that the level of N7-methyldeoxyguanosine of gastric cancerous tissues was significantly higher than that of normal gastric mucosa (P=0.01685). (author)

  16. Phosphorus Use Efficiency by Brazilian Common Bean Genotypes Assessed by the 32P Dilution Technique

    The objectives of this work were to identify the most efficient common bean (Phaseolus vulgaris L.) genotypes on phosphorus (P) utilization, and verify if P from the seed affects the classification of common bean genotypes on P uptake efficiency when the 32P isotopic dilution technique is used. The experiment was conducted in a greenhouse, and plants were grown in pots with surface samples of a dystrophic Typic Haplustox. The treatments consisted of 50 common bean genotypes and two standard plant species, efficient or inefficient in P uptake. The results were assessed through correlation and cluster analysis (multivariate). Sangue de Boi, Rosinha, Thayu, Grafite, Horizonte, Pioneiro and Jalo Precoce common bean genotypes were the most efficient on P uptake, and Carioca 80, CNF 10, Perola, IAPAR 31, Roxao EEP, Apore, Pioneiro, Pontal, Timbo and Ruda were the most efficient in P utilization. The P derived from seed influences the identification of common bean genotypes for P uptake efficiency. (author)

  17. Phosphorus Use Efficiency by Brazilian Upland Rice Genotypes Evaluated by the 32P Dilution Technique

    The objectives of this work were to identify the most efficient upland rice genotypes in phosphorus (P) utilization, and to verify if P from the seed affects the classification of upland rice genotypes on P uptake efficiency. The experiment was conducted in a greenhouse of the Center for Nuclear Energy in Agriculture (CENA/USP), Piracicaba, Sao Paulo, Brazil, using the 32P isotope technique, and plants were grown in pots with samples of dystrophic Typic Haplustox (Oxisol). The experimental design was completely randomized with four replications. The treatments consisted of 47 upland rice genotypes and two standard plant species, efficient or inefficient in P uptake. The results were assessed through correlation and cluster analysis (multivariate). The Carisma upland rice genotype was the most efficient in P uptake, and Caripuna was the most efficient on P utilization. The P derived from seed does not influence the identification of upland rice genotypes in P uptake efficiency. (author)

  18. 32P analysis of DNA adducts in tissues of benzene-treated rats

    Solid tumors have been reported in the Zymbal gland, oral and nasal cavities, liver, and mammary gland of Sprague-Dawley rats following chronic, high-dose administration of benzene. The carcinogenic activity of benzene is thought to be caused by activation to toxic metabolites that can interact with DNA, forming covalent adducts. A nuclease P1-enhanced 32P-postlabeling assay, having a sensitivity limit of 1 adduct in 10(9-10) DNA nucleotides, was found suitable for measuring aromatic DNA adducts derived in vitro from catechol, benzenetriol (BT), phenol, hydroquinone (HQ), and benzoquinone (BQ), potential metabolites of benzene. When DNA specimens isolated from tissues of female Sprague-Dawley rats at 24 hr after an oral gavage dose of 200 to 500 mg/kg, 5 days/week, in olive oil (3 mL/kg) for 1 day, 1 week, 5 weeks, and 10 weeks were analyzed by the 32P-postlabeling procedure, no aromatic adducts were detected unequivocally with DNA samples of liver, kidney, bone marrow, and mammary gland. With Zymbal gland DNA, three weak spots at levels totaling four lesions per 10(9) DNA nucleotides were seen only after 10 weeks of treatment, and these adducts did not correspond chromatographically to major adducts in vitro from the above specified compounds. Consequently, this finding requires confirmatory experiments. This distinct adduct pattern may relate to tumor induction in this organ following benzene administration. Our results also indicate that DNA adducts derived from catechol, BT, phenol, HQ, and BQ are either not formed in vivo with benzene or formed at levels below the detection limit of 1 adduct per 10(9-10) DNA nucleotides

  19. Effect of fasting on 32P translocations in pre-labelled pancreatic islets

    The rapid, short-lived efflux of inorganic 32P-orthophosphate that occurs when pre-labelled pancreatic islets are exposed to nutrient insulin secretagogues (the ''phosphate flush'') has been proposed to reflect some early step in β-cell secretory activation. In the present study, glucose-initiated phosphate efflux was studied during fasting.Pancreatic islets were isolated from fed and 48-h fasted rats by collagenase digestion. After pre-labelling with 32P-orthophosphate and basal perifusion with 0.5 mg/ml glucose, tissue analyses disclosed similar stores of radioactivity in the two groups of islets. Stimulatory perfusion with glucose at this time failed to promote insulin release from islets which had been secured from fasted donors although the ''phosphate flush'' was preserved. However, the characteristics of phosphate efflux were altered. Maximal glucose-induced phosphate release was greater with islets from fasted animals whereas phosphate release in response to low level stimulation with glucose was diminished. Accordingly, the dose-response curve for glucose-initiated phosphate efflux in islets from fasted rats was displaced to the right and compatible with a decreased sensitivity to glucose at the activation site for the ''phosphate flush.'' Thus, while glucose is unable to enhance insulin release in vitro after fasting, glucose still elicits increased phosphate efflux. However, the phenomenon appears to be attended by an impaired responsiveness to activation by glucose, supporting the contention that some early step in the sequence of stimulus secretion coupling in the β-cell may be obtunded after food deprivation. (author)

  20. The Use of 32P and 15N to Estimate Fertilizer Efficiency in Oil Palm

    Oil palm has become an important commodity for Indonesia reaching an area of 2.6 million ha at the end of 1998. It is mostly cultivated in highly weathered acid soil usually Ultisols and Oxisols which are known for their low fertility, concerning the major nutrients like N and P. This study most conducted to search for the most active root-zone of oil palm and applied urea fertilizer at such soils to obtain high N-efficiency. Carrier free KH232PO4 solution was used to determine the active root-zone of oil palm by applying 32P around the plant in twenty holes. After the most active root-zone have been determined, urea in one, two and three splits were respectively applied at this zone. To estimate N-fertilizer efficiency of urea labelled 15N Ammonium Sulphate was used by adding them at the same amount of 16 g 15N plan-1. This study showed that the most active root-zone was found at a 1.5 m distance from the plant-stem and at 5 cm soil depth. For urea the highest N-efficiency was obtained from applying it at two splits. The use of 32P was able to distinguish several root zones: 1.5 m - 2.5 m from the plant-stem at a 5 cm and 15 cm soil depth. Urea placed at the most active root-zone, which was at a 1.5 m distance from the plant-stem and at a 5 cm depth in one, two, and three splits respectively showed difference N-efficiency. The highest N-efficiency of urea was obtained when applying it in two splits at the most active root-zone. (author)

  1. Absorbed dose assessment of cardiac and other tissues around the cardiovascular system in brachytherapy with 90Sr/90Y source by Monte Carlo simulation

    Cardiac disease is one of the most important causes of death in the world. Coronary artery stenosis is a very common cardiac disease. Intravascular brachytherapy (IVBT) is one of the radiotherapy methods which have been used recently in coronary artery radiation therapy for the treatment of restenosis. 90Sr/90Y, a beta-emitting source, is a proper option for cardiovascular brachytherapy. In this research, a Monte Carlo simulation was done to calculate dosimetry parameters and effective equivalent doses to the heart and its surrounding tissues during IVBT. The results of this study were compared with the published experimental data and other simulations performed by different programs but with the same source of radiation. A very good agreement was found between results of this work and the published data. An assessment of the risk for cardiac and other sensitive soft tissues surrounding the treated vessel during 90Sr/90Y IVBT was also performed in the study. (authors)

  2. Dosimetry analysis of distributions radials dose profiles of 90Sr + 90Y beta therapy applicators using the MCNP-4C code and radio chromium films

    Although they are no longer manufactured, the applicators of 90Sr + 90Y acquired in the decades of 1990 are still in use, by having half-life of 28.5 years. These applicators have calibration certificate given by their manufacturers, where few have been re calibrated. Thus it becomes necessary to accomplish thorough dosimetry of these applicators. This paper presents a dosimetric analysis distribution radial dose profiles for emitted by an 90Sr + 90Y beta therapy applicator, using the MCNP-4C code to simulate the distribution radial dose profiles and radio chromium films to get them experimentally . The results with the simulated values were compared with the results of experimental measurements, where both curves show similar behavior, which may validate the use of MCNP-4C and radio chromium films for this type of dosimetry. (author)

  3. Dosimetry analysis of distribution radial dose profiles of 90Sr + 90Y beta therapy applicators using the MCNP-4C code and radio chromium films

    Although they are no longer manufactured, the applicators of 90Sr +90Y acquired in the decades of 1990 are still in use, by having half-life of 28.5 years. These applicators have calibration certificate given by their manufacturers, where few have been recalibrated. Thus it becomes necessary to accomplish thorough dosimetry of these applicators. This paper presents a dosimetric analysis distribution radial dose profiles for emitted by an 90Sr+90Y beta therapy applicator, using the MCNP-4C code to simulate the distribution radial dose profiles and radiochromium films to get them experimentally . The results with the simulated values were compared with the results of experimental measurements, where both curves show similar behavior, which may validate the use of MCNP-4C and radiochromium films for this type of dosimetry. (author)

  4. Optimization of energy window for {sup 90}Y bremsstrahlung SPECT imaging for detection tasks using the ideal observer with model-mismatch

    Rong Xing; Ghaly, Michael; Frey, Eric C. [Department of Radiology, Johns Hopkins University, Baltimore, Maryland 21287-0859 (United States)

    2013-06-15

    Purpose: In yttrium-90 ({sup 90}Y) microsphere brachytherapy (radioembolization) of unresectable liver cancer, posttherapy {sup 90}Y bremsstrahlung single photon emission computed tomography (SPECT) has been used to document the distribution of microspheres in the patient and to help predict potential side effects. The energy window used during projection acquisition can have a significant effect on image quality. Thus, using an optimal energy window is desirable. However, there has been great variability in the choice of energy window due to the continuous and broad energy distribution of {sup 90}Y bremsstrahlung photons. The area under the receiver operating characteristic curve (AUC) for the ideal observer (IO) is a widely used figure of merit (FOM) for optimizing the imaging system for detection tasks. The IO implicitly assumes a perfect model of the image formation process. However, for {sup 90}Y bremsstrahlung SPECT there can be substantial model-mismatch (i.e., difference between the actual image formation process and the model of it assumed in reconstruction), and the amount of the model-mismatch depends on the energy window. It is thus important to account for the degradation of the observer performance due to model-mismatch in the optimization of the energy window. The purpose of this paper is to optimize the energy window for {sup 90}Y bremsstrahlung SPECT for a detection task while taking into account the effects of the model-mismatch. Methods: An observer, termed the ideal observer with model-mismatch (IO-MM), has been proposed previously to account for the effects of the model-mismatch on IO performance. In this work, the AUC for the IO-MM was used as the FOM for the optimization. To provide a clinically realistic object model and imaging simulation, the authors used a background-known-statistically and signal-known-statistically task. The background was modeled as multiple compartments in the liver with activity parameters independently following a

  5. Optimization of energy window for 90Y bremsstrahlung SPECT imaging for detection tasks using the ideal observer with model-mismatch

    Purpose: In yttrium-90 (90Y) microsphere brachytherapy (radioembolization) of unresectable liver cancer, posttherapy 90Y bremsstrahlung single photon emission computed tomography (SPECT) has been used to document the distribution of microspheres in the patient and to help predict potential side effects. The energy window used during projection acquisition can have a significant effect on image quality. Thus, using an optimal energy window is desirable. However, there has been great variability in the choice of energy window due to the continuous and broad energy distribution of 90Y bremsstrahlung photons. The area under the receiver operating characteristic curve (AUC) for the ideal observer (IO) is a widely used figure of merit (FOM) for optimizing the imaging system for detection tasks. The IO implicitly assumes a perfect model of the image formation process. However, for 90Y bremsstrahlung SPECT there can be substantial model-mismatch (i.e., difference between the actual image formation process and the model of it assumed in reconstruction), and the amount of the model-mismatch depends on the energy window. It is thus important to account for the degradation of the observer performance due to model-mismatch in the optimization of the energy window. The purpose of this paper is to optimize the energy window for 90Y bremsstrahlung SPECT for a detection task while taking into account the effects of the model-mismatch. Methods: An observer, termed the ideal observer with model-mismatch (IO-MM), has been proposed previously to account for the effects of the model-mismatch on IO performance. In this work, the AUC for the IO-MM was used as the FOM for the optimization. To provide a clinically realistic object model and imaging simulation, the authors used a background-known-statistically and signal-known-statistically task. The background was modeled as multiple compartments in the liver with activity parameters independently following a Gaussian distribution; the

  6. Peptide receptor radionuclide therapy with 90Y/177Lu-labelled peptides for inoperable head and neck paragangliomas (glomus tumours)

    Head and neck paragangliomas (HNPGLs) are rare tumours arising from autonomic nervous system ganglia. Although surgery offers the best chance of complete cure, there is associated morbidity due to the crucial location of these tumours. Radiotherapy arrests tumour growth and provides symptomatic improvement, but has long-term consequences. These tumours express somatostatin receptors (SSTR) and hence peptide receptor radionuclide therapy (PRRT) is now a treatment option. We assessed the molecular, morphological and clinical responses of inoperable HNPGLs to PRRT. Nine patients with inoperable HNPGL assessed between June 2006 and June 2014 were included. Four patients had a solitary lesion, four had multifocal involvement and one had distant metastases (bone and lungs). The patients were treated with PRRT using 90Y/177Lu-labelled peptides after positive confirmation of SSTR expression on 68Ga-DOTATOC PET/CT. All patients received two to four courses of PRRT. Subsequent serial imaging with 68Ga-DOTATOC PET/CT was carried out every 6 months to assess response to treatment. Clinical (symptomatic) response was also assessed. Based on molecular response (EORTC) criteria, four of the nine patients showed a partial molecular response to treatment seen as significant decreases in SUVmax, accompanied by a reduction in tumour size. Five patients showed stable disease on both molecular and morphological criteria. Six out of nine patients were symptomatic at presentation with manifestations of cranial nerve involvement, bone destruction at the primary site and metastatic bone pain. Molecular responses were correlated with symptomatic improvement in four out of these six patients; while two patients showed small reductions in tumour size and SUVmax. The three asymptomatic patients showed no new lesions or symptomatic worsening. PRRT was effective in all patients, with no disease worsening seen, either in the form of neurological symptoms or distant spread. Though these are

  7. Investigation of a 90Sr/90Y source for intra-ocular treatment of wet age-related macular degeneration

    Purpose: The purpose of this study is to perform an extensive investigation of an approximately 2.5 mm long 90Sr/90Y source designed for treating wet age-related macular degeneration. Methods: As part of this investigation, a NIST-traceable absorbed dose to water calibration technique was established, and a source deployment verification test was developed. The influence of treatment cannula construction tolerance on the measurements as well as the dose delivered to the patient was investigated using the Monte Carlo code MCNP5. Variation between production cannulae was quantified experimentally using a well-type ionization chamber, and additional measurements along with Monte Carlo calculations of the collimating insert used for source deployment verification were performed to validate the model. Results: Maximum variation in the integrated target dose was seen when the source was shifted laterally within the treatment cannula. For the well chamber measurements, the observed standard deviation in ionization current for a single source placed in different reference cannulae was ±0.3%, with a maximum observed range of less than ±0.5%. Clinical cannulae in the collimating insert showed an average of 17.8%±0.4% of the reference signal when sources were fully deployed compared to 18.5% predicted by Monte Carlo calculations. This discrepancy has been attributed primarily to construction of the collimator since the collimation gap was observed to be approximately 0.025-0.075 mm smaller than specified. Construction tolerance of the well chamber insert as well as position tolerance of the cannula tip were both investigated, and their influence on the predicted signal was quantified. Additional measurements along with Monte Carlo based calculations of the collimating insert with polyethylene spacers added to the setup were performed to validate the Monte Carlo model. The shimmed Monte Carlo and measured data agree to within 1%, which is a magnitude difference of

  8. A study of 32P-phosphate uptake in a plant by a real-time RI imaging system

    It is very important to visualize the process of nutrient absorption and distribution to study the physiological activity of the plant. We developed a real-time radioisotope (RI) imaging system, where RI tracers were applied to the plant sample. This system allowed the quantitative measurement concerning the uptake of nutrients labeled with radioisotopes, such as 45Ca, 35S, 32P and 14C as long as several days. The β-rays emitted from the sample were converted to light by a CsI(Tl) scintillator and were guided to a highly sensitive CCD camera. The scintillator surface was covered with an Al plate to avoid LED light penetration but allow selected β-ray penetration. We employed Lotus japonicus for the plant sample and observed the 32P-phosphate absorption in roots and the accumulation to the aboveground part of the plant. The environment condition of daytime and night was simulated by the ON/OFF of LED timer and the accumulation manner of the 32P-phosphate in roots and leaves during daytime and night was analyzed. The accumulation of 32P-phosphate in leaves was highly dependant on light irradiation and higher when the LEDs was turned on, whereas the absorption of 32P-phosphate in root was higher when the LEDs was turned off. The transfer function concerning the transportation of phosphate within the plant during the developmental stage was obtained from the analysis of 32P uptake images. We are now trying to get specific moving images of each radioisotope when two kinds of isotopes, such as 32P and 32S, were applied at the same time to the plant, through an image analysis. (orig.)

  9. Sustained safety and efficacy of extended-shelf-life 90Y glass microspheres: long-term follow-up in a 134-patient cohort

    To validate our initial pilot study and confirm sustained safety and tumor response of extended-shelf-life 90Y glass microspheres. We hypothesized that for the same planned tissue dose, the increase in number of glass microspheres (decayed to the second week of their allowable shelf-life) administered for the same absorbed dose would result in better tumor distribution of the microspheres without causing additional adverse events. Between June 2007 and January 2010, 134 patients underwent radioembolization with extended-shelf-life 90Y glass microspheres; data from 84 new patients were combined with data from our 50-patient pilot study cohort. Baseline and follow-up imaging and laboratory data were obtained 1 and 3 months after therapy and every 3 months thereafter. Clinical and biochemical toxicities were prospectively captured and categorized according to the Common Terminology Criteria. Response in the index lesion was assessed using WHO and EASL guidelines. The mean delivered radiation dose was 123 Gy to the target liver tissue. The mean increase in number of microspheres with this approach compared to standard 90Y glass microsphere dosimetry was 103 %, corresponding to an increase from 3.84 to 7.78 million microspheres. Clinical toxicities included fatigue (89 patients, 66 %), abdominal pain (49 patients, 36.6 %), and nausea/vomiting (25 patients, 18.7 %). Grade 3/4 bilirubin toxicity was seen in three patients (2 %). Two (1 %) of the initial 50-patient cohort showed gastroduodenal ulcers; gastroduodenal ulcers were not seen in any of the subsequent 84 patients. According to WHO and EASL guidelines, response rates were 48 % and 57 %, respectively, and 21 % demonstrated a complete EASL response. This study showed sustained safety and efficacy of extended-shelf-life 90Y glass microspheres in a larger, 134-patient cohort. The increase in number of microspheres administered theoretically resulted in better tumor distribution of the microspheres without an increase

  10. 90Y-daclizumab, an anti-CD25 monoclonal antibody, provided responses in 50% of patients with relapsed Hodgkin’s lymphoma

    Janik, John E.; Morris, John C.; O’Mahony, Deirdre; Pittaluga, Stefania; Jaffe, Elaine S.; Redon, Christophe E.; Bonner, William M.; Brechbiel, Martin W.; Paik, Chang H.; Whatley, Millie; Chen, Clara; Lee, Jae-Ho; Fleisher, Thomas A.; Brown, Maggie; White, Jeffrey D.; Stewart, Donn M.; Fioravanti, Suzanne; Lee, Cathryn C.; Goldman, Carolyn K.; Bryant, Bonita R.; Junghans, Richard P.; Carrasquillo, Jorge A.; Worthy, Tat’Yana; Corcoran, Erin; Conlon, Kevin C.; Waldmann, Thomas A.

    2015-01-01

    Despite significant advances in the treatment of Hodgkin’s lymphoma (HL), a significant proportion of patients will not respond or will subsequently relapse. We identified CD25, the IL-2 receptor alpha subunit, as a favorable target for systemic radioimmunotherapy of HL. The scientific basis for the clinical trial was that, although most normal cells with exception of Treg cells do not express CD25, it is expressed by a minority of Reed–Sternberg cells and by most polyclonal T cells rosetting around Reed–Sternberg cells. Forty-six patients with refractory and relapsed HL were evaluated with up to seven i.v. infusions of the radiolabeled anti-CD25 antibody 90Y-daclizumab. 90Y provides strong β emissions that kill tumor cells at a distance by a crossfire effect. In 46 evaluable HL patients treated with 90Y-daclizumab there were 14 complete responses and nine partial responses; 14 patients had stable disease, and nine progressed. Responses were observed both in patients whose Reed–Sternberg cells expressed CD25 and in those whose neoplastic cells were CD25− provided that associated rosetting T cells expressed CD25. As assessed using phosphorylated H2AX (γ-H2AX) as a bioindicator of the effects of radiation exposure, predominantly nonmalignant cells in the tumor microenvironment manifested DNA damage, as reflected by increased expression of γ-H2AX. Toxicities were transient bone-marrow suppression and myelodysplastic syndrome in six patients who had not been evaluated with bone-marrow karyotype analyses before therapy. In conclusion, repeated 90Y-daclizumab infusions directed predominantly toward nonmalignant T cells rosetting around Reed–Sternberg cells provided meaningful therapy for select HL patients. PMID:26438866

  11. 90Y-daclizumab, an anti-CD25 monoclonal antibody, provided responses in 50% of patients with relapsed Hodgkin's lymphoma.

    Janik, John E; Morris, John C; O'Mahony, Deirdre; Pittaluga, Stefania; Jaffe, Elaine S; Redon, Christophe E; Bonner, William M; Brechbiel, Martin W; Paik, Chang H; Whatley, Millie; Chen, Clara; Lee, Jae-Ho; Fleisher, Thomas A; Brown, Maggie; White, Jeffrey D; Stewart, Donn M; Fioravanti, Suzanne; Lee, Cathryn C; Goldman, Carolyn K; Bryant, Bonita R; Junghans, Richard P; Carrasquillo, Jorge A; Worthy, Tat'Yana; Corcoran, Erin; Conlon, Kevin C; Waldmann, Thomas A

    2015-10-20

    Despite significant advances in the treatment of Hodgkin's lymphoma (HL), a significant proportion of patients will not respond or will subsequently relapse. We identified CD25, the IL-2 receptor alpha subunit, as a favorable target for systemic radioimmunotherapy of HL. The scientific basis for the clinical trial was that, although most normal cells with exception of Treg cells do not express CD25, it is expressed by a minority of Reed-Sternberg cells and by most polyclonal T cells rosetting around Reed-Sternberg cells. Forty-six patients with refractory and relapsed HL were evaluated with up to seven i.v. infusions of the radiolabeled anti-CD25 antibody (90)Y-daclizumab. (90)Y provides strong β emissions that kill tumor cells at a distance by a crossfire effect. In 46 evaluable HL patients treated with (90)Y-daclizumab there were 14 complete responses and nine partial responses; 14 patients had stable disease, and nine progressed. Responses were observed both in patients whose Reed-Sternberg cells expressed CD25 and in those whose neoplastic cells were CD25(-) provided that associated rosetting T cells expressed CD25. As assessed using phosphorylated H2AX (γ-H2AX) as a bioindicator of the effects of radiation exposure, predominantly nonmalignant cells in the tumor microenvironment manifested DNA damage, as reflected by increased expression of γ-H2AX. Toxicities were transient bone-marrow suppression and myelodysplastic syndrome in six patients who had not been evaluated with bone-marrow karyotype analyses before therapy. In conclusion, repeated (90)Y-daclizumab infusions directed predominantly toward nonmalignant T cells rosetting around Reed-Sternberg cells provided meaningful therapy for select HL patients. PMID:26438866

  12. Sustained safety and efficacy of extended-shelf-life {sup 90}Y glass microspheres: long-term follow-up in a 134-patient cohort

    Lewandowski, Robert J.; Minocha, Jeet; Memon, Khairuddin; Riaz, Ahsun; Gates, Vanessa L.; Ryu, Robert K.; Sato, Kent T.; Omary, Reed; Salem, Riad [Northwestern University, Department of Radiology, Chicago, IL (United States)

    2014-03-15

    To validate our initial pilot study and confirm sustained safety and tumor response of extended-shelf-life {sup 90}Y glass microspheres. We hypothesized that for the same planned tissue dose, the increase in number of glass microspheres (decayed to the second week of their allowable shelf-life) administered for the same absorbed dose would result in better tumor distribution of the microspheres without causing additional adverse events. Between June 2007 and January 2010, 134 patients underwent radioembolization with extended-shelf-life {sup 90}Y glass microspheres; data from 84 new patients were combined with data from our 50-patient pilot study cohort. Baseline and follow-up imaging and laboratory data were obtained 1 and 3 months after therapy and every 3 months thereafter. Clinical and biochemical toxicities were prospectivel